Testing under a Modified Cox Regression Model
Testing under a Modified Cox Regression Model Dissertation zur Erlangung des Doktorgrades der Mathematical Model . . . . . . . . . . . . . . . . . . . 4 1.3 The Modified Cox Regression Model.1 On the Existence of the Modified Cox Regression Model . . . . 141 5.2 Checking Further Conditions
Mixed discrete and continuous Cox regression model.
Prentice, Ross L; Kalbfleisch, John D
2003-06-01
The Cox (1972) regression model is extended to include discrete and mixed continuous/discrete failure time data by retaining the multiplicative hazard rate form of the absolutely continuous model. Application of martingale arguments to the regression parameter estimating function show the Breslow(1974) estimator to be consistent and asymptotically Gaussian under this model. A computationally convenient estimator of the variance of the score function can be developed, again using martingale arguments. This estimator reduces to the usual hypergeometric form in the special case of testing equality of several survival curves, and it leads more generally to a convenient consistent variance estimator for the regression parameter. A small simulation study is carried out to study the regression parameter estimator and its variance estimator under the discrete Cox model special case and an application to a bladder cancer recurrence dataset is provided. PMID:12735496
Hable, Robert
Setup Optimisation problem Solutions for robust regression Cox regression A simulation study for robust regression Cox regression A simulation study Outline of the talk Subject Estimation) and approximate solution Approximate solution in semiparametric regression models Cox regression Simulation study
Understanding the Cox Regression Models with Time-Change Covariates
Zhou, Mai
Understanding the Cox Regression Models with Time-Change Covariates Mai Zhou University of Kentucky The Cox regression model is a cornerstone of modern survival analysis and is widely used in many other fields as well. But the Cox models with time-change covariates are not easy to understand or visualize
Information and Asymptotic Efficiency of the Case-Cohort Sampling Design in Cox's Regression
Goldstein, Larry
Information and Asymptotic Efficiency of the Case-Cohort Sampling Design in Cox, Semiparametric Model, Epidemiology, Case-Cohort Design, Counting Process, Cox Regression Model. 2 #12; 1 Introduction Cox's proportional hazards regression model (Cox 1972) is often used
Univariate Nonparametric Analysis of Variance Through Multiple Linear Regression
ERIC Educational Resources Information Center
Huitema, Bradley E.
1978-01-01
Many methodologists are aware that parametric tests associated with the analysis of variance and the analysis of covariance can be computed using regression procedures. It is shown that multiple linear regression can also be employed to compute the Kruskal-Wallis nonparametric analysis of variance. (Author)
Partial least squares Cox regression for genome-wide data.
Nygård, Ståle; Borgan, Ornulf; Lingjaerde, Ole Christian; Størvold, Hege Leite
2008-06-01
Most methods for survival prediction from high-dimensional genomic data combine the Cox proportional hazards model with some technique of dimension reduction, such as partial least squares regression (PLS). Applying PLS to the Cox model is not entirely straightforward, and multiple approaches have been proposed. The method of Park etal. (Bioinformatics 18(Suppl. 1):S120-S127, 2002) uses a reformulation of the Cox likelihood to a Poisson type likelihood, thereby enabling estimation by iteratively reweighted partial least squares for generalized linear models. We propose a modification of the method of Park et al. (2002) such that estimates of the baseline hazard and the gene effects are obtained in separate steps. The resulting method has several advantages over the method of Park et al. (2002) and other existing Cox PLS approaches, as it allows for estimation of survival probabilities for new patients, enables a less memory-demanding estimation procedure, and allows for incorporation of lower-dimensional non-genomic variables like disease grade and tumor thickness. We also propose to combine our Cox PLS method with an initial gene selection step in which genes are ordered by their Cox score and only the highest-ranking k% of the genes are retained, obtaining a so-called supervised partial least squares regression method. In simulations, both the unsupervised and the supervised version outperform other Cox PLS methods. PMID:18188699
Cumulants and Bartlett Identities in Cox Regression Per Aslak Mykland1
Mykland, Per A.
Cumulants and Bartlett Identities in Cox Regression by Per Aslak Mykland1 and Jianming Ye2. Running head: Cox regression. #12;Cumulants and Bartlett Identities in Cox Regression by Per Aslak Mykland1 and Jianming Ye2 Abstract Expressions are found for the cumulants needed to analyze Cox re
Cox's Regression Model for Counting Processes: A Large Sample Study
P. K. Andersen; R. D. Gill
1982-01-01
The Cox regression model for censored survival data specifies that covariates have a proportional effect on the hazard function of the life-time distribution of an individual. In this paper we discuss how this model can be extended to a model where covariate processes have a proportional effect on the intensity process of a multivariate counting process. This permits a statistical
Reid, Nancy
Cox Proportional-Hazards Regression for Survival Data Appendix to An R and S-PLUS Companion in the survival-analysis literature. The subject of this appendix is the Cox proportional-hazards regression model (introduced in a seminal paper by Cox, 1972), a broadly applicable and the most widely used method of survival
van Houwelingen, Hans C; Putter, Hein
2015-04-01
By far the most popular model to obtain survival predictions for individual patients is the Cox model. The Cox model does not make any assumptions on the underlying hazard, but it relies heavily on the proportional hazards assumption. The most common ways to circumvent this robustness problem are 1) to categorize patients based on their prognostic risk score and to base predictions on Kaplan-Meier curves for the risk categories, or 2) to include interactions with the covariates and suitable functions of time. Robust estimators of the t(0)-year survival probabilities can also be obtained from a "stopped Cox" regression model, in which all observations are administratively censored at t(0). Other recent approaches to solve this robustness problem, originally proposed in the context of competing risks, are pseudo-values and direct binomial regression, based on unbiased estimating equations. In this paper stopped Cox regression is compared with these direct approaches. This is done by means of a simulation study to assess the biases of the different approaches and an analysis of breast cancer data to get some feeling for the performance in practice. The tentative conclusion is that stopped Cox and direct models agree well if the follow-up is not too long. There are larger differences for long-term follow-up data. There stopped Cox might be more efficient, but less robust. PMID:25084763
Cox regression model for dissecting genetic architecture of survival time.
Jiang, Dan; Wang, Hongwei; Li, Jiahan; Wu, Yang; Fang, Ming; Yang, Runqing
2014-12-01
Common quantitative trait locus (QTL) mapping methods fail to analyze survival traits of skewed normal distributions. As a result, some mapping methods for survival traits have been proposed based on survival analysis. Under a single QTL model, however, those methods perform poorly in detecting multiple QTLs and provide biased estimates of QTL parameters. For sparse oversaturated model used to map survival time loci, the least absolute shrinkage and selection operator (LASSO) for Cox regression model can be employed to efficiently shrink most of genetic effects to zero. Then, a few non-zero genetic effects are re-estimated and statistically tested using the standard maximum Cox partial likelihood method. Simulation shows that the proposed method has higher statistic power for QTL detection than that of the LASSO for logarithmic linear model or the interval mapping based on Cox model, although it somewhat underestimates QTL effects. Especially, computational speed of the method is very fast. An application of this method illustrates mapping main effect and interacting QTLs for heading time in the North American Barley Genome Mapping Project. PMID:25311647
Flood Frequency Analysis Using the Cox Regression Model
NASA Astrophysics Data System (ADS)
Smith, James A.; Karr, Alan F.
1986-06-01
Procedures for incorporating time-varying exogenous information into flood frequency analyses are developed using the Cox regression model for counting processes. In this statistical model the probability of occurrence of a flood peak in a short interval [t, t + dt) depends in an explicit manner on the values at t of k "covariate" processes Z1, …, Zk. Specifically, letting dN(t) be 1 if a flood peak occurs in [t, t + dt) and 0 otherwise, dN(t) = a(t) exp {?j=1kbjZj(t)} + dM(t) where a, the "baseline intensity," is an unknown function, b is a vector of unknown "regression" parameters, and the error dM(t) is (conditionally) orthogonal to the past history. Two applications, assessment of relative importance of physical processes such as snow melt or soil moisture storage on flood frequency at a site and derivation of time-varying flood frequency estimates, are considered.
Cox regression methods for two-stage randomization designs.
Lokhnygina, Yuliya; Helterbrand, Jeffrey D
2007-06-01
Two-stage randomization designs (TSRD) are becoming increasingly common in oncology and AIDS clinical trials as they make more efficient use of study participants to examine therapeutic regimens. In these designs patients are initially randomized to an induction treatment, followed by randomization to a maintenance treatment conditional on their induction response and consent to further study treatment. Broader acceptance of TSRDs in drug development may hinge on the ability to make appropriate intent-to-treat type inference within this design framework as to whether an experimental induction regimen is better than a standard induction regimen when maintenance treatment is fixed. Recently Lunceford, Davidian, and Tsiatis (2002, Biometrics 58, 48-57) introduced an inverse probability weighting based analytical framework for estimating survival distributions and mean restricted survival times, as well as for comparing treatment policies at landmarks in the TSRD setting. In practice Cox regression is widely used and in this article we extend the analytical framework of Lunceford et al. (2002) to derive a consistent estimator for the log hazard in the Cox model and a robust score test to compare treatment policies. Large sample properties of these methods are derived, illustrated via a simulation study, and applied to a TSRD clinical trial. PMID:17425633
BIOMETRICS55, 580-584 A Global Goodness-of-Fit Statistic for Cox Regression Models
Wolfe, Patrick J.
BIOMETRICS55, 580-584 June 1999 A Global Goodness-of-Fit Statistic for Cox Regression Models@biostat.harvard.edu SUMMARY.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
Misspecification of Cox regression models with composite endpoints
Wu, Longyang; Cook, Richard J
2012-01-01
Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22736519
Factors Associated with Methadone Treatment Duration: A Cox Regression Analysis
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
Parzen, Michael
Approximate Median Regression via the Box-Cox Transformation Garrett M. Fitzmaurice, Stuart R regression parameters via Gaussian estimating equa- tions after applying a Box-Cox transformation to both applying a Box-Cox transformation (Box and Cox 1964) to both the out- come and linear predictor. We relate
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…
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…
Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.
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
Estimation of treatment effects based on possibly misspecified Cox regression.
Hattori, Satoshi; Henmi, Masayuki
2012-10-01
In randomized clinical trials, a treatment effect on a time-to-event endpoint is often estimated by the Cox proportional hazards model. The maximum partial likelihood estimator does not make sense if the proportional hazard assumption is violated. Xu and O'Quigley (Biostatistics 1:423-439, 2000) proposed an estimating equation, which provides an interpretable estimator for the treatment effect under model misspecification. Namely it provides a consistent estimator for the log-hazard ratio among the treatment groups if the model is correctly specified, and it is interpreted as an average log-hazard ratio over time even if misspecified. However, the method requires the assumption that censoring is independent of treatment group, which is more restricted than that for the maximum partial likelihood estimator and is often violated in practice. In this paper, we propose an alternative estimating equation. Our method provides an estimator of the same property as that of Xu and O'Quigley under the usual assumption for the maximum partial likelihood estimation. We show that our estimator is consistent and asymptotically normal, and derive a consistent estimator of the asymptotic variance. If the proportional hazards assumption holds, the efficiency of the estimator can be improved by applying the covariate adjustment method based on the semiparametric theory proposed by Lu and Tsiatis (Biometrika 95:679-694, 2008). PMID:22527680
Insan Tunali; JONATHAN B. PRITCHETT
1997-01-01
Event data can often be analysed using different concepts of waiting time. Our application offers three choices: calendar-time, age, and duration of residence in New Orleans. We exploit the semi-parametric features of Cox regression and estimate parallel specifications in which mortality risk is treated as an arbitrary function of one of the three alternative time measures, while the remaining two
NETWORK-REGULARIZED HIGH-DIMENSIONAL COX REGRESSION FOR ANALYSIS OF GENOMIC DATA
Sun, Hokeun; Lin, Wei; Feng, Rui; Li, Hongzhe
2015-01-01
We consider estimation and variable selection in high-dimensional Cox regression when a prior knowledge of the relationships among the covariates, described by a network or graph, is available. A limitation of the existing methodology for survival analysis with high-dimensional genomic data is that a wealth of structural information about many biological processes, such as regulatory networks and pathways, has often been ignored. In order to incorporate such prior network information into the analysis of genomic data, we propose a network-based regularization method for high-dimensional Cox regression; it uses an ?1-penalty to induce sparsity of the regression coefficients and a quadratic Laplacian penalty to encourage smoothness between the coefficients of neighboring variables on a given network. The proposed method is implemented by an efficient coordinate descent algorithm. In the setting where the dimensionality p can grow exponentially fast with the sample size n, we establish model selection consistency and estimation bounds for the proposed estimators. The theoretical results provide insights into the gain from taking into account the network structural information. Extensive simulation studies indicate that our method outperforms Lasso and elastic net in terms of variable selection accuracy and stability. We apply our method to a breast cancer gene expression study and identify several biologically plausible subnetworks and pathways that are associated with breast cancer distant metastasis.
Dynamics of HPV vaccination initiation in Flanders (Belgium) 2007-2009: a Cox regression model
Eva Lefevere; Niel Hens; Frank De Smet; Pierre Van Damme
2011-01-01
Background We investigated dynamic patterns and predictors of HPV vaccination initiation in Flanders (Belgium) by girls aged 12 to 18,\\u000a between 2007 and 2009, the period immediately after the introduction of the HPV vaccines on the Belgian market. During this\\u000a period the initiative for vaccination was taken by the girl, her family or the general practitioner\\/pediatrician\\/gynecologist.\\u000a \\u000a \\u000a \\u000a \\u000a Methods We used a Cox regression
Adelian, R.; Jamali, J.; Zare, N.; Ayatollahi, S. M. T.; Pooladfar, G. R.; Roustaei, N.
2015-01-01
Background: Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. Objective: To compare Cox’s regression model with parametric models for determining the independent factors for predicting adults’ and pediatrics’ survival after liver transplantation. Method: This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Result: Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Conclusion: Parametric regression model is a good alternative for the Cox’s regression model. PMID:26306158
Power of logrank test and Cox regression model in clinical trials with heterogeneous samples.
Akazawa, K; Nakamura, T; Palesch, Y
1997-03-15
This paper evaluates the loss of power of the simple and stratified logrank tests due to heterogeneity of patients in clinical trials and proposes a flexible and efficient method of estimating treatment effects adjusting for prognostic factors. The results of the paper are based on the analyses of survival data from a large clinical trial which includes more than 6000 cancer patients. Major findings from the simulation study on power are: (i) for a heterogeneous sample, such as advanced cancer patients, a simple logrank test can yield misleading results and should not be used; (ii) the stratified logrank test may suffer some power loss when many prognostic factors need to be considered and the number of patients within stratum is small. To address the problems due to heterogeneity, the Cox regression method with a special hazard model is recommended. We illustrate the method using data from a gastric cancer clinical trial. PMID:9089965
Accommodating measurements below a limit of detection: a novel application of Cox regression.
Dinse, Gregg E; Jusko, Todd A; Ho, Lindsey A; Annam, Kaushik; Graubard, Barry I; Hertz-Picciotto, Irva; Miller, Frederick W; Gillespie, Brenda W; Weinberg, Clarice R
2014-04-15
In environmental epidemiology, measurements of exposure biomarkers often fall below the assay's limit of detection. Existing methods for handling this problem, including deletion, substitution, parametric regression, and multiple imputation, can perform poorly if the proportion of "nondetects" is high or parametric models are mis-specified. We propose an approach that treats the measured analyte as the modeled outcome, implying a role reversal when the analyte is a putative cause of a health outcome. Following a scale reversal as well, our approach uses Cox regression to model the analyte, with confounder adjustment. The method makes full use of quantifiable analyte measures, while appropriately treating nondetects as censored. Under the proportional hazards assumption, the hazard ratio for a binary health outcome is interpretable as an adjusted odds ratio: the odds for the outcome at any particular analyte concentration divided by the odds given a lower concentration. Our approach is broadly applicable to cohort studies, case-control studies (frequency matched or not), and cross-sectional studies conducted to identify determinants of exposure. We illustrate the method with cross-sectional survey data to assess sex as a determinant of 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration and with prospective cohort data to assess the association between 2,4,4'-trichlorobiphenyl exposure and psychomotor development. PMID:24671072
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.
Maximum Likelihood Inference for the Cox Regression Model with Applications to Missing Covariates.
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
Dehesh, Tania; Zare, Najaf; Ayatollahi, Seyyed Mohammad Taghi
2015-01-01
Background. Univariate meta-analysis (UM) procedure, as a technique that provides a single overall result, has become increasingly popular. Neglecting the existence of other concomitant covariates in the models leads to loss of treatment efficiency. Our aim was proposing four new approximation approaches for the covariance matrix of the coefficients, which is not readily available for the multivariate generalized least square (MGLS) method as a multivariate meta-analysis approach. Methods. We evaluated the efficiency of four new approaches including zero correlation (ZC), common correlation (CC), estimated correlation (EC), and multivariate multilevel correlation (MMC) on the estimation bias, mean square error (MSE), and 95% probability coverage of the confidence interval (CI) in the synthesis of Cox proportional hazard models coefficients in a simulation study. Result. Comparing the results of the simulation study on the MSE, bias, and CI of the estimated coefficients indicated that MMC approach was the most accurate procedure compared to EC, CC, and ZC procedures. The precision ranking of the four approaches according to all above settings was MMC ? EC ? CC ? ZC. Conclusion. This study highlights advantages of MGLS meta-analysis on UM approach. The results suggested the use of MMC procedure to overcome the lack of information for having a complete covariance matrix of the coefficients.
High-dimensional, massive sample-size Cox proportional hazards regression for survival analysis
Mittal, Sushil; Madigan, David; Burd, Randall S.; Suchard, Marc A.
2014-01-01
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
High-dimensional, massive sample-size Cox proportional hazards regression for survival analysis.
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
Effect of Berkson measurement error on parameter estimates in Cox regression models.
Küchenhoff, Helmut; Bender, Ralf; Langner, Ingo
2007-06-01
We study the effect of additive and multiplicative Berkson measurement error in Cox proportional hazard model. By plotting the true and the observed survivor function and the true and the observed hazard function dependent on the exposure one can get ideas about the effect of this type of error on the estimation of the slope parameter corresponding to the variable measured with error. As an example, we analyze the measurement error in the situation of the German Uranium Miners Cohort Study both with graphical methods and with a simulation study. We do not see a substantial bias in the presence of small measurement error and in the rare disease case. Even the effect of a Berkson measurement error with high variance, which is not unrealistic in our example, is a negligible attenuation of the observed effect. However, this effect is more pronounced for multiplicative measurement error. PMID:17401682
On the use of Cox regression in the presence of an irregularly observed time-dependent covariate.
de Bruijne, M H; le Cessie, S; Kluin-Nelemans, H C; van Houwelingen, H C
2001-12-30
We consider the joint modelling of longitudinal and event time data. The longitudinal data are irregularly collected and the event times are subject to right censoring. Most methods described in the literature are quite complex and do not belong to the standard statistical tools. We propose a more practical approach using Cox regression with time-dependent covariates. Since the longitudinal data are observed irregularly, we have to account for differences in observation frequency between individual patients. Therefore, the time elapsed since last observation (TEL) is added to the model. TEL and its interaction with the time-dependent covariate show a strong effect on the hazard. The latter indicates that older recordings have less impact than recent recordings. Pros and cons of this methodology are discussed and a simulation study is performed to study the effect of TEL on the hazard. The fitted Cox model serves as a starting point for the prediction of future patient's events. Our method is applied to a study on chronic myeloid leukaemia (CML) with longitudinal white blood cell counts (WBC) as time-dependent covariate and patient's death as event. PMID:11782036
Zemmour, Christophe; Bertucci, François; Finetti, Pascal; Chetrit, Bernard; Birnbaum, Daniel; Filleron, Thomas; Boher, Jean-Marie
2015-01-01
BACKGROUND DNA microarray studies identified gene expression signatures predictive of metastatic relapse in early breast cancer. Standard feature selection procedures applied to reduce the set of predictive genes did not take into account the correlation between genes. In this paper, we studied the performances of three high-dimensional regression methods – CoxBoost, LASSO (Least Absolute Shrinkage and Selection Operator), and Elastic net – to identify prognostic signatures in patients with early breast cancer. METHODS We analyzed three public retrospective datasets, including a total of 384 patients with axillary lymph node-negative breast cancer. The Amsterdam van’t Veer’s training set of 78 patients was used to determine the optimal gene sets and classifiers using sensitivity thresholds resulting in mis-classification of no more than 10% of the poor-prognosis group. To ensure the comparability between different methods, an automatic selection procedure was used to determine the number of genes included in each model. The van de Vijver’s and Desmedt’s datasets were used as validation sets to evaluate separately the prognostic performances of our classifiers. The results were compared to the original Amsterdam 70-gene classifier. RESULTS The automatic selection procedure reduced the number of predictive genes up to a minimum of six genes. In the two validation sets, the three models (Elastic net, LASSO, and CoxBoost) led to the definition of genomic classifiers predicting the 5-year metastatic status with similar performances, with respective 59, 56, and 54% accuracy, 83, 75, and 83% sensitivity, and 53, 52, and 48% specificity in the Desmedt’s dataset. In comparison, the Amsterdam 70-gene signature showed 45% accuracy, 97% sensitivity, and 34% specificity. The gene overlap and the classification concordance between the three classifiers were high. All the classifiers added significant prognostic information to that provided by the traditional prognostic factors and showed a very high overlap with respect to gene ontologies (GOs) associated with genes overexpressed in the predicted poor-prognosis vs. good-prognosis classes and centred on cell proliferation. Interestingly, all classifiers reported high sensitivity to predict the 4-year status of metastatic disease. CONCLUSIONS High-dimensional regression methods are attractive in prognostic studies because finding a small subset of genes may facilitate the transfer to the clinic, and also because they strengthen the robustness of the model by limiting the selection of false-positive predictive genes. With only six genes, the CoxBoost classifier predicted the 4-year status of metastatic disease with 93% sensitivity. Selecting a few genes related to ontologies other than cell proliferation might further improve the overall sensitivity performance. PMID:25983547
Liu, Wei; Wang, Qiuyu; Zhao, Jianmei; Zhang, Chunlong; Liu, Yuejuan; Zhang, Jian; Bai, Xuefeng; Li, Xuecang; Feng, Houming; Liao, Mingzhi; Wang, Wei; Li, Chunquan
2015-07-01
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
Leffondré, Karen; Abrahamowicz, Michal; Siemiatycki, Jack
2003-12-30
Case-control studies are typically analysed using the conventional logistic model, which does not directly account for changes in the covariate values over time. Yet, many exposures may vary over time. The most natural alternative to handle such exposures would be to use the Cox model with time-dependent covariates. However, its application to case-control data opens the question of how to manipulate the risk sets. Through a simulation study, we investigate how the accuracy of the estimates of Cox's model depends on the operational definition of risk sets and/or on some aspects of the time-varying exposure. We also assess the estimates obtained from conventional logistic regression. The lifetime experience of a hypothetical population is first generated, and a matched case-control study is then simulated from this population. We control the frequency, the age at initiation, and the total duration of exposure, as well as the strengths of their effects. All models considered include a fixed-in-time covariate and one or two time-dependent covariate(s): the indicator of current exposure and/or the exposure duration. Simulation results show that none of the models always performs well. The discrepancies between the odds ratios yielded by logistic regression and the 'true' hazard ratio depend on both the type of the covariate and the strength of its effect. In addition, it seems that logistic regression has difficulty separating the effects of inter-correlated time-dependent covariates. By contrast, each of the two versions of Cox's model systematically induces either a serious under-estimation or a moderate over-estimation bias. The magnitude of the latter bias is proportional to the true effect, suggesting that an improved manipulation of the risk sets may eliminate, or at least reduce, the bias. PMID:14673938
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.
Log Gaussian Cox processes Jesper Mller,
Watkins, Joseph C.
Log Gaussian Cox processes by Jesper Møller, Anne Randi Syversveen, and Rasmus Plenge Waagepetersen. #12;#12;Log Gaussian Cox processes JESPER MØLLER Aalborg University ANNE RANDI SYVERSVEEN. Planar Cox processes directed by a log Gaussian intensity process are investigated in the univariate
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…
... series of sudden spurts interspersed with periods of little apparent improvement. At times, a child may even regress in her learning—that is, lose skills she has recently acquired or even take a few steps back in her learning process. Regression during toilet ...
Counting decomposable univariate polynomials
Gathen, Joachim von zur
2009-01-01
A univariate polynomial f over a field is decomposable if it is the composition f = g(h) of two polynomials g and h whose degree is at least 2. We determine the dimension (over an algebraically closed field) of the set of decomposables, and an approximation to their number over a finite field. The tame case, where the field characteristic p does not divide the degree n of f, is reasonably well understood, and we obtain exponentially decreasing error bounds. The wild case, where p divides n, is more challenging and our error bounds are weaker.
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
NSDL National Science Digital Library
2010-01-01
In this activity, students click on a coordinate plane to plot points and view the best-fit line for those points. Students can also adjust their own fit line to test their skills at predicting the best-fit line. This activity allows students to explore linear regression and the correlation coefficient, r. This activity includes supplemental materials, including background information about the topics covered, a description of how to use the application, and exploration questions for use with the java applet.
Univariate time series forecasting algorithm validation
NASA Astrophysics Data System (ADS)
Ismail, Suzilah; Zakaria, Rohaiza; Muda, Tuan Zalizam Tuan
2014-12-01
Forecasting is a complex process which requires expert tacit knowledge in producing accurate forecast values. This complexity contributes to the gaps between end users and expert. Automating this process by using algorithm can act as a bridge between them. Algorithm is a well-defined rule for solving a problem. In this study a univariate time series forecasting algorithm was developed in JAVA and validated using SPSS and Excel. Two set of simulated data (yearly and non-yearly); several univariate forecasting techniques (i.e. Moving Average, Decomposition, Exponential Smoothing, Time Series Regressions and ARIMA) and recent forecasting process (such as data partition, several error measures, recursive evaluation and etc.) were employed. Successfully, the results of the algorithm tally with the results of SPSS and Excel. This algorithm will not just benefit forecaster but also end users that lacking in depth knowledge of forecasting process.
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.)
There Is More Than One Univariate Normal Distribution: What Is the Normal Distribution, Really?
ERIC Educational Resources Information Center
Team, Rachel M.
Many univariate statistical methods, such as the analysis of variance, t-test, and regression, assume that the dependent variable data have a univariate normal distribution (Hinkle, Weirsma, and Jurs, 1998). Various other statistical methods assume that the error scores are normally distributed (Thompson, 1992). Violating this assumption can be…
Small sample bias in the gamma frailty model for univariate survival.
Barker, Peter; Henderson, Robin
2005-06-01
The gamma frailty model is a natural extension of the Cox proportional hazards model in survival analysis. Because the frailties are unobserved, an E-M approach is often used for estimation. Such an approach is shown to lead to finite sample underestimation of the frailty variance, with the corresponding regression parameters also being underestimated as a result. For the univariate case, we investigate the source of the bias with simulation studies and a complete enumeration. The rank-based E-M approach, we note, only identifies frailty through the order in which failures occur; additional frailty which is evident in the survival times is ignored, and as a result the frailty variance is underestimated. An adaption of the standard E-M approach is suggested, whereby the non-parametric Breslow estimate is replaced by a local likelihood formulation for the baseline hazard which allows the survival times themselves to enter the model. Simulations demonstrate that this approach substantially reduces the bias, even at small sample sizes. The method developed is applied to survival data from the North West Regional Leukaemia Register. PMID:15938549
Zhou, Mai
March 13, 2006 15:13 WSPC/Trim Size: 9in x 6in for Proceedings Cox4 THE COX PROPORTIONAL HAZARDS Lexington, KY 40506-0027, U.S.A. The Cox proportional hazards regression model has been widely used function that is completely unspecified. We study here the statis- tical inference of the Cox model where
COX 10 GENOTYPING PROTOCOL GENE NAME: COX 10
Shoubridge, Eric
COX 10 GENOTYPING PROTOCOL GENE NAME: COX 10 PCR PROTOCOL NAME: COX10Delta (not COX10) PCR REAGENTS Concentration) PRIMERS: COX10Delta Forward (20uM Standard Working Concentration) COX10Delta maximum volume per well Run 80 V for 1 hour Score 1 to 3 bands per lane: 1.4 kb = floxed COX10allele
HyperStat Online: Describing Univariate Data
NSDL National Science Digital Library
David M. Lane
This site from David Lane features the univariate data chapter of an online statistics text. Median, mean, and mode are discussed along with spreads, skews and different types of graphs. There are also exercises and links to other statistics sites.
Cox, Kelli; Helmer, Lauren
2010-12-30
Oral history interview with Kelli Cox conducted by Lauren Helmer in Lawrence, Kansas, on December 30, 2010. In this inteview, Kelli Cox discusses her experiences attending a variety of churches in Lawrence, including the Christ Community Church...
VC-dimension of univariate decision trees.
Yildiz, Olcay Taner
2015-02-01
In this paper, we give and prove the lower bounds of the Vapnik-Chervonenkis (VC)-dimension of the univariate decision tree hypothesis class. The VC-dimension of the univariate decision tree depends on the VC-dimension values of its subtrees and the number of inputs. Via a search algorithm that calculates the VC-dimension of univariate decision trees exhaustively, we show that our VC-dimension bounds are tight for simple trees. To verify that the VC-dimension bounds are useful, we also use them to get VC-generalization bounds for complexity control using structural risk minimization in decision trees, i.e., pruning. Our simulation results show that structural risk minimization pruning using the VC-dimension bounds finds trees that are more accurate as those pruned using cross validation. PMID:25594983
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.
NASA Astrophysics Data System (ADS)
Novacoski, Ezequiel J.; dos Santos, Felipe R.; Melquiades, Fábio L.
2013-05-01
The objective of this study was to use the EDXRF spectra to perform a multivariate calibration via partial least square (PLS) regression for Mn, Ni, Cu, Zn, Sr, Rb, Y, Zr and Nb, in soil samples and compare with univariate calibration method. The advantage of multivariate calibration is that it is not necessary to determine the net peak areas.
Cox, Matt; Stratton, Emily
2013-07-16
Oral history interview with Matt Cox conducted by Emily Stratton in Lawrence, Kansas, on July 16, 2013. This interview features Matt Cox, the planter and lead pastor of EastLake Community Church. EastLake Community Church is a non...
Properties of Generalized Univariate Hypergeometric Functions
NASA Astrophysics Data System (ADS)
van de Bult, F. J.; Rains, E. M.; Stokman, J. V.
2007-10-01
Based on Spiridonov’s analysis of elliptic generalizations of the Gauss hypergeometric function, we develop a common framework for 7-parameter families of generalized elliptic, hyperbolic and trigonometric univariate hypergeometric functions. In each case we derive the symmetries of the generalized hypergeometric function under the Weyl group of type E 7 (elliptic, hyperbolic) and of type E 6 (trigonometric) using the appropriate versions of the Nassrallah-Rahman beta integral, and we derive contiguous relations using fundamental addition formulas for theta and sine functions. The top level degenerations of the hyperbolic and trigonometric hypergeometric functions are identified with Ruijsenaars’ relativistic hypergeometric function and the Askey-Wilson function, respectively. We show that the degeneration process yields various new and known identities for hyperbolic and trigonometric special functions. We also describe an intimate connection between the hyperbolic and trigonometric theory, which yields an expression of the hyperbolic hypergeometric function as an explicit bilinear sum in trigonometric hypergeometric functions.
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. ...
Plots for Survival Regression David J. Olive
Olive, David
Plots for Survival Regression David J. Olive February 9, 2011 In the most used survival regression groups and plotting the Cox survival curve versus the Kaplan Meier estimator for each group can be used the p × 1 vector of nontrivial predictors x. In survival regression, Y is the time until an event
Cox Process Learning Gerard Biau
Boyer, Edmond
Cox Process Learning G´erard Biau Universit´e Pierre et Marie Curie1 & Ecole Normale Sup´erieure2 This article addresses the problem of supervised classification of Cox process trajectories, whose random in this context and fully exploit the functional na- ture of the problem. Index Terms -- Cox process, supervised
Curriculum Vitae John Vincent Cox
Cui, Yan
Curriculum Vitae John Vincent Cox Associate Professor EDUCATION: 1975 B.S. in Biology Department-REVIEWED JOURNAL ARTICLES: 1. Cox, J.V., Schenk, E.A. and Olmsted, J.B. 1983. Human anticentromere antibodies, J.B., Cox, J.V., Asnes, C.F., Parysek, L.M. and Lyon, H.D. 1984. Cellular regulation of microtubule
Radeloff, Volker C.
CURRICULUM VITA THOMAS L. COX May, 2002 Department of Agricultural and Applied Economics University) 262-9493 FAX: (608) 262-4376 INTERNET: cox@aae.wisc.edu I. EDUCATION Ph.D., Agricultural Economics.,J.P. Chavas,, T.L. Cox, and V. Requillart (2002). " EU Dairy Policy Reform and Future WTO Negotations
Univariate input models for stochastic simulation , NM Steiger4
Univariate input models for stochastic simulation ME Kuhl1 , JS Ivy2 , EK Lada3 , NM Steiger4 , MA of the continuous univariate probabilistic input processes that drive discrete-event simulation experiments manufacturing and medical decision analysis to smart-materials research and health-care systems analysis
Zhang, Hui; Schaubel, Douglas E; Kalbfleisch, John D
2011-03-01
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
The Robust Inference for the Cox Proportional Hazards Model
D. Y. Lin; L. J. Wei
1989-01-01
We derive the asymptotic distribution of the maximum partial likelihood estimator ? for the vector of regression coefficients ? under a possibly misspecified Cox proportional hazards model. As in the parametric setting, this estimator ? converges to a well-defined constant vector ?*. In addition, the random vector n (? – ?*) is asymptotically normal with mean 0 and with a
Quantile Regression with Censored Data
ERIC Educational Resources Information Center
Lin, Guixian
2009-01-01
The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where the…
Warner, Parveen; Fusai, Giuseppe; Glantzounis, Georgios K; Sabin, Caroline A; Rolando, Nancy; Patch, David; Sharma, Dinesh; Davidson, Brian R; Rolles, Keith; Burroughs, Andrew K
2011-04-01
Hepatic artery thrombosis (HAT) is a serious complication in patients undergoing orthotopic liver transplantation (OLT). It is associated with a high graft loss and mortality rate. In this study, possible risk factors associated with early HAT (occurring within the first postoperative month) were evaluated using univariable and multivariable analyses. Nine-hundred-and-fourteen consecutive OLTs in our institution were examined by univariable and multivariable analyses. Early HAT occurred in 43 patients (4.7%). Graft number, abnormal donor arterial anatomy, bench arterial reconstruction, aortic conduit use, multiple anastomoses, reperfusion time (interval between portal vein reperfusion and restoration of arterial flow) and the number of units of blood received intraoperatively were significantly associated with early HAT in the univariable analysis(P<0.1). These variables were included in a multivariable regression model which showed that bench arterial reconstruction was associated with a fourfold risk of early HAT(P<0.0001), whereas each additional 10min delay in reperfusion was associated with a 27% increase in the risk of early HAT (P<0.04). The main risk factors associated with early HAT are abnormal arterial anatomy in the graft requiring bench reconstruction and a delay in arterial reperfusion. Early recognition of these factors, strict surveillance protocols with arterial Doppler and selective anticoagulation for patients at risk need to be evaluated prospectively. PMID:21210866
2014-01-01
Background The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. Methods We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). Results The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p?=?0.037), lower CDH-1 mRNA expression (p?=?0.020), and advanced T-classification (p?=?0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p?=?0.041). Conclusions These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC. PMID:24887090
ERIC Educational Resources Information Center
Johns, Stephanie
2010-01-01
Kathy Cox, the superintendent of schools for Georgia, believes "excellence is not an accident". She made a name for herself by winning $1 million proving she was smarter than a fifth-grader on a popular television show. This article presents a profile of Cox, her family, her role as school superintendent, and her accomplishments. Although she…
Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza
2013-01-01
OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763
Bayesian random threshold estimation in a Cox proportional hazards cure model.
Zhao, Lili; Feng, Dai; Bellile, Emily L; Taylor, Jeremy M G
2014-02-20
In this paper, we develop a Bayesian approach to estimate a Cox proportional hazards model that allows a threshold in the regression coefficient, when some fraction of subjects are not susceptible to the event of interest. A data augmentation scheme with latent binary cure indicators is adopted to simplify the Markov chain Monte Carlo implementation. Given the binary cure indicators, the Cox cure model reduces to a standard Cox model and a logistic regression model. Furthermore, the threshold detection problem reverts to a threshold problem in a regular Cox model. The baseline cumulative hazard for the Cox model is formulated non-parametrically using counting processes with a gamma process prior. Simulation studies demonstrate that the method provides accurate point and interval estimates. Application to a data set of oropharynx cancer patients suggests a significant threshold in age at diagnosis such that the effect of gender on disease-specific survival changes after the threshold. PMID:24009083
High Dimensional Model Representation Supported by Products of Univariate Functions
NASA Astrophysics Data System (ADS)
Demiralp, Metin
2009-09-01
This work extends the High Dimensional Model Representation (HDMR) proposed by Sobol and many contributions to the development have been made by some other authors including Rabitz and his group and the author and his group. The additivity measurers developed and used by the author and his group enabled us to measure the truncation approximation quality of HDMR. Now it is very well known that the multiplicativity in the target function of HDMR prevents to truncate it at univariate or at most bivariate level. It requires all expansion. In HDMR an ascending multivariance structure is used. Hence the leading constant component is followed by the univariate, bivariate terms and so on. This work extends the representation by feeding univariate factors to support each such term in missing variables. The result is a new representation which is enable us to exactly have the target function at the first component even if it is purely multiplicative.
Univariate Analysis of Multivariate Outcomes in Educational Psychology.
ERIC Educational Resources Information Center
Hubble, L. M.
1984-01-01
The author examined the prevalence of multiple operational definitions of outcome constructs and an estimate of the incidence of Type I error rates when univariate procedures were applied to multiple variables in educational psychology. Multiple operational definitions of constructs were advocated and wider use of multivariate analysis was…
Univariate Modeling and Forecasting of Monthly Energy Demand Time Series
Abdel-Aal, Radwan E.
electricity tariffs. Short-term load forecasting (STLF) (one hour to one week) is important for scheduling forecasting. Demand for electricity changes with time, weather, socio-economic variables, and populationUnivariate Modeling and Forecasting of Monthly Energy Demand Time Series Using Abductive and Neural
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…
Individual Fitness and the Measurement of Univariate Selection
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
Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease
Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease Christian Habeck Medical Center, PH18, 622 West 168th Street, New York, NY 10032, USA b Center for Alzheimer's Care analysis of FDGPET scans to evaluate their ability to identify Alzheimer's disease (AD). FDGPET scans
Strokes for Representing Univariate Vector David Fowler and Colin Ware
Ware, Colin
Strokes for Representing Univariate Vector Field Maps David Fowler and Colin Ware School Abstract Particle systems make an excellent tool for creating tracks (which we call strokes) in vector in order to reveal properties such as local direction and strength of the field. We find that for strokes
Other Point Processes 1. Cox Point Processes.
Zhang, Tonglin
Other Point Processes 1. Cox Point Processes. A Cox point process N is a Poisson point process used Cox point processes are: · The mixed Poisson process: there is a determinstic function (s) and a nonnegative random variable Y such that (A) = Y A (s)ds. Then, the Cox point process is called the mixed
Evaluation of univariate ranges with a multivariate standard.
Stamhuis, I H; Bezemer, P D; Kuik, D J
1988-01-01
In medical decision making generally many test results are produced. Several authors have discussed the problems involved and concluded that a multivariate approach often has to be preferred. Because until now such an approach has not often been used in practice and qualitative arguments for a multivariate approach are seldom supported by quantitative results, in this paper the use of univariate reference ranges is evaluated with a multivariate range as the standard, taking into account correlation coefficients. Probabilities of false positive and false negative results and predictive values are computed and displayed for decision rules based on two separate test results with an elliptic region as the gold standard. The conclusion is that the quality of the univariate approach is dependent on the correlation coefficient and on the choice of the decision rule. In the most important cases, however, it falls short compared with a multivariate approach. For example, the probability that a univariate positive result is false is around 50% for all values of the correlation coefficient, which is unacceptably high. PMID:3351543
Evaluation of droplet size distributions using univariate and multivariate approaches.
Gaunø, Mette Høg; Larsen, Crilles Casper; Vilhelmsen, Thomas; Møller-Sonnergaard, Jørn; Wittendorff, Jørgen; Rantanen, Jukka
2013-01-01
Pharmaceutically relevant material characteristics are often analyzed based on univariate descriptors instead of utilizing the whole information available in the full distribution. One example is droplet size distribution, which is often described by the median droplet size and the width of the distribution. The current study was aiming to compare univariate and multivariate approach in evaluating droplet size distributions. As a model system, the atomization of a coating solution from a two-fluid nozzle was investigated. The effect of three process parameters (concentration of ethyl cellulose in ethanol, atomizing air pressure, and flow rate of coating solution) on the droplet size and droplet size distribution using a full mixed factorial design was used. The droplet size produced by a two-fluid nozzle was measured by laser diffraction and reported as volume based size distribution. Investigation of loading and score plots from principal component analysis (PCA) revealed additional information on the droplet size distributions and it was possible to identify univariate statistics (volume median droplet size), which were similar, however, originating from varying droplet size distributions. The multivariate data analysis was proven to be an efficient tool for evaluating the full information contained in a distribution. PMID:23215949
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Wednesday, September 9, 2009 In Attendance: Arnie Peskin, Ken Mohring, Dave Cox, Myron Strongin, Eena-Mai Franz, Martine O'Connor, Ronnie Evans, Sonja was adjourned at 1.14 pm following a motion made by Ken Mohring and seconded by Dave Cox. #12;
Karin M. Cox 3720 Walnut Street
Kable, Joe
Karin M. Cox 3720 Walnut Street University of Pennsylvania Philadelphia, PA 19104 (412-Reviewed Publications Cox, K. M., Aizenstein, H. J., & Fiez, J. A. (2008). Striatal outcome processing in healthy aging. Cognitive, Affective, & Behavioral Neuroscience, 8(3), 304-317. Manuscripts in Preparation Cox., K
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Wednesday, December 9, 2009 In Attendance: Arnie Peskin, Ken Mohring, Dave Cox, Myron Strongin, Eena-Mai Franz, J. Tichler (via conference phone with local government officials. Dave Cox explained that they were interested in meeting with Brookhaven Town
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Wednesday, June 10th , 2009 In Attendance: Arnie Peskin, Ken Mohring, Dave Cox, Graham Campbell, Alyce Daly, Florence O'Brien, Eena-Mai Franz, Frances by Ken Mohring seconded by Dave Cox. #12;
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Wednesday, January 13, 2010 In Attendance: Arnie Peskin, Dave Cox, Eena-Mai Franz, Sonja Santos, Ronnie Evans, Martine O'Connor, Alyce Daly, J. Tichler of new officers. Dave Cox reported that about 25% of BREA's approximately 300 members had returned
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Thursday, November 12, 2009 In Attendance: Arnie Peskin, Ken Mohring, Dave Cox, Myron Strongin, Alyce Daly, Ronnie Evans, J. Tichler (via conference phone Cox reported that the latest issue of the Newsletter, including the ballot sheet for the forthcoming
BREA Minutes From: Dave Cox (Secretary)
BREA Minutes From: Dave Cox (Secretary) Date: Wednesday, July 1, 2009 In Attendance: Arnie Peskin, Ken Mohring, Dave Cox, Alyce Daly, Florence O'Brien, Eena- Mai Franz, Elliot Auerbach, Martine O newsletter. Arnie agreed to serve as CAC representative, and Dave Cox and Joyce Tichler agreed to serve
Kable, Joe
Page 1 of 3 Karin M. Cox 3720 Walnut Street University of Pennsylvania Philadelphia, PA 19104 (215, University of Pennsylvania, in the lab of Dr. Joseph Kable #12;Page 2 of 3 Peer-Reviewed Publications Cox, K, Affective, & Behavioral Neuroscience, 8(3), 304-317. Manuscripts in Preparation Cox., K.M., & Fiez, J.A. (in
DAVID R. COX PRIZE FOR RARE COMPASSION
Emmons, Scott
DAVID R. COX PRIZE FOR RARE COMPASSION ESSAY CONTEST FOR FIRST AND SECOND YEAR MEDICAL STUDENTS David R. Cox Prize for Rare Compassion, in recognition of the inspiring essays of student doctors who David R. Cox, MD, PhD was an extraordinary physi- cian scientist, becoming Professor of Genetics
ERIC Educational Resources Information Center
Sun, Anji; Valiga, Michael J.
In this study, the reliability of the American College Testing (ACT) Program's "Survey of Academic Advising" (SAA) was examined using both univariate and multivariate generalizability theory approaches. The primary purpose of the study was to compare the results of three generalizability theory models (a random univariate model, a mixed univariate…
Mass univariate analysis of event-related brain potentials/fields I: A critical tutorial review
Kutas, Marta
REVIEW Mass univariate analysis of event-related brain potentials/fields I: A critical tutorial power and statistics have produced an alternative, mass univariate analyses consisting of thousands. Mass univariate analyses complement and, at times, obviate traditional analyses. Here we review
Selectivity in analytical chemistry: two interpretations for univariate methods.
Dorkó, Zsanett; Verbi?, Tatjana; Horvai, George
2015-01-01
Selectivity is extremely important in analytical chemistry but its definition is elusive despite continued efforts by professional organizations and individual scientists. This paper shows that the existing selectivity concepts for univariate analytical methods broadly fall in two classes: selectivity concepts based on measurement error and concepts based on response surfaces (the response surface being the 3D plot of the univariate signal as a function of analyte and interferent concentration, respectively). The strengths and weaknesses of the different definitions are analyzed and contradictions between them unveiled. The error based selectivity is very general and very safe but its application to a range of samples (as opposed to a single sample) requires the knowledge of some constraint about the possible sample compositions. The selectivity concepts based on the response surface are easily applied to linear response surfaces but may lead to difficulties and counterintuitive results when applied to nonlinear response surfaces. A particular advantage of this class of selectivity is that with linear response surfaces it can provide a concentration independent measure of selectivity. In contrast, the error based selectivity concept allows only yes/no type decision about selectivity. PMID:25476364
The pyrrole moiety as a template for COX1\\/COX2 inhibitors
Gerd Dannhardt; Werner Kiefer; Godehard Krämer; Sabine Maehrlein; Ulrike Nowe; Bernd Fiebich
2000-01-01
Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1\\/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and
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
RENCI Engagement Steven Cox: http://osglog.wordpress.com
Deelman, Ewa
High Throughput Parallel Molecular Dynamics HTPMD Steve Cox RENCI Engagement #12;Steven Cox: http Workflow and Hybrid Computing #12;Steven Cox: http://osglog.wordpress.comSteven Cox: http configuration High Throughput Parallel Computing (HTPC) #12;Steven Cox: http://osglog.wordpress.comSteven Cox
NASA Astrophysics Data System (ADS)
Grégoire, G.
2014-01-01
The logistic regression originally is intended to explain the relationship between the probability of an event and a set of covariables. The model's coefficients can be interpreted via the odds and odds ratio, which are presented in introduction of the chapter. The observations are possibly got individually, then we speak of binary logistic regression. When they are grouped, the logistic regression is said binomial. In our presentation we mainly focus on the binary case. For statistical inference the main tool is the maximum likelihood methodology: we present the Wald, Rao and likelihoods ratio results and their use to compare nested models. The problems we intend to deal with are essentially the same as in multiple linear regression: testing global effect, individual effect, selection of variables to build a model, measure of the fitness of the model, prediction of new values… . The methods are demonstrated on data sets using R. Finally we briefly consider the binomial case and the situation where we are interested in several events, that is the polytomous (multinomial) logistic regression and the particular case of ordinal logistic regression.
G. Davies; L.-A. Martin; N. Sacks; M. Dowsett
2002-01-01
breast. The main target of NSAID activity is the cyclooxygenase (COX) enzyme. Two isoforms of COX have been identified: COX-1, the constitutive isoform; and COX-2, the inducible form of the enzyme. COX-2 can undergo rapid induction in response to many factors such as bacterial lipopolysaccharides, growth factors, cytokines and phorbol esters. COX-2 is overexpressed in some malignancies including carcinoma of
Forecasting electricity usage using univariate time series models
NASA Astrophysics Data System (ADS)
Hock-Eam, Lim; Chee-Yin, Yip
2014-12-01
Electricity is one of the important energy sources. A sufficient supply of electricity is vital to support a country's development and growth. Due to the changing of socio-economic characteristics, increasing competition and deregulation of electricity supply industry, the electricity demand forecasting is even more important than before. It is imperative to evaluate and compare the predictive performance of various forecasting methods. This will provide further insights on the weakness and strengths of each method. In literature, there are mixed evidences on the best forecasting methods of electricity demand. This paper aims to compare the predictive performance of univariate time series models for forecasting the electricity demand using a monthly data of maximum electricity load in Malaysia from January 2003 to December 2013. Results reveal that the Box-Jenkins method produces the best out-of-sample predictive performance. On the other hand, Holt-Winters exponential smoothing method is a good forecasting method for in-sample predictive performance.
Certified counting of roots of random univariate polynomials
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.
Cox’s Chair Revisited: Can Spinning Alter Mood States?
Winter, Lotta; Wollmer, M. Axel; Laurens, Jean; Straumann, Dominik; Kruger, Tillmann H. C.
2013-01-01
Although there is clinical and historical evidence for a vivid relation between the vestibular and emotional systems, the neuroscientific underpinnings are poorly understood. The “spin doctors” of the nineteenth century used spinning chairs (e.g., Cox’s chair) to treat conditions of mania or elevated arousal. On the basis of a recent study on a hexapod motion-simulator, in this prototypic investigation we explore the impact of yaw stimulation on a spinning chair on mood states. Using a controlled experimental stimulation paradigm on a unique 3-D-turntable at the University of Zurich we included 11 healthy subjects and assessed parameters of mood states and autonomic nervous system activity. The Multidimensional Mood State Questionnaire and Visual Analog Scales (VAS) were used to assess changes of mood in response to a 100?s yaw stimulation. In addition heart rate was continuously monitored during the experiment. Subjects indicated feeling less “good,” “relaxed,” “comfortable,” and “calm” and reported an increased alertness after vestibular stimulation. However, there were no objective adverse effects of the stimulation. Accordingly, heart rate did not significantly differ in response to the stimulation. This is the first study in a highly controlled setting using the historical approach of stimulating the vestibular system to impact mood states. It demonstrates a specific interaction between the vestibular system and mood states and thereby supports recent experimental findings with a different stimulation technique. These results may inspire future research on the clinical potential of this method. PMID:24133463
NASA Astrophysics Data System (ADS)
Coe, Rob; Dalrymple, Brent
More than 1000 friends, students, and colleagues from all over the country filled Stanford Memorial Chapel (Stanford, Calif.) on February 3, 1987, to join in “A Celebration of the Life of Allan Cox.” Allan died early on the morning of January 27 while bicycling, the sport he had come to love the most. Between pieces of his favorite music by Bach and Mozart, Stanford administrators and colleagues spoke in tribute of Allan's unique qualities as friend, scientist, teacher, and dean of the School of Earth Sciences. James Rosse, Vice President and Provost of Stanford University, struck a particularly resonant chord with his personal remarks: "Allan reached out to each person he knew with the warmth and attention that can only come from deep respect and affection for others. I never heard him speak ill of others, and I do not believe he was capable of doing anything that would harm another being. He cared too much to intrude where he was not wanted, but his curiosity about people and the loving care with which he approached them broke down reserve to create remarkable friendships. His enthusiasm and good humor made him a welcome guest in the hearts of the hundreds of students and colleagues who shared the opportunity of knowing Allan Cox as a person."
ERIC Educational Resources Information Center
Matson, Johnny L.; Kozlowski, Alison M.
2010-01-01
Autistic regression is one of the many mysteries in the developmental course of autism and pervasive developmental disorders not otherwise specified (PDD-NOS). Various definitions of this phenomenon have been used, further clouding the study of the topic. Despite this problem, some efforts at establishing prevalence have been made. The purpose of…
NSDL National Science Digital Library
2009-12-03
This site, created by Michelle Lacey of Yale University, gives an explanation, a definition and an example of linear regression. Topics include: least-squares, residuals, extrapolation, outliers, and influential observations. Lacey's presentation is thoughtful in its layout. The author intertwines useful graphs within her textual explanations, this makes it accessible for almost any mathematics audience. Overall, this is a useful resource.
Survival analysis and regression models.
George, Brandon; Seals, Samantha; Aban, Inmaculada
2014-08-01
Time-to-event outcomes are common in medical research as they offer more information than simply whether or not an event occurred. To handle these outcomes, as well as censored observations where the event was not observed during follow-up, survival analysis methods should be used. Kaplan-Meier estimation can be used to create graphs of the observed survival curves, while the log-rank test can be used to compare curves from different groups. If it is desired to test continuous predictors or to test multiple covariates at once, survival regression models such as the Cox model or the accelerated failure time model (AFT) should be used. The choice of model should depend on whether or not the assumption of the model (proportional hazards for the Cox model, a parametric distribution of the event times for the AFT model) is met. The goal of this paper is to review basic concepts of survival analysis. Discussions relating the Cox model and the AFT model will be provided. The use and interpretation of the survival methods model are illustrated using an artificially simulated dataset. PMID:24810431
Joint regression analysis of correlated data using Gaussian copulas.
Song, Peter X-K; Li, Mingyao; Yuan, Ying
2009-03-01
This article concerns a new joint modeling approach for correlated data analysis. Utilizing Gaussian copulas, we present a unified and flexible machinery to integrate separate one-dimensional generalized linear models (GLMs) into a joint regression analysis of continuous, discrete, and mixed correlated outcomes. This essentially leads to a multivariate analogue of the univariate GLM theory and hence an efficiency gain in the estimation of regression coefficients. The availability of joint probability models enables us to develop a full maximum likelihood inference. Numerical illustrations are focused on regression models for discrete correlated data, including multidimensional logistic regression models and a joint model for mixed normal and binary outcomes. In the simulation studies, the proposed copula-based joint model is compared to the popular generalized estimating equations, which is a moment-based estimating equation method to join univariate GLMs. Two real-world data examples are used in the illustration. PMID:18510653
Towards a universal barcode of oomycetes - a comparison of the cox1 and cox2 loci.
Choi, Young-Joon; Beakes, Gordon; Glockling, Sally; Kruse, Julia; Nam, Bora; Nigrelli, Lisa; Ploch, Sebastian; Shin, Hyeon-Dong; Shivas, Roger G; Telle, Sabine; Voglmayr, Hermann; Thines, Marco
2015-11-01
Oomycetes are a diverse group of eukaryotes in terrestrial, limnic and marine habitats worldwide and include several devastating plant pathogens, for example Phytophthora infestans (potato late blight). The cytochrome c oxidase subunit 2 gene (cox2) has been widely used for identification, taxonomy and phylogeny of various oomycete groups. However, recently the cox1 gene was proposed as a DNA barcode marker instead, together with ITS rDNA. The cox1 locus has been used in some studies of Pythium and Phytophthora, but has rarely been used for other oomycetes, as amplification success of cox1 varies with different lineages and sample ages. To determine which out of cox1 or cox2 is best suited as a universal oomycete barcode, we compared these two genes in terms of (i) PCR efficiency for 31 representative genera, as well as for historic herbarium specimens, and (ii) sequence polymorphism, intra- and interspecific divergence. The primer sets for cox2 successfully amplified all oomycete genera tested, while cox1 failed to amplify three genera. In addition, cox2 exhibited higher PCR efficiency for historic herbarium specimens, providing easier access to barcoding-type material. Sequence data for several historic type specimens exist for cox2, but there are none for cox1. In addition, cox2 yielded higher species identification success, with higher interspecific and lower intraspecific divergences than cox1. Therefore, cox2 is suggested as a partner DNA barcode along with ITS rDNA instead of cox1. The cox2-1 spacer could be a useful marker below species level. Improved protocols and universal primers are presented for all genes to facilitate future barcoding efforts. PMID:25728598
Cyclooxygenase2 (COX2) – Independent Anticarcinogenic Effects of Selective COX2 Inhibitors
Sabine Grösch; Thorsten Jürgen Maier; Susanne Schiffmann; Gerd Geisslinger
Nonsteroidal antiinfl ammatory drugs (NSAIDs) appear to reduce the risk of developing cancer. One mechanism through which NSAIDs act to reduce carcinogenesis is to inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in various cancer tissues. Overexpression of COX-2 increases cell proliferation and inhibits apoptosis. However, selective COX-2 inhibitors can also act through COX-independent mechanisms. In this
Dynamic treatment of invariant and univariant reactions in metamorphic systems
Lasaga, A.C.; Luettge, A.; Rye, D.M.; Bolton, E.W.
2000-03-01
A simple model is presented that incorporates the essential dynamics of metamorphic processes leading to reactions along univariant curves and up to and beyond the invariant point. The model includes both heat flow by conduction and convection as well as fluid flow in and out of a representative volume. Overall mineral reactions can then take place within this rock volume in response to internal and external factors. The paper derives a simple back-of-the-envelope expression for the steady state reached by the system. The steady state composition of the fluid and the steady state temperature are then compared with the composition and temperature predicted by the assumption of thermodynamic equilibrium. Expressions for the amount of fluid passing through the system based on the kinetic model are compared with previous calculations of the mass of fluid added to the system using the equilibrium assumptions. The approach to this steady state is also analyzed and an analytical solution is obtained for the time evolution up to the steady state. Both the steady state and the time evolution solution are then applied to an understanding of the dynamics involved in obtaining T-X-t paths in nature. The results of the kinetic approach lead to major revisions in many of the previously held concepts used in petrologic fluid flow models. These include the expected reaction pathway, the role of metastable reactions, the calculation of fluid flux, the role of the invariant point, and the interpretation of mineral textures and modal abundances of minerals.
Intrinsic priors for model comparison in multivariate normal regression
Francisco Torres-Ruiz; Elías Moreno; Francisco J. Girón
In Moreno et al. (Rev R Acad Cien Ser A Mat 97:53–61, 2003) an objective Bayesian model comparison procedure for univariate normal regression models based on intrinsic priors was provided.\\u000a However, in many applications the regression models entertained are multidimensional, and hence an extension of the procedure\\u000a to this setting is required. This technical paper provides the intrinsic priors and their
ERIC Educational Resources Information Center
Rollins, Dahl A.
Many univariate statistical methods assume that dependent variable data have a univariate distribution. Some statistical methods assume that the error scores are normally distributed. It is clear that the concept of data normality is an important one in statistics. This paper explains that, notwithstanding common misconceptions to the contrary,…
The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia.
Colaizzo, Donatella; Fofi, Laura; Tiscia, Gianluca; Guglielmi, Renzo; Cocomazzi, Nicola; Prencipe, Massimiliano; Margaglione, Maurizio; Toni, Danilo
2006-03-01
In the atherosclerotic plaque, cyclooxygenase-2 (COX-2) catalyzes prostaglandin E formation, which acts as a pro-atherogenic factor. A polymorphism, G/C -765, within the COX-2 promoter region modulates gene expression and the risk of cerebrovascular disease. We have evaluated the relation between COX-2 G/C -765 genotypes and the occurrence of cerebrovascular ischemia. We evaluated the COX-2 G/C -765 polymorphism in 110 consecutive patients with a documented history of acute ischemic cerebrovascular disease, in 110 age-matched and sex-matched subjects without such history, and in a general population (n = 324) from the same ethnical background. The frequency of the COX-2 -765C allele in patients [0.21; 95% confidence interval (CI), 0.16-0.26] was similar to those found in controls (0.28; 95% CI, 0.22-0.34) and in the general population (0.26; 95% CI, 0.23-0.29). Carriers of the CC genotype differed between patients (0.02; 95% CI, 0.00-0.05) and controls [0.10 (95% CI, 0.04-0.16), P = 0.019; odds ratio, 0.17 (95% CI, 0.04-0.79)] or the general population [0.08 (95% CI, 0.05-0.11), P = 0.023; odds ratio, 0.22 (95% CI, 0.05-0.95)]. In a multiple logistic regression analysis adjusted for confounding variables, smoking status (P < 0.001), atrial fibrillation (P = 0.004) and COX-2 G/C-765 polymorphism (P = 0.016) independently contributed to cerebrovascular ischemia, with CC carriers exhibiting a lower risk (odds ratio, 0.07; 95% CI, 0.01-0.61). Our data show an association between the COX-2 G/C-765 gene polymorphism and cerebrovascular ischemia, suggesting that the COX-2 gene is a susceptibility locus for the risk of cerebrovascular ischemic disease. PMID:16479190
Imputing missing covariate values for the Cox model.
White, Ian R; Royston, Patrick
2009-07-10
Multiple imputation is commonly used to impute missing data, and is typically more efficient than complete cases analysis in regression analysis when covariates have missing values. Imputation may be performed using a regression model for the incomplete covariates on other covariates and, importantly, on the outcome. With a survival outcome, it is a common practice to use the event indicator D and the log of the observed event or censoring time T in the imputation model, but the rationale is not clear.We assume that the survival outcome follows a proportional hazards model given covariates X and Z. We show that a suitable model for imputing binary or Normal X is a logistic or linear regression on the event indicator D, the cumulative baseline hazard H(0)(T), and the other covariates Z. This result is exact in the case of a single binary covariate; in other cases, it is approximately valid for small covariate effects and/or small cumulative incidence. If we do not know H(0)(T), we approximate it by the Nelson-Aalen estimator of H(T) or estimate it by Cox regression.We compare the methods using simulation studies. We find that using logT biases covariate-outcome associations towards the null, while the new methods have lower bias. Overall, we recommend including the event indicator and the Nelson-Aalen estimator of H(T) in the imputation model. PMID:19452569
A Closer Look at Exploratory Learning of Interactive Devices Anna L Cox (a.cox@herts.ac.uk)
Blandford, Ann
A Closer Look at Exploratory Learning of Interactive Devices Anna L Cox (a.cox@herts.ac.uk) Richard exploratory learning of interactive devices, first presented in Young & Cox (2000). The framework has been
Yang, Xue; Lauzon, Carolyn B; Crainiceanu, Ciprian; Caffo, Brian; Resnick, Susan M; Landman, Bennett A
2012-09-01
Massively univariate regression and inference in the form of statistical parametric mapping have transformed the way in which multi-dimensional imaging data are studied. In functional and structural neuroimaging, the de facto standard "design matrix"-based general linear regression model and its multi-level cousins have enabled investigation of the biological basis of the human brain. With modern study designs, it is possible to acquire multi-modal three-dimensional assessments of the same individuals--e.g., structural, functional and quantitative magnetic resonance imaging, alongside functional and ligand binding maps with positron emission tomography. Largely, current statistical methods in the imaging community assume that the regressors are non-random. For more realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional consideration of all observations is appropriate. Herein, we discuss two unified regression and inference approaches, model II regression and regression calibration, for use in massively univariate inference with imaging data. These methods use the design matrix paradigm and account for both random and non-random imaging regressors. We characterize these methods in simulation and illustrate their use on an empirical dataset. Both methods have been made readily available as a toolbox plug-in for the SPM software. PMID:22609453
Inhibitory mode of 2-acetoxyphenyl alkyl sulfides against COX1 and COX2: QSAR analyses
Hemant Kumar Jain; V. K. Mourya; R. K. Agrawal
2006-01-01
Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important strategy in design of potent anti-inflammatory compounds with significantly reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1 inhibition. The analyses have produced good predictive and statistically significant QSAR models. These studies suggest that lipophilicity affects
Viscum album-Mediated COX-2 Inhibition Implicates Destabilization of COX-2 mRNA
Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V.
2015-01-01
Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1?-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. PMID:25664986
Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.
Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V
2015-01-01
Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1?-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. PMID:25664986
COX RINGS AND PSEUDOEFFECTIVE CONES OF PROJECTIVIZED TORIC VECTOR BUNDLES
Payne, Sam
COX RINGS AND PSEUDOEFFECTIVE CONES OF PROJECTIVIZED TORIC VECTOR BUNDLES JOS´E GONZ´ALEZ, MILENA and a presentation of the Cox ring as a polynomial algebra over the Cox ring of a blowup of a projective space along Cox rings are isomorphic to that of M0,n. 1. Introduction Projectivizations of toric vector bundles
S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity
Kim, Sangwon F.
S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity Jing Tian*, Sangwon F. Kim*, Lynda cyclooxygenase (COX)-2. We demonstrate that this neurotoxicity reflects activation of COX-2 by S-nitrosylation after selective binding of neuronal nitric oxide synthase (nNOS) to COX-2. nNOS, via its PDZ domain
Tatsuo Yamamoto; Natsuko Nozaki-Taguchi
1996-01-01
Prostaglandins are now thought to play an important role in nociceptive information transmission in the spinal cord. Prostaglandins are known to be produced by cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid. Two forms of COX have been identified: COX-1, which is constitutively expressed in most tissues and organs, and COX-2, which is an inducible enzyme and is localized
Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator.
Almada, M; Piscitelli, F; Fonseca, B M; Di Marzo, V; Correia-da-Silva, G; Teixeira, N
2015-11-01
Recently, endocannabinoids have emerged as signalling mediators in reproduction. It is widely accepted that anandamide (AEA) levels must be tightly regulated, and that a disturbance in AEA levels may impact decidual stability and regression. We have previously characterized the endocannabinoid machinery in rat decidual tissue and reported the pro-apoptotic action of AEA on rat decidual cells. Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays a crucial role in early pregnancy, and is also a key modulator in the crosstalk between endocannabinoids and prostaglandins. On the other hand, AEA-oxidative metabolism by COX-2 is not merely a mean to inactivate its action, but it yields the formation of a new class of mediators, named prostaglandin-ethanolamides, or prostamides. In this study we found that AEA-induced apoptosis in decidual cells involves COX-2 metabolic pathway. AEA induced COX-2 expression through p38 MAPK, resulting in the formation of prostamide E2 (PME2). Our findings also suggest that AEA-induced effect is associated with NF-kB activation. Finally, we describe the involvement of PME2 in the induction of the intrinsic apoptotic pathway in rat decidual cells. Altogether, our findings highlight the role of COX-2 as a gatekeeper in the uterine environment and clarify the impact of the deregulation of AEA levels on the decidual remodelling process. PMID:26335727
Box-Cox transformation of firm size data in statistical analysis
NASA Astrophysics Data System (ADS)
Chen, Ting Ting; Takaishi, Tetsuya
2014-03-01
Firm size data usually do not show the normality that is often assumed in statistical analysis such as regression analysis. In this study we focus on two firm size data: the number of employees and sale. Those data deviate considerably from a normal distribution. To improve the normality of those data we transform them by the Box-Cox transformation with appropriate parameters. The Box-Cox transformation parameters are determined so that the transformed data best show the kurtosis of a normal distribution. It is found that the two firm size data transformed by the Box-Cox transformation show strong linearity. This indicates that the number of employees and sale have the similar property as a firm size indicator. The Box-Cox parameters obtained for the firm size data are found to be very close to zero. In this case the Box-Cox transformations are approximately a log-transformation. This suggests that the firm size data we used are approximately log-normal distributions.
Censored Regression Trend Analyses for Ambient Water Quality Data
Smyth, Gordon K.
Censored Regression Trend Analyses for Ambient Water Quality Data Gordon K. Smyth 1 , Melanie Cox 2 environments requires an understanding of the im- pacts on water quality and an understanding of the e#11;ectiveness of man- agement actions. Monitoring programs to assess water quality typically aim to assess
Int J Cancer. Author manuscript COX-2 and p53 in human sinonasal cancer: COX-2 expression is
Paris-Sud XI, Université de
Int J Cancer. Author manuscript Page /1 8 COX-2 and p53 in human sinonasal cancer: COX-2 expression, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2 to development of cancer. Many signals
Synthesis and biological evaluation of 2,3-diarylthiophenes as selective Cox2 and Cox1 inhibitors
Yves Leblanc; JacquesYves Gauthier; Diane Ethier; Jocelyne Guay; Joseph Mancini; Denis Riendeau; Philip Tagari; Philip Vickers; Elizabeth Wong; Petpiboon Prasit
1995-01-01
A series of 2,3-diarylthiophene compounds was prepared and their biological activities were evaluated against human Cox-1 and Cox-2 enzymes. It appears that the methylsulfone group is essential for both the activity and selectivity for the Cox-2 enzyme. Removal of the methylsulfone group gave relatively selective Cox-1 inhibitors.
Structural basis for selective inhibition of COX-2 by nimesulide.
Fabiola, G F; Pattabhi, V; Nagarajan, K
1998-12-01
Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity. A comparative study with SC-558 2 has also been performed. PMID:9925294
NSAIDs: gastroprotection or selective COX-2 inhibitor?
Dickman, Andrew; Ellershaw, John
2004-05-01
Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and cost-effective use of these drugs in the palliative care population. PMID:15198117
Covariate analysis of survival data: a small-sample study of Cox's model
Johnson, M.E. (Los Alamos National Lab., NM); Tolley, H.D.; Bryson, M.C.; Goldman, A.S.
1982-09-01
Cox's proportional-hazards model is frequently used to adjust for covariate effects in survival-data analysis. The small-sample performances of the maximum partial likelihood estimators of the regression parameters in a two-covariate hazard function model are evaluated with respect to bias, variance, and power in hypothesis tests. Previous Monte Carlo work on the two-sample problem is reviewed.
E. M. Weinheimer; B. Jemiolo; C. C. Carroll; M. P. Harber; J. M. Haus; N. A. Burd; J. K. LeMoine; S. W. Trappe; T. A. Trappe
2007-01-01
ABSTRACT We have,shown,that ibuprofen and,acetaminophen,block cyclooxygenase,(COX) synthesis of prostaglandin PGF2? and the muscle,protein synthesis increase following resistance exercise. Confusingly, these two drugs are purported to work through different mechanisms, with acetaminophen apparently unable to block COX and ibuprofen able to non-specifically block COX-1 and,COX-2. A recently discovered intron-retaining COX, now known to have three variants, has been shown to be
Heckman, Michael G.; Tzou, Katherine S.; Parker, Alexander S.; Pisansky, Thomas M.; Schild, Steven E.; Hilton, Tracy W.; Patel, Vivek N.; Pelaez, Liset; Khor, Li Yan; Peterson, Jennifer L.; Daugherty, Larry C.; Vallow, Laura A.; Pollack, Alan; Buskirk, Steven J.
2013-01-01
Objective The ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer following radical prostatectomy has potential for improvement. Cyclooxygenase-2 (COX-2) overexpression has previously correlated with poor clinical outcomes following primary treatment for prostate cancer, however its predictive ability in the specific setting of SRT has not been examined to date. This study evaluated the association between COX-2 staining intensity and BCR following SRT for recurrent prostate cancer. Methods We utilized a cohort of 151 patients who underwent SRT between July 1987 and July 2003. COX-2 staining intensity in primary tumor samples was detected using monoclonal antibodies and quantified using a computer-assisted method. The association between COX-2 staining intensity and BCR was evaluated using multivariable Cox regression models. Results When examining COX-2 staining level as three-level categorical variable (low, moderate, high) based on approximate sample tertiles, there was no evidence of an association with BCR (P=0.18). More specifically, in comparison to patients with low staining intensity, there was no significant difference in risk of BCR for moderate (Relative risk [RR]: 1.17, P=0.56) or high (RR: 0.72, P=0.22) COX-2 staining intensity patients. This lack of association was also observed when considering COX-2 staining intensity as a continuous variable (RR: 0.83, P=0.15). Conclusion Our results indicate that COX-2 staining intensity is likely of little use in discriminating prognosis of SRT. It appears that the search for prognostic factors associated with BCR should continue elsewhere in order to further enhance patient selection for SRT. PMID:24073305
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
Andras Bardossy; Istvan Bogardi; Lucien Duckstein
1990-01-01
A general methodology for fuzzy regression is developed and illustrated by an actual hydrological case study. Fuzzy regression may be used whenever a relationship between variables is imprecise and\\/or data are inaccurate and\\/or sample sizes are insufficient. In such cases fuzzy regression may be used as a complement or an alternative to statistical regression analysis. In fuzzy regression, several ``goodness
Matzkin, María Eugenia; Ambao, Verónica; Carino, Mónica Herminia; Rossi, Soledad Paola; González, Lorena; Turyn, Daniel; Campo, Stella; Calandra, Ricardo Saúl; Frungieri, Mónica Beatriz
2012-01-01
Serum prolactin (PRL) variations play a crucial role in the photoperiodic-induced testicular regression-recrudescence transition in hamsters. We have previously shown that cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins (PGs), is expressed mostly in Leydig cells of reproductively active hamsters with considerable circulating and pituitary levels of PRL. In this study, we describe a stimulatory effect of PRL on COX2/PGs in hamster Leydig cells, which is mediated by IL-1? and prevented by P38-MAPK and JAK2 inhibitors. Furthermore, by preparative isoelectric focusing (IEF), we isolated PRL charge analogues from pituitaries of active [isoelectric points (pI): 5.16, 4.61, and 4.34] and regressed (pI: 5.44) hamsters. More acidic PRL charge analogues strongly induced COX2 expression, while less acidic ones had no effect. Our studies suggest that PRL induces COX2/PGs in hamster Leydig cells through IL-1? and activation of P38-MAPK and JAK2. PRL microheterogeneity detected in active/inactive hamsters may be responsible for the photoperiodic variations of COX2 expression in Leydig cells. PMID:21803118
Julie M.Bork1 , Michael M.Cox2
Cox, Michael M.
Julie M.Bork1 , Michael M.Cox2 and Ross B.Inman Department of Biochemistry, University of Wisconsin 20850, USA 2 Corresponding author e-mail: cox@biochem.wisc.edu The Escherichia coli RecF, RecO and Rec, 1999; Cox et al., 2000; Marians, 2000; Cox, 2001a,b). Encounters with base lesions can derail the fork
Analysis of Censored Environmental Data with Box-Cox Transformations
District of Columbia, University of the
Analysis of Censored Environmental Data with Box-Cox Transformations Jade Freeman1,2 and Reza the detection limits. The method uses a Box-Cox transformation, of which the parameters are found by maximizing data. Key Words: Box-Cox Transformation, Censored Data, E-M Algorithm, Maximum Likelihood, Delta
Principles of Statistical Inference Nancy Reid and David Cox
Reid, Nancy
Principles of Statistical Inference Nancy Reid and David Cox August 30, 2013 #12;Introduction Inference Reid & Cox, WSC2013 2 #12;... introduction A formal theory of inference is just a small part Reid & Cox, WSC2013 3 #12;Outline 1. the role of probability 2. some classical principles: sufficiency
Palm calculus for stationary Cox processes on iterated random tessellations
Schmidt, Volker
1 Palm calculus for stationary Cox processes on iterated random tessellations Florian Voss, Catherine Gloaguen,Member, IEEE, and Volker Schmidt Abstract--We investigate Cox processes of random point patterns in the Euclidean plane, which are located on the edges of random geometric graphs. Such Cox
Bayesian Inferences in the Cox Model for Order Restricted Hypotheses
West, Mike
Bayesian Inferences in the Cox Model for Order Restricted Hypotheses David B. Dunson1, and Amy H of the different levels of the predictor in a Cox model. One can then use a multiple degree of freedom score reparameterize the Cox model in terms of a cumulative product of parameters having conjugate prior densities
UNIVERSAL TORSORS AND COX RINGS Brendan Hassett and Yuri Tschinkel
Hassett, Brendan
UNIVERSAL TORSORS AND COX RINGS by Brendan Hassett and Yuri Tschinkel Abstract. | We study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. Generalities on the Cox ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 and such that the ring Cox(X) := M L2Pic(X) (X;L); is #12;nitely generated. This ring admits a natural action of the N#19
Bayesian Inferences in the Cox Model for Order Restricted Hypotheses
West, Mike
Bayesian Inferences in the Cox Model for Order Restricted Hypotheses David B. Dunson 1,# and Amy H of the di#erent levels of the predictor in a Cox model. One can then use a multiple degree of freedom score reparameterize the Cox model in terms of a cumulative product of parameters having conjugate prior densities
UNIVERSAL TORSORS AND COX RINGS Brendan Hassett and Yuri Tschinkel
Tschinkel, Yuri
UNIVERSAL TORSORS AND COX RINGS by Brendan Hassett and Yuri Tschinkel Abstract. -- We study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. Generalities on the Cox ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 and such that the ring Cox(X) := LPic(X) (X, L), is finitely generated. This ring admits a natural action of the N
UNIVERSAL TORSORS AND COX RINGS Brendan Hassett and Yuri Tschinkel
Tschinkel, Yuri
UNIVERSAL TORSORS AND COX RINGS by Brendan Hassett and Yuri Tschinkel Abstract. -- We study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. Generalities on the Cox ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 such that the Picard and the N´eron- Severi groups of X coincide and such that the ring Cox(X) := LPic(X) (X, L
Principles of Statistical Inference Nancy Reid and David Cox
Reid, Nancy
Principles of Statistical Inference Nancy Reid and David Cox August 30, 2013 #12;#12;Introduction structure must be continually tested against new applications Principles of Statistical Inference Reid & Cox of Statistical Inference Reid & Cox, WSC2013 4 #12;Introduction Statistics needs a healthy interplay between
Faculty Search Tench Coxe Distinguished Professorship of Management
Myers, Lawrence C.
Faculty Search Tench Coxe Distinguished Professorship of Management September, 2012 The Tuck School interest in execution on social goals, can fill the Tench Coxe Distinguished Professorship of Management an accomplished scholar and teacher for the tenured position of the Tench Coxe Distinguished Professorship
Original article Potent, orally available, selective COX-2 inhibitors based
Hammock, Bruce D.
]; a view of COX-2 inhibition being innately linked to adverse effects on vasocon- striction, plateletOriginal article Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300
Selective COX-1 inhibition: A therapeutic target to be reconsidered.
Perrone, M G; Scilimati, A; Simone, L; Vitale, P
2010-01-01
Since cyclooxygenase (COX) isozymes discovery, many papers and reviews have been published to describe the structural bases of COX inhibition, and to debate on the therapeutic and adverse effects of worldwide clinically used nonsteroidal anti-inflammatory drugs (NSAIDs), included COX-2 selective inhibitors (well known as Coxibs). COX-2 inhibition has been widely investigated, whereas the role of COX-1 in human pathophysiology is mostly not yet well ascertained. As time goes on, the cliché that the constitutively expressed isoform COX-1 is only involved in normal physiological functions, such as platelet aggregation, gastric mucosa protection and renal electrolyte homeostasis is going to be shattered. Low-dose aspirin, behaving as a preferential inhibitor of platelet COX-1, allowed to enlighten the role exerted by this isoenzyme in many mammalian cell types. This review would elucidate the most recent findings on selective COX-1 inhibition and their relevance to human pathology such as cancer, neuro-inflammation, cardioprotection, fever and pain. It would also focus on the design and development of new highly selective COX-1 inhibitors, useful tools in pharmacological studies aimed at gaining a deeper insight of the role of COX-1 in human health and disease. Among the traditional NSAIDs, other then aspirin and indomethacin, only few examples of selective COX-1 inhibitors (SC-560, FR122047, mofezolac, P6 and TFAP) have been so far identified. This review has also the scope to stimulate the development of novel drugs, which activity is COX-1 mediated. PMID:20858219
The Usability of Transparent Overview Layers Donald A. Cox
Greenberg, Saul
The Usability of Transparent Overview Layers Donald A. Cox , Jasdeep S. Chugh , Carl Gutwin and Saul Greenberg Research Report 97-609-11 December, 1997 Cite as: Cox, D., Chugh, J.S., Gutwin, C of Computer Science, University of Calgary, Calgary, Alberta, Canada. December. #12;Cox, Chugh, Gutwin
Leffondré, Karen; Jager, Kitty J; Boucquemont, Julie; Stel, Vianda S; Heinze, Georg
2014-10-01
Regression models are being used to quantify the effect of an exposure on an outcome, while adjusting for potential confounders. While the type of regression model to be used is determined by the nature of the outcome variable, e.g. linear regression has to be applied for continuous outcome variables, all regression models can handle any kind of exposure variables. However, some fundamentals of representation of the exposure in a regression model and also some potential pitfalls have to be kept in mind in order to obtain meaningful interpretation of results. The objective of this educational paper was to illustrate these fundamentals and pitfalls, using various multiple regression models applied to data from a hypothetical cohort of 3000 patients with chronic kidney disease. In particular, we illustrate how to represent different types of exposure variables (binary, categorical with two or more categories and continuous), and how to interpret the regression coefficients in linear, logistic and Cox models. We also discuss the linearity assumption in these models, and show how wrongly assuming linearity may produce biased results and how flexible modelling using spline functions may provide better estimates. PMID:24366898
COX-2 inhibitors: pharmacological data and adverse effects.
Mattia, C; Coluzzi, F
2005-01-01
The nonsteroidal anti-inflammatory drugs (NSAIDs) cover a wide range of selectivity, from the nonselective cyclooxygenase (COX) inhibitors to the preferential COX-2, and the newest coxibs, selective COX-2, with 1000-fold selectivities for COX-2. Coxibs belong to the distinct classes of sulphonamides, methylsulphones, and phenylacetic acid derivatives. The affinity of an inhibitor for COX-1 and COX-2 determinates its relative selectivity. Minor changes in the amino acid structure between the 2 enzymes results in different forms of their active sites. However, the primitive hypothesis of a dualism between an isoform totally inducible (COX-2) and the other isoform constitutive (COX-1) was not completely true. Thus, also selective COX-2 inhibitors have been shown to interact with gastrointestinal, renal, and cardiovascular systems. New insights into pharmacological data and side effect profile of coxibs have been reported in this review. They may reduce gastrointestinal-related risks, but when administered with low-dose aspirin, they could create an ulcerogenic dual-COX inhibitor. Moreover, by inhibiting COX-2, they could delay ulcer healing. Similarly to traditional NSAIDs, coxibs compromise the glomerular filtration rate in patients at increased risk, and may cause peripheral oedema and hypertension. According to the traditional ''COX-2 hypothesis'', they should not impair efficacy of coagulation. However, in combination with an oral anticoagulant they increase the International Normalized Ratio (INR) and, in some cases, cause bleeding. The altered balance between prostacyclin and thromboxane, due to selective inhibition of COX-2 without reducing COX-1, could promote a prothrombotic state and explain the observed increased cardiovascular risk. Finally, the role of COX-2 expression in the ischemic preconditioning mechanism and the recent discovery of a pro-oxidant activity of sulphones has been analysed. PMID:16012420
Namita Kundu; Amy M. Fulton
2002-01-01
Using a highly metastatic mammary tumor cell line that expresses both cyclooxygenase (COX) isoforms, we now show that oral administration of either a selective COX-2 inhibitor (celecoxib) or a selective COX-1 inhib- itor (SC560) to mice with established tumors results in significant inhibi- tion of tumor growth. Administration of the dual inhibitor, indomethacin, leads to even better growth control. Metastatic
Optimizing the Classification Performance of Logistic Regression and Fisher's Discriminant Analyses.
ERIC Educational Resources Information Center
Yarnold, Paul R.; And Others
1994-01-01
A methodology is proposed to optimize the training classification performance of any suboptimal model. The method, referred to as univariate optimal discriminant analysis (UniODA), is illustrated through application to a two-group logistic regression analysis with 12 empirical examples. Maximizing percentage accuracy in classification is…
Mass univariate analysis of event-related brain potentials/fields II: Simulation studies
Kutas, Marta
the null hypothesis. Here we report the results of simulations assessing the accuracy, permissivenessMass univariate analysis of event-related brain potentials/fields II: Simulation studies DAVID M, Permutation test, Hypothesis testing As detailed in a companion article (Groppe, Urbach, & Kutas, 2011
Degeneracy in the maximum likelihood estimation of univariate Gaussian mixtures with EM
Biernacki, Christophe
Degeneracy in the maximum likelihood estimation of univariate Gaussian mixtures with EM Christophe, France September 24, 2002 Abstract As is wellÂknown, the likelihood in the Gaussian mixture is unbounded algorithm, Gaussian mixtures, speed of convergence. 1 Introduction Because finite mixtures of distributions
Univariate Polynomials: Nearly Optimal Algorithms for Numerical Factorization and Root-finding
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
Epileptic Seizure Prediction based on Ratio and Differential Linear Univariate Features
Rasekhi, Jalil; Mollaei, Mohammad Reza Karami; Bandarabadi, Mojtaba; Teixeira, César A.; Dourado, António
2015-01-01
Bivariate features, obtained from multichannel electroencephalogram recordings, quantify the relation between different brain regions. Studies based on bivariate features have shown optimistic results for tackling epileptic seizure prediction problem in patients suffering from refractory epilepsy. A new bivariate approach using univariate features is proposed here. Differences and ratios of 22 linear univariate features were calculated using pairwise combination of 6 electroencephalograms channels, to create 330 differential, and 330 relative features. The feature subsets were classified using support vector machines separately, as one of the two classes of preictal and nonpreictal. Furthermore, minimum Redundancy Maximum Relevance feature reduction method is employed to improve the predictions and reduce the number of false alarms. The studies were carried out on features obtained from 10 patients. For reduced subset of 30 features and using differential approach, the seizures were on average predicted in 60.9% of the cases (28 out of 46 in 737.9 h of test data), with a low false prediction rate of 0.11 h?1. Results of bivariate approaches were compared with those achieved from original linear univariate features, extracted from 6 channels. The advantage of proposed bivariate features is the smaller number of false predictions in comparison to the original 22 univariate features. In addition, reduction in feature dimension could provide a less complex and the more cost-effective algorithm. Results indicate that applying machine learning methods on a multidimensional feature space resulting from relative/differential pairwise combination of 22 univariate features could predict seizure onsets with high performance. PMID:25709936
A consistent framework for Horton regression statistics that leads to a modified Hack's law
Furey, P.R.; Troutman, B.M.
2008-01-01
A statistical framework is introduced that resolves important problems with the interpretation and use of traditional Horton regression statistics. The framework is based on a univariate regression model that leads to an alternative expression for Horton ratio, connects Horton regression statistics to distributional simple scaling, and improves the accuracy in estimating Horton plot parameters. The model is used to examine data for drainage area A and mainstream length L from two groups of basins located in different physiographic settings. Results show that confidence intervals for the Horton plot regression statistics are quite wide. Nonetheless, an analysis of covariance shows that regression intercepts, but not regression slopes, can be used to distinguish between basin groups. The univariate model is generalized to include n > 1 dependent variables. For the case where the dependent variables represent ln A and ln L, the generalized model performs somewhat better at distinguishing between basin groups than two separate univariate models. The generalized model leads to a modification of Hack's law where L depends on both A and Strahler order ??. Data show that ?? plays a statistically significant role in the modified Hack's law expression. ?? 2008 Elsevier B.V.
Model selection in competing risks regression.
Kuk, Deborah; Varadhan, Ravi
2013-08-15
In the analysis of time-to-event data, the problem of competing risks occurs when an individual may experience one, and only one, of m different types of events. The presence of competing risks complicates the analysis of time-to-event data, and standard survival analysis techniques such as Kaplan-Meier estimation, log-rank test and Cox modeling are not always appropriate and should be applied with caution. Fine and Gray developed a method for regression analysis that models the hazard that corresponds to the cumulative incidence function. This model is becoming widely used by clinical researchers and is now available in all the major software environments. Although model selection methods for Cox proportional hazards models have been developed, few methods exist for competing risks data. We have developed stepwise regression procedures, both forward and backward, based on AIC, BIC, and BICcr (a newly proposed criteria that is a modified BIC for competing risks data subject to right censoring) as selection criteria for the Fine and Gray model. We evaluated the performance of these model selection procedures in a large simulation study and found them to perform well. We also applied our procedures to assess the importance of bone mineral density in predicting the absolute risk of hip fracture in the Women's Health Initiative-Observational Study, where mortality was the competing risk. We have implemented our method as a freely available R package called crrstep. PMID:23436643
COX-2 inhibition versus gastroprotection with dual COX inhibitors: an evidence-based approach.
Thompson, Alexander J V; Yeomans, Neville D
2003-01-01
Highly selective inhibitors of cyclooxygenase-2 (COX-2i) were introduced to minimize peptic ulcers and their complications caused by dual COX inhibitors (COXi). Co-prescribing a (generally cheap) dual COXi with a gastroprotectant is an alternative strategy, proven to reduce the incidence of NSAID-associated endoscopic ulcers. This review compares the efficacies of these two strategies and makes some estimates of their relative cost-effectiveness. In standard risk patients, endoscopic ulcers are reduced to about the same extent (around 70-80%) by either co-prescribing omeprazole or lansoprazole with a dual COXi or preferring a COX-2i alone. COX-2i reduced ulcer complications by a weighted mean of around 60% in comparative studies with dual COXi. There is little information about the influence of PPI on this endpoint, although one study using H. pylori treatment as a possible surrogate for placebo intervention found 77% protection against recurrent upper gastrointestinal bleeding by co-administered omeprazole. One direct comparison of the two strategies in high-risk patients (recent ulcer bleed) found quite high rates of re-presentation with bleeding ulcer using either strategy, and the differences between them were not significant. Drug costs in four Western countries were compared for each strategy. In one, the costs were similar, but in the others the combination of a cheap dual COXi with omeprazole was usually more expensive than using a COX-2i. The safest strategy in highest risk patients may be to co-prescribe a gastroprotectant with a COX-2i, with resulting higher drug costs but possibly offset by savings in other health costs. The efficacy and cost-benefit of this alternative approach warrants investigation. PMID:14529403
Zidar, Nina; Odar, Katarina; Glava?, Damjan; Jerše, Maja; Zupanc, Tomaž; Štajer, Dušan
2009-01-01
Cyclooxygenase (COX) is a key enzyme in prostanoid synthesis. It exists in two isoforms, COX-1 and COX-2. COX-1 is referred to as a ‘constitutive isoform’, and is considered to be expressed in most tissues under basal conditions. In contrast, COX-2 is referred to as an ‘inducible isoform’, which is believed to be undetectable in most normal tissues, but can be up-regulated during various conditions, many of them pathological. Even though the role of COX in homeostasis and disease in now well appreciated, controversial information is available concerning the distribution of COX isoforms in normal human tissues. There is mounting evidence that it is much more complex than generally believed. Our aim was therefore to analyse the expression and distribution of COX isoforms in normal human tissues, using immunohistochemistry, Western blotting and real-time RT-PCR. Autopsy samples from 20 healthy trauma victims and samples from 48 biopsy surgical specimens were included. COX-1 was found in blood vessels, interstitial cells, smooth muscle cells, platelets and mesothelial cells. In contrast, COX-2 was found predominantly in the parenchymal cells of many tissues, with few exceptions, for example the heart. Our results confirm the hypothesis that the distribution of COX isoforms in healthy tissues is much more complex than generally believed. This and previous studies indicate that both isoforms, not only COX-1, are present in many normal human tissues, and that both isoforms, not only COX-2, are up-regulated in various pathological conditions. We may have to revise the concept of ‘constitutive’ and ‘inducible’ COX isoforms. PMID:18657230
Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation
Colleselli, Daniela [Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria); Bijuklic, Klaudija [Inflammation Research, Laboratory Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck (Austria); Mosheimer, Birgit A. [Inflammation Research, Laboratory Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck (Austria); Kaehler, Christian M. [Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria)]. E-mail: C.M.Kaehler@uibk.ac.at
2006-09-10
Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in the pathogenesis of inflammatory disorders and various types of cancer. Endothelial progenitor cells recruited from the bone marrow have been shown to be involved in the formation of new vessels in malignancies and discussed for being a key point in tumour progression and metastasis. However, until now, nothing is known about an interaction between COX and endothelial progenitor cells (EPC). Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were analysed by MTT test and FACS analysis. Further analyses revealed an implication of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2 inhibition leads to a significant reduction in proliferation of endothelial progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2 inhibition leads further to an increased cleavage of caspase-3 protein and inversely to inhibition of Akt activation. Highly proliferating endothelial progenitor cells can be targeted by selective COX-2 inhibition in vitro. These results indicate that upcoming therapy strategies in cancer patients targeting COX-2 may be effective in inhibiting tumour vasculogenesis as well as angiogenic processes.
REGULARIZATION FOR COX'S PROPORTIONAL HAZARDS MODEL WITH NP-DIMENSIONALITY.
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
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…
Introduction Linear Regression
Lega, Joceline
Introduction Linear Regression Calculus in AI and Machine Learning 1 Qiyam Tung G-TEAMS Department Linear Regression Introduction Linear Regression is one of the tools we use in machine learning variables). Predicting the effect of factories on environments. Qiyam Tung Calculus and AI 1 #12
López, M Isabel; Callao, M Pilar; Ruisánchez, Itziar
2015-09-01
This tutorial provides an overview of the validation of qualitative analytical methods, with particular focus on their main performance parameters, for both univariate and multivariate methods. We discuss specific parameters (sensitivity, specificity, false positive and false negative rates), global parameters (efficiency, Youden's index and likelihood ratio) and those parameters that have a quantitative connotation since they are usually associated to concentration values (decision limit, detection capability and unreliability region). Some methodologies that can be used to estimate these parameters are also described: the use of contingency tables for the specific and global parameters and the performance characteristic curve (PCC) for the ones with quantitative connotation. To date, PCC has been less commonly used in multivariate methods. To illustrate the proposals summarized in this tutorial, two cases study are discussed at the end, one for a univariate qualitative analysis and the other for multivariate one. PMID:26388364
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.
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.
Norouzi, Mahnaz; Norouzi, Shaghayegh; Amini, Mohsen; Amanzadeh, Amir; Irian, Saeed; Salimi, Mona
2015-01-01
Recently, much effort has been directed toward the search for compounds that influence apoptosis and to understand their mechanisms of action. Cyclooxygenase (COX)-2 inhibitors may induce apoptosis through the COX-2-independent mechanism via a mitochondrial pathway. In view of the reported antiproliferative activities of two COX-2 inhibitor derivatives (1, 2) in breast cancer cells (MCF-7), the present study was undertaken to evaluate the potential of these compounds to induce apoptosis and unravel the associated mechanisms. The apoptotic activities of the two compounds were assessed using flow cytometry, fluorescence microscope, and Western blot analysis. Compounds 1 and 2-treated MCF-7 cells revealed the apoptotic cell death, as confirmed by the changes in nuclear morphology and the increased annexin-V/PI staining. Elevation of Bax to Bcl-2 ratio and activation of caspase-3 were found to be associated with the initiation of apoptosis induced by compound 1. Further investigation showed that compounds 1 and 2 inhibited NF-?B, FHC, and ERK activation, while no dramatic change was revealed in c-Myc and EGR-1 levels. Our data suggest that induction of apoptosis by compounds 1 and 2 is not associated with COX-2 expression and occurs through the NF-?B pathway, which sequentially inhibits P-ERK and FHC expression. PMID:25142612
Osborn, Pamela
2014-01-17
inhibitor, 10^(-7) M), or VP+NS-398 (NS, selective COX-2 inhibitor, 10^(-5) M). The KHB was analyzed by specific radioimmunoassays (RIA) for 6-keto-PGF_(1?) (stable metabolite of PGI_(2) and TxB_(2) (stable metabolite of TxA2). Basal PGI_(2) was similar in M...
COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.
Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael
2009-12-15
The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition. PMID:19880317
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
Censored quantile regression with recursive partitioning-based weights
Wey, Andrew; Wang, Lan; Rudser, Kyle
2014-01-01
Censored quantile regression provides a useful alternative to the Cox proportional hazards model for analyzing survival data. It directly models the conditional quantile of the survival time and hence is easy to interpret. Moreover, it relaxes the proportionality constraint on the hazard function associated with the popular Cox model and is natural for modeling heterogeneity of the data. Recently, Wang and Wang (2009. Locally weighted censored quantile regression. Journal of the American Statistical Association 103, 1117–1128) proposed a locally weighted censored quantile regression approach that allows for covariate-dependent censoring and is less restrictive than other censored quantile regression methods. However, their kernel smoothing-based weighting scheme requires all covariates to be continuous and encounters practical difficulty with even a moderate number of covariates. We propose a new weighting approach that uses recursive partitioning, e.g. survival trees, that offers greater flexibility in handling covariate-dependent censoring in moderately high dimensions and can incorporate both continuous and discrete covariates. We prove that this new weighting scheme leads to consistent estimation of the quantile regression coefficients and demonstrate its effectiveness via Monte Carlo simulations. We also illustrate the new method using a widely recognized data set from a clinical trial on primary biliary cirrhosis. PMID:23975800
Censored quantile regression with recursive partitioning-based weights.
Wey, Andrew; Wang, Lan; Rudser, Kyle
2014-01-01
Censored quantile regression provides a useful alternative to the Cox proportional hazards model for analyzing survival data. It directly models the conditional quantile of the survival time and hence is easy to interpret. Moreover, it relaxes the proportionality constraint on the hazard function associated with the popular Cox model and is natural for modeling heterogeneity of the data. Recently, Wang and Wang (2009. Locally weighted censored quantile regression. Journal of the American Statistical Association 103, 1117-1128) proposed a locally weighted censored quantile regression approach that allows for covariate-dependent censoring and is less restrictive than other censored quantile regression methods. However, their kernel smoothing-based weighting scheme requires all covariates to be continuous and encounters practical difficulty with even a moderate number of covariates. We propose a new weighting approach that uses recursive partitioning, e.g. survival trees, that offers greater flexibility in handling covariate-dependent censoring in moderately high dimensions and can incorporate both continuous and discrete covariates. We prove that this new weighting scheme leads to consistent estimation of the quantile regression coefficients and demonstrate its effectiveness via Monte Carlo simulations. We also illustrate the new method using a widely recognized data set from a clinical trial on primary biliary cirrhosis. PMID:23975800
Cyclooxygenase2 (COX2) in Inflammatory and Degenerative Brain Diseases
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
COX-2 expression and tumor angiogenesis in colorectal cancer
Wu, Ai-Wen; Gu, Jin; Li, Zhen-Fu; Ji, Jia-Fu; Xu, Guang-Wei
2004-01-01
AIM: Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes in metabolism of arachidonic acid, and COX-2 inhibitors demonstrate preventive effects on cancer, especially on colorectal cancer. The underlying mechanism remains unclear. The aim of this study was to illustrate the relationship between angiogenesis and COX-2 in carcinogenesis of colorectal cancer. METHODS: One hundred and seventy patients with colorectal cancer were enrolled in our study from January 1993 to September 2001 in School of Oncology, Peking University. COX-2 and VEGF expression were detected with the immunohistochemistry (IHC) technique. IHC assays were carried out with the aid of tissue microarray (TMA) procedure. Specimens from 35 of these patients were examined with reverse transcriptase PCR (RT-PCR). RESULTS: COX-2 and VEGF expressions were stronger in colorectal cancer than those in the corresponding normal tissues, at both protein and mRNA levels. One hundred patients were eligible for analysis after IHC assay of COX-2 and VEGF. The positive rate of VEGF was much higher in COX-2 positive group (47/85) than in COX-2 negative group (?2 = 4.181, P = 0.041). The result was further verified by the result of RT-PCR (?2 = 8.517, P = 0.003). Correlation coefficient was 0.409 after Spearman correlation analysis (P = 0.015). CONCLUSION: COX-2 may be involved in the course of tumor angiogenesis of colorectal cancer and acts through VEGF. PMID:15285012
Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer
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
COX-2 overexpression and -8473 T/C polymorphism in 3' UTR in non-small cell lung cancer.
Bhat, Imtiyaz A; Rasool, Roohi; Qasim, Iqbal; Masoodi, Khalid Z; Paul, Shabeer A; Bhat, Bashir A; Ganaie, Farooq A; Aziz, Sheikh A; Shah, Zafar A
2014-11-01
A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0%) than in the controls (36%), suggesting that the 8473 C variant allele is related with lower susceptibility in NSCLC (OR = 0.79, 95% CI 0.54-1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P = 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (?CT)?= 9.25 ± 4.67 vs 5.63 ± 3.85, P = 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P = 0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473 C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future. PMID:25113252
Autistic epileptiform regression.
Canitano, Roberto; Zappella, Michele
2006-01-01
Autistic regression is a well known condition that occurs in one third of children with pervasive developmental disorders, who, after normal development in the first year of life, undergo a global regression during the second year that encompasses language, social skills and play. In a portion of these subjects, epileptiform abnormalities are present with or without seizures, resembling, in some respects, other epileptiform regressions of language and behaviour such as Landau-Kleffner syndrome. In these cases, for a more accurate definition of the clinical entity, the term autistic epileptifom regression has been suggested. As in other epileptic syndromes with regression, the relationships between EEG abnormalities, language and behaviour, in autism, are still unclear. We describe two cases of autistic epileptiform regression selected from a larger group of children with autistic spectrum disorders, with the aim of discussing the clinical features of the condition, the therapeutic approach and the outcome. PMID:16796825
Predicting cognitive data from medical images using sparse linear regression.
Kandel, Benjamin M; Wolk, David A; Gee, James C; Avants, Brian
2013-01-01
We present a new framework for predicting cognitive or other continuous-variable data from medical images. Current methods of probing the connection between medical images and other clinical data typically use voxel-based mass univariate approaches. These approaches do not take into account the multivariate, network-based interactions between the various areas of the brain and do not give readily interpretable metrics that describe how strongly cognitive function is related to neuroanatomical structure. On the other hand, high-dimensional machine learning techniques do not typically provide a direct method for discovering which parts of the brain are used for making predictions. We present a framework, based on recent work in sparse linear regression, that addresses both drawbacks of mass univariate approaches, while preserving the direct spatial interpretability that they provide. In addition, we present a novel optimization algorithm that adapts the conjugate gradient method for sparse regression on medical imaging data. This algorithm produces coefficients that are more interpretable than existing sparse regression techniques. PMID:24683960
Predicting Cognitive Data from Medical Images Using Sparse Linear Regression
Kandel, Benjamin M.; Wolk, David A.; Gee, James C.; Avants, Brian
2015-01-01
We present a new framework for predicting cognitive or other continuous-variable data from medical images. Current methods of probing the connection between medical images and other clinical data typically use voxel-based mass univariate approaches. These approaches do not take into account the multivariate, network-based interactions between the various areas of the brain and do not give readily interpretable metrics that describe how strongly cognitive function is related to neuroanatomical structure. On the other hand, high-dimensional machine learning techniques do not typically provide a direct method for discovering which parts of the brain are used for making predictions. We present a framework, based on recent work in sparse linear regression, that addresses both drawbacks of mass univariate approaches, while preserving the direct spatial interpretability that they provide. In addition, we present a novel optimization algorithm that adapts the conjugate gradient method for sparse regression on medical imaging data. This algorithm produces coefficients that are more interpretable than existing sparse regression techniques. PMID:24683960
Recurrent events and the exploding Cox model
Gjessing, Håkon K.; Røysland, Kjetil; Pena, Edsel A.; Aalen, Odd O.
2014-01-01
Counting process models have played an important role in survival and event history analysis for more than 30 years. Nevertheless, almost all models that are being used have a very simple structure. Analyzing recurrent events invites the application of more complex models with dynamic covariates. We discuss how to define valid models in such a setting. One has to check carefully that a suggested model is well defined as a stochastic process. We give conditions for this to hold. Some detailed discussion is presented in relation to a Cox type model, where the exponential structure combined with feedback lead to an exploding model. In general, counting process models with dynamic covariates can be formulated to avoid explosions. In particular, models with a linear feedback structure do not explode, making them useful tools in general modeling of recurrent events. PMID:20625827
Modeling age-of-onset: Cox model with latent major gene effects
Li, H.; Thompson, E.A.
1994-09-01
Analysis of age-of-onset is a key factor in the segregation and linkage analysis of complex genetic traits, but is complicated by the censoring of unaffected individuals. Most previous work has used parametric distributional assumptions, but it is hard to characterize the distribution of age-of-onset by a single distribution. Other approaches discretize age-of-onset and use logistic regression to model incidence; this approach does not use the information fully. Frailty models have been used for age-of-oset in the biostatistics literature, but these models do not lend themselves to modeling the correlations due to genetic effects which segregate within a family. Here, we propose use of the Cox model with latent major gene effects; conditional on the major genotypes, Cox`s proportional hazards model is used for age-of-onset for each individual. This is a semiparametric model; we do not specify the baseline hazard function. Likelihood analysis of such models is restricted by the difficulty in evaluating of maximizing the likelihood, especially when data are available for some of the members of an extended pedigree. Markov chain Monte Carlo permits genotypic configurations to be realized from the posterior distributions given a current model and the observed data. Hence methods for likelihood analysis can be developed: Monte Carlo EM is used for estimation of the parameters and their variance-covariance matrix. Markers and observed covariates are easily incorporated into this analysis. We present the model, methods for likelihood analysis and the results of a simulation study. The results are comparable with those based on a Cox model with known genotypic dependence in a pedigree. An early-onset Alzheimer`s pedigree and some breast cancer pedigrees have been used as real data examples. Some possible extensions are also discussed.
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.
CURRICULUM VITAE L. Clarke Cox, Ph.D.
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
Alveolate and chlorophycean mitochondrial cox2 genes split twice independently
Keeling, Patrick
members of two unrelated groups, Apicomplexa and Chlorophyceae, cox2 is split into two genes, and both. Dinoflagellates form the sister taxon to Apicomplexa, and therefore the state of their cox2 is essential. © 2006 Elsevier B.V. All rights reserved. Keywords: Dinoflagellate; Apicomplexa; Rare genomic changes
Does Cox analysis of a randomized survival study yield a causal treatment effect?
Aalen, Odd O; Cook, Richard J; Røysland, Kjetil
2015-10-01
Statistical methods for survival analysis play a central role in the assessment of treatment effects in randomized clinical trials in cardiovascular disease, cancer, and many other fields. The most common approach to analysis involves fitting a Cox regression model including a treatment indicator, and basing inference on the large sample properties of the regression coefficient estimator. Despite the fact that treatment assignment is randomized, the hazard ratio is not a quantity which admits a causal interpretation in the case of unmodelled heterogeneity. This problem arises because the risk sets beyond the first event time are comprised of the subset of individuals who have not previously failed. The balance in the distribution of potential confounders between treatment arms is lost by this implicit conditioning, whether or not censoring is present. Thus while the Cox model may be used as a basis for valid tests of the null hypotheses of no treatment effect if robust variance estimates are used, modeling frameworks more compatible with causal reasoning may be preferrable in general for estimation. PMID:26100005
J. H. Jakobsen; P. Madsen; J. Jensen; J. Pedersen; L. G. Christensen; D. A. Sorensen
2002-01-01
Co)variance components for milk, fat, and protein yield of 8075 first-parity Danish Holsteins (DH) were estimated in random regression models by REML. For all analyses, the fixed part of the model was held con- stant, whereas four different functions were applied to model the additive genetic effect and the permanent environment effect. Homogeneous residual variance was assumed throughout lactation. Univariate
Masci, Frank
. Bowman, D. Sheehan Source: Journal of the Royal Statistical Society. Series B (Methodological), Vol. 33, Sampling Moments of Moments Associated withUnivariate Distributions By L. R. SHENTON,1K. 0. BOWMAN2and D
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
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…
Lega, Joceline
Introduction AI/Regression Technology/Search Simple Equations, Deep Understanding How Topics and Alison Cornell Simple Equations, Deep Meaning #12;Introduction AI/Regression Technology/Search Who are we helps out) Qiyam Tung and Alison Cornell Simple Equations, Deep Meaning #12;Introduction AI
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.
Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Piotrowska, Katarzyna; Korbecki, Jan; Kurzawski, Mateusz; Chlubek, Dariusz
2015-06-01
The aim of this study was to examine the effects of cadmium in concentrations relevant to those detected in human serum on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression at mRNA, protein, and enzyme activity levels in THP-1 macrophages. Macrophages were incubated with various cadmium chloride (CdCl2) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 ?M CdCl2. The mRNA expression and protein levels of COXs were analyzed with RT-PCR and Western blotting, respectively. Prostaglandin E2 (PGE2) and stable metabolite of thromboxane B2 (TXB2) concentrations in culture media were determined using ELISA method. Our study demonstrates that cadmium at the highest tested concentrations modulates COX-1 and COX-2 at mRNA level in THP-1 macrophages; however, the lower tested cadmium concentrations appear to inhibit COX-1 protein expression. PGE2 and TXB2 production is not altered by all tested Cd concentrations; however, the significant stimulation of PGE2 and TXB2 production is observed when macrophages are exposed to both cadmium and COX-2 selective inhibitor, NS-398. The stimulatory effect of cadmium on COXs at mRNA level is not reflected at protein and enzymatic activity levels, suggesting the existence of some posttranscriptional, translational, and posttranslational events that result in silencing of those genes' expression. PMID:25645360
Evaluation dam overtopping risk based on univariate and bivariate flood frequency analysis
NASA Astrophysics Data System (ADS)
Goodarzi, E.; Mirzaei, M.; Shui, L. T.; Ziaei, M.
2011-11-01
There is a growing tendency to assess the safety levels of existing dams based on risk and uncertainty analysis using mathematical and statistical methods. This research presents the application of risk and uncertainty analysis to dam overtopping based on univariate and bivariate flood frequency analyses by applying Gumbel logistic distribution for the Doroudzan earth-fill dam in south of Iran. The bivariate frequency analysis resulted in six inflow hydrographs with a joint return period of 100-yr. The overtopping risks were computed for all of those hydrographs considering quantile of flood peak discharge (in particular 100-yr), initial depth of water in the reservoir, and discharge coefficient of spillway as uncertain variables. The maximum height of the water, as most important factor in the overtopping analysis, was evaluated using reservoir routing and the Monte Carlo and Latin hypercube techniques were applied for uncertainty analysis. Finally, the achieved results using both univariate and bivariate frequency analysis have been compared to show the significance of bivariate analyses on dam overtopping.
NASA Technical Reports Server (NTRS)
Narkawicz, Anthony J.; Munoz, Cesar A.
2014-01-01
Sturm's Theorem is a well-known result in real algebraic geometry that provides a function that computes the number of roots of a univariate polynomial in a semiopen interval. This paper presents a formalization of this theorem in the PVS theorem prover, as well as a decision procedure that checks whether a polynomial is always positive, nonnegative, nonzero, negative, or nonpositive on any input interval. The soundness and completeness of the decision procedure is proven in PVS. The procedure and its correctness properties enable the implementation of a PVS strategy for automatically proving existential and universal univariate polynomial inequalities. Since the decision procedure is formally verified in PVS, the soundness of the strategy depends solely on the internal logic of PVS rather than on an external oracle. The procedure itself uses a combination of Sturm's Theorem, an interval bisection procedure, and the fact that a polynomial with exactly one root in a bounded interval is always nonnegative on that interval if and only if it is nonnegative at both endpoints.
Burkhard H. A. von Rahden; Hubert J. Stein; Franziska Puhringer; Rupert Langer; Guido Piontek; J. Rudiger Siewert; Heinz Hofler; Mario Sarbia
2005-01-01
Cyclooxygenases (COX), especially COX-2, are considered to be involved in carcinogenesis. Our study was initiated to test whether expression of COX isoforms (COX-1 and COX-2) is linked to expression of potent inducers of angiogenesis (vascular endothelial growth factor (VEGF)-A) and lymphan- giogenesis (VEGF-C) in esophageal adenocarcinoma. One hundred twenty-three esophageal adenocarcinomas were investigated by means of quantitative reverse transcription- PCR
Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma
2014-01-01
A cure rate model is a survival model incorporating the cure rate with the assumption that the population contains both uncured and cured individuals. It is a powerful statistical tool for prognostic studies, especially in cancer. The cure rate is important for making treatment decisions in clinical practice. The proportional hazards (PH) cure model can predict the cure rate for each patient. This contains a logistic regression component for the cure rate and a Cox regression component to estimate the hazard for uncured patients. A measure for quantifying the predictive accuracy of the cure rate estimated by the Cox PH cure model is required, as there has been a lack of previous research in this area. We used the Cox PH cure model for the breast cancer data; however, the area under the receiver operating characteristic curve (AUC) could not be estimated because many patients were censored. In this study, we used imputation-based AUCs to assess the predictive accuracy of the cure rate from the PH cure model. We examined the precision of these AUCs using simulation studies. The results demonstrated that the imputation-based AUCs were estimable and their biases were negligibly small in many cases, although ordinary AUC could not be estimated. Additionally, we introduced the bias-correction method of imputation-based AUCs and found that the bias-corrected estimate successfully compensated the overestimation in the simulation studies. We also illustrated the estimation of the imputation-based AUCs using breast cancer data. PMID:25044997
Wang, X; Jiao, Y; Tang, T; Wang, H; Lu, Z
2013-12-19
Intrinsic connectivity networks (ICNs) are composed of spatial components and time courses. The spatial components of ICNs were discovered with moderate-to-high reliability. So far as we know, few studies focused on the reliability of the temporal patterns for ICNs based their individual time courses. The goals of this study were twofold: to investigate the test-retest reliability of temporal patterns for ICNs, and to analyze these informative univariate metrics. Additionally, a correlation analysis was performed to enhance interpretability. Our study included three datasets: (a) short- and long-term scans, (b) multi-band echo-planar imaging (mEPI), and (c) eyes open or closed. Using dual regression, we obtained the time courses of ICNs for each subject. To produce temporal patterns for ICNs, we applied two categories of univariate metrics: network-wise complexity and network-wise low-frequency oscillation. Furthermore, we validated the test-retest reliability for each metric. The network-wise temporal patterns for most ICNs (especially for default mode network, DMN) exhibited moderate-to-high reliability and reproducibility under different scan conditions. Network-wise complexity for DMN exhibited fair reliability (ICC<0.5) based on eyes-closed sessions. Specially, our results supported that mEPI could be a useful method with high reliability and reproducibility. In addition, these temporal patterns were with physiological meanings, and certain temporal patterns were correlated to the node strength of the corresponding ICN. Overall, network-wise temporal patterns of ICNs were reliable and informative and could be complementary to spatial patterns of ICNs for further study. PMID:24042040
Bayesian isotonic density regression.
Wang, Lianming; Dunson, David B
2011-09-01
Density regression models allow the conditional distribution of the response given predictors to change flexibly over the predictor space. Such models are much more flexible than nonparametric mean regression models with nonparametric residual distributions, and are well supported in many applications. A rich variety of Bayesian methods have been proposed for density regression, but it is not clear whether such priors have full support so that any true data-generating model can be accurately approximated. This article develops a new class of density regression models that incorporate stochastic-ordering constraints which are natural when a response tends to increase or decrease monotonely with a predictor. Theory is developed showing large support. Methods are developed for hypothesis testing, with posterior computation relying on a simple Gibbs sampler. Frequentist properties are illustrated in a simulation study, and an epidemiology application is considered. PMID:22822259
Multiple Roles of the Cox20 Chaperone in Assembly of Saccharomyces cerevisiae Cytochrome c Oxidase
Elliott, Leah E.; Saracco, Scott A.; Fox, Thomas D.
2012-01-01
The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the intermembrane space. Processing is chaperoned by Cox20, an integral inner membrane protein whose hydrophilic domains are located in the intermembrane space, and Cox20 remains associated with mature, unassembled Cox2. The Cox2 C-tail domain is exported post-translationally by the highly conserved translocase Cox18 and associated proteins. We have found that Cox20 is required for efficient export of the Cox2 C-tail. Furthermore, Cox20 interacts by co-immune precipitation with Cox18, and this interaction requires the presence of Cox2. We therefore propose that Cox20 binding to Cox2 on the trans side of the inner membrane accelerates dissociation of newly exported Cox2 from the Cox18 translocase, promoting efficient cycling of the translocase. The requirement for Cox20 in cytochrome c oxidase assembly and respiratory growth is partially bypassed by yme1, mgr1 or mgr3 mutations, each of which reduce i-AAA protease activity in the intermembrane space. Thus, Cox20 also appears to stabilize unassembled Cox2 against degradation by the i-AAA protease. Pre-Cox2 leader peptide processing by Imp1 occurs in the absence of Cox20 and i-AAA protease activity, but is greatly reduced in efficiency. Under these conditions some mature Cox2 is assembled into cytochrome c oxidase allowing weak respiratory growth. Thus, the Cox20 chaperone has important roles in leader peptide processing, C-tail export, and stabilization of Cox2. PMID:22095077
Lazer, E S; Miao, C K; Cywin, C L; Sorcek, R; Wong, H C; Meng, Z; Potocki, I; Hoermann, M; Snow, R J; Tschantz, M A; Kelly, T A; McNeil, D W; Coutts, S J; Churchill, L; Graham, A G; David, E; Grob, P M; Engel, W; Meier, H; Trummlitz, G
1997-03-14
Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothizines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5. PMID:9083488
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 C(cross), 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 C(cross) 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. PMID:25768589
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.
Compounding approach for univariate time series with non-stationary variances
Schäfer, Rudi; Guhr, Thomas; Stöckmann, Hans-Jürgen; Kuhl, Ulrich
2015-01-01
A defining feature of non-stationary systems is the time dependence of their statistical parameters. Measured time series may exhibit Gaussian statistics on short time horizons, due to the central limit theorem. The sample statistics for long time horizons, however, averages over the time-dependent parameters. To model the long-term statistical behavior, we compound the local distribution with the distribution of its parameters. Here we consider two concrete, but diverse examples of such non-stationary systems, the turbulent air flow of a fan and a time series of foreign exchange rates. Our main focus is to empirically determine the appropriate parameter distribution for the compounding approach. To this end we have to estimate the parameter distribution for univariate time series in a highly non-stationary situation.
Parameter induction in continuous univariate distributions: Well-established G families.
Tahir, Muhammad H; Nadarajah, Saralees
2015-01-01
The art of parameter(s) induction to the baseline distribution has received a great deal of attention in recent years. The induction of one or more additional shape parameter(s) to the baseline distribution makes the distribution more flexible especially for studying the tail properties. This parameter(s) induction also proved helpful in improving the goodness-of-fit of the proposed generalized family of distributions. There exist many generalized (or generated) G families of continuous univariate distributions since 1985. In this paper, the well-established and widely-accepted G families of distributions like the exponentiated family, Marshall-Olkin extended family, beta-generated family, McDonald-generalized family, Kumaraswamy-generalized family and exponentiated generalized family are discussed. We provide lists of contributed literature on these well-established G families of distributions. Some extended forms of the Marshall-Olkin extended family and Kumaraswamy-generalized family of distributions are proposed. PMID:26131628
An, Ying; Belevych, Natalya; Wang, Yufen; Zhang, Hao; Herschman, Harvey; Chen, Qun; Quan, Ning
2014-04-01
Treating acute brain injuries with COX-2 inhibitors can produce both neuroprotective and neurotoxic effects. This study investigated the role of COX-2 in modulating acute brain injury induced by excitotoxic neural damage. Intrastriatal injection of excitotoxin (RS)-(tetrazole-5yl) glycine elicited COX-2 expression in two distinct groups of cells. cortical neurons surrounding the lesion and vascular cells in the lesion core. The vascular COX-2 was expressed in two cell types, endothelial cells and monocytes. Selective deletion of COX-2 in vascular cells in Tie2Cre Cox-2(flox/flox) mice did not affect the induction of COX-2 in neurons after the excitotoxin injection but resulted in increased lesion volume, indicating a neuroprotective role for the COX-2 expressed in the vascular cells. Selective deletion of monocyte COX-2 in LysMCre Cox-2(flox/flox) mice did not reduce COX-2-dependent neuroprotection, suggesting that endothelial COX-2 is sufficient to confer neuroprotection. Pharmacological inhibition of COX-2 activity in Tie2Cre Cox-2(flox/flox) mice reduced lesion volume, indicating a neurotoxic role for the COX-2 expressed in neurons. Furthermore, COX-2-dependent neurotoxicity was mediated, at least in part, via the activation of the EP1 receptor. These results show that Cox-2 expression induced in different cell types can confer opposite effects. PMID:24375716
Micro-Raman spectroscopy and univariate analysis for monitoring disease follow-up.
Camerlingo, Carlo; Delfino, Ines; Perna, Giuseppe; Capozzi, Vito; Lepore, Maria
2011-01-01
Micro-Raman spectroscopy is a very promising tool for medical applications, thanks to its sensitivity to subtle changes in the chemical and structural characteristics of biological specimens. To fully exploit these promises, building a method of data analysis properly suited for the case under study is crucial. Here, a linear or univariate approach using a R2 determination coefficient is proposed for discriminating Raman spectra even with small differences. The validity of the proposed approach has been tested using Raman spectra of high purity glucose solutions collected in the 600 to 1,600 cm(-1) region and also from solutions with two known solutes at different concentrations. After this validation step, the proposed analysis has been applied to Raman spectra from oral human tissues affected by Pemphigus Vulgaris (PV), a rare life-threatening autoimmune disease, for monitoring disease follow-up. Raman spectra have been obtained in the wavenumber regions from 1,050 to 1,700 cm(-1) and 2,700 to 3,200 cm(-1) from tissues of patients at different stages of pathology (active PV, under therapy and PV in remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage have been detected at 1,150-1,250 cm(-1) (amide III) and 1,420-1,450 cm(-1) (CH3 deformation) regions and around 1,650 cm(-1) (amide I) and 2,930 cm(-1) (CH3 symmetric stretch). The analysis of tissue Raman spectra by the proposed univariate method has allowed us to effectively differentiate tissues at different stages of pathology. PMID:22164077
Micro-Raman Spectroscopy and Univariate Analysis for Monitoring Disease Follow-Up
Camerlingo, Carlo; Delfino, Ines; Perna, Giuseppe; Capozzi, Vito; Lepore, Maria
2011-01-01
Micro-Raman spectroscopy is a very promising tool for medical applications, thanks to its sensitivity to subtle changes in the chemical and structural characteristics of biological specimens. To fully exploit these promises, building a method of data analysis properly suited for the case under study is crucial. Here, a linear or univariate approach using a R2 determination coefficient is proposed for discriminating Raman spectra even with small differences. The validity of the proposed approach has been tested using Raman spectra of high purity glucose solutions collected in the 600 to 1,600 cm?1 region and also from solutions with two known solutes at different concentrations. After this validation step, the proposed analysis has been applied to Raman spectra from oral human tissues affected by Pemphigus Vulgaris (PV), a rare life-threatening autoimmune disease, for monitoring disease follow-up. Raman spectra have been obtained in the wavenumber regions from 1,050 to 1,700 cm?1 and 2,700 to 3,200 cm?1 from tissues of patients at different stages of pathology (active PV, under therapy and PV in remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage have been detected at 1,150–1,250 cm?1 (amide III) and 1,420–1,450 cm?1 (CH3 deformation) regions and around 1,650 cm?1 (amide I) and 2,930 cm?1 (CH3 symmetric stretch). The analysis of tissue Raman spectra by the proposed univariate method has allowed us to effectively differentiate tissues at different stages of pathology. PMID:22164077
Characterization of Etoricoxib, a Novel, Selective COX2 Inhibitor
Aimee Dallob; Christopher J. Hawkey; Howard Greenberg; Nicholas Wight; Paul De Schepper; Scott Waldman; Peggy Wong; Lisa De Tora; Barry Gertz; Nancy Agrawal; John Wagner; Keith Gottesdiener
2003-01-01
Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect
NSAID-induced small intestinal damage: role of COX inhibition
Akiko Tanaka; Masahiro Matsumoto; Akari Nakagiri; Shinichi Kato; Koji Takeuchi
2002-01-01
Indomethacin, the nonselective COX inhibitor, decreased mucosal PGE2 content and caused damage in the intestine within 24 h, accompanied by increase in intestinal motility, bacterial number and MPO, as well as iNOS activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither SC-560 nor rofecoxib alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not
2012-01-01
Background Projection pursuit regression, multilayer feed-forward networks, multivariate adaptive regression splines and trees (including survival trees) have challenged classic multivariable models such as the multiple logistic function, the proportional hazards life table Cox model (Cox), the Poisson’s model, and the Weibull’s life table model to perform multivariable predictions. However, only artificial neural networks (NN) have become popular in medical applications. Results We compared several Cox versus NN models in predicting 45-year all-cause mortality (45-ACM) by 18 risk factors selected a priori: age; father life status; mother life status; family history of cardiovascular diseases; job-related physical activity; cigarette smoking; body mass index (linear and quadratic terms); arm circumference; mean blood pressure; heart rate; forced expiratory volume; serum cholesterol; corneal arcus; diagnoses of cardiovascular diseases, cancer and diabetes; minor ECG abnormalities at rest. Two Italian rural cohorts of the Seven Countries Study, made up of men aged 40 to 59 years, enrolled and first examined in 1960 in Italy. Cox models were estimated by: a) forcing all factors; b) a forward-; and c) a backward-stepwise procedure. Observed cases of deaths and of survivors were computed in decile classes of estimated risk. Forced and stepwise NN were run and compared by C-statistics (ROC analysis) with the Cox models. Out of 1591 men, 1447 died. Model global accuracies were extremely high by all methods (ROCs > 0.810) but there was no clear-cut superiority of any model to predict 45-ACM. The highest ROCs (> 0.838) were observed by NN. There were inter-model variations to select predictive covariates: whereas all models concurred to define the role of 10 covariates (mainly cardiovascular risk factors), family history, heart rate and minor ECG abnormalities were not contributors by Cox models but were so by forced NN. Forced expiratory volume and arm circumference (two protectors), were not selected by stepwise NN but were so by the Cox models. Conclusions There were similar global accuracies of NN versus Cox models to predict 45-ACM. NN detected specific predictive covariates having a common thread with physical fitness as related to job physical activity such as arm circumference and forced expiratory volume. Future attention should be concentrated on why NN versus Cox models detect different predictors. PMID:22824187
[Understanding logistic regression].
El Sanharawi, M; Naudet, F
2013-10-01
Logistic regression is one of the most common multivariate analysis models utilized in epidemiology. It allows the measurement of the association between the occurrence of an event (qualitative dependent variable) and factors susceptible to influence it (explicative variables). The choice of explicative variables that should be included in the logistic regression model is based on prior knowledge of the disease physiopathology and the statistical association between the variable and the event, as measured by the odds ratio. The main steps for the procedure, the conditions of application, and the essential tools for its interpretation are discussed concisely. We also discuss the importance of the choice of variables that must be included and retained in the regression model in order to avoid the omission of important confounding factors. Finally, by way of illustration, we provide an example from the literature, which should help the reader test his or her knowledge. PMID:23953846
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
THE CANONICAL MODULE OF A COX RING MITSUYASU HASHIMOTO AND KAZUHIKO KURANO
Hashimoto, Mitsuyasu
THE CANONICAL MODULE OF A COX RING MITSUYASU HASHIMOTO AND KAZUHIKO KURANO Dedicated to Professor, in the case of the Cox ring, we prove that the graded canonical module is a graded free module of rank one inverse functor. 1. Introduction D. Cox studied the total coordinate ring (Cox ring) of toric varieties
Gómez, José Manuel
Cox rings and pseudoeffective cones on projectivized toric vector bundles Jose Gonzalez(X), the associated Cox Ring is a finitely generated k-algebra: R(X) := Cox(X, L1, . . . , Lr) := (m1,...,mr)Zr H0 (X of projectivized TVBs are rational polyhedral. They asked whether their Cox rings were indeed finitely generated
Griswold, D E; Adams, J L
1996-03-01
While a great deal has been discovered concerning the potential physiological and pathological role of prostanoids, much is left to be determined. The widespread distribution of both COX-1 and COX-2 coupled with the capacity of most vascular beds, smooth muscle, as well as leukocytes to respond to prostanoids make drawing generalities difficult. The problems with the majority of currently used NSAIDs are clear and ulcerogenic liability is of obvious concern. Interestingly enough, the mechanism of that damage is still the subject of controversy as illustrated by the recent review and hypothesis of Somasundaram et al. In this treatise, the suggestion is made that the initial gastric damage is the result of uncoupling of oxidative phosphorylation which is independent but simultaneous with COX inhibition. At least two currently marketed NSAIDs have improved G.I. liability (nabumetone and etodolac) with efficacy equivalent to other more ulcerogenic NSAIDs. These drugs appear to have achieved that by a mechanism distinct from selective inhibition of COX-2. Whether or not selective COX-2 inhibitors will demonstrate an improved profile over these compounds remains to be shown. Unfortunately, clinical experience with nimsulide and CGP 28238 suggest that NSAID-like toxicity may still be an issue. The promise of selective COX-2 inhibitors remains largely untested. It is with great interest and expectation that the clinical evaluation of the more selective compounds of different structural types is awaited. PMID:8656779
Practical Session: Logistic Regression
NASA Astrophysics Data System (ADS)
Clausel, M.; Grégoire, G.
2014-01-01
An exercise is proposed to illustrate the logistic regression. One investigates the different risk factors in the apparition of coronary heart disease. It has been proposed in Chapter 5 of the book of D.G. Kleinbaum and M. Klein, "Logistic Regression", Statistics for Biology and Health, Springer Science Business Media, LLC (2010) and also by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr341.pdf). This example is based on data given in the file evans.txt coming from http://www.sph.emory.edu/dkleinb/logreg3.htm#data.
Illuminations: Least Squares Regression
NSDL National Science Digital Library
2010-01-01
Created by Illuminations: Resources for Teaching Mathematics, this unit plan contains nine lessons about interpreting the slope and y-intercept of least squares regression lines in the context of real-life data. The applet included allows students to plot the data and calculate the correlation coefficient and the equation of the regression line. Students will view the data in tabular, graphic, and algebraic form and will be able to discuss and display their work. This is a wonderful collection of interactive statistical lessons. They can easily be translated into classroom activities.
Comparing Methods for Multivariate Nonparametric Regression
Comparing Methods for Multivariate Nonparametric Regression David L. Banks Robert T. Olszewskiy Roy, linear regression, stepwise linear regression, additive models, AM, projection pursuit regression, PPR, recursive partitioning regression, RPR, multivariate adaptive regression splines, MARS, alternating
COX-2 expression in chondrosarcoma: a role for celecoxib treatment?
Schrage, Y M; Machado, I; Meijer, D; Briaire-de Bruijn, I; van den Akker, B E; Taminiau, A H M; Kalinski, T; Llombart-Bosch, A; Bovée, J V M G
2010-02-01
Chondrosarcomas are resistant to conventional chemo- and radiotherapy. A subset of chondrosarcomas arises secondarily in the benign tumour syndromes enchondromatosis (EC) and multiple osteochondromas (MO), and prevention of tumour development would greatly improve prognosis. We therefore investigated the effect of selective COX-2 inhibition on chondrosarcoma growth. COX-2 expression was studied in central- and peripheral cartilaginous tumours. The effect of COX-2 inhibition was assessed in four high-grade chondrosarcoma cell lines using celecoxib and NS-398 treatment. COX-2 activity (prostaglandin E(2) (PGE(2)) ELISA) and cell viability were measured. The (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo was studied for 8 weeks using a xenograft model of cell line CH2879 in immunoincompetent nude mice. High COX-2 protein expression was mainly found in solitary peripheral chondrosarcoma and in enchondromatosis-related central chondrosarcoma, which was confirmed by qPCR. After 72h of celecoxib treatment, a significant decrease in cell viability was observed in three chondrosarcoma cell lines. In vivo, celecoxib initially slowed tumour growth in chondrosarcoma xenografts; however, after prolonged treatment relapsed tumour growth was observed. Tumour volume was negatively associated with celecoxib serum levels, and seemed smaller in the high-dose prophylactic treatment group. We confirmed the expression of COX-2 in 65% of chondrosarcomas, and COX-2 inhibition by celecoxib diminished cell viability in vitro. The initial response and the decrease in tumour volume with increased celecoxib serum levels in vivo supported a role for celecoxib, although relapsed tumour growth after 6 weeks was worrisome. Also the role of high-dose prophylactic celecoxib in preventing the development of benign and malignant cartilage tumours in EC and MO patients deserves further investigation. PMID:20004565
Ramírez-Cisneros, M Ángeles; Rios, María Yolanda; Aguilar-Guadarrama, A Berenice; Rao, Praveen P N; Aburto-Amar, Rola; Rodríguez-López, Verónica
2015-10-15
A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0±0.6%) and COX-2 (80.8±4.0%) inhibition at 10?M. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition. PMID:26351040
Kay, Mark A.
David Richard Cox, MD, PhD David R. Cox of Belmont, CA, passed away. David was a renaissance scientist a brilliant geneticist, caring pediatrician around the world. Few people extracted pleasure from life as David did
Novel harmonic regularization approach for variable selection in Cox's proportional hazards model.
Chu, Ge-Jin; Liang, Yong; Wang, Jia-Xuan
2014-01-01
Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq??(1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods. PMID:25506389
Bayesian ARTMAP for regression.
Sasu, L M; Andonie, R
2013-10-01
Bayesian ARTMAP (BA) is a recently introduced neural architecture which uses a combination of Fuzzy ARTMAP competitive learning and Bayesian learning. Training is generally performed online, in a single-epoch. During training, BA creates input data clusters as Gaussian categories, and also infers the conditional probabilities between input patterns and categories, and between categories and classes. During prediction, BA uses Bayesian posterior probability estimation. So far, BA was used only for classification. The goal of this paper is to analyze the efficiency of BA for regression problems. Our contributions are: (i) we generalize the BA algorithm using the clustering functionality of both ART modules, and name it BA for Regression (BAR); (ii) we prove that BAR is a universal approximator with the best approximation property. In other words, BAR approximates arbitrarily well any continuous function (universal approximation) and, for every given continuous function, there is one in the set of BAR approximators situated at minimum distance (best approximation); (iii) we experimentally compare the online trained BAR with several neural models, on the following standard regression benchmarks: CPU Computer Hardware, Boston Housing, Wisconsin Breast Cancer, and Communities and Crime. Our results show that BAR is an appropriate tool for regression tasks, both for theoretical and practical reasons. PMID:23665468
Mechanisms of neuroblastoma regression
Brodeur, Garrett M.; Bagatell, Rochelle
2014-01-01
Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179
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.…
Multivariate Adaptive Regression Splines
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
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.
Yao, Weixin; Lindsay, Bruce G.; Li, Runze
2012-01-01
A local modal estimation procedure is proposed for the regression function in a non-parametric regression model. A distinguishing characteristic of the proposed procedure is that it introduces an additional tuning parameter that is automatically selected using the observed data in order to achieve both robustness and efficiency of the resulting estimate. We demonstrate both theoretically and empirically that the resulting estimator is more efficient than the ordinary local polynomial regression estimator in the presence of outliers or heavy tail error distribution (such as t-distribution). Furthermore, we show that the proposed procedure is as asymptotically efficient as the local polynomial regression estimator when there are no outliers and the error distribution is a Gaussian distribution. We propose an EM type algorithm for the proposed estimation procedure. A Monte Carlo simulation study is conducted to examine the finite sample performance of the proposed method. The simulation results confirm the theoretical findings. The proposed methodology is further illustrated via an analysis of a real data example. PMID:23049230
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.
COX2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model
Hidenori Takahashi; Yasuo Yanagi; Yasuhiro Tamaki; Saiko Uchida; Kimimasa Muranaka
2004-01-01
Cyclooxygenases (COXs) are involved in choroidal neovascularization (CNV). However, the relative contribution of COX-1 and -2 to CNV has not been determined. In this study, the expression of COX-2 was investigated in CNVs in a murine laser-induced model. Subsequently, we found that experimental CNV expressed COX-2, most remarkably around the highly vascularized lesions. To examine the effect of COX-2 inhibition
COX2 CA-Haplotype Is a Risk Factor for the Development of Esophageal Adenocarcinoma
Leon M. G. Moons; Ernst J. Kuipers; Agnieszka M. Rygiel; Anthonie Z. M. Groothuismink; Han Geldof; Willem A. Bode; Kausilia K. Krishnadath; Arnoud H. M. van Vliet; Peter D. Siersema; Johannes G. Kusters
2007-01-01
BACKGROUND:Neoplastic progression of BE towards EAC is associated with increased expression of COX-2. Increased COX-2 expression and enzyme activity is linked to the COX-2 CA haplotype, which consists of two gene polymorphisms in the COX-2 promoter.AIM:To study the impact of COX-2 haplotypes on the risk of developing EAC in patients with different forms of gastroesophageal reflux disease including BE.METHODS: DNA
Logistic regression Weakly informative priors
Gelman, Andrew
Logistic regression Weakly informative priors Conclusions Bayesian generalized linear models default p #12;Logistic regression Weakly informative priors Conclusions Classical logistic regression The problem of separation Bayesian solution Logistic regression -6 -4 -2 0 2 4 6 0.00.20.40.60.81.0 y = logit
Sabine Grösch; Irmgard Tegeder; Ellen Niederberger; Lutz Bräutigam; Gerd Geisslinger
2001-01-01
The regular use of various nonsteroidal anti-inflammatory drugs (NSAIDs) was shown to decrease the incidence of colorectal cancer. This effect is thought to be caused predominantly by inhibition of cyclooxygenase-2 (COX-2) and, subsequently, prostaglandin synthesis. However, recent studies have suggested that COX-independent pathways may contribute considerably to these antiproliferative effects. To evaluate the involvement of COX-dependent and COX- independent mechanisms
Avi Rushinek; Sara Rushinek
2011-01-01
This study deals with live and silent auctions of domain names. It develops a domain name appraisal model for decisions related to marketability, brand, traffic, industry e-commerce value trademark assessment. It focuses on ICANN NAF WIPO IRS type of resolution dispute cost benefit analysis and thereby lets plaintiffs, defendants, and courts budget the worthiness of proceedings compared to settling a
Regression Models: A Brief Introduction
NASA Astrophysics Data System (ADS)
Grégoire, G.
2014-01-01
This brief introduction, without pretension, aims to give some help to non-specialists of statistics to find their way in regression models. What are the basic notions of a regression? A regression model can be linear, generalized linear, nonlinear. Statisticians speak also of parametric, semiparametric, nonparametric regression models. We hope that what is behind these terms will be made clearer after the reading of chapters devoted to simple linear regression, multiple linear regression, logistic regression, survival data and regression, kernel methods... But it can be interesting to have a global view, before reading these chapters, on a rather wide range of regression methods, and to have a first sight on what type of question a particular regression model is answering and what can be expected from such a model on the ground of modelling the data we have in hand.
COX and the control of the pulmonary circulation.
Sprague, Randy S; Stephenson, Alan H; Olearczyk, Jeffery J; Lonigro, Andrew J
2003-06-15
The lung possesses a low resistance circulation that must, at all times, accommodate the entire cardiac output. Moreover, to ensure proper oxygenation of hemoglobin, blood flow must be directed to well-ventilated lung units, i.e., ventilation and perfusion must be matched. Cyclooxygenase (COX)-mediated arachidonic acid (AA) metabolites can influence both pulmonary vascular resistance and ventilation-perfusion matching. In isolated dog and rabbit lungs, ventilation of the right lung with oxygen (O2) and the left lung with nitrogen (N2) resulted in normal perfusion pressures and blood gas tensions. In both species, administration of COX inhibitors resulted in redistribution of blood flow from hypoxic alveoli (N2-ventilated lung) to the well-oxygenated alveoli (O2-ventilated lung) and an increase in arterial oxygen tension, i.e., a COX-mediated AA metabolite or metabolites opposed hypoxic pulmonary vasoconstriction (HPV), but, by virtue of this activity, prevented optimal matching of ventilation with perfusion. The effects of COX inhibition were reversed by prostacyclin (PGI2). These findings are consistent with the hypothesis that COX-derived products of AA metabolism can influence ventilation-perfusion matching in the lung. Moreover, the results of studies in dogs suggest that one such metabolite of AA is PGI2. PMID:14592558
Blandford, Ann
2008-01-01
Preprint. Final version available as: BLANDFORD, A., COX, A. L. & CAIRNS, P. A. (2008) Controlled Experiments. In Cairns, P.A., & Cox, A.L. (eds.) Research Methods for Human Computer Interaction. CUP. 1-16. Controlled experiments Ann Blandford, Anna Cox & Paul Cairns Overview Controlled experiments, an approach
Bode, Manuela; Woellhaf, Michael W.; Bohnert, Maria; van der Laan, Martin; Sommer, Frederik; Jung, Martin; Zimmermann, Richard; Schroda, Michael; Herrmann, Johannes M.
2015-01-01
Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase. PMID:25926683
Bell, Emma; Ponthan, Frida; Whitworth, Claire; Tweddle, Deborah A; Lunec, John; Redfern, Christopher P F
2014-08-01
COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib. PMID:24859418
A closed-form extension to the Black-Cox model A closed-form extension to the Black-Cox
Vallette, Bruno
calibrated to market data. Calibration to Credit Default Swaps (CDS) data has been recently investigatedA closed-form extension to the Black-Cox model A closed-form extension to the Black-Cox model Aur closed-form extension to the Black-Cox model Structure of the talk 1 Introduction and model setup 2 Proof
Bode, Manuela; Woellhaf, Michael W; Bohnert, Maria; Laan, Martin van der; Sommer, Frederik; Jung, Martin; Zimmermann, Richard; Schroda, Michael; Herrmann, Johannes M
2015-07-01
Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase. PMID:25926683
Hohn, M.E. (West Virginia Geological and Economic Survey, Morgantown); Nuhfer, E.B.; Vinopal, R.J.; Klanderman, D.S.
1980-01-01
Classifying very fine-grained rocks through fabric elements provides information about depositional environments, but is subject to the biases of visual taxonomy. To evaluate the statistical significance of an empirical classification of very fine-grained rocks, samples from Devonian shales in four cored wells in West Virginia and Virginia were measured for 15 variables: quartz, illite, pyrite and expandable clays determined by X-ray diffraction; total sulfur, organic content, inorganic carbon, matrix density, bulk density, porosity, silt, as well as density, sonic travel time, resistivity, and ..gamma..-ray response measured from well logs. The four lithologic types comprised: (1) sharply banded shale, (2) thinly laminated shale, (3) lenticularly laminated shale, and (4) nonbanded shale. Univariate and multivariate analyses of variance showed that the lithologic classification reflects significant differences for the variables measured, difference that can be detected independently of stratigraphic effects. Little-known statistical methods found useful in this work included: the multivariate analysis of variance with more than one effect, simultaneous plotting of samples and variables on canonical variates, and the use of parametric ANOVA and MANOVA on ranked data.
NASA Astrophysics Data System (ADS)
Wang, Jiang; Ferguson, Andrew
2015-03-01
The stable conformations and motions of polymers and macromolecules are governed by their underlying free energy surface. By integrating ideas from dynamical systems theory with nonlinear manifold learning, we have developed an approach to recover single-molecule free energy surfaces from univariate time series of a single system observable. Using the method of delays, we expand the time series into a high dimensional phase space in which, by Takens' Theorem, the dynamics are equivalent to those of the molecule in real space. We then apply nonlinear manifold learning algorithm (diffusion maps and nonliear PCA) to extract a low-dimensional representation of the free energy surface that is diffeomorphic (i.e., a smooth transformation) to that which would have been recovered from a complete knowledge of all system degrees of freedom. We have validated our approach in molecular dynamics simulations of a C24H50 n-alkane chain, demonstrating that the free energy surface extracted from the atomistic simulation trajectory is geometrically and topologically equivalent to that recovered from a knowledge of only the head-to-tail distance of the chain. Our approach lays the foundations to extract empirical single-molecule free energy surfaces directly from experimental data.
A Mixed-Effects Model with Time Reparametrization for Longitudinal Univariate Manifold-Valued Data.
Schiratti, J B; Allassonnière, S; Routier, A; Durrleman, S
2015-01-01
Mixed-effects models provide a rich theoretical framework for the analysis of longitudinal data. However, when used to analyze or predict the progression of a neurodegenerative disease such as Alzheimer's disease, these models usually do not take into account the fact that subjects may be at different stages of disease progression and the interpretation of the model may depend on some implicit reference time. In this paper, we propose a generative statistical model for longitudinal data, described in a univariate Riemannian manifold setting, which estimates an average disease progression model, subject-specific time shifts and acceleration factors. The time shifts account for variability in age at disease-onset time. The acceleration factors account for variability in speed of disease progression. For a given individual, the estimated time shift and acceleration factor define an affine reparametrization of the average disease progression model. This statistical model has been used to analyze neuropsychological assessments scores and cortical thickness measurements from the Alzheimer's Disease Neuroimaging Initiative database. The numerical results showed that we can distinguish between slow versus fast progressing and early versus late-onset individuals. PMID:26221703
Stress assessment based on EEG univariate features and functional connectivity measures.
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
Wang, Jiandong
Performance Assessment of Industrial Linear Controllers in Univariate Control Loops for Both Set Research Institute, Jinan, China 250002 ABSTRACT: This paper studies the performance assessment of linear on the robustness. A novel performance assessment method is presented to calculate the proposed performance index
Moustafa, Azza Aziz; Salem, Hesham; Hegazy, Maha; Ali, Omnia
2015-02-25
Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision. PMID:25306132
NASA Astrophysics Data System (ADS)
Moustafa, Azza Aziz; Salem, Hesham; Hegazy, Maha; Ali, Omnia
2015-02-01
Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision.
Cell-type-specific roles for COX-2 in UVB-induced skin cancer.
Jiao, Jing; Mikulec, Carol; Ishikawa, Tomo-o; Magyar, Clara; Dumlao, Darren S; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey
2014-06-01
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
Cell-type-specific roles for COX-2 in UVB-induced skin cancer
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
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.
Gautam, Raju; Karkhile, Kailas V; Bhutani, Kamlesh K; Jachak, Sanjay M
2010-10-01
Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives. PMID:20379952
Tensor learning for regression.
Guo, Weiwei; Kotsia, Irene; Patras, Ioannis
2012-02-01
In this paper, we exploit the advantages of tensorial representations and propose several tensor learning models for regression. The model is based on the canonical/parallel-factor decomposition of tensors of multiple modes and allows the simultaneous projections of an input tensor to more than one direction along each mode. Two empirical risk functions are studied, namely, the square loss and ? -insensitive loss functions. The former leads to higher rank tensor ridge regression (TRR), and the latter leads to higher rank support tensor regression (STR), both formulated using the Frobenius norm for regularization. We also use the group-sparsity norm for regularization, favoring in that way the low rank decomposition of the tensorial weight. In that way, we achieve the automatic selection of the rank during the learning process and obtain the optimal-rank TRR and STR. Experiments conducted for the problems of head-pose, human-age, and 3-D body-pose estimations using real data from publicly available databases, verified not only the superiority of tensors over their vector counterparts but also the efficiency of the proposed algorithms. PMID:21859620
Kirkby, Nicholas S.; Lundberg, Martina H.; Wright, William R.; Warner, Timothy D.; Paul-Clark, Mark J.; Mitchell, Jane A.
2014-01-01
Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE?/?/COX-2?/? mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE?/?/COX-2?/? mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs. PMID:24887395
Smith, Mary; Sprague, Thomas; Serences, John
2015-09-01
Directing attention to a region of visual space facilitates the processing of relevant sensory information, resulting in increased neural and BOLD activity in areas of the brain that process this sensory information. This process is thought to be mediated by a frontoparietal "attentional control" network that biases processing in visual cortex. Electrical microstimulation of frontal area FEF in macaques selectively enhances responses in area V4, and also leads to improved behavior (Moore, Fallah 2001, 2004; Armstrong, Moore 2007). If frontoparietal regions such as the FEF are responsible for the differential modulations in early visual cortex across time, then the magnitude of frontoparietal activity should track the magnitude of attentional modulations in early visual cortex on a trial-by-trial basis. Here, we attempted to test this hypothesis using fMRI. Participants directed spatial attention to either the left or right visual field on each trial while performing a demanding spatial attention task. Consistent with previous data, we found that frontoparietal responses were high when early visual responses were high across trials (i.e. an overall yoking between frontoparietal and occipital regions). In addition, visual areas in the hemisphere contralateral to the attended stimulus showed reliably larger BOLD responses compared to areas in the ipsilateral hemisphere. We compared the magnitude of frontoparietal activity and the differential activity in visual areas contra and ipsilateral to the attended stimulus. However, we found no evidence that the overall magnitude of responses in frontoparietal regions track the magnitude of differential attentional responses in early visual cortex. These findings indicate that the univariate magnitude in frontoparietal ROIs is not related to the magnitude of attention effects in visual cortex, at least as measured with the BOLD signal. Meeting abstract presented at VSS 2015. PMID:26326739
Regression in organizational leadership.
Kernberg, O F
1979-02-01
The choice of good leaders is a major task for all organizations. Inforamtion regarding the prospective administrator's personality should complement questions regarding his previous experience, his general conceptual skills, his technical knowledge, and the specific skills in the area for which he is being selected. The growing psychoanalytic knowledge about the crucial importance of internal, in contrast to external, object relations, and about the mutual relationships of regression in individuals and in groups, constitutes an important practical tool for the selection of leaders. PMID:760132
Steganalysis using logistic regression
NASA Astrophysics Data System (ADS)
Lubenko, Ivans; Ker, Andrew D.
2011-02-01
We advocate Logistic Regression (LR) as an alternative to the Support Vector Machine (SVM) classifiers commonly used in steganalysis. LR offers more information than traditional SVM methods - it estimates class probabilities as well as providing a simple classification - and can be adapted more easily and efficiently for multiclass problems. Like SVM, LR can be kernelised for nonlinear classification, and it shows comparable classification accuracy to SVM methods. This work is a case study, comparing accuracy and speed of SVM and LR classifiers in detection of LSB Matching and other related spatial-domain image steganography, through the state-of-art 686-dimensional SPAM feature set, in three image sets.
Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Fujiwara, Yasuhiro
2013-01-01
In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically “cured.” Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure. PMID:24383004
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.
Recursive Algorithm For Linear Regression
NASA Technical Reports Server (NTRS)
Varanasi, S. V.
1988-01-01
Order of model determined easily. Linear-regression algorithhm includes recursive equations for coefficients of model of increased order. Algorithm eliminates duplicative calculations, facilitates search for minimum order of linear-regression model fitting set of data satisfactory.
A counterexample to the uniqueness result of Cox and Thompson
A. G. Ramm
2001-08-17
A counterexample is given to the uniqueness result given in the paper by J.Cox and K.Thompson, "Note on the uniqueness of the solution of an equation of interest in inverse scattering problem", J. Math.Phys., 11, N3, (1970), 815-817.
On nonsingular potentials of Cox-Thompson inversion scheme
Tamas Palmai; Barnabas Apagyi
2011-11-25
We establish a condition for obtaining nonsingular potentials using the Cox-Thompson inverse scattering method with one phase shift. The anomalous singularities of the potentials are avoided by maintaining unique solutions of the underlying Regge-Newton integral equation for the transformation kernel. As a by-product, new inequality sequences of zeros of Bessel functions are discovered.
MACRO FOR ESTIMATING THE BOX-COX POWER TRANSFORMATION
In their classic paper, Box and Cox (1964) demonstrated how a dependent variable could be transformed to satisfy simultaneously, assumptions implicit in the analysis of linear models. For the class of analyses in which the response of interest is positive and where no transformat...
Marine NOx and COx Emissions under Various Operating Conditions
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
Relationship Between COX2 Specific Inhibitors and Hypertension
Daniel H. Solomon; Sebastian Schneeweiss; Raisa Levin; Jerry Avorn
2010-01-01
There is controversy whether cyclooxygenase-2 (COX-2) specific inhibitors are associated with elevations in blood pressure requiring treatment in typical clinical practice. We examined the risk of new onset hypertension in a retrospective case-control study involving 17 844 subjects aged 65 years from 2 US states. Multivariable logistic models were examined to assess the relative risk of new onset hypertension requiring
COX-2 inhibitors are contraindicated for treatment of combined injury.
Jiao, W; Kiang, J G; Cary, L; Elliott, T B; Pellmar, T C; Ledney, G D
2009-12-01
Casualties of radiation dispersal devices, nuclear detonation or major ionizing radiation accidents, in addition to radiation exposure, may sustain physical and/or thermal trauma. Radiation exposure plus additional tissue trauma is known as combined injury. There are no definitive therapeutic agents. Cyclooxygenase-2 (COX-2), an inducible enzyme expressed in pathological disorders and radiation injury, plays an important role in inflammation and the production of cytokines and prostaglandin E(2) (PGE(2)) and could therefore affect the outcome for victims of combined injury. The COX-2 inhibitors celecoxib and meloxicam were evaluated for their therapeutic value against combined injury in mice. In survival studies, the COX-2 inhibitors had no beneficial effect on 30-day survival, wound healing or body weight gain after radiation injury alone or after combined injury. Meloxicam accelerated death in both wounded and combined injury mice. These drugs also induced severe hepatic toxicity, exaggerated inflammatory processes, and did not enhance hematopoietic cell regeneration. This study points to potential contraindications for use of COX-2 inhibitors in patients undergoing therapy for radiation injury and combined injury. PMID:19929415
Role of COX-2 in microcirculatory disturbance in experimental pancreatitis
Yan, Wen-Wei; Zhou, Zong-Guang; Chen, You-Dai; Gao, Hong-Kai
2004-01-01
AIM: To elucidate the role of COX-2 in the development of capillary leakage in rats with acute interstitial pancreatitis. METHODS: Rats with acute interstitial pancreatitis were induced by caerulein subcutaneous injection. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay the parameters of acute pancreatitis such as the serum amylase and plasma myeloperoxidase, and determination of capillary permeability in the pancreas by quantifying the permeability index (PI) assisted response of pancreatic microvascular via intravital fluorescence microscope video image analysis system. RESULTS: A significant increase of COX-2 expression, elevation of serum amylase, and plasma myeloperoxidase were detected in rats with acute edematous pancreatitis compared with control rats. The changes of pancreatic microvascular after caerulein injection were as following: (a) the decrease of pancreatic capillary blood flow (4th h, 0.56 ± 0.09 nL/min, P < 0.05; 8 th h, 0.34 ± 0.10 nL/min, P < 0.001); (b) reduction of functional capillary density (4 th h, 381 ± 9 cm-1, P > 0.05; 8th h, 277 ± 13 cm-1, P < 0.001); (c) irregular and intermittent capillary perfusion was observed at the 8th h and these vessels were also prone to permeation. CONCLUSION: COX-2 plays an important role in mediating capillary permeability in pancreatitis, thereby contributing to capillary leakage. PMID:15237442
Estimation in the cox proportional hazards model with left-truncated and interval-censored data.
Pan, Wei; Chappell, Rick
2002-03-01
We show that the nonparametric maximum likelihood estimate (NPMLE) of the regression coefficient from the joint likelihood (of the regression coefficient and the baseline survival) works well for the Cox proportional hazards model with left-truncated and interval-censored data, but the NPMLE may underestimate the baseline survival. Two alternatives are also considered: first, the marginal likelihood approach by extending Satten (1996, Biometrika 83, 355-370) to truncated data, where the baseline distribution is eliminated as a nuisance parameter; and second, the monotone maximum likelihood estimate that maximizes the joint likelihood by assuming that the baseline distribution has a nondecreasing hazard function, which was originally proposed to overcome the underestimation of the survival from the NPMLE for left-truncated data without covariates (Tsai, 1988, Biometrika 75, 319-324). The bootstrap is proposed to draw inference. Simulations were conducted to assess their performance. The methods are applied to the Massachusetts Health Care Panel Study data set to compare the probabilities of losing functional independence for male and female seniors. PMID:11890328
Factors Affecting Regression-Discontinuity.
ERIC Educational Resources Information Center
Schumacker, Randall E.
The regression-discontinuity approach to evaluating educational programs is reviewed, and regression-discontinuity post-program mean differences under various conditions are discussed. The regression-discontinuity design is used to determine whether post-program differences exist between an experimental program and a control group. The difference…
Kirkby, Nicholas S.; Zaiss, Anne K.; Wright, William R.; Jiao, Jing; Chan, Melissa V.; Warner, Timothy D.; R. Herschman, Harvey; Mitchell, Jane A.
2013-01-01
Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections and has complex, poorly understood roles in anti-pathogen immunity. Here, we use a knock-in luciferase reporter model to image Cox2 expression across a range of tissues in mice following treatment with the either the prototypical bacterial pathogen-associated molecular pattern (PAMP), LPS, which activates Toll-like receptor (TLR)4, or with poly(I:C), a viral PAMP, which activates TLR3. LPS induced Cox2 expression in all tissues examined. In contrast, poly(I:C) elicited a milder response, limited to a subset of tissues. A panel of cytokines and interferons was measured in plasma of wild-type, Cox1?/? and Cox2?/? mice treated with LPS, poly(I:C), MALP2 (TLR2/6), Pam3CSK4 (TLR2/1), R-848 (TLR7/8) or CpG ODN (TLR9), to establish whether/how each COX isoform modulates specific PAMP/TLR responses. Only LPS induced notable loss of condition in mice (inactivity, hunching, piloerection). However, all TLR agonists produced cytokine responses, many of which were modulated in specific fashions by Cox1 or Cox2 gene deletion. Notably we observed opposing effects of Cox2 gene deletion on the responses to the bacterial PAMP, LPS, and the viral PAMP, poly(I:C), consistent with the differing abilities of the PAMPs to induce Cox2 expression. Cox2 gene deletion limited the plasma IL-1? and interferon-? responses and hypothermia produced by LPS. In contrast, in response to poly(I:C), Cox2?/? mice exhibited enhanced plasma interferon (IFN?,?,?,?) and related cytokine responses (IP-10, IL-12). These observations suggest that a COX-2 selective inhibitor, given early in infection, may enhance and/or prolong endogenous interferon responses, and thereby increase anti-viral immunity. PMID:23850620
Lokwani, Deepak; Azad, Rajaram; Sarkate, Aniket; Reddanna, Pallu; Shinde, Devanand
2015-08-01
The various scaffolds containing 1,4-dihydropyrimidine ring were designed by considering the environment of the active site of COX-1/COX-2 and 5-LOX enzymes. The structure-based library design approach, including the focused library design (Virtual Combinatorial Library Design) and virtual screening was used to select the 1,4-dihydropyrimidine scaffold for simultaneous inhibition of both enzyme pathways (COX-1/COX-2 and 5-LOX). The virtual library on each 1,4-dihydropyrimidine scaffold was enumerated in two alternative ways. In first way, the chemical reagents at R groups were filtered by docking of scaffold with single position substitution, that is, only at R1, or R2, or R3, … Rn on COX-2 enzyme using Glide XP docking mode. The structures that do not dock well were removed and the library was enumerated with filtered chemical reagents. In second alternative way, the single position docking stage was bypassed, and the entire library was enumerated using all chemical reagents by docking on the COX-2 enzyme. The entire library of approximately 15,629 compounds obtained from both ways after screening for drug like properties, were further screened for their binding affinity against COX-1 and 5-LOX enzymes using Virtual Screening Workflow. Finally, 142 hits were obtained and divided into two groups based on their binding affinity for COX-1/COX-2 and for both enzyme pathways (COX-1/COX-2 and 5-LOX). The ten molecules were selected, synthesized and evaluated for their COX-1, COX-2 and 5-LOX inhibiting activity. PMID:26122769
Liquid Foams D. Weaire, S.J. Cox and K. Brakke
Cox, Simon
Liquid Foams D. Weaire, S.J. Cox §and K. Brakke ¶ Department of Physics, Trinity College, Dublin, and the drainage of liquid through it when equilibrium is disturbed. Email: dweaire@tcd.ie §Email: simon.cox
Linear regression in astronomy. I
NASA Technical Reports Server (NTRS)
Isobe, Takashi; Feigelson, Eric D.; Akritas, Michael G.; Babu, Gutti Jogesh
1990-01-01
Five methods for obtaining linear regression fits to bivariate data with unknown or insignificant measurement errors are discussed: ordinary least-squares (OLS) regression of Y on X, OLS regression of X on Y, the bisector of the two OLS lines, orthogonal regression, and 'reduced major-axis' regression. These methods have been used by various researchers in observational astronomy, most importantly in cosmic distance scale applications. Formulas for calculating the slope and intercept coefficients and their uncertainties are given for all the methods, including a new general form of the OLS variance estimates. The accuracy of the formulas was confirmed using numerical simulations. The applicability of the procedures is discussed with respect to their mathematical properties, the nature of the astronomical data under consideration, and the scientific purpose of the regression. It is found that, for problems needing symmetrical treatment of the variables, the OLS bisector performs significantly better than orthogonal or reduced major-axis regression.
6/27/08 B. Cox 1 Review of New Strange Quark Results
Fermilab
6/27/08 B. Cox 1 Review of New Strange Quark Results XXVII Physics In Collision Conference B. Cox. Cox 2 Four Active Kaon Collaborations NA48/2 Future NA62 KLOE Future KLOE II KTeV Project x??* Apologies to the Hyperon advocates Charged and Neutral Kaon Decays* #12;6/27/08 B. Cox 3 KEK E391a First
THE COX RING OF A DEL PEZZO SURFACE VICTOR V. BATYREV AND OLEG N. POPOV
Tschinkel, Yuri
THE COX RING OF A DEL PEZZO SURFACE VICTOR V. BATYREV AND OLEG N. POPOV Abstract. Let Xr, E6, E7, E8}. In this paper, we prove some general properties of the Cox ring of Xr (r 4) and show by the paper of Cox on the homogeneous ring of a toric variety [Cox], Hu and Keel [H-K] suggested a definition
Westreich, Daniel; Cole, Stephen R; Schisterman, Enrique F; Platt, Robert W
2012-08-30
Motivated by a previously published study of HIV treatment, we simulated data subject to time-varying confounding affected by prior treatment to examine some finite-sample properties of marginal structural Cox proportional hazards models. We compared (a)?unadjusted, (b)?regression-adjusted, (c)?unstabilized, and (d)?stabilized marginal structural (inverse probability-of-treatment [IPT] weighted) model estimators of effect in terms of bias, standard error, root mean squared error (MSE), and 95% confidence limit coverage over a range of research scenarios, including relatively small sample sizes and 10 study assessments. In the base-case scenario resembling the motivating example, where the true hazard ratio was 0.5, both IPT-weighted analyses were unbiased, whereas crude and adjusted analyses showed substantial bias towards and across the null. Stabilized IPT-weighted analyses remained unbiased across a range of scenarios, including relatively small sample size; however, the standard error was generally smaller in crude and adjusted models. In many cases, unstabilized weighted analysis showed a substantial increase in standard error compared with other approaches. Root MSE was smallest in the IPT-weighted analyses for the base-case scenario. In situations where time-varying confounding affected by prior treatment was absent, IPT-weighted analyses were less precise and therefore had greater root MSE compared with adjusted analyses. The 95% confidence limit coverage was close to nominal for all stabilized IPT-weighted but poor in crude, adjusted, and unstabilized IPT-weighted analysis. Under realistic scenarios, marginal structural Cox proportional hazards models performed according to expectations based on large-sample theory and provided accurate estimates of the hazard ratio. PMID:22492660
S Tomozawa; H Nagawa; N Tsuno; K Hatano; T Osada; J Kitayama; E Sunami; M E Nita; S Ishihara; H Yano; T Tsuruo; Y Shibata; T Muto
1999-01-01
It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal
2009-01-01
Background Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008) Conclusion H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus. PMID:19463183
NMDA-induced Seizure Intensity is Enhanced in COX-2 Deficient Mice
Toscano, Christopher D.; Kingsley, Philip J.; Marnett, Lawrence J.; Bosetti, Francesca
2008-01-01
Pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not COX-1, has been shown to increase susceptibility to kainic acid (KA)-induced excitotoxicity. However, it is unclear if susceptibility to excitotoxins that act through other neurotransmitter receptors is altered by COX-2 inhibition. To further understand the involvement of COX-2 in regulating susceptibility to excitotoxicity, we investigated the effect of COX-2 deletion on excitotoxicity induced by peripheral injection of N-methyl-D-aspartate (NMDA, a specific agonist of the NMDA receptors) or lindane (a GABAA receptor antagonist). COX-2?/? mice injected intraperitoneally with NMDA (50-100 mg/kg) exhibited significantly increased median seizure intensity when compared to COX-2+/+ mice. Further, COX-2?/? mice exposed to NMDA showed neuronal damage, detected by Fluoro Jade B (FJB) staining, in the CA3 region of the hippocampus. There was no FJB staining nor any significant difference in median or maximal seizure intensity in COX-2+/+ and COX-2?/? mice exposed to lindane. LC-MS/MS analysis of brain prostaglandin profile in COX-2?/? mice demonstrated a significant increase in PGF2?, TXB2, PGE2 and PGD2 expression 1 hour after administration of an excitotoxic dose of KA, but not of NMDA. Our findings demonstrate that COX-2 regulates susceptibility to KA and NMDA excitotoxicity, which directly activate glutamatergic neurotransmission, but not to lindane, which indirectly alters glutamatergic neurotransmission. Furthermore, increased levels of prostaglandins after seizures are associated with consistent manifestation of neuronal damage. PMID:18834901
YIELD OPTION PRICING IN THE GENERALIZED COX-INGERSOLL-ROSS MODEL
Deelstra, Griselda
1 YIELD OPTION PRICING IN THE GENERALIZED COX-INGERSOLL-ROSS MODEL Griselda Deelstra CREST, ENSAE options in the generalized Cox-Ingersoll-Ross (1985) single-factor term structure model with time, Bessel process with time-varying dimension. 1. Introduction It is well-known that the Cox
Estimating a smooth baseline hazard function for the Cox Patrick Royston
Guillas, Serge
Estimating a smooth baseline hazard function for the Cox model 1 Patrick Royston Hub for Trials WC2B 6NH UK. 13 September 2011 Summary The aim of fitting a Cox model to time-to-event data of survival probabilities in independent data. In particular, external validation of a Cox model should
Grübel, Rudolf
Motivation Cox setting Measure changes Examples Case study: Longevity swaps Conclusion Stochastic Louvain), Pierre Devolder (UC Louvain) Talanx, Hanover April 20, 2012 1/32 #12;Motivation Cox setting Measure changes Examples Case study: Longevity swaps Conclusion AGENDA 1 Motivation 2 Cox setting 3
The P174L Mutation in Human Sco1 Severely Compromises Cox17-dependent Metallation but
Leary, Scot
The P174L Mutation in Human Sco1 Severely Compromises Cox17-dependent Metallation but DoesA site in the CoxII subunit of cytochrome c oxidase. The only known missense mutation in human Sco1, a P expressed in bacteria, but Cox17-mediated copper transfer was severely compromised both in vitro
On a connection between the Bradley-Terry model and the Cox proportional hazards model
Zhou, Mai
On a connection between the Bradley-Terry model and the Cox proportional hazards model Yuhua Su This article addresses a connection between the Bradley and Terry (1952A) model and Cox (1972) proportional proportional hazards assumption of Cox (1972) coincides with the likelihood given by the Bradley-Terry (BT
THE SHAPE OF THE TALLEST COLUMN: CORRECTED STEVEN J. COX AND C. MAEVE MCCARTHY
McCarthy, Maeve L.
THE SHAPE OF THE TALLEST COLUMN: CORRECTED STEVEN J. COX AND C. MAEVE MCCARTHY SIAM J. MATH. ANAL.J. Cox and C.M. McCarthy, The shape of the tallest column, SIAM J. Math. Anal., 29 (1998), pp. 547 Mathematics, Rice University, 6100 Main St., Hous- ton, TX 77005 (cox@rice.edu). Department of Mathematics
Estimation of the survival probabilities by adjusting a Cox model to the tail
Paris-Sud XI, Université de
Estimation of the survival probabilities by adjusting a Cox model to the tail Ion Grama a , Jean is to predict the survival probability beyond the largest observed time. A Cox model with a constant underlying survie par l'ajustement sur la queue d'un mod`ele de Cox. Dans le contexte d'un mod`ele d'analyse de
ETUDE MULTICENTRIQUE DE LA SURVENUE D'ESCARRES PAR UN MODELE DE COX BASE
Boyer, Edmond
ETUDE MULTICENTRIQUE DE LA SURVENUE D'ESCARRES PAR UN MODELE DE COX BASE SUR UNE APPROCHE MARGINALE Analysis of a multicenter clinical trial on pressure ulcer develop- ment by a marginal approach in the Cox´el´es Mots Cl´es : Approche marginale. Mod`ele de Cox. Temps de survie corr´el´ees. Escarres Marginal
A Counterexample to Theorems of Cox and Fine Joseph Y. Halpern halpern@cs.cornell.edu
Halpern, Joseph Y.
A Counterexample to Theorems of Cox and Fine Joseph Y. Halpern halpern@cs.cornell.edu Cornell University, Computer Science Department Ithaca, NY 14853 http://www.cs.cornell.edu/home/halpern Abstract Cox. The counterexample also suggests that Cox's assumptions are insufficient to prove the result even in infinite domains
Robyn M. Cox, PhD Professor ofAudiology, University ofMemphis, Memphis, TN
Dasgupta, Dipankar
Robyn M. Cox, PhD Professor ofAudiology, University ofMemphis, Memphis, TN ABSTRACT: Hearing Aids wjdely than they currently are. BIOGRAPHY: Dr. Robyn Cox is a professor of Audiology and serves Language Pathology. She earned her doctorate in 1974 at Indiana University. Dr. Cox's research progranl
COX-2: an in vivo evidence of its participation in heat stress-induced myocardial preconditioning
Paris-Sud XI, Université de
1 COX-2: an in vivo evidence of its participation in heat stress-induced myocardial preconditioning head: COX-2 and heat stress preconditioning. * Please address correspondence to Professor C. Ribuot;58(3):582-8" #12;2 COX-2: an in vivo evidence of its participation in heat stress-induced myocardial
CD36 Deficiency Leads to Choroidal Involution via COX2 Down-Regulation in Rodents
Boyer, Edmond
CD36 Deficiency Leads to Choroidal Involution via COX2 Down-Regulation in Rodents Marianne Houssier leads to choroidal involution via COX2 down- regulation in rodents. PLoS Med 5(2): e39. doi:10 corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD
RESEARCH ARTICLE Open Access Variables with time-varying effects and the Cox
Paris-Sud XI, Université de
RESEARCH ARTICLE Open Access Variables with time-varying effects and the Cox model: Some-Pélissier1,5 Abstract Background: The Cox model relies on the proportional hazards (PH) assumption, implying. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic
Methods for the analysis of sampled cohort data in the Cox proportional hazards model
Goldstein, Larry
Methods for the analysis of sampled cohort data in the Cox proportional hazards estimation in the Cox proportional hazards model when the cohort is sampled according to a predictable process; Cox's reg* *res- sion model; Epidemiology; Marked point process; Martingale; Partial likelihood
FULL LIKELIHOOD INFERENCES IN THE COX MODEL: AN EMPIRICAL LIKELIHOOD APPROACH
Zhou, Mai
FULL LIKELIHOOD INFERENCES IN THE COX MODEL: AN EMPIRICAL LIKELIHOOD APPROACH Jian-Jian Ren1 parameter 0 in the Cox model, there have been several es- timators constructed based on various types of approximated likelihood, but none of them has demonstrated small-sample advantage over Cox's partial likelihood
Advantages and inconveniences of the Cox model compared with the logistic model: application
Paris-Sud XI, Université de
Advantages and inconveniences of the Cox model compared with the logistic model: application'Écopathologie Animale, 26, rue de la Baisse, 69100 Villeurbanne, France Summary ―The survival Cox model factors of nursing cow infertility. The risk factors resulting from the 2 models were the same. The Cox
GUIDELINES FOR NOMINATIONS COX FACULTY AWARD FOR CREATIVE SCHOLARSHIP AND TEACHING
Dyer, Bill
GUIDELINES FOR NOMINATIONS COX FACULTY AWARD FOR CREATIVE SCHOLARSHIP AND TEACHING The following guidelines apply to the nomination and section process for identifying recipients of the Cox Faculty Awards. The potential recipient of the Cox Award shall have no role in the nominating process. 5. Nomination materials
Kinetics and docking studies of a COX-2 inhibitor isolated from Terminalia bellerica fruits.
Reddy, Tamatam Chandramohan; Aparoy, Polamarasetty; Babu, Neela Kishore; Kumar, Kotha Anil; Kalangi, Suresh Kumar; Reddanna, Pallu
2010-10-01
Triphala is an Ayurvedic herbal formulation consisting of equal parts of three myrobalans: Terminalia chebula, Terminalia bellerica and Emblica officinalis. We recently reported that chebulagic acid (CA) isolated from Terminalia chebula is a potent COX-2/5-LOX dual inhibitor. In this study, compounds isolated from Terminalia bellerica were tested for inhibition against COX and 5-LOX. One of the fractionated compounds showed potent inhibition against COX enzymes with no inhibition against 5-LOX. It was identified as gallic acid (GA) by LC-MS, NMR and IR analyses. We report here the inhibitory effects of GA, with an IC(50) value of 74 nM against COX-2 and 1500 nM for COX-1, showing ?20 fold preference towards COX-2. Further docking studies revealed that GA binds in the active site of COX-2 at the non-steroidal anti-inflammatory drug (NSAID) binding site. The carboxylate moiety of GA interacts with Arg120 and Glu524. Based on substrate dependent kinetics, GA was found to be a competitive inhibitor of both COX-1 and COX-2, with more affinity towards COX-2. Taken together, our studies indicate that GA is a selective inhibitor of COX-2. Being a small natural product with selective and reversible inhibition of COX-2, GA would form a lead molecule for developing potent anti-inflammatory drug candidates. PMID:20441561
Multiple Regression (I) 6.1 Multiple Regression Models
Zhang, Tonglin
as Xij = { 1 if the i-th observation is female 0 if the i-th observation if male . We need to use k - 1. The model can be written as Yi =0 + 1Xi1 + 2X2 i1 + i =0 + 1Zi1 + 2Zi2 + i. · Transformation. The model may also be the form of log Yi = 0 + p-1 j=1 jXij + i. The Box-Cox transformation may also be used as Y i
Giovanni de Gaetano; Maria Benedetta Donati; Chiara Cerletti
2003-01-01
Anti-thrombotic therapy with aspirin, which at low doses acts as a selective inhibitor of platelet cyclooxygenase 1 (COX-1) activity, is well established. However, a major limitation of aspirin treatment is its gastrointestinal toxicity, which is thought to be linked to the suppression of COX-1-mediated production of cytoprotective prostaglandins. Selective COX-2 inhibitors are effective anti-inflammatory agents with lower gastrointestinal toxicity than
Tatsuhiro Joki; Oliver Heese; Demetrios C. Nikas; Lorenzo Bello; Jianping Zhang; Stine-Kathrein Kraeft; Nicholas T. Seyfried; Toshiaki Abe; Lan Bo Chen; Rona S. Carroll; Peter M. Black
2000-01-01
The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher
Mary F. Walter; Robert F. Jacob; Charles A. Day; Rachel Dahlborg; Yujia Weng; R. Preston Mason
2004-01-01
Clinical investigations have demonstrated a link between use of the sulfone cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, and increased risk for atherothrombotic events. This increased risk was not observed for a sulfonamide COX-2 inhibitor (celecoxib), indicating a potential non-enzymatic mechanism for rofexocib. To test this hypothesis, we compared the independent effects of COX-2 inhibitors on human LDL oxidation, an important contributor to
Bernhard Heindl; Bernhard F. Becker
2001-01-01
Inhibition of cyclooxygenase (COX) might favour non-enzymatic formation of cardiodepressive isoprostanes from arachidonic acid by radicals generated during reperfusion. This could explain deleterious effects of acetylsalicylic acid (ASA) on cardiac function. We examined the influence of COX inhibition on myocardial function after low-flow ischaemia and reperfusion, employing either ASA (100 µmol\\/l), the partially selective COX-2 inhibitor meloxicam (0.3 µmol\\/l and
Performance of univariate forecasting on seasonal diseases: the case of tuberculosis.
Permanasari, Adhistya Erna; Rambli, Dayang Rohaya Awang; Dominic, P Dhanapal Durai
2011-01-01
The annual disease incident worldwide is desirable to be predicted for taking appropriate policy to prevent disease outbreak. This chapter considers the performance of different forecasting method to predict the future number of disease incidence, especially for seasonal disease. Six forecasting methods, namely linear regression, moving average, decomposition, Holt-Winter's, ARIMA, and artificial neural network (ANN), were used for disease forecasting on tuberculosis monthly data. The model derived met the requirement of time series with seasonality pattern and downward trend. The forecasting performance was compared using similar error measure in the base of the last 5 years forecast result. The findings indicate that ARIMA model was the most appropriate model since it obtained the less relatively error than the other model. PMID:21431557
Cox rings, semigroups and automorphisms of affine algebraic varieties
Arzhantsev, Ivan V; Gaifullin, Sergei A [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)
2010-02-28
We study the Cox realization of an affine variety, that is, a canonical representation of a normal affine variety with finitely generated divisor class group as a quotient of a factorially graded affine variety by an action of the Neron-Severi quasitorus. The realization is described explicitly for the quotient space of a linear action of a finite group. A universal property of this realization is proved, and some results in the divisor theory of an abstract semigroup emerging in this context are given. We show that each automorphism of an affine variety can be lifted to an automorphism of the Cox ring normalizing the grading. It follows that the automorphism group of an affine toric variety of dimension {>=}2 without nonconstant invertible regular functions has infinite dimension. We obtain a wild automorphism of the three-dimensional quadratic cone that rises to the Anick automorphism of the polynomial algebra in four variables. Bibliography: 22 titles.
COX and the control of the pulmonary circulation
Randy S Sprague; Alan H Stephenson; Jeffery J Olearczyk; Andrew J Lonigro
2003-01-01
The lung possesses a low resistance circulation that must, at all times, accommodate the entire cardiac output. Moreover, to ensure proper oxygenation of hemoglobin, blood flow must be directed to well-ventilated lung units, i.e., ventilation and perfusion must be matched.Cyclooxygenase (COX)-mediated arachidonic acid (AA) metabolites can influence both pulmonary vascular resistance and ventilation–perfusion matching. In isolated dog and rabbit lungs,
Potential interaction of natural dietary bioactive compounds with COX2
Wilson Maldonado-Rojas; Jesus Olivero-Verbel
2011-01-01
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
Selective COX2 Inhibitors and Risk of Myocardial Infarction
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
Retargeted Least Squares Regression Algorithm.
Zhang, Xu-Yao; Wang, Lingfeng; Xiang, Shiming; Liu, Cheng-Lin
2015-09-01
This brief presents a framework of retargeted least squares regression (ReLSR) for multicategory classification. The core idea is to directly learn the regression targets from data other than using the traditional zero-one matrix as regression targets. The learned target matrix can guarantee a large margin constraint for the requirement of correct classification for each data point. Compared with the traditional least squares regression (LSR) and a recently proposed discriminative LSR models, ReLSR is much more accurate in measuring the classification error of the regression model. Furthermore, ReLSR is a single and compact model, hence there is no need to train two-class (binary) machines that are independent of each other. The convex optimization problem of ReLSR is solved elegantly and efficiently with an alternating procedure including regression and retargeting as substeps. The experimental evaluation over a range of databases identifies the validity of our method. PMID:25474813
Linear regression in astronomy. II
NASA Technical Reports Server (NTRS)
Feigelson, Eric D.; Babu, Gutti J.
1992-01-01
A wide variety of least-squares linear regression procedures used in observational astronomy, particularly investigations of the cosmic distance scale, are presented and discussed. The classes of linear models considered are (1) unweighted regression lines, with bootstrap and jackknife resampling; (2) regression solutions when measurement error, in one or both variables, dominates the scatter; (3) methods to apply a calibration line to new data; (4) truncated regression models, which apply to flux-limited data sets; and (5) censored regression models, which apply when nondetections are present. For the calibration problem we develop two new procedures: a formula for the intercept offset between two parallel data sets, which propagates slope errors from one regression to the other; and a generalization of the Working-Hotelling confidence bands to nonstandard least-squares lines. They can provide improved error analysis for Faber-Jackson, Tully-Fisher, and similar cosmic distance scale relations.
Linear regression in astronomy. II
NASA Astrophysics Data System (ADS)
Feigelson, Eric D.; Babu, Gutti J.
1992-09-01
A wide variety of least-squares linear regression procedures used in observational astronomy, particularly investigations of the cosmic distance scale, are presented and discussed. The classes of linear models considered are (1) unweighted regression lines, with bootstrap and jackknife resampling; (2) regression solutions when measurement error, in one or both variables, dominates the scatter; (3) methods to apply a calibration line to new data; (4) truncated regression models, which apply to flux-limited data sets; and (5) censored regression models, which apply when nondetections are present. For the calibration problem we develop two new procedures: a formula for the intercept offset between two parallel data sets, which propagates slope errors from one regression to the other; and a generalization of the Working-Hotelling confidence bands to nonstandard least-squares lines. They can provide improved error analysis for Faber-Jackson, Tully-Fisher, and similar cosmic distance scale relations.
An efficient alternative to the stratified Cox model analysis.
Mehrotra, Devan V; Su, Shu-Chih; Li, Xiaoming
2012-07-30
Consider a typical two-treatment randomized clinical trial involving a time-to-event endpoint, with randomization stratified by a categorical prognostic factor (for example gender). At the design stage, it is often assumed that the treatment hazard ratio (HR) is constant across the strata, and the data are commonly analyzed using the stratified Cox proportional hazards model. We caution that this ubiquitous approach is needlessly risky because departures from the assumption of the HR being the same for all the strata can result in a notably biased and/or less powerful analysis. An alternative approach is proposed in which first the [log] HR is estimated separately for each stratum using an unstratified Cox model, and then the stratum-specific estimates are combined for overall inference using either sample size or 'minimum risk' stratum weights. The advantages of the proposed two-step analysis versus the common one-step stratified Cox model analysis are illustrated using simulations that were conducted to support the design of a vaccine clinical trial. PMID:22437375
Log Gaussian Cox processes and spatially aggregated disease incidence data.
Li, Ye; Brown, Patrick; Gesink, Dionne C; Rue, Håvard
2012-10-01
This article presents a methodology for modeling aggregated disease incidence data with the spatially continuous log-Gaussian Cox process. Statistical models for spatially aggregated disease incidence data usually assign the same relative risk to all individuals in the same reporting region (census areas or postal regions). A further assumption that the relative risks in two regions are independent given their neighbor's risks (the Markov assumption) makes the commonly used Besag-York-Mollié model computationally simple. The continuous model proposed here uses a data augmentation step to sample from the posterior distribution of the exact locations at each step of an Markov chain Monte Carlo algorithm, and models the exact locations with an log-Gaussian Cox process. A simulation study shows the log-Gaussian Cox process model consistently outperforming the Besag-York-Mollié model. The method is illustrated by making inference on the spatial distribution of syphilis risk in North Carolina. The effect of several known social risk factors are estimated, and areas with risk well in excess of that expected given these risk factors are identified. PMID:22544855
Bayesian Spatial Quantile Regression.
Reich, Brian J; Fuentes, Montserrat; Dunson, David B
2011-03-01
Tropospheric ozone is one of the six criteria pollutants regulated by the United States Environmental Protection Agency under the Clean Air Act and has been linked with several adverse health effects, including mortality. Due to the strong dependence on weather conditions, ozone may be sensitive to climate change and there is great interest in studying the potential effect of climate change on ozone, and how this change may affect public health. In this paper we develop a Bayesian spatial model to predict ozone under different meteorological conditions, and use this model to study spatial and temporal trends and to forecast ozone concentrations under different climate scenarios. We develop a spatial quantile regression model that does not assume normality and allows the covariates to affect the entire conditional distribution, rather than just the mean. The conditional distribution is allowed to vary from site-to-site and is smoothed with a spatial prior. For extremely large datasets our model is computationally infeasible, and we develop an approximate method. We apply the approximate version of our model to summer ozone from 1997-2005 in the Eastern U.S., and use deterministic climate models to project ozone under future climate conditions. Our analysis suggests that holding all other factors fixed, an increase in daily average temperature will lead to the largest increase in ozone in the Industrial Midwest and Northeast. PMID:23459794
Error bounds in cascading regressions
Karlinger, M.R.; Troutman, B.M.
1985-01-01
Cascading regressions is a technique for predicting a value of a dependent variable when no paired measurements exist to perform a standard regression analysis. Biases in coefficients of a cascaded-regression line as well as error variance of points about the line are functions of the correlation coefficient between dependent and independent variables. Although this correlation cannot be computed because of the lack of paired data, bounds can be placed on errors through the required properties of the correlation coefficient. The potential meansquared error of a cascaded-regression prediction can be large, as illustrated through an example using geomorphologic data. ?? 1985 Plenum Publishing Corporation.
COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA.
Dionne, R
1999-07-01
The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation. PMID:16127636
Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models
ERIC Educational Resources Information Center
Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung
2015-01-01
Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…
Rodríguez-Salinas, Elizabeth; Riveros-Rosas, Héctor; Li, Zhongkui; Fucíková, Karolina; Brand, Jerry J; Lewis, Louise A; González-Halphen, Diego
2012-07-01
In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae. PMID:22724135
The second generation of COX-2 inhibitors: what advantages do the newest offer?
Stichtenoth, Dirk O; Frölich, Jürgen C
2003-01-01
The discovery of two cyclooxygenase (COX)-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prostanoid production, led to the development of new non-steroidal anti-inflammatory drugs (NSAIDs), the selective COX-2 inhibitors, promising minimal NSAID-typical toxicity with full anti-inflammatory efficacy. So far, the strategy of selective COX-2 inhibition has been successful. Selective COX-2 inhibitors have significantly less gastrotoxicity and no effects on platelet aggregation. However, with regard to renal adverse events, selective COX-2 inhibitors do not offer a clinically relevant advantage over non-selective inhibitors. Moreover, concerns over the cardiovascular risk of selective COX-2 inhibitors have recently been raised. The second generation of COX-2 inhibitors with higher COX-2 selectivity was developed with the promise of further reduction of NSAID-typical adverse effects. The leading compounds are valdecoxib, parecoxib, etoricoxib and lumaricoxib. At the present time they have proven efficacy for the treatment of pain and inflammation. Parecoxib as a parenteral, highly selective COX-2 inhibitor has the potential to become the NSAID of choice for treatment of postoperative pain. In clinical trials, valdecoxib, parecoxib, etoricoxib and lumaricoxib have caused no more endoscopic ulcers than placebo. However, to date, no data on the clinically relevant endpoints perforation, symptomatic ulcer and bleeding are available. Furthermore, no definite conclusions on renal and cardiovascular safety are possible. Current evidence points to a marginal, if any, gain of safety compared with the first generation of COX-2 inhibitors. However, trials with the new COX-2 inhibitors offer the chance to address these open questions of highly selective COX-2 inhibition; that is, thrombogenic risk, sodium and water retention, and interference with tissue repair, in particular, healing of mucosal damage. PMID:12487621
Elbert, Yevgeniy; Burkom, Howard S
2009-11-20
This paper discusses further advances in making robust predictions with the Holt-Winters forecasts for a variety of syndromic time series behaviors and introduces a control-chart detection approach based on these forecasts. Using three collections of time series data, we compare biosurveillance alerting methods with quantified measures of forecast agreement, signal sensitivity, and time-to-detect. The study presents practical rules for initialization and parameterization of biosurveillance time series. Several outbreak scenarios are used for detection comparison. We derive an alerting algorithm from forecasts using Holt-Winters-generalized smoothing for prospective application to daily syndromic time series. The derived algorithm is compared with simple control-chart adaptations and to more computationally intensive regression modeling methods. The comparisons are conducted on background data from both authentic and simulated data streams. Both types of background data include time series that vary widely by both mean value and cyclic or seasonal behavior. Plausible, simulated signals are added to the background data for detection performance testing at signal strengths calculated to be neither too easy nor too hard to separate the compared methods. Results show that both the sensitivity and the timeliness of the Holt-Winters-based algorithm proved to be comparable or superior to that of the more traditional prediction methods used for syndromic surveillance. PMID:19725023
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.
NASA Astrophysics Data System (ADS)
Futter, M. R.; Mawdsley, J. A.; Metcalfe, A. V.
1991-07-01
Two models for estimating the risk of a flood exceeding some critical threshold within a few days (Smith and Karr, 1986; Ettrick et al., 1987), which take account of the season and prevailing catchment conditions, have recently been published. The models are fitted to a 1000-year synthetic data set, to compare the results with empirically determined risk estimates. After some modifications to the Smith and Karr method both models demonstrated reasonable accuracy. A second comparison is then made using data from a United Kingdom catchment. The Smith and Karr model was further modified to allow risk estimates for up to 30 days ahead to be made. Both models were applied to both data sets for 30 day ahead estimates, and the results demonstrate the sensitivity of the risk to prevailing conditions at the beginning of the period. The assumptions, data requirements, and accuracy of the models are compared and discussed.
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…
Multiple Regression Assumptions. ERIC Digest.
ERIC Educational Resources Information Center
Osborne, Jason W.; Waters, Elaine
This Digest presents a discussion of the assumptions of multiple regression that is tailored to the practicing researcher. The focus is on the assumptions of multiple regression that are not robust to violation, and that researchers can deal with if violated. Assumptions of normality, linearity, reliability of measurement, and homoscedasticity are…
Estimating Regression Parameters in an Extended Proportional Odds Model
Chen, Ying Qing; Hu, Nan; Cheng, Su-Chun; Musoke, Philippa; Zhao, Lue Ping
2012-01-01
The proportional odds model may serve as a useful alternative to the Cox proportional hazards model to study association between covariates and their survival functions in medical studies. In this article, we study an extended proportional odds model that incorporates the so-called “external” time-varying covariates. In the extended model, regression parameters have a direct interpretation of comparing survival functions, without specifying the baseline survival odds function. Semiparametric and maximum likelihood estimation procedures are proposed to estimate the extended model. Our methods are demonstrated by Monte-Carlo simulations, and applied to a landmark randomized clinical trial of a short course Nevirapine (NVP) for mother-to-child transmission (MTCT) of human immunodeficiency virus type-1 (HIV-1). Additional application includes analysis of the well-known Veterans Administration (VA) Lung Cancer Trial. PMID:22904583
Wild bootstrap for quantile regression
Feng, Xingdong; He, Xuming; Hu, Jianhua
2011-01-01
Summary The existing theory of the wild bootstrap has focused on linear estimators. In this note, we broaden its validity by providing a class of weight distributions that is asymptotically valid for quantile regression estimators. As most weight distributions in the literature lead to biased variance estimates for nonlinear estimators of linear regression, we propose a modification of the wild bootstrap that admits a broader class of weight distributions for quantile regression. A simulation study on median regression is carried out to compare various bootstrap methods. With a simple finite-sample correction, the wild bootstrap is shown to account for general forms of heteroscedasticity in a regression model with fixed design points. PMID:23049133
Wild bootstrap for quantile regression.
Feng, Xingdong; He, Xuming; Hu, Jianhua
2011-12-01
The existing theory of the wild bootstrap has focused on linear estimators. In this note, we broaden its validity by providing a class of weight distributions that is asymptotically valid for quantile regression estimators. As most weight distributions in the literature lead to biased variance estimates for nonlinear estimators of linear regression, we propose a modification of the wild bootstrap that admits a broader class of weight distributions for quantile regression. A simulation study on median regression is carried out to compare various bootstrap methods. With a simple finite-sample correction, the wild bootstrap is shown to account for general forms of heteroscedasticity in a regression model with fixed design points. PMID:23049133
Fiumera, Heather L.; Dunham, Maitreya J.; Saracco, Scott A.; Butler, Christine A.; Kelly, Jessica A.; Fox, Thomas D.
2009-01-01
Members of the Oxa1/YidC/Alb3 family of protein translocases are essential for assembly of energy-transducing membrane complexes. In Saccharomyces cerevisiae, Oxa1 and its paralog, Cox18, are required for assembly of Cox2, a mitochondrially encoded subunit of cytochrome c oxidase. Oxa1 is known to be required for cotranslational export of the Cox2 N-terminal domain across the inner mitochondrial membrane, while Cox18 is known to be required for post-translational export of the Cox2 C-tail domain. We find that overexpression of Oxa1 does not compensate for the absence of Cox18 at the level of respiratory growth. However, it does promote some translocation of the Cox2 C-tail domain across the inner membrane and causes increased accumulation of Cox2, which remains unassembled. This result suggests that Cox18 not only translocates the C-tail, but also must deliver it in a distinct state competent for cytochrome oxidase assembly. We identified respiring mutants from a cox18? strain overexpressing OXA1, whose respiratory growth requires overexpression of OXA1. The recessive nuclear mutations allow some assembly of Cox2 into cytochrome c oxidase. After failing to identify these mutations by methods based on transformation, we successfully located them to MGR1 and MGR3 by comparative hybridization to whole-genome tiling arrays and microarray-assisted bulk segregant analysis followed by linkage mapping. While Mgr1 and Mgr3 are known to associate with the Yme1 mitochondrial inner membrane i-AAA protease and to participate in membrane protein degradation, their absence does not appear to stabilize Cox2 under these conditions. Instead, Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 in the absence of Mrg1 or Mgr3, since respiratory growth and cytochrome c oxidase assembly in a cox18 mgr3 double-mutant strain overexpressing OXA1 is YME1 dependent. PMID:19307606
Paris-Sud XI, Université de
1 Coa1 links the Mss51 post-translational function to Cox1 cofactor insertion in cytochrome c. The respiratory defect in coa1 cells is suppressed by high copy MSS51, MDJ1 and COX10. Mss51 functions in Cox1 translation and elongation, whereas Cox10 participates in the biosynthesis of heme a, a key cofactor of Cc
Vecchiato, G; De Vico Fallani, F; Astolfi, L; Toppi, J; Cincotti, F; Mattia, D; Salinari, S; Babiloni, F
2010-08-30
This paper presents some considerations about the use of adequate statistical techniques in the framework of the neuroelectromagnetic brain mapping. With the use of advanced EEG/MEG recording setup involving hundred of sensors, the issue of the protection against the type I errors that could occur during the execution of hundred of univariate statistical tests, has gained interest. In the present experiment, we investigated the EEG signals from a mannequin acting as an experimental subject. Data have been collected while performing a neuromarketing experiment and analyzed with state of the art computational tools adopted in specialized literature. Results showed that electric data from the mannequin's head presents statistical significant differences in power spectra during the visualization of a commercial advertising when compared to the power spectra gathered during a documentary, when no adjustments were made on the alpha level of the multiple univariate tests performed. The use of the Bonferroni or Bonferroni-Holm adjustments returned correctly no differences between the signals gathered from the mannequin in the two experimental conditions. An partial sample of recently published literature on different neuroscience journals suggested that at least the 30% of the papers do not use statistical protection for the type I errors. While the occurrence of type I errors could be easily managed with appropriate statistical techniques, the use of such techniques is still not so largely adopted in the literature. PMID:20637802
Stretch-induced myoblast proliferation is dependent on the COX2 pathway
Otis, Jeffrey S.; Burkholder, Thomas J.; Pavlath, Grace K. . 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.
Ku80 cooperates with CBP to promote COX-2 expression and tumor growth
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
Characterization and localization of human COX17, a gene involved in mitochondrial copper transport.
Punter, F A; Adams, D L; Glerum, D M
2000-07-01
Deficiencies in cytochrome oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, are relatively rare but most often lethal. The underlying causes are beginning to be elucidated, and most mutations are thought to affect the function of proteins involved in assembling the holoenzyme. COX17 is such an assembly protein and is thought to recruit copper to mitochondria for incorporation into the COX apoenzyme. Here we present the gene structure, the expression, and chromosomal localization for COX17, a candidate gene for COX deficiency. The COXI 7 gene spans approximately 8 kb of human genomic DNA and encodes a transcript of approximately 450 bp that is expressed in all tissues tested. Although the COX17 gene was previously mapped to chromosome 13q14-21, our results suggest that a COX17 pseudogene maps to this region. The pseudogene contains several nucleotide changes, including one that would result in an altered amino acid in the putative copper binding domain. We have localized the gene encoding the COX 17 protein to the long arm of chromosome 3 by radiation hybrid mapping. Deciphering of the COX17 genomic structure will allow this gene to be assessed for mutations in COX deficient patients. PMID:10982038
Yuan, Xing; Anderson, Stewart J
2010-08-01
In Cox proportional hazard models with censored survival data, estimates of treatment effects with some important covariates omitted will be biased toward zero (Gail et al., Biometrika 71: 431-444). This can be especially problematic in meta-analyses that combine estimates of parameters from studies where different covariate adjustments are made. Presently, few constructive solutions have been provided to address this issue. In this paper, we review the existing meta-analysis methodologies for aggregated patient data (APD) and propose two meta-regression models (meta-ANOVA model and meta-polynomial model) with indicators of different covariates in Cox proportional hazard models to adjust the heterogeneity of treatment effects due to omitted covariates across studies. Both parametric and nonparametric estimators for the pooled treatment effect and the heterogeneity variance are presented and compared. We illustrate the advantages of our proposed analytic procedures over the existing methodologies by simulation studies and real data analysis. The existing methodologies yield large estimation bias in the presence of an "incomparability" issue, whereas our proposed models can adjust the bias and thus provide an accurate estimation. PMID:20661952
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
Mbougua, Jules Brice Tchatchueng; Laurent, Christian; Ndoye, Ibra; Delaporte, Eric; Gwet, Henri; Molinari, Nicolas
2013-11-20
Multiple imputation is commonly used to impute missing covariate in Cox semiparametric regression setting. It is to fill each missing data with more plausible values, via a Gibbs sampling procedure, specifying an imputation model for each missing variable. This imputation method is implemented in several softwares that offer imputation models steered by the shape of the variable to be imputed, but all these imputation models make an assumption of linearity on covariates effect. However, this assumption is not often verified in practice as the covariates can have a nonlinear effect. Such a linear assumption can lead to a misleading conclusion because imputation model should be constructed to reflect the true distributional relationship between the missing values and the observed values. To estimate nonlinear effects of continuous time invariant covariates in imputation model, we propose a method based on B-splines function. To assess the performance of this method, we conducted a simulation study, where we compared the multiple imputation method using Bayesian splines imputation model with multiple imputation using Bayesian linear imputation model in survival analysis setting. We evaluated the proposed method on the motivated data set collected in HIV-infected patients enrolled in an observational cohort study in Senegal, which contains several incomplete variables. We found that our method performs well to estimate hazard ratio compared with the linear imputation methods, when data are missing completely at random, or missing at random. PMID:23712767
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."
Bootstrapping a change-point Cox model for survival data
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
The cox-2-specific inhibitor celecoxib inhibits adenylyl cyclase.
Saini, Shamsher S; Gessell-Lee, Deborah L; Peterson, Johnny W
2003-04-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known causes of acute renal insufficiency and gastropathy in patients with chronic inflammatory diseases. This action is presumed to result from nonselective inhibition of both constitutive and inducible forms of prostaglandin H synthases, also known as the cyclooxygenase enzymes (i.e., COX-1 amd COX-2). Celecoxib (Celebrex) is a COX-2 enzyme inhibitor and has emerged as a preferred therapeutic agent for the treatment of rheumatoid arthritis as compared to other NSAIDs. Celecoxib has recently been the subject of criticism for its side effects, mainly arterial thrombosis and renal hemorrhage, although it is considered a superior drug in protecting the gastrointestinal tract. In the present study, we report that celecoxib not only inhibited COX-2, but also exhibited the property of inhibiting adenylyl cyclase, an important enzyme forming the intracellular second messenger 3',5'-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Celecoxib also inhibited cholera toxin-stimulated cAMP formation, which indicated its ability to permeate cell membranes in order to reach intracellular adenylyl cyclase. It inhibited in vitro adenylyl cyclase activity in both human colonic epithelial cells and purified adenylyl cyclase from Bordetella pertussis. The IC50 of celecoxib for B. pertussis adenylyl cyclase was calculated to be 0.375 mM. Lineweaver-Burk analysis showed that the type of enzyme inhibition was competitive. The apparent Km and Vm of adenylyl cyclase was calculated as 25.0 nM and 7.14 nmol/min/mg, respectively. Celecoxib changed the Km value to 66.6 nM without affecting the Vmax. The current study suggests that apart from inflammation, celecoxib therapy could be further extended to diseases involving cAMP upregulation either by endogenous reactions or exogenous agents. These new data showing inhibition of adenylyl cyclase should be considered in light of the drug's pathological effects or in patients specifically excluded from treatment (e.g., asthmatics). PMID:12797547
Practical Session: Simple Linear Regression
NASA Astrophysics Data System (ADS)
Clausel, M.; Grégoire, G.
2014-01-01
Two exercises are proposed to illustrate the simple linear regression. The first one is based on the famous Galton's data set on heredity. We use the lm R command and get coefficients estimates, standard error of the error, R2, residuals …In the second example, devoted to data related to the vapor tension of mercury, we fit a simple linear regression, predict values, and anticipate on multiple linear regression. This pratical session is an excerpt from practical exercises proposed by A. Dalalyan at EPNC (see Exercises 1 and 2 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_4.pdf).
Statistical methods for astronomical data with upper limits. II - Correlation and regression
NASA Technical Reports Server (NTRS)
Isobe, T.; Feigelson, E. D.; Nelson, P. I.
1986-01-01
Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for the slope of a regression line. Monte Carlo simulations demonstrate that survival analysis is reliable in determining correlations between luminosities at different bands. Survival analysis is applied to CO emission in infrared galaxies, X-ray emission in radio galaxies, H-alpha emission in cooling cluster cores, and radio emission in Seyfert galaxies.
ABSOLUTE RISK REGRESSION FOR COMPETING RISKS: INTERPRETATION, LINK FUNCTIONS AND PREDICTION
GERDS, THOMAS A.; SCHEIKE, THOMAS H.; ANDERSEN, PER K.
2015-01-01
In survival analysis with competing risks the transformation model allows different functions between the outcome and explanatory variables. However, the model's prediction accuracy and the interpretation of parameters may be sensitive to the choice of link function. We review the practical implications of different link functions for regression of the absolute risk (or cumulative incidence) of an event. Specifically we consider models in which the regression coefficients ? have the following interpretation: The probability of dying from cause D during the next t years changes with a factor exp(?) for a one unit change of the corresponding predictor variable, given fixed values for the other predictor variables. The models have a direct interpretation for the predictive ability of the risk factors. We propose some tools to justify the models in comparison with traditional approaches which combine a series of cause-specific Cox regression models, or use the Fine-Gray model. The methods are illustrated using bone marrow transplant data. PMID:22865706
Perez-Martinez, Xochitl; Butler, Christine A.; Shingu-Vazquez, Miguel
2009-01-01
Functional interactions of the translational activator Mss51 with both the mitochondrially encoded COX1 mRNA 5?-untranslated region and with newly synthesized unassembled Cox1 protein suggest that it has a key role in coupling Cox1 synthesis with assembly of cytochrome c oxidase. Mss51 is present at levels that are near rate limiting for expression of a reporter gene inserted at COX1 in mitochondrial DNA, and a substantial fraction of Mss51 is associated with Cox1 protein in assembly intermediates. Thus, sequestration of Mss51 in assembly intermediates could limit Cox1 synthesis in wild type, and account for the reduced Cox1 synthesis caused by most yeast mutations that block assembly. Mss51 does not stably interact with newly synthesized Cox1 in a mutant lacking Cox14, suggesting that the failure of nuclear cox14 mutants to decrease Cox1 synthesis, despite their inability to assemble cytochrome c oxidase, is due to a failure to sequester Mss51. The physical interaction between Mss51 and Cox14 is dependent upon Cox1 synthesis, indicating dynamic assembly of early cytochrome c oxidase intermediates nucleated by Cox1. Regulation of COX1 mRNA translation by Mss51 seems to be an example of a homeostatic mechanism in which a positive effector of gene expression interacts with the product it regulates in a posttranslational assembly process. PMID:19710419
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.
Is the gasoline tax regressive?
Poterba, James M.
1990-01-01
Claims of the regressivity of gasoline taxes typically rely on annual surveys of consumer income and expenditures which show that gasoline expenditures are a larger fraction of income for very low income households than ...
COX-2 active agents in the chemoprevention of colorectal cancer.
Kraus, Sarah; Naumov, Inna; Arber, Nadir
2013-01-01
Chemopreventive strategies for colorectal cancer (CRC) have been extensively studied to prevent the recurrence of adenomas and/or delay their development in the gastrointestinal tract. The non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors have been proven as promising and the most attractive candidates for CRC clinical chemoprevention. The preventive efficacy of these agents is supported by a large number of animal and epidemiological studies which have clearly demonstrated that NSAID consumption prevents adenoma formation and decreases the incidence of, and mortality from CRC. On the basis of these studies, aspirin chemoprevention may be effective in preventing CRC within the general population, while aspirin and celecoxib may be effective in preventing adenomas in patients after polypectomy. Nevertheless, the consumption of NSAID and COX-2 inhibitors is not toxic free. Well-known serious adverse events to the gastrointestinal, renal and cardiovascular systems have been reported. These reports have led to some promising studies related to the use of lower doses and in combination with other chemopreventive agents and shown efficacy. In the intriguing jigsaw puzzle of cancer prevention, we now have a definite positive answer for the basic question "if", but several other parts of the equation-proper patient selection, the ultimate drug, optimal dosage and duration are still missing. PMID:22893201
Stark, David T.; Bazan, Nicolas G.
2011-01-01
Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme mediates neuronal functions, COX-2 is also regarded as a key modulator of neuroinflammation and is thought to exacerbate excitotoxicity via overproduction of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro-survival yet are essential for robust neuronal COX-2 expression. We hypothesized that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a physiological to a potentially pathological process. We combined HPLC-ESI-MS/MS-based mediator lipidomics and unbiased image analysis in mouse dissociated and organotypic cortical cultures to uncover that synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2 expression and activity. We show that synaptic NMDARs enhance neuronal COX-2 expression, while sustained synaptic stimulation limits COX-2 activity by suppressing cellular levels of the primary COX-2 substrate, arachidonic acid (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while activating phospholipase A2 (PLA2), which enhances AA levels by hydrolysis of membrane phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic events only drive induction of COX-2 expression through abnormal synaptic network excitability. Finally, we show that non-enzymatic lipid peroxidation of arachidonic and other polyunsaturated fatty acids is a function of network activity history. A new paradigm emerges from our results suggesting that pathological COX-2 signaling associated with models of stroke, epilepsy, and neurodegeneration requires specific spatio-temporal NMDAR stimulation. PMID:21957234
Significance of COX-2 expression in human renal cell carcinoma cell lines.
Chen, Qinzhong; Shinohara, Nobuo; Abe, Takashige; Watanabe, Takafumi; Nonomura, Katsuya; Koyanagi, Tomohiko
2004-03-01
Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas promotion was found in SMKT-R4 sense transfectants by colony-forming assay despite the observation that COX-2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX-2 expression and PGE2 production and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS-RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing RCC, and that suppression of COX-2 expression by antisense-based strategy may have potential utility in treatment of COX-2-expressing RCC. PMID:14712483
COX-Inhibiting Nitric Oxide Donors (CINODs): Potential Benefits on Cardiovascular and Renal Function
Marcelo N. Muscara; John L. Wallace
2006-01-01
The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents designed for the treatment of pain and inflammation. CINODs have a multi-pathway mechanism of action that involves COX inhibition and nitric oxide donation. The anti-inflammatory and analgesic effects of COX inhibition are reinforced through inhibition of caspase-1 regulated cytokine production, while nitric oxide donation provides multiorgan protection. Whereas
Modulation of COX2 expression in peripheral blood cells by increased intake of fruit and vegetables?
K Almendingen; A Brevik; D A Nymoen; H T Hilmarsen; P A Andresen; L F Andersen; M Vatn
2005-01-01
Background:Enhanced cyclooxygenase-2 (COX-2) expression is associated with carcinogenesis, ischemia, angiogenesis, inflammation, and neurodegeneration. The preventing effect of aspirin and nonsteroidal anti-inflammatory drugs is partly due to inhibition of the COX-2 enzyme. Fruit and vegetables (FVs) contain numerous compounds that may decrease disease risk by several different mechanisms, for example through the inhibition of COX-2 activity.Objective:We tested the hypothesis that an
Basis Selection for Wavelet Regression
NASA Technical Reports Server (NTRS)
Wheeler, Kevin R.; Lau, Sonie (Technical Monitor)
1998-01-01
A wavelet basis selection procedure is presented for wavelet regression. Both the basis and the threshold are selected using cross-validation. The method includes the capability of incorporating prior knowledge on the smoothness (or shape of the basis functions) into the basis selection procedure. The results of the method are demonstrated on sampled functions widely used in the wavelet regression literature. The results of the method are contrasted with other published methods.
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.
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.
Teipel, Stefan J.; Kurth, Jens; Krause, Bernd; Grothe, Michel J.
2015-01-01
Selecting a set of relevant markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) has become a challenging task given the wealth of regional pathologic information that can be extracted from multimodal imaging data. Here, we used regularized regression approaches with an elastic net penalty for best subset selection of multiregional information from AV45-PET, FDG-PET and volumetric MRI data to predict conversion from MCI to AD. The study sample consisted of 127 MCI subjects from ADNI-2 who had a clinical follow-up between 6 and 31 months. Additional analyses assessed the effect of partial volume correction on predictive performance of AV45- and FDG-PET data. Predictor variables were highly collinear within and across imaging modalities. Penalized Cox regression yielded more parsimonious prediction models compared to unpenalized Cox regression. Within single modalities, time to conversion was best predicted by increased AV45-PET signal in posterior medial and lateral cortical regions, decreased FDG-PET signal in medial temporal and temporobasal regions, and reduced gray matter volume in medial, basal, and lateral temporal regions. Logistic regression models reached up to 72% cross-validated accuracy for prediction of conversion status, which was comparable to cross-validated accuracy of non-linear support vector machine classification. Regularized regression outperformed unpenalized stepwise regression when number of parameters approached or exceeded the number of training cases. Partial volume correction had a negative effect on the predictive performance of AV45-PET, but slightly improved the predictive value of FDG-PET data. Penalized regression yielded more parsimonious models than unpenalized stepwise regression for the integration of multiregional and multimodal imaging information. The advantage of penalized regression was particularly strong with a high number of collinear predictors. PMID:26199870
Comparing Methods for Multivariate Nonparametric Regression
. Olszewski y Roy A. Maxion y January 1999 CMUCS99102 School of Computer Science Carnegie Mellon University, linear regression, stepwise linear regression, additive models, AM, projection pursuit regression, PPR, recursive partitioning regression, RPR, multivariate adaptive regression splines, MARS, alternating
Coruzzi, Gabriella; Venturi, Nicola; Spaggiari, Silvana
2007-08-01
Nonsteroidal antiinflammatory drugs (NSAIDs) are frequently associated with adverse reactions, related to inhibition of cyclooxygenase (COX) in tissues where prostaglandins exert physiological effects, such as gastric mucosal defense and renal homeostasis. The discovery of two COX isoforms, namely COX-1 constitutively expressed in most tissues and COX-2 induced at sites of inflammation, led to the development of selective COX-2 inhibitors ("coxibs"), with the hope of significantly reducing the gastrointestinal toxicity associated with acute and chronic NSAID use. However, the increased knowledge of physiological roles of COX-2 enzyme in a variety of tissues, including stomach and kidney, together with the withdrawal from the market of rofecoxib and valdecoxib because of cardiovascular toxicity, have challenged the benefits of selective COX-2 inhibition. As a consequence, the interest for novel approaches has re-emerged; new therapeutic options, still under clinical evaluation, are represented by dual COX and 5-lipooxygenase (5-LOX) inhibitors, synthetic lipoxins, nitric oxide (NO)-releasing NSAIDs and, more recently, by NSAIDs releasing hydrogen sulphide (H2S). This review focuses upon the gastrointestinal (GI) safety of selective COX-2 inhibitors and of novel therapeutic strategies, in comparison with traditional NSAIDs. PMID:17933277
Mutagenesis reveals a specific role for Cox17p in copper transport to cytochrome oxidase.
Punter, Fiona A; Glerum, D Moira
2003-08-15
The provision of copper to cytochrome oxidase is one of the requisite steps in the assembly of the holoenzyme. Several proteins are involved in this process including Cox17p, Sco1p, and Cox11p. Cox17p, an 8-kDa protein, is the only molecule thought to be involved in shuttling copper from the cytoplasm into mitochondria. Given the small size of Cox17p, we have taken a random and site-directed mutagenesis approach to studying structure-function relationships in Cox17p. Mutations have been generated in 70% of the Cox17p amino acid residues, with only a small subset leading to a detectable respiration-deficient phenotype. We have characterized the respiration-deficient cox17 mutants and found in addition to the expected cytochrome oxidase deficiency, a specific lack of Cox2p and the presence of a misassembled cytochrome oxidase in a subset of mutants. These results suggest that Cox17p is involved upstream of Sco1p in delivering copper specifically to subunit 2 of cytochrome oxidase and predict the existence of a subunit 1-specific copper chaperone. PMID:12788943
NASA Astrophysics Data System (ADS)
Sircombe, Keith N.
2004-02-01
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 to bias due to arbitrary decisions about bin width. A method for assessing the efficiency of bin widths is presented. Probability density distributions use a variable Gaussian kernel method that accounts for analytical error of individual datum. While providing standardization of the display, these diagrams are limited by the lack of visually accessible frequency information. An approach combining elements of both histograms and probability density distributions is proposed. All methods are applied in an Excel workbook and the procedures for using this are explained.
Girard, Jean-Michel; Deschênes, Jean-Sébastien; Tremblay, Réjean; Gagnon, Jonathan
2013-09-01
The objective of this work is to develop a quick and simple method for the in situ monitoring of sugars in biological cultures. A new technology based on Attenuated Total Reflectance-Fourier Transform Infrared (FT-IR/ATR) spectroscopy in combination with an external light guiding fiber probe was tested, first to build predictive models from solutions of pure sugars, and secondly to use those models to monitor the sugars in the complex culture medium of mixotrophic microalgae. Quantification results from the univariate model were correlated with the total dissolved solids content (R(2)=0.74). A vector normalized multivariate model was used to proportionally quantify the different sugars present in the complex culture medium and showed a predictive accuracy of >90% for sugars representing >20% of the total. This method offers an alternative to conventional sugar monitoring assays and could be used at-line or on-line in commercial scale production systems. PMID:23876970
PSHREG: a SAS macro for proportional and nonproportional subdistribution hazards regression.
Kohl, Maria; Plischke, Max; Leffondré, Karen; Heinze, Georg
2015-02-01
We present a new SAS macro %pshreg that can be used to fit a proportional subdistribution hazards model for survival data subject to competing risks. Our macro first modifies the input data set appropriately and then applies SAS's standard Cox regression procedure, PROC PHREG, using weights and counting-process style of specifying survival times to the modified data set. The modified data set can also be used to estimate cumulative incidence curves for the event of interest. The application of PROC PHREG has several advantages, e.g., it directly enables the user to apply the Firth correction, which has been proposed as a solution to the problem of undefined (infinite) maximum likelihood estimates in Cox regression, frequently encountered in small sample analyses. Deviation from proportional subdistribution hazards can be detected by both inspecting Schoenfeld-type residuals and testing correlation of these residuals with time, or by including interactions of covariates with functions of time. We illustrate application of these extended methods for competing risk regression using our macro, which is freely available at: http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/statistical-software/pshreg, by means of analysis of a real chronic kidney disease study. We discuss differences in features and capabilities of %pshreg and the recent (January 2014) SAS PROC PHREG implementation of proportional subdistribution hazards modelling. PMID:25572709
Expression and prognostic significance of cox-2 and p-53 in hodgkin lymphomas: a retrospective study
2010-01-01
Background Cyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2 (cox-2), which is one of the two isoforms, plays a role in tumor progression and carcinogenesis. p53 contributes to apoptosis, DNA renewal and cell cycle. Studies concerning the relationship of cox-2 and p53 expressions and carcinogenesis are available, but the association between cox-2 and p53 in Hodgkin lymphoma (HL) is not exactly known. In our study, we examined the association of cox-2 and p53 expression, with age, stage, histopathological subtype, and survival in HL. We also examined correlation between cox-2 and p53 expression. Methods Cox-2 and p53 expressions in Hodgkin-Reed Sternberg cells (HRS) were examined in 54 patients with HL depending on cox-2 expression, stained cases were classified as positive, and unstained cases as negative. Nuclear staining of HRS cells with p53 was evaluated as positive. The classifications of positivity were as follows: negative if<10%; (1+) if 10-25%; (2+) if 25-50%; (3+) if 50-75%, (4+) if >75%. Results Cox-2 and p53 expressions were found in 49 (80%) and 29 (46%) patients, respectively. There were differences between histological subtypes according to cox-2 expression (p = 0.012). Mixed cellular (MC) and nodular sclerosing (NS) subtypes were seen most of the patients and cox-2 expression was evaluated mostly in the mixed cellular subtype. There were no statistically significant relationships between p53 and the histopathological subtypes; or between p53, cox-2 and the factors including stage, age and survival; or between p53 and cox-2 expression (p > 0.05). Conclusion Considering the significant relationship between the cox-2 expression and the subtypes of HL, cox-2 expression is higher in MC and NS subtypes. However the difference between these two subtypes was not significant. This submission must be advocated by studies with large series PMID:20346139
Rosado, Eugenio; Rodríguez-Vilarrupla, Aina; Gracia-Sancho, Jorge; Monclús, Montserrat; Bosch, Jaume; García-Pagán, Joan-Carles
2012-01-01
Reduced intrahepatic nitric oxide (NO) bioavailability and increased cyclooxygenase-1 (COX-1)-derived vasoconstrictor prostanoids modulate the hepatic vascular tone in cirrhosis. We aimed at investigating the reciprocal interactions between NO and COX in the hepatic endothelium of control and cirrhotic rats. NO bioavailability (DAF-FM-DA staining), superoxide (O2?) content (DHE staining), prostanoid production (PGI2 and TXA2 by enzyme immunoassays) as well as COX expression (Western Blot), were determined in hepatic endothelial cells (HEC) from control and cirrhotic rats submitted to different experimental conditions: COX activation, COX inhibition, NO activation and NO inhibition. In control and cirrhotic HEC, COX activation with arachidonic acid reduced NO bioavailability and increased O2? levels. These effects were abolished by pre-treating HEC with the COX inhibitor indomethacin. In control, but not in cirrhotic HEC, scavenging of O2? by superoxide dismutase (SOD) incubation partially restored the decrease in NO bioavailability promoted by COX activation. NO supplementation produced a significant and parallel reduction in PGI2 and TXA2 production in control HEC, whereas it only reduced TXA2 production in cirrhotic HEC. By contrast, in control and cirrhotic HEC, NO inhibition did not modify COX expression or activity. Our results demonstrate that NO and COX systems are closely interrelated in HEC. This is especially relevant in cirrhotic HEC where COX inhibition increases NO bioavailability and NO supplementation induces a reduction in TXA2. These strategies may have beneficial effects ameliorating the vasoconstrictor/vasodilator imbalance of the intrahepatic circulation of cirrhotic livers. PMID:22436078
Grover, Jagdeep; Kumar, Vivek; Singh, Vikram; Bairwa, Khemraj; Sobhia, M Elizabeth; Jachak, Sanjay M
2014-06-10
Nepodin and chrysophanol, isolated from Rumex nepalensis roots, showed significant cyclooxygenase (COX) inhibitory activity. To further optimize these lead molecules and study structure activity relationship (SAR), eighteen derivatives of nepodin and nine derivatives of chrysophanol were synthesized and evaluated for COX-1 and COX-2 inhibitory potential. Among the synthesized compounds, four nepodin (1f, 1g, 1h and 1i) and three chrysophanol (2e, 2f and 2h) derivatives displayed more pronounced COX-2 inhibition than their respective lead molecule. Further, compounds 1f, 1g, 2e and 2h exhibited better anti-inflammatory activity than ibuprofen in carrageenan-induced rat paw edema assay. Taking into account the in vitro and in vivo results, molecular docking and in silico prediction of ADMET properties of compounds were carried out respectively. PMID:24763362
Logistic regression for dichotomized counts.
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
Automated Box-Cox Transformations for Improved Visual Encoding.
Maciejewski, R; Pattath, A; Sungahn Ko; Hafen, R; Cleveland, W S; Ebert, D S
2013-01-01
The concept of preconditioning data (utilizing a power transformation as an initial step) for analysis and visualization is well established within the statistical community and is employed as part of statistical modeling and analysis. Such transformations condition the data to various inherent assumptions of statistical inference procedures, as well as making the data more symmetric and easier to visualize and interpret. In this paper, we explore the use of the Box-Cox family of power transformations to semiautomatically adjust visual parameters. We focus on time-series scaling, axis transformations, and color binning for choropleth maps. We illustrate the usage of this transformation through various examples, and discuss the value and some issues in semiautomatically using these transformations for more effective data visualization. PMID:22350197
Soo Sung Kang; Muriel Cuendet; Denise C. Endringer; Vicki L. Croy; John M. Pezzuto; Mark A. Lipton
2009-01-01
Resveratrol (4,3?,5?-trihydroxystilbene) is a naturally occurring antioxidant that inhibits cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and the transcription factor NF-?B. A 78-membered library of resveratrol analogues in which the substituents on the two aryl rings and alkene were varied was synthesized using a solid-phase Wittig olefination reaction. The library contains inhibitors against all three proteins that were more potent than resveratrol itself.
Box-Cox Mixed Logit Model for Travel Behavior Analysis
NASA Astrophysics Data System (ADS)
Orro, Alfonso; Novales, Margarita; Benitez, Francisco G.
2010-09-01
To represent the behavior of travelers when they are deciding how they are going to get to their destination, discrete choice models, based on the random utility theory, have become one of the most widely used tools. The field in which these models were developed was halfway between econometrics and transport engineering, although the latter now constitutes one of their principal areas of application. In the transport field, they have mainly been applied to mode choice, but also to the selection of destination, route, and other important decisions such as the vehicle ownership. In usual practice, the most frequently employed discrete choice models implement a fixed coefficient utility function that is linear in the parameters. The principal aim of this paper is to present the viability of specifying utility functions with random coefficients that are nonlinear in the parameters, in applications of discrete choice models to transport. Nonlinear specifications in the parameters were present in discrete choice theory at its outset, although they have seldom been used in practice until recently. The specification of random coefficients, however, began with the probit and the hedonic models in the 1970s, and, after a period of apparent little practical interest, has burgeoned into a field of intense activity in recent years with the new generation of mixed logit models. In this communication, we present a Box-Cox mixed logit model, original of the authors. It includes the estimation of the Box-Cox exponents in addition to the parameters of the random coefficients distribution. Probability of choose an alternative is an integral that will be calculated by simulation. The estimation of the model is carried out by maximizing the simulated log-likelihood of a sample of observed individual choices between alternatives. The differences between the predictions yielded by models that are inconsistent with real behavior have been studied with simulation experiments.
Survival Data and Regression Models
NASA Astrophysics Data System (ADS)
Grégoire, G.
2014-01-01
We start this chapter by introducing some basic elements for the analysis of censored survival data. Then we focus on right censored data and develop two types of regression models. The first one concerns the so-called accelerated failure time models (AFT), which are parametric models where a function of a parameter depends linearly on the covariables. The second one is a semiparametric model, where the covariables enter in a multiplicative form in the expression of the hazard rate function. The main statistical tool for analysing these regression models is the maximum likelihood methodology and, in spite we recall some essential results about the ML theory, we refer to the chapter "Logistic Regression" for a more detailed presentation.
Functional regression via variational Bayes
Goldsmith, Jeff; Wand, Matt P.; Crainiceanu, Ciprian
2011-01-01
We introduce variational Bayes methods for fast approximate inference in functional regression analysis. Both the standard cross-sectional and the increasingly common longitudinal settings are treated. The methodology allows Bayesian functional regression analyses to be conducted without the computational overhead of Monte Carlo methods. Confidence intervals of the model parameters are obtained both using the approximate variational approach and nonparametric resampling of clusters. The latter approach is possible because our variational Bayes functional regression approach is computationally efficient. A simulation study indicates that variational Bayes is highly accurate in estimating the parameters of interest and in approximating the Markov chain Monte Carlo-sampled joint posterior distribution of the model parameters. The methods apply generally, but are motivated by a longitudinal neuroimaging study of multiple sclerosis patients. Code used in simulations is made available as a web-supplement. PMID:22163061
Regression Verification Using Impact Summaries
NASA Technical Reports Server (NTRS)
Backes, John; Person, Suzette J.; Rungta, Neha; Thachuk, Oksana
2013-01-01
Regression verification techniques are used to prove equivalence of syntactically similar programs. Checking equivalence of large programs, however, can be computationally expensive. Existing regression verification techniques rely on abstraction and decomposition techniques to reduce the computational effort of checking equivalence of the entire program. These techniques are sound but not complete. In this work, we propose a novel approach to improve scalability of regression verification by classifying the program behaviors generated during symbolic execution as either impacted or unimpacted. Our technique uses a combination of static analysis and symbolic execution to generate summaries of impacted program behaviors. The impact summaries are then checked for equivalence using an o-the-shelf decision procedure. We prove that our approach is both sound and complete for sequential programs, with respect to the depth bound of symbolic execution. Our evaluation on a set of sequential C artifacts shows that reducing the size of the summaries can help reduce the cost of software equivalence checking. Various reduction, abstraction, and compositional techniques have been developed to help scale software verification techniques to industrial-sized systems. Although such techniques have greatly increased the size and complexity of systems that can be checked, analysis of large software systems remains costly. Regression analysis techniques, e.g., regression testing [16], regression model checking [22], and regression verification [19], restrict the scope of the analysis by leveraging the differences between program versions. These techniques are based on the idea that if code is checked early in development, then subsequent versions can be checked against a prior (checked) version, leveraging the results of the previous analysis to reduce analysis cost of the current version. Regression verification addresses the problem of proving equivalence of closely related program versions [19]. These techniques compare two programs with a large degree of syntactic similarity to prove that portions of one program version are equivalent to the other. Regression verification can be used for guaranteeing backward compatibility, and for showing behavioral equivalence in programs with syntactic differences, e.g., when a program is refactored to improve its performance, maintainability, or readability. Existing regression verification techniques leverage similarities between program versions by using abstraction and decomposition techniques to improve scalability of the analysis [10, 12, 19]. The abstractions and decomposition in the these techniques, e.g., summaries of unchanged code [12] or semantically equivalent methods [19], compute an over-approximation of the program behaviors. The equivalence checking results of these techniques are sound but not complete-they may characterize programs as not functionally equivalent when, in fact, they are equivalent. In this work we describe a novel approach that leverages the impact of the differences between two programs for scaling regression verification. We partition program behaviors of each version into (a) behaviors impacted by the changes and (b) behaviors not impacted (unimpacted) by the changes. Only the impacted program behaviors are used during equivalence checking. We then prove that checking equivalence of the impacted program behaviors is equivalent to checking equivalence of all program behaviors for a given depth bound. In this work we use symbolic execution to generate the program behaviors and leverage control- and data-dependence information to facilitate the partitioning of program behaviors. The impacted program behaviors are termed as impact summaries. The dependence analyses that facilitate the generation of the impact summaries, we believe, could be used in conjunction with other abstraction and decomposition based approaches, [10, 12], as a complementary reduction technique. An evaluation of our regression verification technique shows that our approach is capable of leveragin
Saracco, Scott A.; Fox, Thomas D.
2002-01-01
The amino- and carboxy-terminal domains of mitochondrially encoded cytochrome c oxidase subunit II (Cox2p) are translocated out of the matrix to the intermembrane space. We have carried out a genetic screen to identify components required to export the biosynthetic enzyme Arg8p, tethered to the Cox2p C terminus by a translational gene fusion inserted into mtDNA. We obtained multiple alleles of COX18, PNT1, and MSS2, as well as mutations in CBP1 and PET309. Focusing on Cox18p, we found that its activity is required to export the C-tail of Cox2p bearing a short C-terminal epitope tag. This is not a consequence of reduced membrane potential due to loss of cytochrome oxidase activity because Cox2p C-tail export was not blocked in mitochondria lacking Cox4p. Cox18p is not required to export the Cox2p N-tail, indicating that these two domains of Cox2p are translocated by genetically distinct mechanisms. Cox18p is a mitochondrial integral inner membrane protein. The inner membrane proteins Mss2p and Pnt1p both coimmunoprecipitate with Cox18p, suggesting that they work together in translocation of Cox2p domains, an inference supported by functional interactions among the three genes. PMID:11950926
Saracco, Scott A; Fox, Thomas D
2002-04-01
The amino- and carboxy-terminal domains of mitochondrially encoded cytochrome c oxidase subunit II (Cox2p) are translocated out of the matrix to the intermembrane space. We have carried out a genetic screen to identify components required to export the biosynthetic enzyme Arg8p, tethered to the Cox2p C terminus by a translational gene fusion inserted into mtDNA. We obtained multiple alleles of COX18, PNT1, and MSS2, as well as mutations in CBP1 and PET309. Focusing on Cox18p, we found that its activity is required to export the C-tail of Cox2p bearing a short C-terminal epitope tag. This is not a consequence of reduced membrane potential due to loss of cytochrome oxidase activity because Cox2p C-tail export was not blocked in mitochondria lacking Cox4p. Cox18p is not required to export the Cox2p N-tail, indicating that these two domains of Cox2p are translocated by genetically distinct mechanisms. Cox18p is a mitochondrial integral inner membrane protein. The inner membrane proteins Mss2p and Pnt1p both coimmunoprecipitate with Cox18p, suggesting that they work together in translocation of Cox2p domains, an inference supported by functional interactions among the three genes. PMID:11950926
Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance.
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
Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F.; Waldner, Maximilian J.
2013-01-01
Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC. PMID:23401648
Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F; Waldner, Maximilian J
2013-01-01
Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC. PMID:23401648
ORIGINAL PAPER G. V. Gibbs D. F. Cox M.B. Boisen, Jr.
Downs, Robert T.
ORIGINAL PAPER G. V. Gibbs Á D. F. Cox Á M.B. Boisen, Jr. R. T. Downs Á N. L. Ross The electron-0420, USA E-mail: ggibbs@vt.edu D. F. Cox Department of Chemical Engineering, Virginia Tech., Blacksburg
The Origins of Racism: The Critical Theory of Oliver C. Cox
Klarlund, Susan E.
1994-04-01
Oliver C. Cox's theory of race relations and its impending problems in connection with the rise of capitalism have not been applied or addressed to the same extent as that of his contemporaries. Why does the work of Oliver Cox continue to be largely...
A New Interpretation of Thalamocortical Circuitry Author(s): Paul Adams and Kingsley Cox
Adams, Paul R.
A New Interpretation of Thalamocortical Circuitry Author(s): Paul Adams and Kingsley Cox SourceU SOCIETY A new interpretation of thalamocortical circuitry Paul Adams* and Kingsley Cox Department, and relay cell feed-forward excitation to and feedback inhibition from reticular nucleus. All these circuits
Rationalizing cyclooxygenase (COX) inhibition for maximal efficacy and minimal adverse events
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
Mori dream spaces of Calabi-Yau type and the log canonicity of the Cox rings
Kawamata, Yujiro
2012-01-01
We prove that a Mori dream space over a field of characteristic zero is of Calabi-Yau type if and only if its Cox ring has at worst log canonical singularities. By slightly modifying the arguments we also reprove the characterization of the varieties of Fano type by the log terminality of the Cox rings.
Kawamura, Michiko; Tada, Yosihito; Kadoya, Yuichi; Obata, Shuichi; Harada, Yoshiteru
2013-10-01
We previously reported the expression of cyclooxygenase (COX)-2 in draining lymph nodes during carrageenin-induced pleurisy of rats. Here, we analyzed histological and immunohistochemical characteristics of COX-2-expressing cells. After carrageenin administration into the pleural cavity of rats, parathymic lymph nodes were enlarged beginning at 8h and peaking from 24 to 48h. Lymphatic follicles disappeared 16h after injection, and numerous macrophages and fibroblasts were observed in the cortical region. COX-2-expressing cells in the cortical region showed characteristic dendritic processes from 16 to 48h and primarily co-localized with stromal fibroblastic reticular cell markers, ?-smooth muscle actin (?-SMA), and desmin. Expression of ?-SMA increased following COX-2 expression. Nimesulide, a COX-2 inhibitor, increased the dendritic processes of COX-2-expressing cells as well as expression of both COX-2 and ?-SMA. These results suggest that COX-2-expressing cells may be stromal fibroblastic cells, which negatively self-regulate their proliferation and modulate tissue remodeling of draining lymph nodes at inflammatory sites. PMID:23587942
Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors.
Badrey, Mohamed G; Abdel-Aziz, Hassan M; Gomha, Sobhi M; Abdalla, Mohamed M; Mayhoub, Abdelrahman S
2015-01-01
The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds. PMID:26307959
Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells
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
Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells.
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
The use of Cox-2 and PPAR? signaling in anti-cancer therapies
KNOPFOVÁ, LUCIA; ŠMARDA, JAN
2010-01-01
Increased production of the pro-inflammatory enzyme cyclooxygenase-2 (Cox-2) and altered expression and activity of peroxisome proliferator-activated receptor ? (PPAR?) have been observed in many malignancies. Both the PPAR? ligands and the Cox-2 inhibitors possess anti-inflammatory and anti-neoplastic effects in vitro and have been assessed for their therapeutic potential in several pre-clinical and clinical studies. Recently, multiple interactions between PPAR? and Cox-2 signaling pathways have been revealed. Understanding of the cross-talk between PPAR? and Cox-2 might provide important novel strategies for the effective treatment and/or prevention of cancer. This article summarizes recent achievements involving the functional interactions between the PPAR? and Cox-2 signaling pathways and discusses the implications of such interplay for clinical use. PMID:22993537
Williams, Siôn L; Valnot, Isabelle; Rustin, Pierre; Taanman, Jan-Willem
2004-02-27
Cytochrome c oxidase contains two redox-active copper centers (Cu(A) and Cu(B)) and two redox-active heme A moieties. Assembly of the enzyme relies on several assembly factors in addition to the constituent subunits and prosthetic groups. We studied fibroblast cultures from patients carrying mutations in the assembly factors COX10, SCO1, or SURF1. COX10 is involved in heme A biosynthesis. SCO1 is required for formation of the Cu(A) center. The function of SURF1 is unknown. Immunoblot analysis of native gels demonstrated severely decreased levels of holoenzyme in the patient cultures compared with controls. In addition, the blots revealed the presence of five subassemblies: three subassemblies involving the core subunit MTCO1 but apparently no other subunits; a subassembly containing subunits MTCO1, COX4, and COX5A; and a subassembly containing at least subunits MTCO1, MTCO2, MTCO3, COX4, and COX5A. As some of the subassemblies correspond to known assembly intermediates of human cytochrome c oxidase, we think that these subassemblies are probably assembly intermediates that accumulate in patient cells. The MTCO1.COX4.COX5A subassembly was not detected in COX10-deficient cells, which suggests that heme A incorporation into MTCO1 occurs prior to association of MTCO1 with COX4 and COX5A. SCO1-deficient cells contained accumulated levels of the MTCO1.COX4.COX5A subassembly, suggesting that MTCO2 associates with the MTCO1.COX4.COX5A subassembly after the Cu(A) center of MTCO2 is formed. Assembly in SURF1-deficient cells appears to stall at the same stage as in SCO1-deficient cells, pointing to a role for SURF1 in promoting the association of MTCO2 with the MTCO1.COX4.COX5A subassembly. PMID:14607829
Improving Your Data Transformations: Applying the Box-Cox Transformation
ERIC Educational Resources Information Center
Osborne, Jason W.
2010-01-01
Many of us in the social sciences deal with data that do not conform to assumptions of normality and/or homoscedasticity/homogeneity of variance. Some research has shown that parametric tests (e.g., multiple regression, ANOVA) can be robust to modest violations of these assumptions. Yet the reality is that almost all analyses (even nonparametric…
Nuñez, Felipe; Bravo, Soraya; Cruzat, Fernando; Montecino, Martín; De Ferrari, Giancarlo V.
2011-01-01
Background Increased expression of the cyclooxygenase-2 enzyme (COX2) is one of the main characteristics of gastric cancer (GC), which is a leading cause of death in the world, particularly in Asia and South America. Although the Wnt/?-catenin signaling pathway has been involved in the transcriptional activation of the COX2 gene, the precise mechanism modulating this response is still unknown. Methodology/Principal Findings Here we studied the transcriptional regulation of the COX2 gene in GC cell lines and assessed whether this phenomenon is modulated by Wnt/?-catenin signaling. We first examined the expression of COX2 mRNA in GC cells and found that there is a differential expression pattern consistent with high levels of nuclear-localized ?-catenin. Pharmacological treatment with either lithium or valproic acid and molecular induction with purified canonical Wnt3a significantly enhanced COX2 mRNA expression in a dose- and time-dependent manner. Serial deletion of a 1.6 Kbp COX2 promoter fragment and gain- or loss-of-function experiments allowed us to identify a minimal Wnt/?-catenin responsive region consisting of 0.8 Kbp of the COX2 promoter (pCOX2-0.8), which showed maximal response in gene-reporter assays. The activity of this pCOX2-0.8 promoter region was further confirmed by site-directed mutagenesis and DNA-protein binding assays. Conclusions/Significance We conclude that the pCOX2-0.8 minimal promoter contains a novel functional T-cell factor/lymphoid enhancer factor (TCF/LEF)-response element (TBE Site II; -689/-684) that responds directly to enhanced Wnt/?-catenin signaling and which may be important for the onset/progression of GC. PMID:21494638
Multiple Regression: A Leisurely Primer.
ERIC Educational Resources Information Center
Daniel, Larry G.; Onwuegbuzie, Anthony J.
Multiple regression is a useful statistical technique when the researcher is considering situations in which variables of interest are theorized to be multiply caused. It may also be useful in those situations in which the researchers is interested in studies of predictability of phenomena of interest. This paper provides an introduction to…
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…
Building Your Own Regression Model
ERIC Educational Resources Information Center
Horton, Robert, M.; Phillips, Vicki; Kenelly, John
2004-01-01
Spreadsheets to explore regression with an algebra 2 class in a medium-sized rural high school are presented. The use of spreadsheets can help students develop sophisticated understanding of mathematical models and use them to describe real-world phenomena.
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…
Logistic Regression with Random Coefficients.
ERIC Educational Resources Information Center
Longford, Nicholas T.
An approximation to the likelihood for the generalized linear models with random coefficients is derived and is the basis for an approximate Fisher scoring algorithm. The method is illustrated on the logistic regression model for one-way classification, but it has an extension to the class of generalized linear models and to more complex data…
Cactus: An Introduction to Regression
ERIC Educational Resources Information Center
Hyde, Hartley
2008-01-01
When the author first used "VisiCalc," the author thought it a very useful tool when he had the formulas. But how could he design a spreadsheet if there was no known formula for the quantities he was trying to predict? A few months later, the author relates he learned to use multiple linear regression software and suddenly it all clicked into…
Linear regression issues in astronomy
Babu, G. Jogesh
Linear regression issues in astronomy Eric Feigelson Summer School in astrostatistics References-dependent & Quantitative Variables in Econometrics 1983) Astronomy: Malmquist bias in Hubble diagram (Deeming, Vistas Astr) Schmitt (ApJ 1985) Presented for astronomy by Isobe, Feigelson & Nelson (ApJ 1986) Implemented
Regression modelling of Dst index
NASA Astrophysics Data System (ADS)
Parnowski, Aleksei
We developed a new approach to the problem of real-time space weather indices forecasting using readily available data from ACE and a number of ground stations. It is based on the regression modelling method [1-3], which combines the benefits of empirical and statistical approaches. Mathematically it is based upon the partial regression analysis and Monte Carlo simulations to deduce the empirical relationships in the system. The typical elapsed time per forecast is a few seconds on an average PC. This technique can be easily extended to other indices like AE and Kp. The proposed system can also be useful for investigating physical phenomena related to interactions between the solar wind and the magnetosphere -it already helped uncovering two new geoeffective parameters. 1. Parnowski A.S. Regression modeling method of space weather prediction // Astrophysics Space Science. — 2009. — V. 323, 2. — P. 169-180. doi:10.1007/s10509-009-0060-4 [arXiv:0906.3271] 2. Parnovskiy A.S. Regression Modeling and its Application to the Problem of Prediction of Space Weather // Journal of Automation and Information Sciences. — 2009. — V. 41, 5. — P. 61-69. doi:10.1615/JAutomatInfScien.v41.i5.70 3. Parnowski A.S. Statistically predicting Dst without satellite data // Earth, Planets and Space. — 2009. — V. 61, 5. — P. 621-624.
Three Steps Toward Robust Regression
ERIC Educational Resources Information Center
Thissen, David; Wainer, Howard
1976-01-01
A new measure of correlation and a measure of scale are proposed which are substantially more robust than their least squares counterparts. Increased robustness may also be obtained by use of equal regression weights, or knowledge of the theoretical structure of the weights. (Author/HG)
CORRESPONDENCE Reduced major axis regression
). The slope of the least-squares regression of Y on X, b, measures the extent to which large body sizes tend continental source (X), where Y and X are log-transformed mean body sizes (summarized by Lomolino, 2005 to decrease and small body sizes to increase. For example, if the mean body size among the island forms
Correlation and Regression Worksheet 2
Watkins, Joseph C.
Correlation and Regression Worksheet 2 1. Observations made by the astronomer Edwin Hubble showed to that galaxy, Hubble's law is the linear relationship. v = Hd. H is known as Hubble's constant. To estimate H.5 Ursa Major #2 700 26.0 Hydra 1100 38.0 (a) What are the units of Hubble's constant? (b) Provide
Regression Test Selection for C++ Software
Gregg Rothermel; Mary Jean Harrold; Jeinay Dedhia
2000-01-01
Regression testing is an important but expensive software maintenance activity performed with the aim of providing condence in modied software. Regression test selection techniques reduce the cost of regression testing by selecting test cases for a modied program from a previously existing test suite. Many researchers have addressed the regression test selection problem for procedural language software, but few have
Robust RVM regression using sparse outlier model
Kaushik Mitra; Ashok Veeraraghavan; Rama Chellappa
2010-01-01
Kernel regression techniques such as Relevance Vector Machine (RVM) regression, Support Vector Regression and Gaussian processes are widely used for solving many computer vision problems such as age, head pose, 3D human pose and lighting estimation. However, the presence of outliers in the training dataset makes the estimates from these regression techniques unreliable. In this paper, we propose robust versions
Arunasree, Kalle M; Roy, Karnati R; Anilkumar, Kotha; Aparna, A; Reddy, Gorla Venkateswara; Reddanna, Pallu
2008-06-01
Selective inhibition of the BCR/ABL tyrosine kinase by imatinib (STI571, Glivec/Gleevec) is the therapeutic strategy in patients with chronic myelogenous leukemia (CML). Despite significant hematologic and cytogenetic responses with imatinib, mainly due to the mutations in the Abl kinase domain, resistance occurs in patients with advanced disease. In the present study on imatinib-resistant K562 cells (IR-K562), however, no such mutations in the Abl kinase domain were observed. Further studies revealed the over-expression of COX-2 and MDR-1 in IR-K562 cells suggesting the possible involvement of COX-2 in the development of resistance to imatinib. So, we sought to examine the effect of celecoxib, a selective COX-2 inhibitor, on IR-K562 cells. The results clearly indicate that celecoxib is more effective in IR-K562 cells with a lower IC50 value of 10 microM compared to an IC50 value of 40 microM in K562 cells. This increase in the sensitivity of IR-K562 cells towards celecoxib suggests that the development of resistance in IR-K562 cells is COX-2 dependent. Further studies revealed down-regulation of MDR-1 by celecoxib and a decline in p-Akt levels. Celecoxib-induced apoptosis of IR-K562 cells led to release of cytochrome c, PARP cleavage and decreased Bcl2/Bax ratio. Also, celecoxib at 1 microM concentration induced apoptosis in IR-K562 cells synergistically with imatinib by reducing the IC50 value of imatinib from 10 to 6 microM. In conclusion, the present study indicates over-expression of COX-2 and MDR-1 in IR-K562 cells and celecoxib, a COX-2 specific inhibitor, induces apoptosis by inhibiting COX-2 and down-regulating MDR-1 expression through Akt/p-Akt signaling pathway. PMID:18083230
Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors
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
Usefulness of selective COX-2 inhibitors as therapeutic agents against canine mammary tumors.
Saito, Teruyoshi; Tamura, Dai; Asano, Ryuji
2014-04-01
Cyclooxygenase-2 (COX-2) is a key enzyme for converting arachidonic acids to prostanoids, which are known to be induced during inflammation and cancer initiation. Previously, it has been reported that COX inhibitors, such as aspirin, reduce the incidence of human colorectal cancer; therefore, it is widely believed that COX-2 is a potential therapeutic and chemoprevention target for several types of human cancer. However, whether selective COX-2 inhibitors have antitumor effects against canine mammary tumor cells remains unclear. In the present study, to elucidate the antitumor effect of selective COX-2 inhibitors against canine mammary tumors, we investigated the antitumor effects of meloxicam, etodolac and celecoxib using COX-2-expressing canine mammary tumor (CF33) cells. We analyzed the effects of selective COX-2 inhibitors on COX-2 protein expression levels in CF33 cells. Celecoxib (100 µM) was found to induce downregulation of COX-2 protein expression. We examined the effect of selective COX-2 inhibitors on CF33 cell proliferation. All the selective COX-2 inhibitors suppressed CF33 cell growth. Specifically, etodolac and celecoxib inhibited cell proliferation via a decrease in S-phase cells and an increase in G0/G1 arrest. We examined the apoptotic effect of selective COX-2 inhibitors on CF33 cells. Our data suggested that etodolac and celecoxib induced apoptosis in CF33 cells. In particular, celecoxib led to apoptosis mediated by the activation of the mitochondrial apoptosis pathway, including the upregulation of BAX expression, downregulation of Bcl-2 expression and activation of caspase-3/7. Furthermore, celecoxib increased the percentages of cells in both early apoptosis and late apoptosis. Our results revealed that celecoxib induced apoptosis and cell cycle arrest in CF33 cells. The data suggested that celecoxib is the most viable candidate as a therapeutic agent for the treatment of canine mammary tumors. Furthermore, our findings provide the first indication that COX-2 inhibition can provide a new therapeutic strategy for treating canine mammary tumors. PMID:24503782
Pernet, C.R.; Latinus, M.; Nichols, T.E.; Rousselet, G.A.
2015-01-01
Background In recent years, analyses of event related potentials/fields have moved from the selection of a few components and peaks to a mass-univariate approach in which the whole data space is analyzed. Such extensive testing increases the number of false positives and correction for multiple comparisons is needed. Method Here we review all cluster-based correction for multiple comparison methods (cluster-height, cluster-size, cluster-mass, and threshold free cluster enhancement – TFCE), in conjunction with two computational approaches (permutation and bootstrap). Results Data driven Monte-Carlo simulations comparing two conditions within subjects (two sample Student's t-test) showed that, on average, all cluster-based methods using permutation or bootstrap alike control well the family-wise error rate (FWER), with a few caveats. Conclusions (i) A minimum of 800 iterations are necessary to obtain stable results; (ii) below 50 trials, bootstrap methods are too conservative; (iii) for low critical family-wise error rates (e.g. p = 1%), permutations can be too liberal; (iv) TFCE controls best the type 1 error rate with an attenuated extent parameter (i.e. power < 1). PMID:25128255
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
NASA Technical Reports Server (NTRS)
Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.
1996-01-01
Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.
H. Ulbrich; O. Soehnlein; X. Xie; E. E. Eriksson; L. Lindbom; W. Albrecht; S. Laufer; G. Dannhardt
2005-01-01
The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX\\/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of
Shoubridge, Eric
Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase identified a specific defect in the synthesis of the mitochondrial DNA (mtDNA)-encoded COX I subunit in a pedigree segregating late-onset Leigh syndrome and cytochrome c oxidase (COX) deficiency. We mapped
Cairns, Paul
The Use of Eyetracking for Measuring Immersion Anna L. Cox, Paul Cairns, Nadia Berthouze game being all that mattered. Furthermore, Cairns, Cox, Dhoparee, Jennett and Hong (under review) found there have been various attempts to measure immersion using questionnaires. For example, Cairns, Cox
Goodman, Wayne
Catalysis Letters Vol. 72, No. 3-4, 2001 197 Catalytic ammonia decomposition: COx-free hydrogen, e.g., COx, formed during reforming of hydrocarbons and alcohols) makes this process an ideal source; COx-free 1. Introduction The interaction of ammonia with metal surfaces has been thoroughly
Am. J. Hum. Genet. 72:101114, 2003 Mutations in COX15 Produce a Defect in the Mitochondrial Heme
Shoubridge, Eric
Am. J. Hum. Genet. 72:101114, 2003 101 Mutations in COX15 Produce a Defect in the Mitochondrial Deficiencies in the activity of cytochrome c oxidase (COX), the terminal enzyme in the respiratory chain for accessory proteins that play important roles in the assembly of the COX holoenzyme complex. Many patients
Cox, Ingemar J.
On Ranking the Effectiveness of Searches Vishwa Vinay, Ingemar J. Cox Natasa Milic-Frayling, Ken) the clustering tendency as measured by the Cox-Lewis statistic, (ii) the sensitivity to document perturbation perturbation and yields Kendall of 0.521. When combined with the clustering tendency based on the Cox
Minutes of the BREA Meeting: November 8, 2011 Members present: Carmen Benkovitz, Dave Cox, Ronnie 2011 meeting were accepted as amended There was no Treasurer's Report OLD BUSINESS Senior Net: D. Cox insurance. BREA, led by Dave Cox, has accumulated 4 documents from retirees where there were written
The influence of Cox-2 and bioactive lipids on hematological cancersa
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
An, Ying; Belevych, Natalya; Wang, Yufen; Zhang, Hao; Nasse, Jason S; Herschman, Harvey; Chen, Qun; Tarr, Andrew; Liu, Xiaoyu; Quan, Ning
2014-01-01
In a previous study, we found that intracerebral administration of excitotoxin (RS)-(tetrazole-5yl) glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox). In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2) in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection. PMID:24971026
COX inhibition abrogates aeroallergen-induced immune tolerance by suppressing PGI2 IP signaling
Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian; Dulek, Daniel E.; Toki, Shinji; Lotz, Matthew T.; Newcomb, Dawn C.; Boswell, Madison G.; Polosukhin, Vasiliy V.; Milne, Ginger L.; Wu, Pingsheng; Moore, Martin L.; FitzGerald, Garret A.; Peebles, R. Stokes
2014-01-01
Background The prevalence of allergic diseases doubled in developed countries in the last several decades. Cyclooxygenase (COX) inhibiting drugs augmented allergic diseases in mice by increasing allergic sensitization and memory immune responses. However, whether COX inhibition can promote allergic airway diseases by inhibiting immune tolerance is not known. Objective To determine the role of the COX pathway and PGI2 signaling through the PGI2 receptor (IP) in aeroallergen-induced immune tolerance. Methods Wild type (WT) BALB/c mice and IP KO mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA/alum. The COX inhibitor indomethacin or vehicle was administered in drinking water to inhibit enzyme activity during the sensitization phase. Two weeks after sensitization, the mice were challenged with OVA aerosols. Mouse bronchoalveolar lavage fluid was harvested for cell counts and Th2 cytokine measurements. Results WT mice treated with indomethacin had greater numbers of total cells, eosinophils, and lymphocytes, and increased IL-5 and IL-13 protein expression in BAL fluid compared to vehicle-treated mice. Similarly, IP KO mice had augmented inflammation and Th2 cytokine responses compared to WT mice. In contrast, the PGI2 analog cicaprost attenuated the anti-tolerance effect of COX inhibition. Conclusion COX inhibition abrogated immune tolerance by suppressing PGI2 IP signaling, suggesting that PGI2 signaling promotes immune tolerance and clinical use of COX inhibiting drugs may increase the risk of developing allergic diseases. PMID:25042746
Carvacrol, a component of thyme oil, activates PPAR? and ? and suppresses COX-2 expression[S
Hotta, Mariko; Nakata, Rieko; Katsukawa, Michiko; Hori, Kazuyuki; Takahashi, Saori; Inoue, Hiroyasu
2010-01-01
Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor superfamily and are involved in the control of COX-2 expression, and vice versa. Here, we show that COX-2 promoter activity was suppressed by essential oils derived from thyme, clove, rose, eucalyptus, fennel, and bergamot in cell-based transfection assays using bovine arterial endothelial cells. Moreover, from thyme oil, we identified carvacrol as a major component of the suppressor of COX-2 expression and an activator of PPAR? and ?. PPAR?-dependent suppression of COX-2 promoter activity was observed in response to carvacrol treatment. In human macrophage-like U937 cells, carvacrol suppressed lipopolysaccharide-induced COX-2 mRNA and protein expression, suggesting that carvacrol regulates COX-2 expression through its agonistic effect on PPAR?. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. PMID:19578162
Correlating carbon monoxide oxidation with cox genes in the abundant Marine Roseobacter Clade
Cunliffe, Michael
2011-01-01
The Marine Roseobacter Clade (MRC) is a numerically and biogeochemically significant component of the bacterioplankton. Annotation of multiple MRC genomes has revealed that an abundance of carbon monoxide dehydrogenase (CODH) cox genes are present, subsequently implying a role for the MRC in marine CO cycling. The cox genes fall into two distinct forms based on sequence analysis of the coxL gene; forms I and II. The two forms are unevenly distributed across the MRC genomes. Most (18/29) of the MRC genomes contain only the putative form II coxL gene. Only 10 of the 29 MRC genomes analysed have both the putative form II and the definitive form I coxL. None have only the form I coxL. Genes previously shown to be required for post-translational maturation of the form I CODH enzyme are absent from the MRC genomes containing only form II. Subsequent analyses of a subset of nine MRC strains revealed that only MRC strains with both coxL forms are able to oxidise CO. PMID:21068776
Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct Carcinoma.
Wang, Ping; He, Yu; Ma, Xiaodong; Sun, Beiwang; Huang, Binyuan; Zhu, Canhua; Liu, Yanmin
2015-01-01
BACKGROUND As an induced enzyme, COX-2 expression is elevated under stimuli from inflammatory mediator or growth factor product. Ki-67, a cell cycle-related proliferative antigen, reflects the tissue proliferative activity. This study analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide evidence for diagnosis and prognosis prediction of disease. MATERIAL AND METHODS A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47) patients were analyzed using immunohistochemical (IHC) staining method for the expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal bile duct tissues (N=30). The relationship between expression pattern of COX-2 and Ki-67 and pathological conditions was also analyzed, in addition to the correlation with positive expression in hepatolithiasis samples. RESULTS The positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and 80.9%, respectively, and was significantly higher than those in the hepatolithiasis group, which was also higher than the control group. Expression of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis, and differentiation stage. They were also correlated with the mortality rate of patients. CONCLUSIONS Both COX-2 and Ki-67 are abundantly expressed in hepatolithiasis and bile duct carcinoma tissues and may play an important role in the disease occurrence, progression, and metastasis. PMID:26423666
Cai, J; Prentice, R L
1997-01-01
Recent 'marginal' methods for the regression analysis of multivariate failure time data have mostly assumed Cox (1972) model hazard functions in which the members of the cluster have distinct baseline hazard functions. In some important applications, including sibling family studies in genetic epidemiology and group randomized intervention trials, a common baseline hazard assumption is more natural. Here we consider a weighted partial likelihood score equation for the estimation of regression parameters under a common baseline hazard model, and provide corresponding asymptotic distribution theory. An extensive series of simulation studies is used to examine the adequacy of the asymptotic distributional approximations, and especially the efficiency gain due to weighting, as a function of strength of dependency within cluster, and cluster size. PMID:9384652
Huang, Jianhua Z; Liu, Linxu
2006-09-01
The Cox proportional hazards model usually assumes an exponential form for the dependence of the hazard function on covariate variables. However, in practice this assumption may be violated and other relative risk forms may be more appropriate. In this article, we consider the proportional hazards model with an unknown relative risk form. Issues in model interpretation are addressed. We propose a method to estimate the relative risk form and the regression parameters simultaneously by first approximating the logarithm of the relative risk form by a spline, and then employing the maximum partial likelihood estimation. An iterative alternating optimization procedure is developed for efficient implementation. Statistical inference of the regression coefficients and of the relative risk form based on parametric asymptotic theory is discussed. The proposed methods are illustrated using simulation and an application to the Veteran's Administration lung cancer data. PMID:16984322
Deacon, Karl; Knox, Alan J
2015-08-01
Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors. Conditioned medium from BK treated HASMC induced CXCL8, VEGF, and COX-2 mRNA and protein accumulation in airway epithelial cells, which were blocked by anti-amphiregulin antibodies and amphiregulin siRNA, suggesting a paracrine effect of HASMC-derived amphiregulin on airway epithelial cells. Consistent with this, recombinant amphiregulin induced CXCL8, VEGF, and COX-2 in airway epithelial cells. Finally, we found that conditioned media from amphiregulin-stimulated airway epithelial cells induced amphiregulin expression in HASMC and that this was dependent on airway epithelial cell COX-2 activity. Our study provides evidence of a dynamic axis of interaction between HASMC and epithelial cells that amplifies CXCL8, VEGF, COX-2, and amphiregulin production. PMID:26047642
Knox, Alan J.
2015-01-01
Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors. Conditioned medium from BK treated HASMC induced CXCL8, VEGF, and COX-2 mRNA and protein accumulation in airway epithelial cells, which were blocked by anti-amphiregulin antibodies and amphiregulin siRNA, suggesting a paracrine effect of HASMC-derived amphiregulin on airway epithelial cells. Consistent with this, recombinant amphiregulin induced CXCL8, VEGF, and COX-2 in airway epithelial cells. Finally, we found that conditioned media from amphiregulin-stimulated airway epithelial cells induced amphiregulin expression in HASMC and that this was dependent on airway epithelial cell COX-2 activity. Our study provides evidence of a dynamic axis of interaction between HASMC and epithelial cells that amplifies CXCL8, VEGF, COX-2, and amphiregulin production. PMID:26047642
Model Selection for Cox Models with Time-Varying Coefficients
Yan, Jun; Huang, Jian
2011-01-01
Summary Cox models with time-varying coefficients offer great flexibility in capturing the temporal dynamics of covariate effects on right censored failure times. Since not all covariate coefficients are time-varying, model selection for such models presents an additional challenge, which is to distinguish covariates with time-varying coefficient from those with time-independent coefficient. We propose an adaptive group lasso method that not only selects important variables but also selects between time-independent and time-varying specifications of their presence in the model. Each covariate effect is partitioned into a time-independent part and a time-varying part, the latter of which is characterized by a group of coefficients of basis splines without intercept. Model selection and estimation are carried out through a fast, iterative group shooting algorithm. Our approach is shown to have good properties in a simulation study that mimics realistic situations with up to 20 variables. A real example illustrates the utility of the method. PMID:22506825
Quantile calculus and censored regression
Huang, Yijian
2010-01-01
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 computat...
Precision and Recall for Regression
NASA Astrophysics Data System (ADS)
Torgo, Luis; Ribeiro, Rita
Cost sensitive prediction is a key task in many real world applications. Most existing research in this area deals with classification problems. This paper addresses a related regression problem: the prediction of rare extreme values of a continuous variable. These values are often regarded as outliers and removed from posterior analysis. However, for many applications (e.g. in finance, meteorology, biology, etc.) these are the key values that we want to accurately predict. Any learning method obtains models by optimizing some preference criteria. In this paper we propose new evaluation criteria that are more adequate for these applications. We describe a generalization for regression of the concepts of precision and recall often used in classification. Using these new evaluation metrics we are able to focus the evaluation of predictive models on the cases that really matter for these applications. Our experiments indicate the advantages of the use of these new measures when comparing predictive models in the context of our target applications.
Nonparametric Mixture of Regression Models
Huang, Mian; Li, Runze; Wang, Shaoli
2013-01-01
Motivated by an analysis of US house price index data, we propose nonparametric finite mixture of regression models. We study the identifiability issue of the proposed models, and develop an estimation procedure by employing kernel regression. We further systematically study the sampling properties of the proposed estimators, and establish their asymptotic normality. A modified EM algorithm is proposed to carry out the estimation procedure. We show that our algorithm preserves the ascent property of the EM algorithm in an asymptotic sense. Monte Carlo simulations are conducted to examine the finite sample performance of the proposed estimation procedure. An empirical analysis of the US house price index data is illustrated for the proposed methodology. PMID:24363475
Binary data regression: Weibull distribution
NASA Astrophysics Data System (ADS)
Caron, Renault; Polpo, Adriano
2009-12-01
The problem of estimation in binary response data has receivied a great number of alternative statistical solutions. Generalized linear models allow for a wide range of statistical models for regression data. The most used model is the logistic regression, see Hosmer et al. [6]. However, as Chen et al. [5] mentions, when the probability of a given binary response approaches 0 at a different rate than it approaches 1, symmetric linkages are inappropriate. A class of models based on Weibull distribution indexed by three parameters is introduced here. Maximum likelihood methods are employed to estimate the parameters. The objective of the present paper is to show a solution for the estimation problem under the Weibull model. An example showing the quality of the model is illustrated by comparing it with the alternative probit and logit models.
Albumin-induced podocyte injury and protection are associated with regulation of COX-2.
Agrawal, Shipra; Guess, Adam J.; Chanley, Melinda A.; Smoyer, and William E.
2014-01-01
Albuminuria is both a hallmark and a risk factor for progressive glomerular disease, and results in increased exposure of podocytes to serum albumin with its associated factors. Here in vivo and in vitro models of serum albumin overload were used to test the hypothesis that albumin-induced proteinuria and podocyte injury directly correlate with COX-2 induction. Albumin induced COX-2, MCP-1, CXCL1 and the stress protein HSP25 in both rat glomeruli and cultured podocytes, while B7-1 and HSP70i were also induced in podocytes. Podocyte exposure to albumin induced both mRNA and protein and enhanced the mRNA stability of COX-2, a key regulator of renal hemodynamics and inflammation, which renders podocytes susceptible to injury. Podocyte exposure to albumin also stimulated several kinases (p38 MAPK, MK2, JNK/SAPK and ERK1/2), inhibitors of which (except JNK/SAPK) down-regulated albumin-induced COX-2. Inhibition of AMPK, PKC and NF?B also down-regulated albumin-induced COX-2. Critically, albumin-induced COX-2 was also inhibited by glucocorticoids and thiazolidinediones, both of which directly protect podocytes against injury. Furthermore, specific albumin-associated fatty acids were identified as important contributors to COX-2 induction, podocyte injury and proteinuria. Thus, COX-2 is associated with podocyte injury during albuminuria, as well as with the known podocyte protection imparted by glucocorticoids and thiazolidinediones. Moreover, COX-2 induction, podocyte damage and albuminuria appear mediated largely by serum albumin-associated fatty acids. PMID:24918154
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.
Adaptive local linear quantile regression
Yu-nan Su; Mao-zai Tian
2011-01-01
In this paper we propose a new method of local linear adaptive smoothing for nonparametric conditional quantile regression.\\u000a Some theoretical properties of the procedure are investigated. Then we demonstrate the performance of the method on a simulated\\u000a example and compare it with other methods. The simulation results demonstrate a reasonable performance of our method proposed\\u000a especially in situations when the
Immune restoration in head and neck cancer patients after in vivo COX2 inhibition
Stephan Lang; Sanjay Tiwari; Michaela Andratschke; Iren Loehr; Lina Lauffer; Christoph Bergmann; Brigitte Mack; Annette Lebeau; Andreas Moosmann; Theresa L. Whiteside; Reinhard Zeidler
2007-01-01
Purpose To determine the immunomodulatory effects of in vivo COX-2 inhibition on leukocyte infiltration and function in patients with\\u000a head and neck cancer.\\u000a \\u000a \\u000a \\u000a Experimental design Patients with squamous cell carcinoma of the head and neck preoperatively received a specific COX-2 inhibitor (rofecoxib,\\u000a 25 mg daily) orally for 3 weeks. Serum and tumor specimens were collected at the start of COX-2 inhibition (day 0) and
Mixtures of proportional hazards regression models.
Rosen, O; Tanner, M
1999-05-15
This paper presents a mixture model which combines features of the usual Cox proportional hazards model with those of a class of models, known as mixtures-of-experts. The resulting model is more flexible than the usual Cox model in the sense that the log hazard ratio is allowed to vary non-linearly as a function of the covariates. Thus it provides a flexible approach to both modelling survival data and model checking. The method is illustrated with simulated data, as well as with multiple myeloma data. PMID:10378260
Hahm, Ki-Baik; Lim, Ho-Yeong; Sohn, Seongbyang; Kwon, Hyuk-Jae; Lee, K-Myung; Lee, Jeong-Sang; Surh, Young-Joon; Kim, Young-Bae; Joo, Hee-Jae; Kim, Won-Seok; Cho, Seung-Won
2002-01-01
Although gastric adenocarcinoma is one of the most common malignancies in the world, little is known about its exact molecular processes in development and progression. Recent studies suggest that COX-2 is important in carcinogenesis of gastrointestinal cancers, and is especially involved in carcinogenesis in a mouse model of familial adenomatosis polyposis. To understand the role of COX-2 in gastric carcinogenesis and Helicobacter pylori-associated gastritis, we measured COX-2 expression in 170 human gastric carcinoma tissues byimmunohistochemical analysis and compared the expression of COX-2 in paired tissues obtained from normal-looking and cancer-bearing mucosa. Further evidence of the involvement of COX-2 in gastritis and gastric carcinogenesis was obtained by establishing stable cell lines overexpressing COX-2. After subcloning of COX-2 into pCB7 mammalian expression vector, two stable cell lines named MKN-28-COX-2 and MKN-45-COX-2 were generated by transfection of COX-2 cDNA. To understand the effect of COX-2 on gastritis, we performed an electrophoretic mobility shift assay of NF-kappaB (inflammation-associated transcription factor), and measured malondialdehyde levels and chemiluminescence activities in both mock-transfected MKN and MKN-COX-2 cells after stimulation of H. pylori (1 x 10(6) CFU/mL) and neutrophils (10(2) cells/mL). A marked attenuation of NF-kappaB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-beta treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-beta through decreasing TGF-beta RII expression and increased cell invasiveness. In conclusion, COX-2 expression seems to be induced to attenuate the degree of atrophic gastritis, the initial event in gastric carcinogenesis, and promote gastric carcinogenesis. PMID:12086403
Infinite mixture-of-experts model for sparse survival regression with application to breast cancer
2010-01-01
Background We present an infinite mixture-of-experts model to find an unknown number of sub-groups within a given patient cohort based on survival analysis. The effect of patient features on survival is modeled using the Cox’s proportionality hazards model which yields a non-standard regression component. The model is able to find key explanatory factors (chosen from main effects and higher-order interactions) for each sub-group by enforcing sparsity on the regression coefficients via the Bayesian Group-Lasso. Results Simulated examples justify the need of such an elaborate framework for identifying sub-groups along with their key characteristics versus other simpler models. When applied to a breast-cancer dataset consisting of survival times and protein expression levels of patients, it results in identifying two distinct sub-groups with different survival patterns (low-risk and high-risk) along with the respective sets of compound markers. Conclusions The unified framework presented here, combining elements of cluster and feature detection for survival analysis, is clearly a powerful tool for analyzing survival patterns within a patient group. The model also demonstrates the feasibility of analyzing complex interactions which can contribute to definition of novel prognostic compound markers. PMID:21034433
Giap, Andrew Q; Tarnawski, Andrzej; Hoa, Neil T; Akotia, Vimesh; Ma, Thomas Y
2002-05-10
Clinical studies indicate that specific cyclooxygenase-2 (Cox-2) inhibitors are less ulcerogenic than their non-selective predecessors (e.g. indomethacin). However, Cox-2 inhibitors may also interfere with ulcer healing. Re-epithelialization is a crucial factor in both gastrointestinal mucosal injury and ulcer healing. This study was aimed to compare the effects of selective Cox-2 inhibitor (NS398) versus non-selective Cox inhibitor (indomethacin) on basal and basic fibroblast growth factor (bFGF) - stimulated gastric wound re-epithelialization. In-vitro epithelial wounds were created in confluent monolayers of RGM1 rat gastric epithelial cells by a razor blade scrape. Following wounding there was a significant re-epithelialization by 24 hrs. Indomethacin (0.25 mM and 0.5 mM) significantly inhibited basal wound re-epithelialization in a dose dependent manner. In contrast, selective Cox-2 inhibitor NS398 did not inhibit the basal re-epithelialization process. Basic FGF treatment produced significant enhancement of wound re-epitheliazation at the various concentrations [10, 20, 30, 40, 50 and 70 ng/ml] studied. Both indomethacin and NS398 inhibited bFGF stimulated wound re-epithelialization, with indomethacin having a greater inhibitory effect. The extent of NS398 inhibition was limited to the bFGF-stimulated component, whereas indomethacin inhibition extended to both the bFGF-stimulated and the basal re-epithelialization components. These findings indicate that specific Cox-2 inhibitor (NS398) does not interfere with the basal re-epithelialization but significantly inhibits the bFGF - stimulated re-epithelialization, whereas indomethacin interferes with both the basal as well as the bFGF-stimulated wound re-epithelialization. PMID:12138016
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...
Dadiboyena, Sureshbabu; Nefzi, Adel
2011-01-01
Non-steroidal anti-inflammatory drugs are widely used therapeutic agents in the treatment of inflammation, pain and fever. Cyclooxygenase catalyzes the initial step of biotransformation of arachidonic acid to prostanoids, and exist as three distinct isozymes; COX-I, COX-II and COX-III. Selective COX-II inhibitors are a class of potential anti-inflammatory, analgesic, and antipyretic drugs with reduced gastrointestinal (GI) side effects compared to nonselective inhibitors. 3,4-diarylisoxazole scaffold is recurrently found in a wide variety of NSAIDs, protein kinase inhibitors, hypertensive agents, and estrogen receptor (ER) modulators. In the present review, we document on the recent synthetic strategies of 3,4-diarylisoxazolyl scaffolds of valdecoxib and its relevant structural analogues. PMID:20724040
Celebration of the contributions of Art Cox to stellar pulsation interpretations
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.
Students Speak With Gary Cox, EPIC Project Manager - Duration: 19 minutes.
From NASAâ??s International Space Station Mission Control Center Gary Cox EPIC Project Manager, participates in a Digital Learning Network (DLN) event with students at South Effingham Middle School...
Ban-Ishihara, Reiko; Tomohiro-Takamiya, Shiho; Tani, Motohiro; Baudier, Jacques; Ishihara, Naotada; Kuge, Osamu
2015-10-01
Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology. PMID:26358295
Expression of COX-2 and HER-2 in colorectal cancer and their correlation
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. PMID:26034355
Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor.
Hasegawa, Kiyoshi; Ishikawa, Kunimi; Kawai, Satoshi; Torii, Yutaka; Kawamura, Kyoko; Kato, Rina; Tsukada, Kazuhiko; Udagawa, Yasuhiro
2013-12-01
Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel treatment. Co-administration of paclitaxel and etodolac in both cell lines resulted in decreased rhodamine 123 efflux. The actual concentration of intracellular paclitaxel in OMC-2P cells was significantly lower than that in OMC-2 cells treated with paclitaxel alone and was significantly increased after co-administration of paclitaxel and etodolac. These findings suggest that paclitaxel resistance may be associated with COX-2 and MDR1 expression in cancer cells. Co-administration of COX-2 inhibitors and paclitaxel may have a key role in modulating or overcoming paclitaxel resistance in endometrial cancers. PMID:24100466
Multiple imputation in quantile regression
Wei, Ying; Ma, Yanyuan; Carroll, Raymond J.
2014-01-01
Summary We propose a multiple imputation estimator for parameter estimation in a quantile regression model when some covariates are missing at random. The estimation procedure fully utilizes the entire dataset to achieve increased efficiency, and the resulting coefficient estimators are root-n consistent and asymptotically normal. To protect against possible model misspecification, we further propose a shrinkage estimator, which automatically adjusts for possible bias. The finite sample performance of our estimator is investigated in a simulation study. Finally, we apply our methodology to part of the Eating at American’s Table Study data, investigating the association between two measures of dietary intake. PMID:24944347
Multiple imputation in quantile regression.
Wei, Ying; Ma, Yanyuan; Carroll, Raymond J
2012-01-01
We propose a multiple imputation estimator for parameter estimation in a quantile regression model when some covariates are missing at random. The estimation procedure fully utilizes the entire dataset to achieve increased efficiency, and the resulting coefficient estimators are root-n consistent and asymptotically normal. To protect against possible model misspecification, we further propose a shrinkage estimator, which automatically adjusts for possible bias. The finite sample performance of our estimator is investigated in a simulation study. Finally, we apply our methodology to part of the Eating at American's Table Study data, investigating the association between two measures of dietary intake. PMID:24944347
Nonlinear regression Gordon K. Smyth
Smyth, Gordon K.
Nonlinear regression Gordon K. Smyth Volume 3, pp 14051411 in Encyclopedia of Environmetrics (ISBN-order exponential function models, of the form f x, q D Â1 C k jD1 Â2j exp Â2jC1x 6 where k is the order common form of model is the rational function: f x, q D k jD1 Âjxj 1 1 C m jD1 ÂkCjxj 7 Rational
Regression analysis of cytopathological data
Whittemore, A.S.; McLarty, J.W.; Fortson, N.; Anderson, K.
1982-12-01
Epithelial cells from the human body are frequently labelled according to one of several ordered levels of abnormality, ranging from normal to malignant. The label of the most abnormal cell in a specimen determines the score for the specimen. This paper presents a model for the regression of specimen scores against continuous and discrete variables, as in host exposure to carcinogens. Application to data and tests for adequacy of model fit are illustrated using sputum specimens obtained from a cohort of former asbestos workers.
Regression analysis with missing data
Michelli, Frank Anthony
1968-01-01
REGRESSIOM ANALYSIS WITH NISSIBG IIATA A Thesis FRANK ARTHORY NICHELLI Su'bmitted to the Graduate College of the Texas AAN University in partial fulfillment of the requirements for the degree of NASTER OF SCIENCE January 1968 Najor Subject...: Statistios REGRESSION ANALYSIS WITH MISS1NG DATA A Thesis FRANK ANTHONY MICHELLI Approved as to style and content by: hairman of o ttee Member Head of Department Member Member Zanuary 196B ACZNOWLED ONE NT S I can only begin to express my sincere...
Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.
Rose, Tyler M; Reilly, Christopher A; Deering-Rice, Cassandra E; Brewster, Clinton; Brewster, Chelsea
2014-12-15
Serotonin was linked by amidation to the carboxylic acid groups of a series of structurally diverse NSAIDs. The resulting NSAID-serotonin conjugates were tested in vitro for their ability to inhibit FAAH, TRPV1, and COX2. Ibuprofen-5-HT and Flurbiprofen-5-HT inhibited all three targets with approximately the same potency as N-arachidonoyl serotonin (AA-5-HT), while Fenoprofen-5-HT and Naproxen-5-HT showed activity as dual inhibitors of TRPV1 and COX2. PMID:25467164
Regulated Expression of PTPRJ by COX-2/PGE2 Axis in Endothelial Cells
Jin, Xinxin; Wang, Bin; Yan, Hongbo; Chen, Xi; Lai, Xiaowei; Zhang, Li; Zhang, Xiaohua; Li, Zhaoshen
2014-01-01
Background This study was designed to examine a novel role of COX-2/PGE2 signaling as a regulator of PTPRJ expression in endothelial cells. Methods A bioinformatics analysis of a whole genome array was carried out to search for regulators of PTPRJ expression in endothelial cells. PTPRJ expression was also measured in endothelial cells derived from a balloon injury-induced neointimal hyperplasia model in male New Zealand Rabbits. Changes in PTPRJ expression in HUVEC cells was examined by RT-PCR and western blotting after transfection of COX-2 plasmids or treatment with varying concentrations of a COX-2 inhibitor. Results A significant correlation was identified between COX-2 and PTPRJ in GSE39264 (Pearson correlation coefficient ?=??0.87; n?=?22; P<0.01, two-tailed). PTPRJ expression was reduced during the progression of neointimal hyperplasia after balloon injury, which correlated with an increase in COX-2 expression. In HUVECs, after transfection with 1 µg/ml, 0.5 µg/ml, or 0.25 µg/ml COX-2 plasmids, PTPRJ protein expression was reduced to 0.60- (±0.08), 0.75- (±0.09), and 0.88- (±0.04) fold, respectively, while mRNA expression was reduced to 0.15- (±0.03), 0.26- (±0.05), and 0.47- (±0.09) fold, respectively. After treatment of HUVECs with 10 µmol/L or 20 µmol/L celecoxib, the reduction in PTPRJ expression induced by COX-2 over-expression was not only rescued but in fact increased by 2.05-fold (±0.28) and 3.34-fold (±0.37), respectively, compared with control. Conclusions Our results suggest that COX-2/PGE2 signaling may function as a negative regulator of PTPRJ expression in endothelial cells both in vivo and vitro. PMID:25532119
Selective cyclooxygenase-2 (COX2) inhibitors and potential risk of cardiovascular events
Debabrata Mukherjee
2002-01-01
Selective cyclooxygenase-2 (COX-2) inhibitors were developed as a response to the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents (NSAIDs). However, COX-2 inhibitors decrease vascular prostacyclin (PGI2) production and may disrupt the homeostatic mechanisms that limit the effects of platelet activation. Basic and clinical data raise concerns about a potential prothrombotic effect of this class of drugs. The widespread popularity of
Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX2) inhibitors
Randall E Harris; Joanne Beebe-Donk; Galal A Alshafie
2006-01-01
BACKGROUND: Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were
Roles of COX inhibition in pathogenesis of NSAID-induced small intestinal damage
Koji Takeuchi; Akiko Tanaka; Shinichi Kato; Kikuko Amagase; Hiroshi Satoh
2010-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE2 content by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS
Harald Lenz; Johan Raeder; Tomas Draegni; Fridtjof Heyerdahl; Martin Schmelz; Audun Stubhaug
2011-01-01
Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen
Thorsten Jürgen Maier; Karin Schilling; Ronald Schmidt; Gerd Geisslinger; Sabine Grösch
2004-01-01
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anticarcinogenic effects of celecoxib is still not fully understood. To investigate the extent to which the anticarcinogenic effect of celecoxib depends on COX-2 expression,
Martin Aldasoro; Maria D. Mauricio; Eva Serna; Belen Cortina; Pascual Medina; Gloria Segarra; Susana Novella; José M. Vila
2007-01-01
Background: The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine.Methods: Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied
Giuseppe Perrone; Daniele Santini; Mariagiovanna Zagami; Bruno Vincenzi; Alfio Verzì; Sergio Morini; Domenico Borzomati; Roberto Coppola; Armando Antinori; Paolo Magistrelli; Giuseppe Tonini; Carla Rabitti
2006-01-01
Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced\\u000a incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable\\u000a to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas\\u000a and its possible correlation with clinicopathological parameters.
Nonparametric Model Selection in Hazard Regression
Chenlei Leng; Hao Zhang
Abstract We propose a novel model selection method for a nonparametric extension of the Cox proportional hazard model, in the framework of smoothing splines ANOVA models. The method automates the model building and model selection process simultaneously by imposing a penalty on the norms instead of squared norms. It is a natural extension of the LASSO to the situation where
Model selection in nonparametric hazard regression
Chenlei Leng; Hao Helen Zhang
2006-01-01
We propose a novel model selection method for a nonparametric extension of the Cox proportional hazard model, in the framework of smoothing splines ANOVA models. The method automates the model building and model selection processes simultaneously by penalizing the reproducing kernel Hilbert space norms. On the basis of a reformulation of the penalized partial likelihood, we propose an efficient algorithm
Semiparametric regression during 2003–2007*
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
?9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling
Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu
2013-01-01
SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to ?9-tetrahydrocannabinol (?9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by ?9-THC is mediated via CB1 receptor-coupled G-protein ?? subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated ?9-THC exposures. Ablation of COX-2 also eliminates ?9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing ?-amyloid plaques and neurodegeneration by ?9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894
Fiumera, Heather L.; Broadley, Sarah A.; Fox, Thomas D.
2007-01-01
The N-terminal and C-terminal domains of mitochondrially synthesized cytochrome c oxidase subunit II, Cox2, are translocated through the inner membrane to the intermembrane space (IMS). We investigated the distinct mechanisms of N-tail and C-tail export by analysis of epitope-tagged Cox2 variants encoded in Saccharomyces cerevisiae mitochondrial DNA. Both the N and C termini of a truncated protein lacking the Cox2 C-terminal domain were translocated to the IMS via a pathway dependent upon the conserved translocase Oxa1. The topology of this Cox2 variant, accumulated at steady state, was largely but not completely unaffected in mutants lacking proteins required for export of the C-tail domain, Cox18 and Mss2. C-tail export was blocked by truncation of the last 40 residues from the C-tail domain, indicating that sequence and/or structural features of this domain are required for its translocation. Mss2, a peripheral protein bound to the inner surface of the inner membrane, coimmunoprecipitated with full-length newly synthesized Cox2, whose leader peptide had already been cleaved in the IMS. Our data suggest that the C-tail domain is recognized posttranslationally by a specialized translocation apparatus after the N-tail has been translocated by Oxa1. PMID:17452441
Fiumera, Heather L; Broadley, Sarah A; Fox, Thomas D
2007-07-01
The N-terminal and C-terminal domains of mitochondrially synthesized cytochrome c oxidase subunit II, Cox2, are translocated through the inner membrane to the intermembrane space (IMS). We investigated the distinct mechanisms of N-tail and C-tail export by analysis of epitope-tagged Cox2 variants encoded in Saccharomyces cerevisiae mitochondrial DNA. Both the N and C termini of a truncated protein lacking the Cox2 C-terminal domain were translocated to the IMS via a pathway dependent upon the conserved translocase Oxa1. The topology of this Cox2 variant, accumulated at steady state, was largely but not completely unaffected in mutants lacking proteins required for export of the C-tail domain, Cox18 and Mss2. C-tail export was blocked by truncation of the last 40 residues from the C-tail domain, indicating that sequence and/or structural features of this domain are required for its translocation. Mss2, a peripheral protein bound to the inner surface of the inner membrane, coimmunoprecipitated with full-length newly synthesized Cox2, whose leader peptide had already been cleaved in the IMS. Our data suggest that the C-tail domain is recognized posttranslationally by a specialized translocation apparatus after the N-tail has been translocated by Oxa1. PMID:17452441
Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells.
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
Bayesian Unimodal Density Regression for Causal Inference
ERIC Educational Resources Information Center
Karabatsos, George; Walker, Stephen G.
2011-01-01
Karabatsos and Walker (2011) introduced a new Bayesian nonparametric (BNP) regression model. Through analyses of real and simulated data, they showed that the BNP regression model outperforms other parametric and nonparametric regression models of common use, in terms of predictive accuracy of the outcome (dependent) variable. The other,…
Statistics II Lesson 4. Simple linear regression
Gil, Ana Arribas
Statistics II Lesson 4. Simple linear regression Academic Year 2010/11 #12;Lesson 4. Simple linear #12;Lesson 4. Simple linear regression Learning objectives Know how to construct a simple linear future values for the dependent (response) variable Y #12;Lesson 4. Simple linear regression Recommended
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…
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.
Muñoz-Mas, Rafael; Martínez-Capel, Francisco; Schneider, Matthias; Mouton, Ans M
2012-12-01
The implementation of the Water Framework Directive implies the determination of an environmental flow (E-flow) in each running water body. In Spain, many of the minimum flow assessments were determined with the physical habitat simulation system based on univariate habitat suitability curves. Multivariate habitat suitability models, widely applied in habitat assessment, are potentially more accurate than univariate suitability models. This article analyses the microhabitat selection by medium-sized (10-20 cm) brown trout (Salmo trutta fario) in three streams of the Jucar River Basin District (eastern Iberian Peninsula). The data were collected with an equal effort sampling approach. Univariate habitat suitability curves were built with a data-driven process for depth, mean velocity and substrate classes; three types of data-driven fuzzy models were generated with the FISH software: two models of presence-absence and a model of abundance. FISH applies a hill-climbing algorithm to optimize the fuzzy rules. A hydraulic model was calibrated with the tool River-2D in a segment of the Cabriel River (Jucar River Basin). The fuzzy-logic models and three methods to produce a suitability index from the three univariate curves were applied to evaluate the river habitat in the tool CASiMiR©. The comparison of results was based on the spatial arrangement of habitat suitability and the curves of weighted usable area versus discharge. The differences were relevant in different aspects, e.g. in the estimated minimum environmental flow according to the Spanish legal norm for hydrological planning. This work demonstrates the impact of the model's selection on the habitat suitability modelling and the assessment of environmental flows, based on an objective data-driven procedure; the conclusions are important for the water management in the Jucar River Basin and other river systems in Europe, where the environmental flows are a keystone for the achievement of the goals established in the European Water Framework Directive. PMID:22909786
Stevens, David
Computational Stability of Bryan-Semtner-Cox type models (Draft) David P. Stevens, School a multitude of stability critera for Bryan-Semtner-Cox [Bryan (1969), Semtner (1974), Cox (1984)] type ocean t periodically. Cox (1984) makes provision for using an Euler backward timestep, which is an improvement
Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand
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.
John Zhang; Mahmud Ibrahim
2005-01-01
This study compares the SPSS ordinary least squares (OLS) regression and ridge regression procedures in dealing with multicollinearity data. The LS regression method is one of the most frequently applied statistical procedures in application. It is well documented that the LS method is extremely unreliable in parameter estimation while the independent variables are dependent (multicollinearity problem). The Ridge Regression procedure
Practical Session: Multiple Linear Regression
NASA Astrophysics Data System (ADS)
Clausel, M.; Grégoire, G.
2014-01-01
Three exercises are proposed to illustrate the simple linear regression. In the first one investigates the influence of several factors on atmospheric pollution. It has been proposed by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr33.pdf) and is based on data coming from 20 cities of U.S. Exercise 2 is an introduction to model selection whereas Exercise 3 provides a first example of analysis of variance. Exercises 2 and 3 have been proposed by A. Dalalyan at ENPC (see Exercises 2 and 3 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_5.pdf).
Optimal designs for indirect regression
NASA Astrophysics Data System (ADS)
Biedermann, Stefanie; Bissantz, Nicolai; Dette, Holger; Jones, Edmund
2011-10-01
In many real life applications, it is impossible to observe the feature of interest directly. For example, non-invasive medical imaging techniques rely on indirect observations to reconstruct an image of the patient's internal organs. In this paper, we investigate optimal designs for such indirect regression problems. We use the optimal designs as benchmarks to investigate the efficiency of designs commonly used in applications. Several examples are discussed for illustration. Our designs provide guidelines to scientists regarding the experimental conditions at which the indirect observations should be taken in order to obtain an accurate estimate for the object of interest. Moreover, we demonstrate that in many cases the commonly used uniform design is close to optimal.
Tao, Li; Wang, Sheng; Zhao, Yang; Sheng, Xiaobo; Wang, Aiyun; Zheng, Shizhong; Lu, Yin
2014-09-25
Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [d-(+)-?-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. PMID:24916702
Kim, Sang-Eun; Mori, Ryoichi; Komatsu, Toshimitsu; Chiba, Takuya; Hayashi, Hiroko; Park, Seongjoon; Sugawa, Michiru D; Dencher, Norbert A; Shimokawa, Isao
2015-06-01
Calorie restriction (CR), a non-genetic intervention that promotes longevity in animals, may exert anti-aging effects by modulating mitochondrial function. Based on our prior mitochondrial proteome analysis, we focused on the potential roles of cytochrome c oxidase (Cox or Complex IV) subunit 6b1 on formation of mitochondrial supercomplexes comprised of Complex I, III, and IV. Blue native polyacrylamide gel electrophoresis followed by immunoblotting showed that the amount of Cox6b1 and the proportion of high molecular weight supercomplexes (SCs) comprised of Complexes I, III, and IV were increased in the liver of mice subjected to 30 % CR, compared with the liver of mice fed ad libitum. In in vitro experiments, in Cox6b1-overexpressing NIH3T3 (Cox6b1-3T3) cells, Cox6b1 was increased in the SC, III2IV1, and III2IV2 complexes and Cox was concomitantly recruited abundantly into the SC, compared with control (Con)-3T3 cells. The proportions of III2IV1, and III2IV2, relative to IV monomer were also increased in Cox6b1-3T3 cells. Cox6b1-3T3 cells showed increased oxygen consumption rates, Cox activity, and intracellular ATP concentrations, indicating enhanced mitochondrial respiration, compared with Con-3T3 cells. Despite the increased basal level of mitochondrial reactive oxygen species (ROS), cell viability after inducing oxidative stress was greater in Cox6b1-3T3 cells than in Con-3T3 cells, probably because of prompt activation of protective mechanisms, such as nuclear translocation of nuclear factor E2-related factor-2. These in vivo and in vitro studies show that Cox6b1 is involved in regulation of mitochondrial function by promoting the formation of SC, suggesting that Cox6b1 contributes to the anti-aging effects of CR. PMID:25929654
NASA Astrophysics Data System (ADS)
Tawakkol, Shereen M.; Farouk, M.; Elaziz, Omar Abd; Hemdan, A.; Shehata, Mostafa A.
2014-12-01
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.
Kumagai, Kousuke; Kubo, Mitsuhiko; Imai, Shinji; Toyoda, Futoshi; Maeda, Tsutomu; Okumura, Noriaki; Matsuura, Hiroshi; Matsusue, Yoshitaka
2013-01-01
Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNF?-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNF? resulted in an obvious increase in membrane Cl- conductance. The TNF?-evoked Cl- current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNF? as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNF?. Thus, the COX-2-selective blocker had an inhibitory effect on TNF?-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. PMID:24084720
The Characterization And Role of Zinc Binding in Yeast Cox4
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.
Virtual screening of compounds from the patchouli oil of Pogostemon herba for COX-1 inhibition
Raharjo, Sentot Joko; Fatchiyah, Fatchiyah
2013-01-01
Our interest is to identify compounds from the patchouli oil of Pogostemon herba to inhibit the cyclooxygenase-1 (COX-1) enzyme activity. The data for the major compounds (alpha-patchouli alcohol isomer (CD521903, CD442384, and/or CD6432585), alphabulnusene, seychellene and alpha-guaiene) of patchouli oil were explored from the PubChem database. The compounds to COX-1 interactions were studied using the molecular docking tools Hex 6.12 and LeadIT2 Bisolve. The interactions were further visualized using the Chimera 1.7s viewer software tool. The analysis of the major compounds of patchouli oil showed that alpha-Patchouli alcohol (CD521903) binds to COX-1 at many active sites including: Leu223B, Asp228B, Leu237B, Arg332B, Trp138A, Glu139A, Ser142A, and Asn143A. Further analysis revealed that these binding sites are maintained by hydrogen bonds with Ser142A, Glu139A, and Asp228B. The interaction energy between COX-1 and alpha-patchouli alcohol (CD521903) is -6 kJ/mol (without solvent) and -15 kJ/ mol (with solvent DMSO). These theoretical data suggests alpha-patchouli alcohol as a potential inhibitor of the COX-1 enzyme. However, these observations should be investigated and confirmed using experimental evidence. PMID:23559751
In -silico molecular docking analysis of prodigiosin and cycloprodigiosin as COX-2 inhibitors.
Krishna, Pabba Shiva; Vani, Kompally; Prasad, Metuku Ram; Samatha, Burra; Bindu, Nidadavolu Shesha Venkata Sathya Siva Surya Laxmi Hima; Charya, Maringanti Alaha Singara; Reddy Shetty, Prakasham
2013-12-01
Prodigiosin and cycloprodigiosin are tripyrrole red pigmented compounds with medical importance for their anticancer property. In the present investigation, molecular docking studies were performed for both prodigiosin and cycloprodigiosins to evaluate the in- silico anti-inflammatory activity against Cycloxigenase-2 (COX-2) protein as model compound and the data compared with rofecoxib and celcoxid. Cycloprodigiosin showed higher initial potential, initial RMS gradient and potential energy values compared to prodigiosin. Analysis of COX-2 protein and ligand binding revealed that cyclprodigiosin interacted with COX-2 protein amino acid residues of Tyr(324), Phe(487) and Arg(89) while prodigiosin interaction was observed with two amino acids i.e. Leu(321) and Tyr(324). The computational ligand binding interaction suggested > 45% higher fitness score value for prodigiosin to that of cycloprodigiosin with COX-2 protein while the standard compounds rofecoxib and celecoxid revealed fitness score of 44 and 62, respectively. The prodigiosin ligand revealed the best fitness score compared with the standard drug rofecoxib suggesting the prodigiosin could be effective as the potential inhibitor compound against COX-2 protein and can be evaluated as anti-inflammatory drug molecule using clinical trials. PMID:23741639
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
Celecoxib exerts antitumor effects in canine mammary tumor cells via COX?2?independent mechanisms.
Tamura, Dai; Saito, Teruyoshi; Murata, Kanae; Kawashima, Masafumi; Asano, Ryuji
2015-03-01
Celecoxib plays antitumor roles via multiple mechanisms in a variety of human cancers. The aim of this study was to clarify the mechanism of action of celecoxib in canine mammary tumors. We examined the antitumor effects of celecoxib in AZACB canine mammary tumor cells expressing low levels of cyclooxygenase?2 (COX?2) to minimize the effect of COX?2 on its activity. Our data revealed that celecoxib inhibited cell proliferation mainly via COX?2?independent mechanisms. Specifically, celecoxib decreased the proportion of cells in S phase and increased G2/M arrest, which was associated with increased expression of the cyclin?dependent kinase inhibitors (CDKIs) p21 and p27. In addition, treatment with celecoxib downregulated COX?2 expression, and induced apoptosis via both the intrinsic and extrinsic pathways. These findings suggest that celecoxib might be a useful agent for the treatment of canine mammary tumors, regardless of COX?2 expression. In the future, it might be possible to use a combination of celecoxib and other antitumor agents to treat canine mammary tumors. PMID:25571853
Apolipoprotein E3 Inhibits Rho to Regulate the Mechanosensitive Expression of Cox2
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
Kang, Soyeong; Min, Ahrum; Im, Seock-Ah; Song, Sang-Hyun; Kim, Sang Gyun; Kim, Hyun-Ah; Kim, Hee-Jun; Oh, Do-Youn; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue
2015-01-01
Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor ? (TGF-?) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-? can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-?-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-?. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-?. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-?, suggesting that TGF-?–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-? rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-?. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-?. Conclusion The results of this study show that TGF-? down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells. PMID:25544576
Thi Aurore Pham-Marcou; Hélène Beloeil; Xueging Sun; Marc Gentili; Djouer Yaici; Gérard Benoit; Dan Benhamou; Jean-Xavier Mazoit
2008-01-01
Resveratrol is a natural polyphenol that protects from cancer and cardiovascular diseases. Resveratrol is able to induce apoptotic cell death and it inhibits the cyclooxygenase (COX) cascade. We measured the antinociceptive effect of resveratrol on carrageenan-induced hyperalgesia, prostaglandin-E2 (PGE2) concentration in CSF and COX-1\\/COX-2 gene expression in the spinal cord and dorsal root ganglion (DRG) in rats. Resveratrol induced a
Expression of COX2, iNOS, p53 and Ki67 in gastric mucosa-associated lymphoid tissue lymphoma
Hong-Ling Li; Bing-Zhong Sun; Fu-Cheng Ma
2004-01-01
AIM: To assess the expression of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosa- associated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients. METHODS: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens
Robust linear least squares regression
Audibert, Jean-Yves
2010-01-01
We consider the problem of robustly predicting as well as the best linear combination of d given functions in least squares regression, and variants of this problem including constraints on the parameters of the linear combination. For the ridge estimator and the ordinary least squares estimator, and their variants, we provide new risk bounds of order d/n without logarithmic factor unlike some standard results, where n is the size of the training data. We also provide a new estimator with better deviations in presence of heavy-tailed noise. It is based on truncating differences of losses in a min-max framework and satisfies a d/n risk bound both in expectation and in deviations. The key common surprising factor of these results is the absence of exponential moment condition on the output distribution while achieving exponential deviations. All risk bounds are obtained through a PAC-Bayesian analysis on truncated differences of losses. Experimental results strongly back up our truncated min-max estimator.
Insulin Resistance: Regression and Clustering
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
Insulin resistance: regression and clustering.
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
Functional Regression for Quasar Spectra
Ciollaro, Mattia; Freeman, Peter; Genovese, Christopher; Lei, Jing; O'Connell, Ross; Wasserman, Larry
2014-01-01
The Lyman-alpha forest is a portion of the observed light spectrum of distant galactic nuclei which allows us to probe remote regions of the Universe that are otherwise inaccessible. The observed Lyman-alpha forest of a quasar light spectrum can be modeled as a noisy realization of a smooth curve that is affected by a `damping effect' which occurs whenever the light emitted by the quasar travels through regions of the Universe with higher matter concentration. To decode the information conveyed by the Lyman-alpha forest about the matter distribution, we must be able to separate the smooth `continuum' from the noise and the contribution of the damping effect in the quasar light spectra. To predict the continuum in the Lyman-alpha forest, we use a nonparametric functional regression model in which both the response and the predictor variable (the smooth part of the damping-free portion of the spectrum) are function-valued random variables. We demonstrate that the proposed method accurately predicts the unobserv...
Hye Jung Kim; Tae-Yoon Kim
2004-01-01
We monitored cyclooxygenase-2 (COX-2) expression in the insulin-like growth factor-II (IGF-II) treated human keratinocytes and explored the IGF-II signaling pathways with respect to the expression of COX-2. IGF-II induced COX-2 mRNA and protein levels, and the up-regulation of COX-2 expression by IGF-II was reduced by pretreatment with inhibitors of tyrosine kinase, Src and PI3-kinase. The inhibition of extracellular signal-regulated kinase
2014-01-01
Background Big data is steadily growing in epidemiology. We explored the performances of methods dedicated to big data analysis for detecting independent associations between exposures and a health outcome. Methods We searched for associations between 303 covariates and influenza infection in 498 subjects (14% infected) sampled from a dedicated cohort. Independent associations were detected using two data mining methods, the Random Forests (RF) and the Boosted Regression Trees (BRT); the conventional logistic regression framework (Univariate Followed by Multivariate Logistic Regression - UFMLR) and the Least Absolute Shrinkage and Selection Operator (LASSO) with penalty in multivariate logistic regression to achieve a sparse selection of covariates. We developed permutations tests to assess the statistical significance of associations. We simulated 500 similar sized datasets to estimate the True (TPR) and False (FPR) Positive Rates associated with these methods. Results Between 3 and 24 covariates (1%-8%) were identified as associated with influenza infection depending on the method. The pre-seasonal haemagglutination inhibition antibody titer was the unique covariate selected with all methods while 266 (87%) covariates were not selected by any method. At 5% nominal significance level, the TPR were 85% with RF, 80% with BRT, 26% to 49% with UFMLR, 71% to 78% with LASSO. Conversely, the FPR were 4% with RF and BRT, 9% to 2% with UFMLR, and 9% to 4% with LASSO. Conclusions Data mining methods and LASSO should be considered as valuable methods to detect independent associations in large epidemiologic datasets. PMID:25154404
Quantile regression applied to spectral distance decay
Rocchini, D.; Cade, B.S.
2008-01-01
Remotely sensed imagery has long been recognized as a powerful support for characterizing and estimating biodiversity. Spectral distance among sites has proven to be a powerful approach for detecting species composition variability. Regression analysis of species similarity versus spectral distance allows us to quantitatively estimate the amount of turnover in species composition with respect to spectral and ecological variability. In classical regression analysis, the residual sum of squares is minimized for the mean of the dependent variable distribution. However, many ecological data sets are characterized by a high number of zeroes that add noise to the regression model. Quantile regressions can be used to evaluate trend in the upper quantiles rather than a mean trend across the whole distribution of the dependent variable. In this letter, we used ordinary least squares (OLS) and quantile regressions to estimate the decay of species similarity versus spectral distance. The achieved decay rates were statistically nonzero (p < 0.01), considering both OLS and quantile regressions. Nonetheless, the OLS regression estimate of the mean decay rate was only half the decay rate indicated by the upper quantiles. Moreover, the intercept value, representing the similarity reached when the spectral distance approaches zero, was very low compared with the intercepts of the upper quantiles, which detected high species similarity when habitats are more similar. In this letter, we demonstrated the power of using quantile regressions applied to spectral distance decay to reveal species diversity patterns otherwise lost or underestimated by OLS regression. ?? 2008 IEEE.
[From clinical judgment to linear regression model.
Palacios-Cruz, Lino; Pérez, Marcela; Rivas-Ruiz, Rodolfo; Talavera, Juan O
2013-01-01
When we think about mathematical models, such as linear regression model, we think that these terms are only used by those engaged in research, a notion that is far from the truth. Legendre described the first mathematical model in 1805, and Galton introduced the formal term in 1886. Linear regression is one of the most commonly used regression models in clinical practice. It is useful to predict or show the relationship between two or more variables as long as the dependent variable is quantitative and has normal distribution. Stated in another way, the regression is used to predict a measure based on the knowledge of at least one other variable. Linear regression has as it's first objective to determine the slope or inclination of the regression line: Y = a + bx, where "a" is the intercept or regression constant and it is equivalent to "Y" value when "X" equals 0 and "b" (also called slope) indicates the increase or decrease that occurs when the variable "x" increases or decreases in one unit. In the regression line, "b" is called regression coefficient. The coefficient of determination (R(2)) indicates the importance of independent variables in the outcome. PMID:24290018
Geodesic least squares regression on information manifolds
NASA Astrophysics Data System (ADS)
Verdoolaege, Geert
2014-12-01
We present a novel regression method targeted at situations with significant uncertainty on both the dependent and independent variables or with non-Gaussian distribution models. Unlike the classic regression model, the conditional distribution of the response variable suggested by the data need not be the same as the modeled distribution. Instead they are matched by minimizing the Rao geodesic distance between them. This yields a more flexible regression method that is less constrained by the assumptions imposed through the regression model. As an example, we demonstrate the improved resistance of our method against some flawed model assumptions and we apply this to scaling laws in magnetic confinement fusion.
Boosted regression trees with errors in variables.
Sexton, Joseph; Laake, Petter
2007-06-01
In this article, we consider nonparametric regression when covariates are measured with error. Estimation is performed using boosted regression trees, with the sum of the trees forming the estimate of the conditional expectation of the response. Both binary and continuous response regression are investigated. An approach to fitting regression trees when covariates are measured with error is described, and the boosting algorithms consist of its repeated application. The main feature of the approach is that it handles situations where multiple covariates are measured with error. Some simulation results are given as well as its application to data from the Framingham Heart Study. PMID:17688511
Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts.
Gutiérrez-Venegas, Gloria; Luna, Oscar Alonso; Arreguín-Cano, Juan Antonio; Hernández-Bermúdez, Cristina
2014-03-01
Periodontitis is an infectious disease caused by microorganisms present in dental bacterial plaque. Lipoteichoic acid (LTA) is a component of the external membrane of Gram-positive bacteria. It causes septic shock. Ingested flavonoids have been reported to directly affect the regulation of cyclooxygenase-2 (COX-2) expression induced by bacterial toxins. In this study, we examined the effects of four flavonoids (luteolin, fisetin, morin and myricetin) on the activation of ERK1/2, p38 and AKT, and on the synthesis of COX-2 in human gingival fibroblasts treated with LTA from Streptococcus sanguinis. We found that luteolin and myricetin blocked AKT and p38 activation and that myricetin blocked LTA-induced COX-2 expression. The results of our study are important for elucidating the mechanism of action of flavonoid regulation of inflammatory responses. PMID:24569980