Sample records for univariate cox regression

  1. Calibration transfer employing univariate correction and robust regression.

    PubMed

    Galvão, Roberto Kawakami Harrop; Soares, Sófacles Figueredo Carreiro; Martins, Marcelo Nascimento; Pimentel, Maria Fernanda; Araújo, Mário César Ugulino

    2015-03-15

    This paper proposes a new method for calibration transfer, which was specifically designed to work with isolated variables, rather than the full spectrum or spectral windows. For this purpose, a univariate procedure is initially employed to correct the spectral measurements of the secondary instrument, given a set of transfer samples. A robust regression technique is then used to obtain a model with low sensitivity with respect to the univariate correction residuals. The proposed method is employed in two case studies involving near infrared spectrometric determination of specific mass, research octane number and naphthenes in gasoline, and moisture and oil in corn. In both cases, better calibration transfer results were obtained in comparison with piecewise direct standardization (PDS). The proposed method should be of a particular value for use with application-targeted instruments that monitor only a small set of spectral variables. PMID:25732421

  2. EMPIRICAL LIKELIHOOD FOR COX REGRESSION MODEL UNDER RANDOM CENSORSHIP

    Microsoft Academic Search

    Gengsheng Qin; Bing-Yi Jing

    2001-01-01

    In this paper we investigate the empirical likelihood method for Cox regression model when the failure times are subject to random censoring. An empirical likelihood ratio for the vector of regression coefficients is defined and it is shown that its limiting distribution is a chi-square distributions with p degrees of freedom. Some simulation studies are presented to compare the empirical

  3. Cox's Regression Model for Counting Processes: A Large Sample Study

    Microsoft Academic Search

    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

  4. Cox regression model for dissecting genetic architecture of survival time.

    PubMed

    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

  5. Factors Associated with Methadone Treatment Duration: A Cox Regression Analysis

    PubMed Central

    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

  6. 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…

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

    PubMed

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

    2010-05-01

    A useful approach to reduce the number of discarded marginal kidneys and to increase the nephron mass is double kidney transplantation (DKT). In this study, we retrospectively evaluated the potential predictors for patient and graft survival in a single-center series of 59 DKT procedures performed between April 21, 1999, and September 21, 2008. The kidney recipients of mean age 63.27 +/- 5.17 years included 16 women (27%) and 43 men (73%). The donors of mean age 69.54 +/- 7.48 years included 32 women (54%) and 27 men (46%). The mean posttransplant dialysis time was 2.37 +/- 3.61 days. The mean hospitalization was 20.12 +/- 13.65 days. Average serum creatinine (SCr) at discharge was 1.5 +/- 0.59 mg/dL. In view of the limited numbers of recipient deaths (n = 4) and graft losses (n = 8) that occurred in our series, the proportional hazards assumption for each Cox regression model with P < .05 was tested by using correlation coefficients between transformed survival times and scaled Schoenfeld residuals, and checked with smoothed plots of Schoenfeld residuals. For patient survival, the variables that reached statistical significance were donor SCr (P = .007), donor creatinine cleararance (P = .023), and recipient age (P = .047). Each significant model passed the Schoenfeld test. By entering these variables into a multivariate Cox model for patient survival, no further significance was observed. In the univariate Cox models performed for graft survival, statistical significance was noted for donor SCr (P = .027), SCr 3 months post-DKT (P = .043), and SCr 6 months post-DKT (P = .017). All significant univariate models for graft survival passed the Schoenfeld test. A final multivariate model retained SCr at 6 months (beta = 1.746, P = .042) and donor SCr (beta = .767, P = .090). In our analysis, SCr at 6 months seemed to emerge from both univariate and multivariate Cox models as a potential predictor of graft survival among DKT. Multicenter studies with larger recipient populations and more graft losses should be performed to confirm our findings. PMID:20534233

  8. Investigating the utility of clinical outcome-guided mutual information network in network-based Cox regression

    PubMed Central

    2015-01-01

    Background Network-based approaches have recently gained considerable popularity in high- dimensional regression settings. For example, the Cox regression model is widely used in expression analysis to predict the survival of patients. However, as the number of genes becomes substantially larger than the number of samples, the traditional Cox or L2-regularized Cox models are still prone to noise and produce unreliable estimations of regression coefficients. A recent approach called the network-based Cox (Net-Cox) model attempts to resolve this issue by incorporating prior gene network information into the Cox regression. The Net-Cox model has shown to outperform the models that do not use this network information. Results In this study, we demonstrate an alternative network construction method for the outcome-guided gene interaction network, and we investigate its utility in survival analysis using Net-Cox regression as compared with conventional networks, such as co-expression or static networks obtained from the existing knowledgebase. Our network edges consist of gene pairs that are significantly associated with the clinical outcome. We measure the strength of this association using mutual information between the gene pair and the clinical outcome. We applied this approach to ovarian cancer patients' data in The Cancer Genome Atlas (TCGA) and compared the predictive performance of the proposed approach with those that use other types of networks. Conclusions We found that the alternative outcome-guided mutual information network further improved the prediction power of the network-based Cox regression. We expect that a modification of the network regularization term in the Net-Cox model could further improve its prediction power because the properties of our network edges are not optimally reflected in its current form. PMID:25708115

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

    PubMed

    Parzen, M; Lipsitz, S R

    1999-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. Box–Cox Transformation and Random Regression Models for Fecal egg Count Data

    PubMed Central

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

    2012-01-01

    Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box–Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box–Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26?weeks in a 26-week experimental challenge period are genetically correlated. PMID:22303406

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  13. Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning.

    PubMed

    van Dijk, M R; Steyerberg, E W; Stenning, S P; Dusseldorp, E; Habbema, J D F

    2004-03-22

    The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c=0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification. British Journal of Cancer (2004) 90, 1176-1183. doi:10.1038/sj.bjc.6601665 www.bjcancer.com Published online 24 February 2004 PMID:15026798

  14. Comparing the importance of prognostic factors in Cox and logistic regression using SAS

    Microsoft Academic Search

    Georg Heinze; Michael Schemper

    2003-01-01

    Two SAS macro programs are presented that evaluate the relative importance of prognostic factors in the proportional hazards regression model and in the logistic regression model. The importance of a prognostic factor is quantified by the proportion of variation in the outcome attributable to this factor. For proportional hazards regression, the program %RELIMPCR uses the recently proposed measure V to

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

    PubMed

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

    2014-09-01

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

  16. An overview on standard statistical methods for assessing exposure-outcome link in survival analysis (Part II): the Kaplan-Meier analysis and the Cox regression method.

    PubMed

    Abd ElHafeez, Samar; Torino, Claudia; D'Arrigo, Graziella; Bolignano, Davide; Provenzano, Fabio; Mattace-Raso, Francesco; Zoccali, Carmine; Tripepi, Giovanni

    2012-06-01

    The Kaplan-Meier and the Cox regression methods are the most used statistical techniques for performing "time to event analysis" in epidemiological and clinical research. The Kaplan-Meier analysis allows to build up one or more survival curves describing the occurrence of the outcome of interest over time according to the presence/absence of one or more exposures. The Cox regression method models the relationship between a specific exposure (either a continuous one like age, and systolic blood pressure or a categorical one like diabetes, degree of obesity, etc.) and the occurrence of a given outcome taking into account multiple confounders and/or predictors. PMID:23114547

  17. Privacy-Preserving Cox Regression for Survival Analysis Shipeng Yu, Glenn Fung, Romer Rosales, Sriram Krishnan, R. Bharat Rao

    E-print Network

    Rosales, Rómer E.

    Department of Radiation Oncology (Maastro), GROW Research Institute, University Hospital Maastricht to data mining techniques. In this paper we propose a privacy-preserving (PP) Cox model for sur- vival institutions. The proposed model is based on linearly projecting the data to a lower dimensional space through

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

    PubMed

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

    2015-04-01

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

  19. Factors determining disease duration in Alzheimer's disease: a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression.

    PubMed

    Armstrong, R A

    2014-01-01

    Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation?=?5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration. PMID:24579083

  20. Factors Determining Disease Duration in Alzheimer's Disease: A Postmortem Study of 103 Cases Using the Kaplan-Meier Estimator and Cox Regression

    PubMed Central

    Armstrong, R. A.

    2014-01-01

    Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks–30 years, standard deviation?=?5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration. PMID:24579083

  1. Univariate and Bivariate Data

    NSDL National Science Digital Library

    Shodor

    2012-03-30

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

  2. 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…

  3. Regression

    NSDL National Science Digital Library

    Laval, Philippe B.

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

  4. Reweighting estimators for Cox regression with missing covariate data: Analysis of insulin resistance and risk of stroke in the Northern Manhattan Study

    PubMed Central

    Xu, Qiang; Paik, Myunghee Cho; Rundek, Tatjana; Elkind, Mitchell S. V.; Sacco, Ralph L.

    2015-01-01

    Incomplete covariates often obscure analysis results from a Cox regression. In an analysis of the Northern Manhattan Study (NOMAS) to determine the influence of insulin resistance on the incidence of stroke in non-diabetic individuals, insulin level is unknown for 34.1% of the subjects. The available data suggest that the missingness mechanism depends on outcome variables, which may generate biases in estimating the parameters of interest if only using the complete observations. This article aimed to introduce practical strategies to analyze the NOMAS data and present sensitivity analyses by using the reweighting method in standard statistical packages. When the data set structure is in counting process style, the reweighting estimates can be obtained by built-in procedures with variance estimated by the jackknife method. Simulation results indicate that the jackknife variance estimate provides reasonable coverage probability in moderate sample sizes. We subsequently conducted sensitivity analyses for the NOMAS data, showing that the risk estimates are robust to a variety of missingness mechanisms. At the end of this article, we present the core SAS and R programs used in the analysis. PMID:21965165

  5. Cox Regression for Survey Data

    Cancer.gov

    For complex sampling designs, the program maximizes a weighted partial log-likelihood and calculates robust design-based standard errors (assuming with-replacement sampling at the first stage). For further details see Binder, DA (1992), Biometrika, 79, pp. 139-47.

  6. Regression

    NSDL National Science Digital Library

    2011-05-26

    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.

  7. 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.

  8. 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.)

  9. Unified univariate and multivariate random field theory

    Microsoft Academic Search

    Keith J. Worsley; Jonathan E. Taylor; Francesco Tomaiuolo; Jason Lerch; J. E. Taylor

    2004-01-01

    We report new random field theory P-values for peaks of canonical correlation SPMs for detecting multiple contrasts in a linear model for multivariate image data. This completes results for all types of univariate and multivariate image data analysis. All other known univariate and multivariate random field theory results are now special cases, so these new results present a true unification

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

    PubMed

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

    2013-10-15

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

  11. 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.

  12. Exchangeability and regression models Peter McCullagh

    E-print Network

    McCullagh, Peter

    for rainfall (Cox and Isham 1988; Rodriguez-Iturbe, Cox and Isham 1987, 1988), and models for the spreadExchangeability and regression models by Peter McCullagh University of Chicago January 2004 Revised). Subsequent applications include hydrology and long-range dependence (Davison and Cox 1989; Cox 1991), models

  13. Dennis Cox, USGS Volunteer

    USGS Multimedia Gallery

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

  14. Cooperative Coevolution and Univariate Estimation of Distribution Algorithms

    E-print Network

    Tomkins, Andrew

    assumes that each population has a (typically) finite set of genotypes, and that all populations haveCooperative Coevolution and Univariate Estimation of Distribution Algorithms [Extended Abstract Univariate EDAs. 1 Introduction Over the last decade, the field of estimation of distribution algorithms

  15. Computational survey of univariate and multivariate learning curve models

    Microsoft Academic Search

    Adedeji B. Badiru

    1992-01-01

    A computational survey of the various univariate and multivariate learning curve models that have evolved over the past several years is presented. Discussions are presented to show how the models might be used for cost analysis or productivity assessment in engineering management. A computational experiment comparing a univariate model to a bivariate model is presented. While the bivariate model provides

  16. Multiple Linear Regression

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-01-01

    This chapter deals with the multiple linear regression. That is we investigate the situation where the mean of a variable depends linearly on a set of covariables. The noise is supposed to be gaussian. We develop the least squared method to get the parameter estimators and estimates of their precisions. This leads to design confidence intervals, prediction intervals, global tests, individual tests and more generally tests of submodels defined by linear constraints. Methods for model's choice and variables selection, measures of the quality of the fit, residuals study, diagnostic methods are presented. Finally identification of departures from the model's assumptions and the way to deal with these problems are addressed. A real data set is used to illustrate the methodology with software R. Note that this chapter is intended to serve as a guide for other regression methods, like logistic regression or AFT models and Cox regression.

  17. Methods for the analysis of sampled cohort data in the Cox proportional hazards model

    E-print Network

    Goldstein, Larry

    . 1 Introduction Epidemiologic cohort studies are considered the most reliable method Methods for the analysis of sampled cohort data in the Cox proportional hazards Abstract Methods are provided for regression parameter and cumulative base- line hazard

  18. CONCEPTUALLY-BASED UNIVARIATE STOCHASTIC MODELLING OF RIVER RUNOFF

    E-print Network

    Poggi, Davide

    . In the last three decades, univariate modelling of runoff series has been performed, to a great extent, using are inadequate for multipurpose reservoir (water supply and flood peak reduction) since at that scale information

  19. A GENERAL PURPOSE UNIVARIATE PROBABILITY MODEL FOR ENVIRONMENTAL DATA ANALYSIS

    EPA Science Inventory

    Analysis of environmental quality data for decision making purposes (evaluation of compliance with standards, examination of environmental trends, determination of confidence intervals) generally requires a suitable univariate probability model. It sometimes is difficult, when ma...

  20. 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…

  1. Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma

    PubMed Central

    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

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

    PubMed Central

    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

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

    PubMed

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

    2015-04-01

    Five, accurate, precise, and sensitive univariate and multivariate spectrophotometric methods were developed for the simultaneous determination of a ternary mixture containing Trimethoprim (TMP), Sulphamethoxazole (SMZ) and Oxytetracycline (OTC) in waste water samples collected from different cites either production wastewater or livestock wastewater after their solid phase extraction using OASIS HLB cartridges. In univariate methods OTC was determined at its ?max 355.7nm ((0)D), while (TMP) and (SMZ) were determined by three different univariate methods. Method (A) is based on successive spectrophotometric resolution technique (SSRT). The technique starts with the ratio subtraction method followed by ratio difference method for determination of TMP and SMZ. Method (B) is successive derivative ratio technique (SDR). Method (C) is mean centering of the ratio spectra (MCR). The developed multivariate methods are principle component regression (PCR) and partial least squares (PLS). The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures containing different ratios of the three drugs. The obtained results are statistically compared with those obtained by the official methods, showing no significant difference with respect to accuracy and precision at p=0.05. PMID:25637816

  4. 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.

  5. Evaluating Univariate, Bivariate, and Multivariate Normality Using Graphical Procedures.

    ERIC Educational Resources Information Center

    Burdenski, Thomas K., Jr.

    This paper reviews graphical and nongraphical procedures for evaluating multivariate normality by guiding the reader through univariate and bivariate procedures that are necessary, but insufficient, indications of a multivariate normal distribution. A data set using three dependent variables for two groups provided by D. George and P. Mallery…

  6. A Root Isolation Algorithm for Sparse Univariate Polynomials

    E-print Network

    Paris-Sud XI, Université de

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

  7. Individual Fitness and the Measurement of Univariate Selection

    E-print Network

    Walsh, Bruce

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

  8. Strokes for Representing Univariate Vector David Fowler and Colin Ware

    E-print Network

    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

  9. 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…

  10. Assessing the Impact of Evaluation: A Univariate Time Series Technique.

    ERIC Educational Resources Information Center

    Shapiro, Jonathan

    A statistical definition of information utilization for policy making decisions and an evaluation impact test to determine its occurrence are proposed. A univariate time series analysis is used to identify the internal trend for a given policy output variable and to control its effect. Two problems are identified in implementing an evaluation…

  11. Constructing Generalized FGM Copulas by Means of Certain Univariate Distributions

    Microsoft Academic Search

    Matthias Fischer; Ingo Klein

    2007-01-01

    In this paper we focus on specific generalized Fairlie- Gumbel-Morgenstern (or Sarmanov) copulas which are generated by a\\u000a single function (so-called generator or generator function) defined on the unit interval. In particular, we introduce a class\\u000a of generators based on density-quantile functions of certain univariate distributions. Many of the generator functions from\\u000a the literature are recovered as special cases. Moreover,

  12. ccsd00004622, Univariate spline quasi-interpolants and

    E-print Network

    to numerical analysis Paul Sablonni#18;ere INSA and IRMAR, Rennes Abstract We describe some new univariate of weighted mean values of f , i.e. of quantities R b a fw j where w j can be, for example, a linear],[19]. e r (x) = x r = X j2J #18; (r) j B j (x); #18; (r) j = #18; d r #19; 1 symm r (N j ); 0 #20; r #20

  13. External validation of a Cox prognostic model: principles and methods

    PubMed Central

    2013-01-01

    Background A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. PMID:23496923

  14. P-Divisors of Cox Rings

    Microsoft Academic Search

    Klaus Altmann; Jarek Wisniewski

    2009-01-01

    The Cox ring of a so-called Mori Dream Space (MDS) is finitely generated and it is graded over the divisor class group. Hence the spectrum of the Cox ring comes with an action of an algebraic torus whose GIT quotient is the variety in question. We present the associated description of this Cox ring as a polyhedral divisor. Via the

  15. ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL

    PubMed Central

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

    2013-01-01

    We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. However, the presented oracle inequalities are sharper since the compatibility and cone invertibility factors are always greater than the corresponding restricted eigenvalue. In the Cox regression model, the Hessian matrix is based on time-dependent covariates in censored risk sets, so that the compatibility and cone invertibility factors, and the restricted eigenvalue as well, are random variables even when they are evaluated for the Hessian at the true regression coefficients. Under mild conditions, we prove that these quantities are bounded from below by positive constants for time-dependent covariates, including cases where the number of covariates is of greater order than the sample size. Consequently, the compatibility and cone invertibility factors can be treated as positive constants in our oracle inequalities. PMID:24086091

  16. Detection of synchronization from univariate data using wavelet transform

    NASA Astrophysics Data System (ADS)

    Hramov, Alexander E.; Koronovskii, Alexey A.; Ponomarenko, Vladimir I.; Prokhorov, Mikhail D.

    2007-05-01

    A method is proposed for detecting from univariate data the presence of synchronization of a self-sustained oscillator by external driving with varying frequency. The method is based on the analysis of difference between the oscillator instantaneous phases calculated using continuous wavelet transform at time moments shifted by a certain constant value relative to each other. We apply our method to a driven asymmetric van der Pol oscillator, experimental data from a driven electronic oscillator with delayed feedback and human heartbeat time series. In the latest case, the analysis of the heart rate variability data reveals synchronous regimes between the respiration and slow oscillations in blood pressure.

  17. Detection of synchronization from univariate data using wavelet transform

    E-print Network

    Alexander E. Hramov; Alexey A. Koronovskii; Vladimir I. Ponomarenko; Mikhail D. Prokhorov

    2007-05-24

    A method is proposed for detecting from univariate data the presence of synchronization of a self-sustained oscillator by external driving with varying frequency. The method is based on the analysis of difference between the oscillator instantaneous phases calculated using continuous wavelet transform at time moments shifted by a certain constant value relative to each other. We apply our method to a driven asymmetric van der Pol oscillator, experimental data from a driven electronic oscillator with delayed feedback and human heartbeat time series. In the latest case, the analysis of the heart rate variability data reveals synchronous regimes between the respiration and slow oscillations in blood pressure.

  18. Cox’s Chair Revisited: Can Spinning Alter Mood States?

    PubMed Central

    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

  19. Logistic Regression and Artificial Neural Networks for Classification of Ovarian Tumors

    E-print Network

    Logistic Regression and Artificial Neural Networks for Classification of Ovarian Tumors C. Lu1 , J to generate and evaluate both logistic regression models and artificial neural network (ANN) models to predict, including explorative univariate and multivariate analysis, and the development of the logistic regression

  20. Prognostic factors of survival time after hematopoietic stem cell transplant in acute lymphoblastic leukemia patients: Cox proportional hazard versus accelerated failure time models

    PubMed Central

    Sayehmiri, Kourosh; Eshraghian, Mohammad R; Mohammad, Kazem; Alimoghaddam, Kamran; Foroushani, Abbas Rahimi; Zeraati, Hojjat; Golestan, Banafsheh; Ghavamzadeh, Ardeshir

    2008-01-01

    Background The aim of this study is to evaluate the prognostic factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute lymphoblastic leukaemia (ALL) patients using accelerated failure time (AFT), Cox proportional hazard (PH), and Cox time-varying coefficient models. Methods 206 patients were enrolled after HSCH in Shariati Hospital between 1993 and 2007. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, relapse and chronic graft-versus-host disease (cGVHD) (P < .001). Performance among AFT and Cox's models was assessed using explained variation and goodness of fit methods. Discrimination among the exponential, Weibull, generalized gamma (GG), log-logistic, and lognormal distributions was done using maximum likelihood and Akaike information criteria. Results The 5-year OS was 52% (95%CI: 47.3–56.7). Peak mortality hazard occurred at months 6–7 after HSCT followed by a decreasing trend. In univariate analysis, the data was better fitted by GG distribution than by other distributions. Univariate analysis using GG distribution showed a positive association between OS with acute graft-versus-host disease (aGVHD) (P = .021), no relapse (P < .001), cGVHD (P < .001), neutrophil recovery (P < .001) and platelet recovery (P < .001). Based on Cox PH models; however cGVHD and relapse were the predictive factors of OS (P < .001). Multivariate analysis indicated that, OS is related to relapse (P < .001) and platelet recovery (P = .037), where predictive power of Weibull AFT models was superior to Cox PH model and Cox with time-varying coefficient (R2 = 0.46 for AFT, R2 = .21 for Cox PH and R2 = .34 for Cox time-varying coefficient). Cox-Snell residual shows Weibull AFT fitted to data better than other distributions in multivariate analysis. Conclusion We concluded that AFT distributions can be a useful tool for recognizing prognostic factors of OS in acute lymphoblastic leukemia patients. PMID:19025609

  1. Allan Cox 1926”1987

    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."

  2. Proportional hazards regression with interval-censored and left-truncated data

    Microsoft Academic Search

    Pao-Sheng Shen

    2012-01-01

    This paper considers the estimation of the regression coefficients in the Cox proportional hazards model with left-truncated and interval-censored data. Using the approaches of Pan [A multiple imputation approach to Cox regression with interval-censored data, Biometrics 56 (2000), pp. 199–203] and Heller [Proportional hazards regression with interval censored data using an inverse probability weight, Lifetime Data Anal. 17 (2011), pp.

  3. COX2 inhibitors in rheumatoid arthritis

    Microsoft Academic Search

    John S. Sundy

    2001-01-01

    The selective cyclooxygenase 2 (COX-2) inhibitors have emerged as an important option in the treatment of rheumatoid arthritis\\u000a (RA). Rofecoxib and celecoxib, the selective COX-2 inhibitors currently available, have shown efficacy in reducing symptoms\\u000a of RA comparable with that of traditional nonsteroidal antiinflammatory drugs (NSAIDs). The primary advantage of selective\\u000a COX-2 inhibitors relates to reduced gastrointestinal (GI) toxicity. Gastroduodenal ulcers

  4. Regression Activity

    NSDL National Science Digital Library

    This activity focuses on basic ideas of linear regression. It covers creating scatterplots from data, describing the association between two variables, and correlation as a measure of linear association. After this activity students will have the knowledge to create output that yields R-square, the slope and intercept, as well as their interpretations. This activity also covers some of the basics about residual analysis and the fit of the linear regression model in certain settings.

  5. MARITIME STUDIES Chair, Professor RNADH COX

    E-print Network

    Aalberts, Daniel P.

    1 MARITIME STUDIES Chair, Professor RÓNADH COX Advisory Committee: Professor: ART*, COX. Associate of the humanities, social sciences, and physical sciences. Maritime Studies is an interdisciplinary, cross for the concentration in Maritime Studies must complete a minimum of seven courses: the interdisciplinary introductory

  6. Simulation from a known Cox MSM using standard parametric models for the g-formula

    PubMed Central

    Young, Jessica G.; Tchetgen Tchetgen, Eric J.

    2013-01-01

    It is routinely argued that, unlike standard regression-based estimates, inverse probability weighted (IPW) estimates of the parameters of a correctly specified Cox marginal structural model (MSM) may remain unbiased in the presence of a time-varying confounder affected by prior treatment. Previously proposed methods for simulating from a known Cox MSM lack knowledge of the law of the observed outcome conditional on the measured past. While unbiased IPW estimation does not require this knowledge, standard regression-based estimates rely on correct specification of this law. Thus, in typical high-dimensional settings, such simulation methods cannot isolate bias due to complex time-varying confounding as it may be conflated with bias due to misspecification of the outcome regression model. In this paper, we describe an approach to Cox MSM data generation that allows for a comparison of the bias of IPW estimates versus that of standard regression-based estimates in the complete absence of model misspecification. This approach involves simulating data from a standard parametrization of the likelihood and solving for the underlying Cox MSM. We prove that solutions exist and computations are tractable under many data generating mechanisms. We show analytically and confirm in simulations that, in the absence of model misspecification, the bias of standard regression-based estimates for the parameters of a Cox MSM is indeed a function of the coefficients in observed data models quantifying the presence of a time-varying confounder affected by prior treatment. We discuss limitations of this approach including that implied by the “g-null paradox”. PMID:24151138

  7. Bayesian Random Threshold Estimation in a Cox Proportional Hazards Cure Model

    PubMed Central

    Zhao, Lili; Feng, Dai; Bellile, Emily L.; Taylor, Jeremy M.G.

    2014-01-01

    In this paper, we develop a Bayesian approach to estimate a Cox proportional hazards model that allows a threshold in the regression coefficient based on a threshold in a covariate, 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

  8. Autistic Regression

    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…

  9. Survival analysis and regression models

    PubMed Central

    George, Brandon; Seals, Samantha; Aban, Inmaculada

    2014-01-01

    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

  10. Survival analysis and regression models.

    PubMed

    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

  11. Dynamic treatment of invariant and univariant reactions in metamorphic systems

    SciTech Connect

    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.

  12. Comparison of univariate and transfer function models of groundwater fluctuations

    NASA Astrophysics Data System (ADS)

    Tankersley, Claude D.; Graham, Wendy D.; Hatfield, Kirk

    1993-10-01

    Seasonal autoregressive integrated moving average (SARIMA) univariate models and single input-single output transfer function (SARIMA with externalities or SARIMAX) models of groundwater head fluctuations are developed for 21 Upper Floridan aquifer observation wells in northeast Florida. These models incorporate empirical relationships between rainfall input and head response based on historical correlations and cross correlations between these two time series. The magnitude of the forecast error terms indicates that the SARIMA and SARIMAX models explain an average of 84-87% of the variation observed in the monthly piezometric head levels for 1-month lead forecasts. Thus the models account for the dominant processes which affect temporal groundwater fluctuations. Both the SARIMA and SARIMAX models provide unbiased forecasts of piezometric head levels; however, the SARIMAX models produce more accurate forecasts (i.e., smaller forecast probability limits) than the SARIMA models, particularly as lead time increases. Modeling efforts reveal consistent model structures over the study region, with local hydrologic and geologic conditions causing site-specific variability in the time series model parameters.

  13. Detecting and Dealing with Outliers in Univariate and Multivariate Contexts.

    ERIC Educational Resources Information Center

    Wiggins, Bettie Caroline

    Because multivariate statistics are increasing in popularity with social science researchers, the challenge of detecting multivariate outliers warrants attention. Outliers are defined as cases which, in regression analyses, generally lie more than three standard deviations from Yhat and therefore distort statistics. There are, however, some…

  14. A General Method for Optimal Design of Univariate and Multivariate Population Pharmacokinetic Experiments

    E-print Network

    Bogacka, Barbara

    A General Method for Optimal Design of Univariate and Multivariate Population Pharmacokinetic Experiments Kay Ogungbenro and Leon Aarons School of Pharmacy and Pharmaceutical Sciences, The University of Manchester ABSTRACT We will present a general method for optimal design of univariate and multivariate

  15. Karin M. Cox 3720 Walnut Street

    E-print Network

    Kable, Joe

    (summa cum laude) in Psychology and Spanish 2004-2011 University of Pittsburgh, Pittsburgh, PA Master Presentations Wahlstrom, D., Luciana, M., Cox, K.M., & Gilles, E.E. (2005, April). Autonomic correlates of Iowa

  16. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

    PubMed Central

    Smith, Francine G.; Wade, Andrew W.; Lewis, Megan L.; Qi, Wei

    2012-01-01

    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function. PMID:24281306

  17. Viscum album-Mediated COX-2 Inhibition Implicates Destabilization of COX-2 mRNA

    PubMed Central

    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

  18. Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (COX-2) in ovine endometrium

    PubMed Central

    Kim, Seokwoon; Choi, Youngsok; Spencer, Thomas E; Bazer, Fuller W

    2003-01-01

    In sheep, the uterus produces luteolytic pulses of prostaglandin F2? (PGF) on Days 15 to 16 of estrous cycle to regress the corpus luteum (CL). These PGF pulses are produced by the endometrial lumenal epithelium (LE) and superficial ductal glandular epithelium (sGE) in response to binding of pituitary and/or luteal oxytocin to oxytocin receptors (OTR) and liberation of arachidonic acid, the precursor of PGF. Cyclooxygenase-one (COX-1) and COX-2 are rate-limiting enzymes in PGF synthesis, and COX-2 is the major form expressed in ovine endometrium. During pregnancy recognition, interferon tau (IFN?), produced by the conceptus trophectoderm, acts in a paracrine manner to suppress development of the endometrial epithelial luteolytic mechanism by inhibiting transcription of estrogen receptor ? (ER?) (directly) and OTR (indirectly) genes. Conflicting studies indicate that IFN? increases, decreases or has no effect on COX-2 expression in bovine and ovine endometrial cells. In Study One, COX-2 mRNA and protein were detected solely in endometrial LE and sGE of both cyclic and pregnant ewes. During the estrous cycle, COX-2 expression increased from Days 10 to 12 and then decreased to Day 16. During early pregnancy, COX-2 expression increased from Days 10 to 12 and remained higher than in cyclic ewes. In Study Two, intrauterine infusion of recombinant ovine IFN? in cyclic ewes from Days 11 to 16 post-estrus did not affect COX-2 expression in the endometrial epithelium. These results clearly indicate that IFN? has no effect on expression of the COX-2 gene in the ovine endometrium. Therefore, antiluteolytic effects of IFN? are to inhibit ER? and OTR gene transcription, thereby preventing endometrial production of luteolytic pulses of PGF. Indeed, expression of COX-2 in the endometrial epithelia as well as conceptus is likely to have a beneficial regulatory role in implantation and development of the conceptus. PMID:12956885

  19. 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.

  20. Oxidative switches in functioning of mammalian copper chaperone Cox17.

    PubMed

    Voronova, Anastassia; Meyer-Klaucke, Wolfram; Meyer, Thomas; Rompel, Annette; Krebs, Bernt; Kazantseva, Jekaterina; Sillard, Rannar; Palumaa, Peep

    2007-11-15

    Cox17, a copper chaperone for cytochrome-c oxidase, is an essential and highly conserved protein in eukaryotic organisms. Yeast and mammalian Cox17 share six conserved cysteine residues, which are involved in complex redox reactions as well as in metal binding and transfer. Mammalian Cox17 exists in three oxidative states, each characterized by distinct metal-binding properties: fully reduced mammalian Cox17(0S-S) binds co-operatively to four Cu+; Cox17(2S-S), with two disulfide bridges, binds to one of either Cu+ or Zn2+; and Cox17(3S-S), with three disulfide bridges, does not bind to any metal ions. The E(m) (midpoint redox potential) values for two redox couples of Cox17, Cox17(3S-S)<-->Cox17(2S-S) (E(m1)) and Cox17(2S-S)<-->Cox17(0S-S) (E(m2)), were determined to be -197 mV and -340 mV respectively. The data indicate that an equilibrium exists in the cytosol between Cox17(0S-S) and Cox17(2S-S), which is slightly shifted towards Cox17(0S-S). In the IMS (mitochondrial intermembrane space), the equilibrium is shifted towards Cox17(2S-S), enabling retention of Cox17(2S-S) in the IMS and leading to the formation of a biologically competent form of the Cox17 protein, Cox17(2S-S), capable of copper transfer to the copper chaperone Sco1. XAS (X-ray absorption spectroscopy) determined that Cu4Cox17 contains a Cu4S6-type copper-thiolate cluster, which may provide safe storage of an excess of copper ions. PMID:17672825

  1. An appreciation of Richard Threlkeld Cox

    NASA Astrophysics Data System (ADS)

    Tribus, Myron

    2002-05-01

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

  2. Regression: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

  3. Stress and expression of cyclooxygenases (cox1, cox2a, cox2b) and intestinal eicosanoids, in Atlantic salmon, Salmo salar L.

    PubMed

    Olsen, R E; Svardal, A; Eide, T; Wargelius, A

    2012-08-01

    Prostaglandin H synthetases (cyclooxygenases) catalyze the initial reactions leading to prostanoids in animals. They form interesting links between diet and fish physiology as the type and nature of eicosanoids are affected by dietary lipid sources. Their expression is likely to be affected by tissues and environmental conditions leading to altered amount and ratio of eicosanoids. These mechanisms are, however, poorly understood in fish. In the present study, Atlantic salmon Salmo salar L. (1,000 g, 10°C, seawater) were subjected to acute chasing stress. Liver, kidney, spleen, gill, muscle, midgut and hindgut were extracted before and 1 h post-stress and analyzed for mRNA expression of cox1, cox2a and cox2b. Intestinal samples were further sampled over 24 h for both cox expression and analysis of 15 eicosanoids and isoprostanes of the n-3 and n-6 series. Results show a highly variable but consecutively expression of cox1, cox2a and cox2b in most of the tissues analyzed. Low levels were only found for cox2a in liver and cox2b in liver and kidney. The study reveals the general trend that cox1 is about 10 times the level of cox2b, which again is about 10 times the level of cox2a. Cox2b shows the highest level of expression in the gills indicating a possible higher requirement for this protein in gills. Imposing stress to the fish induces a temporal increase in the expression of cox2a in the midgut, while the gene expression of the other genes is not affected in any of the tissues analyzed. There is, however, a general tendency to increased expression of both cox2 genes that merits further studies. Stress had a profound effect on the intestinal eicosanoid content which showed a general decrease in midgut sections after stress that persisted for at least 24 h. PMID:22131071

  4. Molecular Dynamics Simulations of Arachidonic Acid Complexes with COX-1 and COX-2

    PubMed Central

    Furse, Kristina E.; Pratt, Derek A.; Porter, Ned A.; Lybrand, Terry P.

    2008-01-01

    The cyclooxygenase (COX) enzymes are responsible for the committed step in prostaglandin biosynthesis, the generation of prostaglandin H2. As a result, these enzymes are pharmacologically important targets for non-steroidal anti-inflammatory drugs, such as aspirin and newer COX-2 selective inhibitors. The cyclooxygenases are functional homodimers, and each subunit contains both a cyclooxygenase and a peroxidase active site. These enzymes are quite interesting mechanistically, as the conversion of arachidonic acid to prostaglandin H2 requires two oxygenation and two cyclization reactions, resulting in the formation of five new chiral centers with nearly absolute regio- and stereochemical fidelity. We have used molecular dynamics (MD) simulations to investigate the equilibrium behavior of both COX-1 and COX-2 enzyme isoforms with bound arachidonate. These simulations were compared with reference simulations of arachidonate in solution to explore the effect of enzyme on substrate conformation and positioning in the active site. The simulations suggest that the substrate has greater conformational freedom in the COX-2 active site, consistent with the larger COX-2 active site volume observed in X-ray crystal structures. The simulations reveal different conformational behavior for arachidonate in each subunit over the course of extended equilibrium MD simulations. The simulations also provide detailed information for several protein channels that might be important for oxygen and water transport to or from active sites, or for intermediate trafficking between the cyclooxygenase and peroxidase active sites. The detailed comparisons for COX-1 versus COX-2 active site structural fluctuations may also provide useful information for design of new isozyme-selective inhibitors. PMID:16519514

  5. Thinking outside the box about COX-1 in Alzheimer's disease.

    PubMed

    Frautschy, Sally A

    2010-06-01

    This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in Abeta pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention. PMID:20206264

  6. Thinking outside the box about COX-1 in Alzheimer's disease

    PubMed Central

    Frautschy, Sally A.

    2015-01-01

    This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in A? pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention. PMID:20206264

  7. EMPIRICAL LIKELIHOOD INFERENCE FOR THE COX MODEL WITH TIME-DEPENDENT COEFFICIENTS VIA LOCAL PARTIAL LIKELIHOOD

    PubMed Central

    Sun, Yanqing; Sundaram, Rajeshwari; Zhao, Yichuan

    2009-01-01

    The Cox model with time-dependent coefficients has been studied by a number of authors recently. In this paper, we develop empirical likelihood (EL) pointwise confidence regions for the time-dependent regression coefficients via local partial likelihood smoothing. The EL simultaneous confidence bands for a linear combination of the coefficients are also derived based on the strong approximation methods. The empirical likelihood ratio is formulated through the local partial log-likelihood for the regression coefficient functions. Our numerical studies indicate that the EL pointwise/simultaneous confidence regions/bands have satisfactory finite sample performances. Compared with the confidence regions derived directly based on the asymptotic normal distribution of the local constant estimator, the EL confidence regions are overall tighter and can better capture the curvature of the underlying regression coefficient functions. Two data sets, the gastric cancer data and the Mayo Clinic primary biliary cirrhosis data, are analyzed using the proposed method. PMID:19838322

  8. High-dimensional Cox models: the choice of penalty as part of the model building process.

    PubMed

    Benner, Axel; Zucknick, Manuela; Hielscher, Thomas; Ittrich, Carina; Mansmann, Ulrich

    2010-02-01

    The Cox proportional hazards regression model is the most popular approach to model covariate information for survival times. In this context, the development of high-dimensional models where the number of covariates is much larger than the number of observations (p>n) is an ongoing challenge. A practicable approach is to use ridge penalized Cox regression in such situations. Beside focussing on finding the best prediction rule, one is often interested in determining a subset of covariates that are the most important ones for prognosis. This could be a gene set in the biostatistical analysis of microarray data. Covariate selection can then, for example, be done by L(1)-penalized Cox regression using the lasso (Tibshirani (1997). Statistics in Medicine 16, 385-395). Several approaches beyond the lasso, that incorporate covariate selection, have been developed in recent years. This includes modifications of the lasso as well as nonconvex variants such as smoothly clipped absolute deviation (SCAD) (Fan and Li (2001). Journal of the American Statistical Association 96, 1348-1360; Fan and Li (2002). The Annals of Statistics 30, 74-99). The purpose of this article is to implement them practically into the model building process when analyzing high-dimensional data with the Cox proportional hazards model. To evaluate penalized regression models beyond the lasso, we included SCAD variants and the adaptive lasso (Zou (2006). Journal of the American Statistical Association 101, 1418-1429). We compare them with "standard" applications such as ridge regression, the lasso, and the elastic net. Predictive accuracy, features of variable selection, and estimation bias will be studied to assess the practical use of these methods. We observed that the performance of SCAD and adaptive lasso is highly dependent on nontrivial preselection procedures. A practical solution to this problem does not yet exist. Since there is high risk of missing relevant covariates when using SCAD or adaptive lasso applied after an inappropriate initial selection step, we recommend to stay with lasso or the elastic net in actual data applications. But with respect to the promising results for truly sparse models, we see some advantage of SCAD and adaptive lasso, if better preselection procedures would be available. This requires further methodological research. PMID:20166132

  9. Simple Logistic Regression

    NSDL National Science Digital Library

    Lowry, Richard, 1940-

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

  10. Cayley-Dixon Resultant Matrices of Multi-univariate Composed Polynomials

    Microsoft Academic Search

    Arthur D. Chtcherba; Deepak Kapur; Manfred Minimair

    2005-01-01

    The behavior of the Cayley-Dixon resultant construction and the structure of Dixon matrices are analyzed for composed polynomial systems constructed from a multivariate system in which each variable is substituted by a univariate polynomial in a distinct variable. It is shown that a Dixon projection operator (a multiple of the resultant) of the composed system can be expressed as a

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

    Microsoft Academic Search

    Victor Y. Pan

    2002-01-01

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

  12. Renal and cardiovascular characterization of COX-2 knockdown mice.

    PubMed

    Seta, Francesca; Chung, Andrew D; Turner, Patricia V; Mewburn, Jeffrey D; Yu, Ying; Funk, Colin D

    2009-06-01

    Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) increase the incidence of cardiovascular and cerebrovascular events. Complete disruption of the murine gene encoding COX-2 (Ptgs2) leads to renal developmental problems, as well as female reproductive anomalies and patent ductus arteriosus of variable penetrance in newborns, thus rendering this genetic approach difficult to compare with coxib administration. Here, we created hypomorphic Ptgs2 (COX-2(Neo/Neo)) mice in which COX-2 expression is suppressed to an extent similar to that achieved with coxibs, but not eliminated, in an attempt to circumvent these difficulties. In LPS-challenged macrophages and cytokine-stimulated endothelial cells obtained from COX-2(Neo/Neo) mice, COX-2 expression was reduced 70-90%, and these mice developed a mild renal phenotype compared with COX-2 mice possessing an active site mutation (COX-2(Y385F/Y385F)), with minimal signs of renal dysfunction as measured by FITC-inulin clearance and blood urea nitrogen. These COX-2 knockdown mice displayed an increased propensity for thrombogenesis compared with their wild-type (COX-2(+/+)) littermates observed by intravital microscopy in cremaster muscle arterioles upon ferric chloride challenge. Measurement of urinary prostanoid metabolites indicated that COX-2(Neo/Neo) mice produced 50% less prostacyclin but similar levels of PGE(2) and thromboxane compared with COX-2(+/+) mice in the absence of any blood pressure and ex vivo platelet aggregation abnormalities. COX-2(Neo/Neo) mice, therefore, provide a genetic surrogate of coxib therapy with disrupted prostacyclin biosynthesis that predisposes to induced arterial thrombosis. PMID:19357295

  13. The mitochondrial genome of Conus textile, coxI-coxII intergenic sequences and Conoidean evolution.

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Choquistic Regression: Generalizing Logistic Regression using the Choquet Integral

    E-print Network

    Hüllermeier, Eyke

    Choquistic Regression: Generalizing Logistic Regression using the Choquet Integral Ali Fallah preserv- ing two important properties of logistic regression, namely the comprehensibility of the model and benchmark data, choquistic regression consistently improves upon standard logistic regression in terms

  16. A consistent framework for Horton regression statistics that leads to a modified Hack's law

    USGS Publications Warehouse

    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.

  17. COX-2 signaling and cancer: new players in old arena.

    PubMed

    Misra, Shashank; Sharma, Kulbhushan

    2014-03-01

    Cancer is a leading cause of death worldwide. The expression of COX-2 and prostaglandins has not only been associated with various types of cancer but is also directly proportional to their aggressiveness including metastasis. Thus, inhibition of COX-2 activity has been one of the preferred targets for cancer reduction. Broad spectrum inhibition of all forms of COX (using NSAIDs) is associated with various side effects ranging from gastric ulceration to renal problems. Even specific COX-2 inhibitors (COXIBs) are associated with side effects like myocardial infarction. Alternative strategies including siRNA technology are also not very victorious due to their off-target associated problems. Thus, there is an urgent need for the development of strategies where COX-2 activity may be reduced without inducing any side effects. One of the approaches for designing novel inhibitors may be to target various molecules downstream of COX-2. In this review, we have tried to cover the basic biology of COX-2 and its association with different types of cancer. Various generations of COX-2 inhibitors have been covered with their merits and demerits. Possible exploitation of novel targets like EP receptors, mPGES and various other downstream molecules which can be utilized for a better COX-2 signaling inhibition and thus efficient cancer reduction with minimal side effects has been discussed. PMID:24467618

  18. Information and Asymptotic Efficiency of the Case-Cohort Sampling Design in Cox's Regression

    E-print Network

    Goldstein, Larry

    @cord.edu Larry Goldsteiny Department of Mathematics University: larry@math.usc.edu August 24, 2001 of the maximum pseudolikelihood and some related estimators for the case-cohort de* *sign in an i.i.d. setting

  19. Information and Asymptotic Eciency of the Case-Cohort Sampling Design in Cox's Regression

    E-print Network

    Goldstein, Larry

    email: zhang@cord.edu Larry Goldstein y Department of Mathematics University of Southern California Los Angeles, CA 90089-1113 email: larry@math.usc.edu August 24, 2001 #3; Phone: (218)299-4742; Fax: (218 of the maximum pseudolikelihood and some related estimators for the case-cohort design in an i.i.d. setting show

  20. Information and Asymptotic Efficiency of the Case-Cohort Sampling Design in Cox's Regression

    E-print Network

    Goldstein, Larry

    : zhang@cord.edu Larry Goldstein Department of Mathematics University of Southern California Los Angeles, CA 90089-1113 email: larry@math.usc.edu August 24, 2001 Phone: (218)299-4742; Fax: (218 of the maximum pseudolikelihood and some related estimators for the case-cohort design in an i.i.d. setting show

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

    E-print Network

    Parzen, Michael

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

  2. 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.

  3. Modeling and forecasting pelagic fish production using univariate and multivariate ARIMA models

    Microsoft Academic Search

    Efthymia V Tsitsika; Christos D Maravelias; John Haralabous

    2007-01-01

    Univariate and multivariate autoregressive integrated moving average (ARIMA) models were used to model and forecast the monthly\\u000a pelagic production of fish species in the Mediterranean Sea during 1990–2005. Autocorrelation (AC) and partial autocorrelation\\u000a (PAC) functions were estimated, which led to the identification and construction of seasonal ARIMA models, suitable in explaining\\u000a the time series and forecasting the future catch per

  4. Optimizing the design of an activated sludge\\/secondary clarifier system via univariate search technique

    Microsoft Academic Search

    S. L. Ong; G. S. Lee

    1987-01-01

    This article presents a simple and effective univariate search technique which is suitable for optimizing the design of an activated sludge\\/secondary clarifier system on microcomputers. The usefulness of the proposed optimal design procedure was tested on an IBM personal computer (IBM-PC). The results of this study indicated that the least-cost design of a typical activated sludge\\/secondary clarifier system can be

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

  6. 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…

  7. Preprocessing effects of 22 linear univariate features on the performance of seizure prediction methods.

    PubMed

    Rasekhi, Jalil; Mollaei, Mohammad Reza Karami; Bandarabadi, Mojtaba; Teixeira, Cesar A; Dourado, Antonio

    2013-07-15

    Combining multiple linear univariate features in one feature space and classifying the feature space using machine learning methods could predict epileptic seizures in patients suffering from refractory epilepsy. For each patient, a set of twenty-two linear univariate features were extracted from 6 electroencephalogram (EEG) signals to make a 132 dimensional feature space. Preprocessing and normalization methods of the features, which affect the output of the seizure prediction algorithm, were studied in terms of alarm sensitivity and false prediction rate (FPR). The problem of choosing an optimal preictal time was tackled using 4 distinct values of 10, 20, 30, and 40 min. The seizure prediction problem has traditionally been considered a two-class classification problem, which is also exercised here. These studies have been conducted on the features obtained from 10 patients. For each patient, 48 different combinations of methods are compared to find the best configuration. Normalization by dividing by the maximum and smoothing are found to be the best configuration in most of the patients. The results also indicate that applying machine learning methods on a multidimensional feature space of 22 univariate features predicted seizure onsets with high performance. On average, the seizures were predicted in 73.9% of the cases (34 out of 46 in 737.9h of test data), with a FPR of 0.15 h(-1). PMID:23567810

  8. Pulmonary Cyclooxygenase-1 (COX-1) and COX-2 Cellular Expression and Distribution After Respiratory Syncytial Virus and Parainfluenza Virus Infection

    PubMed Central

    Meyerholz, David K.; Ackermann, Mark R.

    2010-01-01

    Abstract Prostaglandins (PGs) play an important role in pulmonary physiology and various pathophysiological processes following infection. The initial step in the biosynthesis of PGs is regulated by two distinct cyclooxygenase enzymes, cyclooxygenase-1 (COX-1) and COX-2. The goal of this study was to investigate the pulmonary cellular localization and distribution of COX-1 and COX-2 in a neonatal lamb model following respiratory syncytial virus (RSV) and parainfluenza virus 3 (PI3) infection, organisms that also cause significant respiratory disease in children. No significant differences were seen in pulmonary COX-1 expression at various microanatomical locations following RSV or PI3 infection compared to controls. In contrast, COX-2 was upregulated following RSV and PI3 infection. Strong expression was restricted to bronchial and bronchiolar epithelial cells and macrophages, while minimal expression was present in the same microanatomical locations in the uninfected lungs. Other microanatomical locations in both the controls and the infected lungs lacked expression. This work suggests that during RSV or PI3 infection: (1) COX-1 cellular expression is not altered, (2) COX-2 cellular expression is upregulated in airway bronchiolar and bronchial epithelial cells and macrophages, (3) respiratory epithelium along with macrophages are important microanatomical compartments regulating the host inflammatory response during viral infection, and (4) COX-2 may be a potential target for RSV and PI3 therapy. PMID:20121401

  9. The Heme a Synthase Cox15 Associates with Cytochrome c Oxidase Assembly Intermediates during Cox1 Maturation

    PubMed Central

    Bareth, Bettina; Dennerlein, Sven; Mick, David U.; Nikolov, Miroslav; Urlaub, Henning

    2013-01-01

    Cox1, the core subunit of the cytochrome c oxidase, receives two heme a cofactors during assembly of the 13-subunit enzyme complex. However, at which step of the assembly process and how heme is inserted into Cox1 have remained an enigma. Shy1, the yeast SURF1 homolog, has been implicated in heme transfer to Cox1, whereas the heme a synthase, Cox15, catalyzes the final step of heme a synthesis. Here we performed a comprehensive analysis of cytochrome c oxidase assembly intermediates containing Shy1. Our analyses suggest that Cox15 displays a role in cytochrome c oxidase assembly, which is independent of its functions as the heme a synthase. Cox15 forms protein complexes with Shy1 and also associates with Cox1-containing complexes independently of Shy1 function. These findings indicate that Shy1 does not serve as a mobile heme carrier between the heme a synthase and maturing Cox1 but rather cooperates with Cox15 for heme transfer and insertion in early assembly intermediates of cytochrome c oxidase. PMID:23979592

  10. The predictive value of histological tumor regression grading (TRG) for therapeutic evaluation in locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy.

    PubMed

    Guo, Kang; Cai, Ling; Zhang, Yu; Zhu, Jian-Fei; Rong, Tie-Hua; Lin, Peng; Hao, Chong-Li; Wang, Wu-Ping; Li, Zhe; Zhang, Lan-Jun

    2012-08-01

    Response criteria remain controversial in therapeutic evaluation for locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy. We aimed to identify the predictive value of tumor regression grading (TRG) in tumor response and prognosis. Fifty-two patients who underwent neoadjuvant chemotherapy followed by esophagectomy and radical 2-field lymphadenectomy between June 2007 and June 2011 were included in this study. All tissue specimens were reassessed according to the TRG scale. Potential prognostic factors, including clinicopathologic factors, were evaluated. Survival curves were generated by using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors were determined with multivariate analysis by using the Cox regression model. Our results showed that of 52 cases, 43 (83%) were squamous cell carcinoma and 9 (17%) were adenocarcinoma. TRG was correlated with pathologic T(P = 0.006) and N (P < 0.001) categories. Median overall survival for the entire cohort was 33 months. The 1- and 2-year overall survival rates were 71% and 44%, respectively. Univariate survival analysis results showed that favorable prognostic factors were histological subtype (P = 0.003), pathologic T category (P = 0.026), pathologic N category (P < 0.001), and TRG G0 (P = 0.041). Multivariate analyses identified pathologic N category (P < 0.001) as a significant independent prognostic parameter. Our results indicate that histomorphologic TRG can be considered as an alternative option to predict the therapeutic efficacy and prognostic factor for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy. PMID:22572013

  11. Censored quantile regression with recursive partitioning-based weights.

    PubMed

    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

  12. Censored quantile regression with recursive partitioning-based weights

    PubMed Central

    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

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

    E-print Network

    Guenther, Frank

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

  14. THE COX-MAZE IV PROCEDURE: PREDICTORS OF LATE RECURRENCE

    PubMed Central

    Damiano, Ralph J.; Schwartz, Forrest H.; Bailey, Marci S.; Maniar, Hersh S.; Munfakh, Nabil A.; Moon, Marc R.; Schuessler, Richard B.

    2010-01-01

    Objectives The Cox-Maze III procedure(CMP) achieved high cure rates and became the surgical gold standard for the treatment of atrial fibrillation(AF). Due to its invasiveness, a more simplified ablation-assisted procedure(CMP-IV) has been performed at our institution since January, 2002. The study examined multiple preoperative and perioperative variables to determine predictors of late recurrence. Methods Data were collected prospectively on 282 patients who underwent the CMP-IV from January 2002 through December 2009. Forty-two percent of patients had paroxysmal and 58% had either persistent or long-standing persistent AF. All patients were available for follow-up. Follow-up included ECGs in all patients. Since 2006, 24 hour holter monitoring was obtained in 94% of patients at 3, 6 and 12 months. Data were analyzed by logistic regression analysis at 12 months with 13 preoperative and perioperative variables used as co-variants. Results Sixty-six percent of patients had a concomitant procedure. Following an ablation-assisted CMP, the freedom from AF was 89%, 93%, and 89% at 3, 6, and 12 months, respectively. The freedom from both AF and antiarrhythmic drugs was 63%, 79%, and 78% at 3, 6, and 12 months. The risk factors for AF recurrence at one year were enlarged left atrial(LA) diameter(p=0.027), failure to isolate the entire posterior left atrium(p=0.022), and early atrial tachyarrhythmias (ATAs)(p=0.010). Conclusions The CMP-IV has a high success rate at one year, even with improved follow-up and stricter definitions of failure. In patients with large LA, there may be a need for more extensive size reduction or expanded lesion sets. PMID:21168019

  15. Choquistic Regression: Generalizing Logistic Regression Using the Choquet Integral

    E-print Network

    Hüllermeier, Eyke

    Choquistic Regression: Generalizing Logistic Regression Using the Choquet Integral Ali Fallah, called choquistic regression, which generalizes conventional logistic regression and takes advantage of the Choquet integral as a flexible and expressive aggregation operator. Outline: (1) Background on logistic

  16. Morse-Smale Regression

    Microsoft Academic Search

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

    2012-01-01

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

  17. Incremental Hierarchical Discriminant Regression

    Microsoft Academic Search

    Juyang Weng; Wey-shiuan Hwang

    2007-01-01

    Abstract This paper presents Incremental Hierarchical Discriminant Regression (IHDR) which incrementally builds a decision tree or regression tree for very high dimensional regression or decision spaces by an online, real-time learning system. Biologically motivated, it is an approximate computational model for automatic development of associative cortex, with both bottom-up sensory inputs and top-down motor projections. At each internal node of

  18. 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.

  19. A comparative study between nonlinear regression and artificial neural network approaches for modelling wild oat (Avena fatua) field emergence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Non-linear regression techniques are used widely to fit weed field emergence patterns to soil microclimatic indices using S-type functions. Artificial neural networks present interesting and alternative features for such modeling purposes. In this work, a univariate hydrothermal-time based Weibull m...

  20. DISCUSS: Regression and Correlation

    NSDL National Science Digital Library

    Hunt, Neville

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

  1. Morse-Smale Regression

    PubMed Central

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

    2012-01-01

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

  2. Lesson 6: Linear Regression

    NSDL National Science Digital Library

    2011-01-01

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

  3. 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…

  4. Incremental Regression Testing

    Microsoft Academic Search

    Hiralal Agrawal; Joseph Robert Horgan; Edward W. Krauser; Saul A. London

    1993-01-01

    The purpose of regression testing is to ensure thatbug #xes and new functionality introduced in a newversion of a software do not adversely a#ect the correctfunctionality inheritedfrom the previous version.This paper explores e#cient methods of selecting smallsubsets of regression test sets that may be usedtoestablishthe same.

  5. Correlation and Regression

    NSDL National Science Digital Library

    Berger, Dale

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

  6. A Formally-Verified Decision Procedure for Univariate Polynomial Computation Based on Sturm's Theorem

    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.

  7. Measurements on Melting Pressure, Metastable Solid Phases, and Molar Volume of Univariant Saturated Helium Mixture

    NASA Astrophysics Data System (ADS)

    Rysti, J.; Manninen, M. S.; Tuoriniemi, J.

    2014-06-01

    A concentration-saturated helium mixture at the melting pressure consists of two liquid phases and one or two solid phases. The equilibrium system is univariant, whose properties depend uniquely on temperature. Four coexisting phases can exist on singular points, which are called quadruple points. As a univariant system, the melting pressure could be used as a thermometric standard. It would provide some advantages compared to the current reference, namely pure He, especially at the lowest temperatures below 1 mK. We have extended the melting pressure measurements of the concentration-saturated helium mixture from 10 to 460 mK. The density of the dilute liquid phase was also recorded. The effect of the equilibrium crystal structure changing from hcp to bcc was clearly seen at mK at the melting pressure MPa. We observed the existence of metastable solid phases around this point. No evidence was found for the presence of another, disputed, quadruple point at around 400 mK. The experimental results agree well with our previous calculations at low temperatures, but deviate above 200 mK.

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

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

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

  9. Post-translational regulation of COX2 activity by FYN in prostate cancer cells

    PubMed Central

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-01-01

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. PMID:24970799

  10. Boosted Beta Regression

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Ismail, A.; Hassan, Noor I.

    2013-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Subramaniyam, Narayan Puthanmadam; Hyttinen, Jari

    2015-02-01

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

  13. Univariate modelling of summer-monsoon rainfall time series: Comparison between ARIMA and ARNN

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Surajit; Chattopadhyay, Goutami

    2010-02-01

    The present article reports studies to develop a univariate model to forecast the summer monsoon (June-August) rainfall over India. Based on the data pertaining to the period 1871-1999, the trend and stationarity within the time series have been investigated. After revealing the randomness and non-stationarity within the time series, the autoregressive integrated moving average (ARIMA) models have been attempted and the ARIMA(0,1,1) has been identified as a suitable representative model. Consequently, an autoregressive neural network (ARNN) model has been attempted and the neural network has been trained as a multilayer perceptron with the extensive variable selection procedure. Sigmoid non-linearity has been used while training the network. Finally, a three-three-one architecture of the ARNN model has been obtained and after thorough statistical analysis the supremacy of ARNN has been established over ARIMA(0,1,1). The usefulness of ARIMA(0,1,1) has also been described.

  14. Compounding approach for univariate time series with non-stationary variances

    E-print Network

    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.

  15. Reliability and Regression Analysis

    NSDL National Science Digital Library

    Lane, David M.

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

  16. A comparative assessment of univariate longevity measures using zoological animal records

    PubMed Central

    Moorad, Jacob A.; Promislow, Daniel E. L.; Flesness, Nate; Miller, Richard A.

    2012-01-01

    Summary Comparative biogerontology evaluates cellular, molecular, physiological, and genomic properties that distinguish short-lived from long-lived species. These studies typically use maximum reported lifespan (MRLS) as the index against which to compare traits, but there is a general awareness that MRLS is not ideal due to statistical shortcomings that include bias resulting from small sample sizes. Nevertheless, MRLS has enough species-specific information to show strong associations with many other species-specific traits, such as body mass, stress resistance, and codon usage. The major goal of this study was to see if we could identify surrogate measures with better statistical properties than MRLS but that still capture inter-species differences in extreme lifespan. Using zoological records of 181 bird and mammal species, we evaluated 16 univariate metrics of aging and longevity, including non-parametric quantile-based measures and parameters derived from demographic models of aging, for three desirable statistical properties. We wished to identify those measures that: 1) correlated well with MRLS when the biasing effects of sample size were removed; 2) correlated weakly with population size; and 3) are highly robust to the effects of sampling error. Non-parametric univariate descriptors of the distribution of lifespans clearly outperformed the measures derived from demographic analyses. Mean adult lifespan and quantile-based measures, and in particular the 90th quantile of longevity, performed particularly well, demonstrating far less sensitivity to small-sample size effects than MRLS while preserving much of the information contained in the maximum lifespan measure. These measures should take the place of MRLS in comparative studies of lifespan. PMID:22805302

  17. Multivariate Real-Time Signal Extraction by a Robust Adaptive Regression Filter

    Microsoft Academic Search

    Matthias Borowski; Karen Schettlinger; Ursula Gather

    2009-01-01

    We propose a new regression-based filter for extracting signals online from multivariate high frequency time series. It separates relevant signals of several variables from noise and (multivariate) outliers.Unlike parallel univariate filters, the new procedure takes into account the local covariance structure between the single time series components. It is based on high-breakdown estimates, which makes it robust against (patches of)

  18. Logistic Regression Longitudinal Data Analysis

    E-print Network

    Bardsley, John

    Logistic Regression Longitudinal Data Analysis Stat 491: Biostatistics Chapter 13: Methods for Epidemiological Studies Stat 491: Biostatistics #12;Logistic Regression Longitudinal Data Analysis Simple Logistic. Chapter 13: Methods for Epidemiological Studies Stat 491: Biostatistics #12;Logistic Regression

  19. Novel Harmonic Regularization Approach for Variable Selection in Cox's Proportional Hazards Model

    PubMed Central

    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

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

    Microsoft Academic Search

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

    1996-01-01

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

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

    PubMed

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

    2014-12-30

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

  2. Vascular COX-2 Modulates Blood Pressure and Thrombosis in Mice

    PubMed Central

    Yu, Ying; Ricciotti, Emanuela; Scalia, Rosario; Tang, Soon Yew; Grant, Gregory; Yu, Zhou; Landesberg, Gavin; Crichton, Irene; Wu, Weichen; Puré, Ellen; Funk, Colin D.; FitzGerald, Garret A.

    2013-01-01

    Prostacyclin (PGI2) is a vasodilator and platelet inhibitor, properties consistent with cardioprotection. More than a decade ago, inhibition of cyclooxygenase-2 (COX-2) by the nonsteroidal anti-inflammatory drugs (NSAIDs) rofecoxib and celecoxib was found to reduce the amount of the major metabolite of PGI2 (PGI-M) in the urine of healthy volunteers. This suggested that NSAIDs might cause adverse cardiovascular events by reducing production of cardioprotective PGI2. This prediction was based on the assumption that the concentration of PGI-M in urine likely reflected vascular production of PGI2 and that other cardioprotective mediators, especially nitric oxide (NO), were not able to compensate for the loss of PGI2. Subsequently, eight placebo-controlled clinical trials showed that NSAIDs that block COX-2 increase adverse cardiovascular events. We connect tissue-specific effects of NSAID action and functional correlates in mice with clinical outcomes in humans by showing that deletion of COX-2 in the mouse vasculature reduces excretion of PGI-M in urine and predisposes the animals to both hypertension and thrombosis. Furthermore, vascular disruption of COX-2 depressed expression of endothelial NO synthase and the consequent release and function of NO. Thus, suppression of PGI2 formation resulting from deletion of vascular COX-2 is sufficient to explain the cardiovascular hazard from NSAIDs, which is likely to be augmented by secondary mechanisms such as suppression of NO production. PMID:22553252

  3. RNA editing intermediates of cox2 transcripts in maize mitochondria.

    PubMed Central

    Yang, A J; Mulligan, R M

    1991-01-01

    Eighteen cytidines are changed to uridines in the coding sequence of transcripts for cytochrome c oxidase subunit 2 (cox2) in maize mitochondria. The temporal relationship of editing and splicing was examined in cox2 transcripts by sequence analysis of spliced and unspliced cDNAs. Cloned cDNAs of unspliced cox2 transcripts ranged from clones with no edited nucleotides to completely edited forms, while spliced cDNAs were nearly completely edited. Incompletely edited transcripts in the nascent pool of unspliced transcripts represent intermediates of the editing process. These results indicate that editing proceeds without a strong directional bias and suggest that RNA editing is a posttranscriptional process. Images PMID:1712908

  4. Tobacco taxes and regressivity.

    PubMed

    Gospodinov, Nikolay; Irvine, Ian

    2009-03-01

    Recent literature on tobacco taxation suggests that optimal tax rates should be very high. But such high taxes raise concerns over regressivity. Most econometric estimates of elasticities by income group use historic price data that are low, and the usefulness of such estimates is therefore questionable on account of the serious 'out of sample' prediction problem. To address that problem, this paper estimates price elasticities for different socioeconomic groups using recent Canadian survey data for a period during which prices rose to a level of about $7 per pack. The results provide little reason to overturn the traditional concerns about regressivity. PMID:19091432

  5. 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.

  6. 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.

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

    PubMed

    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

  8. Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis.

    PubMed

    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

  9. Molecular Dynamics Simulations of Arachidonic Acid-Derived Pentadienyl Radical Intermediate Complexes with COX-1 and COX-2

    PubMed Central

    Furse, Kristina E.; Pratt, Derek A.; Schneider, Claus; Brash, Alan R.; Porter, Ned A.; Lybrand, Terry P.

    2008-01-01

    The two cyclooxygenase enzymes, COX-1 and COX-2, are responsible for the committed step in prostaglandin biosynthesis, and are the targets of the non-steroidal anti-inflammatory drugs aspirin, ibuprofen and the COX-2 selective inhibitors, Celebrex™, Vioxx™ and Bextra™. The enzymes are remarkable in that they catalyze two dioxygenations and two cyclizations of the native substrate, arachidonic acid, with near absolute regio- and stereoselectivity. Several theories have been advanced to explain the nature of enzymatic control over this series of reactions, including suggestions of steric shielding and oxygen channeling. As proposed here, selective radical trapping and spin localization in the substrate-derived pentadienyl radical intermediate can also be envisioned. Herein we describe the results of explicit, 10 ns molecular dynamics simulations of both COX-1 and COX-2 with the substrate-derived pentadienyl radical intermediate bound in the active site. The enzymes’ influence on the conformation of the pentadienyl radical was investigated, along with the accessible space above and below the radical plane, and the width of several channels to the active site that could function as access routes for molecular oxygen. Additional simulations demonstrated the extent of molecular oxygen mobility within the active site. The results suggest that spin localization is unlikely to play a role in enzymatic control of this reaction. Instead, a combination of oxygen channeling, steric shielding and selective radical trapping appears to be responsible. This work adds a dynamic perspective to the strong foundation of static structural data available for these enzymes. PMID:16519515

  10. Induction of COX-2 Enzyme and Down-regulation of COX-1 Expression by Lipopolysaccharide (LPS) Control Prostaglandin E2 Production in Astrocytes*

    PubMed Central

    Font-Nieves, Miriam; Sans-Fons, M. Glòria; Gorina, Roser; Bonfill-Teixidor, Ester; Salas-Pérdomo, Angélica; Márquez-Kisinousky, Leonardo; Santalucia, Tomàs; Planas, Anna M.

    2012-01-01

    Pathological conditions and pro-inflammatory stimuli in the brain induce cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism mediating the production of prostanoids that, among other actions, have strong vasoactive properties. Although low basal cerebral COX-2 expression has been reported, COX-2 is strongly induced by pro-inflammatory challenges, whereas COX-1 is constitutively expressed. However, the contribution of these enzymes in prostanoid formation varies depending on the stimuli and cell type. Astrocyte feet surround cerebral microvessels and release molecules that can trigger vascular responses. Here, we investigate the regulation of COX-2 induction and its role in prostanoid generation after a pro-inflammatory challenge with the bacterial lipopolysaccharide (LPS) in astroglia. Intracerebral administration of LPS in rodents induced strong COX-2 expression mainly in astroglia and microglia, whereas COX-1 expression was predominant in microglia and did not increase. In cultured astrocytes, LPS strongly induced COX-2 and microsomal prostaglandin-E2 (PGE2) synthase-1, mediated by the MyD88-dependent NF?B pathway and influenced by mitogen-activated protein kinase pathways. Studies in COX-deficient cells and using COX inhibitors demonstrated that COX-2 mediated the high production of PGE2 and, to a lesser extent, other prostanoids after LPS. In contrast, LPS down-regulated COX-1 in an MyD88-dependent fashion, and COX-1 deficiency increased PGE2 production after LPS. The results show that astrocytes respond to LPS by a COX-2-dependent production of prostanoids, mainly vasoactive PGE2, and suggest that the coordinated down-regulation of COX-1 facilitates PGE2 production after TLR-4 activation. These effects might induce cerebral blood flow responses to brain inflammation. PMID:22219191

  11. Impact of Blood Type, Functional Polymorphism (T-1676C) of the COX-1 Gene Promoter and Clinical Factors on the Development of Peptic Ulcer during Cardiovascular Prophylaxis with Low-Dose Aspirin

    PubMed Central

    Wang, Pin-Yao; Chen, Hsiu-Ping; Chen, Angela; Tsay, Feng-Woei; Kao, Sung-Shuo; Peng, Nan-Jing; Tseng, Hui-Hwa; Hsu, Ping-I

    2014-01-01

    Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin. PMID:25243161

  12. Morse-Smale Regression

    E-print Network

    Samuel Gerber

    2011-01-01

    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

  13. Multiple Linear Regressions Analysis

    NSDL National Science Digital Library

    Arsham, Hossein

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

  14. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

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

  15. Logistic Regression Diagnostics

    Microsoft Academic Search

    Daryl Pregibon

    1981-01-01

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

  16. Multivariate Adaptive Regression Splines

    Microsoft Academic Search

    Jerome H. Friedman

    1991-01-01

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

  17. Multiple Linear Regression

    NSDL National Science Digital Library

    Lacey, Michelle

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

  18. 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.…

  19. Mechanisms of neuroblastoma regression

    PubMed Central

    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

  20. Bayesian ARTMAP for regression.

    PubMed

    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

  1. Adaptation of a one-step worst-case optimal univariate algorithm of bi-objective Lipschitz optimization to multidimensional problems

    NASA Astrophysics Data System (ADS)

    Žilinskas, Antanas; Žilinskas, Julius

    2015-04-01

    A bi-objective optimization problem with Lipschitz objective functions is considered. An algorithm is developed adapting a univariate one-step optimal algorithm to multidimensional problems. The univariate algorithm considered is a worst-case optimal algorithm for Lipschitz functions. The multidimensional algorithm is based on the branch-and-bound approach and trisection of hyper-rectangles which cover the feasible region. The univariate algorithm is used to compute the Lipschitz bounds for the Pareto front. Some numerical examples are included.

  2. The three-class ideal observer for univariate normal data: Decision variable and ROC surface properties.

    PubMed

    Edwards, Darrin C; Metz, Charles E

    2012-08-01

    Although a fully general extension of ROC analysis to classification tasks with more than two classes has yet to be developed, the potential benefits to be gained from a practical performance evaluation methodology for classification tasks with three classes have motivated a number of research groups to propose methods based on constrained or simplified observer or data models. Here we consider an ideal observer in a task with underlying data drawn from three univariate normal distributions. We investigate the behavior of the resulting ideal observer's decision variables and ROC surface. In particular, we show that the pair of ideal observer decision variables is constrained to a parametric curve in two-dimensional likelihood ratio space, and that the decision boundary line segments used by the ideal observer can intersect this curve in at most six places. From this, we further show that the resulting ROC surface has at most four degrees of freedom at any point, and not the five that would be required, in general, for a surface in a six-dimensional space to be non-degenerate. In light of the difficulties we have previously pointed out in generalizing the well-known area under the ROC curve performance metric to tasks with three or more classes, the problem of developing a suitable and fully general performance metric for classification tasks with three or more classes remains unsolved. PMID:23162165

  3. Univariate and multivariate analysis of tannin-impregnated wood species using vibrational spectroscopy.

    PubMed

    Schnabel, Thomas; Musso, Maurizio; Tondi, Gianluca

    2014-01-01

    Vibrational spectroscopy is one of the most powerful tools in polymer science. Three main techniques--Fourier transform infrared spectroscopy (FT-IR), FT-Raman spectroscopy, and FT near-infrared (NIR) spectroscopy--can also be applied to wood science. Here, these three techniques were used to investigate the chemical modification occurring in wood after impregnation with tannin-hexamine preservatives. These spectroscopic techniques have the capacity to detect the externally added tannin. FT-IR has very strong sensitivity to the aromatic peak at around 1610 cm(-1) in the tannin-treated samples, whereas FT-Raman reflects the peak at around 1600 cm(-1) for the externally added tannin. This high efficacy in distinguishing chemical features was demonstrated in univariate analysis and confirmed via cluster analysis. Conversely, the results of the NIR measurements show noticeable sensitivity for small differences. For this technique, multivariate analysis is required and with this chemometric tool, it is also possible to predict the concentration of tannin on the surface. PMID:24694706

  4. Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood.

    PubMed

    Ribeiro, Daniela; Freitas, Marisa; Tomé, Sara M; Silva, Artur M S; Laufer, Stefan; Lima, José L F C; Fernandes, Eduarda

    2015-04-01

    Cyclooxygenase 2 (COX-2) and the production of cytokines/chemokines are important targets for the modulation of the inflammatory response. Although a large variety of inhibitors of these pathways have been commercialized, some of those inhibitors present severe side effects, governing the search for new molecules, as alternative anti-inflammatory agents. This study was undertaken to study an hitherto not evaluated group of flavonoids, concerning its capacity to inhibit COX-1 and COX-2 enzymes, as well as to inhibit the production of the cytokines and a chemokine, in a complex matrix involved in the systemic inflammatory process, the blood, aiming the establishment of a structure-activity relationship. The results obtained reveal promising flavonoids for the modulation of the inflammatory process, namely the ones presenting a catechol group in B ring, as some flavonoids were able to simultaneously inhibit the production of inflammatory prostaglandin E2 and pro-inflammatory cytokines. PMID:25139581

  5. Orthogonal Regression: A Teaching Perspective

    ERIC Educational Resources Information Center

    Carr, James R.

    2012-01-01

    A well-known approach to linear least squares regression is that which involves minimizing the sum of squared orthogonal projections of data points onto the best fit line. This form of regression is known as orthogonal regression, and the linear model that it yields is known as the major axis. A similar method, reduced major axis regression, is…

  6. Logistic regression Weakly informative priors

    E-print Network

    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

  7. ENSO Nonlinear Regression Model

    NASA Astrophysics Data System (ADS)

    Kondrashov, D.; Kravtsov, S.; Ghil, M.

    2003-04-01

    A multiple polynomial regression of sea-surface temperature anomalies (SSTA) is used to build and compare linear and nonlinear stochastically forced models of ENSO. It is shown that the nonlinear model has a significantly better forecast skill for Nino3.4 SSTA than its linear counterpart, in particular during strong warm ENSO events. The 1950-2002 Kaplan extended SSTA dataset (IRI/LDEO Climate Data Library), 60N-30S, 30E-110W, is used to train and validate the models. Both linear and nonlinear models are trained on 1950-1996, and validated on1997-2002 SSTA data, which includes the strong 1997-1998 warm ENSO event. We apply a multi-layer generalization of multiple polynomial regression where the residual stochastic forcing at a given level is modeled as a function of variables at the current, and all preceding levels. The number of levels is determined so that the lag-0 covariance of the residual forcing converges to a constant matrix, while its lag-1 covariance vanishes. Regression models are obtained via partial least-square (PLS) cross-validation procedure, where the leading empirical orthogonal functions (EOFs) of SSTA are chosen to build predictor variables for the regression model’s first level. PLS finds the so-called factors, or latent variables that both capture the maximum variance in the predictor variables, and achieve high correlation with response variables. The phase-locking of ENSO to annual cycle in the model is achieved by adding the linear seasonal forcing on the first regression level. A better performance of the nonlinear model is associated with its ability to simulate a non-Gaussian distribution of ENSO events, with warm events having larger amplitude than cold events. This property cannot be captured in a linear model.

  8. The issue of multiple univariate comparisons in the context of neuroelectric brain mapping: An application in a neuromarketing experiment

    Microsoft Academic Search

    G. Vecchiato; F. De Vico Fallani; L. Astolfi; J. Toppi; F. Cincotti; D. Mattia; S. Salinari; F. Babiloni

    2010-01-01

    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

  9. Univariate and Multivariate Omnibus Hypothesis Tests Selected to Control Type I Error Rates When Population Variances Are Not Necessarily Equal.

    ERIC Educational Resources Information Center

    Coombs, William T.; And Others

    1996-01-01

    Methods to compare population means in the univariate case and population mean vectors in the multivariate case are presented in terms of hypotheses tested by various procedures. Tests relevant to each hypothesis are described and compared in terms of maximizing power while controlling Type I error rates over the widest variety of conditions. (SLD)

  10. Two Dimensions Are Not Better than One: STREAK and the Univariate Signal Detection Model of Remember/Know Performance

    ERIC Educational Resources Information Center

    Starns, Jeffrey J.; Ratcliff, Roger

    2008-01-01

    We evaluated STREAK and the univariate signal detection model of Remember/Know (RK) judgments in terms of their ability to fit empirical data and produce psychologically meaningful parameter estimates. Participants studied pairs of words and completed item recognition tests with RK judgments as well as associative recognition tests. Fits to the RK…

  11. COX-2 Protects against Atherosclerosis Independently of Local Vascular Prostacyclin: Identification of COX-2 Associated Pathways Implicate Rgl1 and Lymphocyte Networks

    PubMed Central

    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

  12. Evaluating the efficiency of spectral resolution of univariate methods manipulating ratio spectra and comparing to multivariate methods: an application to ternary mixture in common cold preparation.

    PubMed

    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

  13. Evaluating the efficiency of spectral resolution of univariate methods manipulating ratio spectra and comparing to multivariate methods: An application to ternary mixture in common cold preparation

    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.

  14. Determining Factors That Predict Technique Survival on Peritoneal Dialysis: Application of Regression and Artificial Neural Network Methods

    Microsoft Academic Search

    Navdeep Tangri; David Ansell; David Naimark

    2011-01-01

    Background\\/Aims: Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of patients with end-stage renal disease. PD technique failure has been cited as one of the reasons for this decline. The purpose of this study was to compare the factors that predict technique survival using artificial neural network (ANN) and logistic and Cox regression methods.

  15. Bias Correction Methods for Misclassified Covariates in the Cox Model: comparison offive correction methods by simulation and data analysis

    PubMed Central

    Bang, Heejung; Chiu, Ya-Lin; Kaufman, Jay S.; Patel, Mehul D.; Heiss, Gerardo; Rose, Kathryn M.

    2013-01-01

    Measurement error/misclassification is commonplace in research when variable(s) can notbe measured accurately. A number of statistical methods have been developed to tackle this problemin a variety of settings and contexts. However, relatively few methods are available to handlemisclassified categorical exposure variable(s) in the Cox proportional hazards regression model. Inthis paper, we aim to review and compare different methods to handle this problem - naïvemethods, regression calibration, pooled estimation, multiple imputation, corrected score estimation,and MC-SIMEX - by simulation. These methods are also applied to a life course study with recalleddata and historical records. In practice, the issue of measurement error/misclassification should beaccounted for in design and analysis, whenever possible. Also, in the analysis, it could be moreideal to implement more than one correction method for estimation and inference, with properunderstanding of underlying assumptions. PMID:24072991

  16. James R. Cox Auditorium, Alumni Hall The University of Tennessee

    E-print Network

    Grissino-Mayer, Henri D.

    James R. Cox Auditorium, Alumni Hall The University of Tennessee SCHOOL OF MUSIC UNDERGRADUATE;#12;2008-2009 Undergraduate Handbook iii SCHOOL OF MUSIC UNIVERSITY OF TENNESSEE KNOXVILLE UNDERGRADUATE HANDBOOK SCHOOL the musical and educational lives of its students, the university community and citizens of Tennessee

  17. English in the National Curriculum: The Cox Report.

    ERIC Educational Resources Information Center

    Use of English, 1989

    1989-01-01

    Discusses implications of the Cox Report on English instruction in Great Britain. Questions the definitions of aims and responsibilities outlined in the report. Suggests that the magnitude of what teachers are called upon to teach and assess will diffuse rather than concentrate attention on what matters most in English as a distinctive subject.…

  18. Analysis of Censored Environmental Data with Box-Cox Transformations

    E-print Network

    District of Columbia, University of the

    Modarres2 1 Office of Water, U.S. Environmental Protection Agency E-Mail: lee-freeman.jade@epa.gov 2 the detection limits. The method uses a Box-Cox transformation, of which the parameters are found by maximizing transformations and the coverage rate for highly skew data sets. The method is applied to water quality monitoring

  19. On nonsingular potentials of Cox-Thompson inversion scheme

    SciTech Connect

    Palmai, Tamas; Apagyi, Barnabas [Department of Theoretical Physics, Budapest University of Technology and Economics, H-1111 Budapest (Hungary)

    2010-02-15

    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.

  20. [Atypical tumor regression].

    PubMed

    Heitplatz, B; Müller, K-M

    2013-11-01

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

  1. Fast Censored Linear Regression

    PubMed Central

    HUANG, YIJIAN

    2013-01-01

    Weighted log-rank estimating function has become a standard estimation method for the censored linear regression model, or the accelerated failure time model. Well established statistically, the estimator defined as a consistent root has, however, rather poor computational properties because the estimating function is neither continuous nor, in general, monotone. We propose a computationally efficient estimator through an asymptotics-guided Newton algorithm, in which censored quantile regression methods are tailored to yield an initial consistent estimate and a consistent derivative estimate of the limiting estimating function. We also develop fast interval estimation with a new proposal for sandwich variance estimation. The proposed estimator is asymptotically equivalent to the consistent root estimator and barely distinguishable in samples of practical size. However, computation time is typically reduced by two to three orders of magnitude for point estimation alone. Illustrations with clinical applications are provided. PMID:24347802

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

    PubMed

    Maldonado-Rojas, Wilson; Olivero-Verbel, Jesus

    2011-09-01

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

  3. Linear Regression and Correlation

    NSDL National Science Digital Library

    2011-05-24

    This lesson is designed to further students' understanding of the concept of correlation as it relates to linear regression. This lesson provides links to discussions and activities related to scatter plots, correlation, and lines of best-fit as well as suggested ways to integrate them into the lesson. Finally, the lesson provides links to follow-up lessons designed for use in succession with the current one.

  4. Univariate and multivariate methods for chemical mapping of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

    2012-01-01

    Visualization of cells and subcellular organelles are currently carried out using available microscopy methods such as cryoelectron microscopy, and fluorescence microscopy. These methods require external labeling using fluorescent dyes and extensive sample preparations to access the subcellular structures. However, Raman micro-spectroscopy provides a non-invasive, label-free method for imaging the cells with chemical specificity at sub-micrometer spatial resolutions. The scope of this paper is to image the biochemical/molecular distributions in cells associated with cancerous changes. Raman map data sets were acquired from the human cervical carcinoma cell lines (HeLa) after fixation under 785 nm excitation wavelength. The individual spectrum was recorded by raster-scanning the laser beam over the sample with 1?m step size and 10s exposure time. Images revealing nucleic acids, lipids and proteins (phenylalanine, amide I) were reconstructed using univariate methods. In near future, the small pixel to pixel variations will also be imaged using different multivariate methods (PCA, clustering (HCA, K-means, FCM)) to determine the main cellular constitutions. The hyper-spectral image of cell was reconstructed utilizing the spectral contrast at different pixels of the cell (due to the variation in the biochemical distribution) without using fluorescent dyes. Normal cervical squamous cells will also be imaged in order to differentiate normal and cancer cells of cervix using the biochemical changes in different grades of cancer. Based on the information obtained from the pseudo-color maps, constructed from the hyper-spectral cubes, the primary cellular constituents of normal and cervical cancer cells were identified.

  5. The resistance to the tumor suppressive effects of COX inhibitors and COX2 gene disruption in TRAMP mice is associated with the loss of COX expression in prostate tissue

    Microsoft Academic Search

    Xingya Wang; Jennifer K. L. Colby; Peiying Yang; Susan M. Fischer; Robert A. Newman; Russell D. Klein

    Over-expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 has been demonstrated to play a significant role in the tumor- igenesis of colon, lung, breast, bladder and skin. However, incon- sistent and controversial reports on the expression and activity of COX-2 in prostate cancer raised the question of whether COX-2 plays a pivotal role in prostate carcinogenesis. To address this question, we

  6. On the Fringe: Community Dynamics at Cox Ranch Pueblo Andrew I. Duff

    E-print Network

    Kohler, Tim A.

    for the last three years. THE COX RANCH PUEBLO COMMUNITY RESEARCH PROJECT Cox Ranch Pueblo is located about 5 of areas above the rim than below, with a broad, dry, and presently barren flood plain, low relief mesas

  7. The close correlation between heparanase and COX-2 expression in lymphangiogenesis of cervical cancer.

    PubMed

    Zeng, Chao; Chen, Lili; Yang, Zheng; Sun, Shijun

    2014-12-01

    Recent observations indicate the vital role of heparanase in tumor lymphangiogenesis. Moreover, heparanase is involved in angiogenesis in esophageal cancer through induction of COX-2. However, it is unclear whether heparanase is also associated with COX-2 in lymphangiogenesis of cervical cancer. In this study, heparanase, COX-2 and VEGF-C expression were examined in 80 cervical cancer cases by immunohistochemical staining. We also studied the correlation of heparanase and COX-2 expression with lymphangiogenesis of cervical cancer quantified as lymphatic vessel density. Our results showed that expressions of heparanase and COX-2 were associated with lymphangiogenesis of cervical cancer. Furthermore, a significant correlation was found between the expression of heparanase and COX-2 (P < 0.0001). Heparanase is positively correlated with expressions of COX-2 and VEGF-C. These findings revealed that heparanase may play important function in lymphangiogenesis of cervical cancer via the regulation of COX-2 expression. PMID:25370734

  8. Aspirin-Induced COX2 Overexpression in Monocytes of Aspirin-Intolerant Patients

    Microsoft Academic Search

    Tina Morgan; Nissera Bajrovic; Mira Silar; Mitja Kosnik; Peter Korosec

    2009-01-01

    Background: We hypothesize that alternate regulation of cyclooxygenase-2 (COX-2) may predispose patients to aspirin-induced exacerbations.Therefore, we want to examine the dynamics of COX-2 up-regulation in whole blood monocytes in the presence and absence of aspirin. Methods: COX-2 expression was evaluated by flow cytometry through intracellular staining of whole blood monocytes with antiCOX-2 antibodies. Enzyme up-regulation was monitored after in vitrostimulation

  9. Consistent Condom Use Increases the Regression Rate of Cervical Intraepithelial Neoplasia 2–3

    PubMed Central

    Munk, Ane Cecilie; Gudlaugsson, Einar; Malpica, Anais; Fiane, Bent; Løvslett, Kjell I.; Kruse, Arnold-Jan; Øvestad, Irene Tveiterås; Voorhorst, Feja; Janssen, Emiel A. M.; Baak, Jan P. A.

    2012-01-01

    Objective Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6–50% regress spontaneously. The aim of this study was to examine the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3. Methods In this prospective population-based cohort study 170 women aged 25–40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ?CIN1 in the cone biopsy. Results The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n?=?20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p?=?0.001, hazard ratio?=?4.4). Conclusion Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate. PMID:23028792

  10. Regression of follicular lymphoma with Devil’s Claw: coincidence or causation?

    PubMed Central

    Wilson, K.S.

    2009-01-01

    Background Cancer patients frequently use alternative therapies. Two follicular lymphoma patients who had objective tumour regression after taking Devil’s Claw without cytotoxic therapy are reported here. Methods and Results Patient 1 presented with coexistent immunoglobulin G plasma cell dyscrasia and stage iiia lymphoma (nodes 5 cm in diameter). Computed tomography scan 10 months later showed partial regression. On enquiry, it was learned that the patient was taking Devil’s Claw and Essiac (Essiac Products Services, Pompano Beach, FL, U.S.A.). This patient later developed overt myeloma, at which time he stopped the herbal supplements and underwent high-dose chemotherapy and stem cell transplantation, since which no lymphoma progression has occurred. Patient 2 presented with stage iiia lymphoma (nodes 2.5 cm in diameter). He learned of patient 1 through our lymphoma patient support group and started Devil’s Claw. Computed tomography scan 11 months later showed decreased adenopathy and splenomegaly, which has been sustained for 4 years. Discussion and Conclusions Devil’s Claw tuberous root has anti-inflammatory properties, probably through suppression of cyclooxygenase 2 (cox-2) and inducible nitric oxide synthase expression. There are no prior reports of anticancer activity. Inhibition of cox-2 has a role in colon cancer prevention, has been implicated in lymphomagenesis, and is associated both with lymphoma stage and with response to treatment. However, spontaneous regression in lymphoma has been reported in 16% of patients in one series, of whom none were on herbal medications or cox-2 inhibitors. The key issue in both these patients is whether disease regression was “spontaneous” or causally related to therapy with Devil’s Claw. The timing of the response suggests a positive effect. Further investigation is warranted, preferably with a cox-2 inhibitor of known purity. PMID:19672427

  11. Hierarchical Regression without Phantom Factors.

    ERIC Educational Resources Information Center

    Bentler, Peter M.; Satorra, Albert

    2000-01-01

    Shows that phantom factors are unnecessary to achieve the objectives of a hierarchical regression and gives a direct approach to computing hierarchical or fixed-order regressions that is equivalent to that proposed by P. de Jong (1999).(SLD)

  12. Empirical Bayes logistic regression.

    PubMed

    Strimenopoulou, Foteini; Brown, Philip J

    2008-01-01

    We construct a diagnostic predictor for patient disease status based on a single data set of mass spectra of serum samples together with the binary case-control response. The model is logistic regression with Bernoulli log-likelihood augmented either by quadratic ridge or absolute L1 penalties. For ridge penalization using the singular value decomposition we reduce the number of variables for maximization to the rank of the design matrix. With log-likelihood loss, 10-fold cross-validatory choice is employed to specify the penalization hyperparameter. Predictive ability is judged on a set-aside subset of the data. PMID:18312223

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

    E-print Network

    Palmer, Jeffrey

    Gene transfer from mitochondrion to nucleus: novel mechanisms for gene activation from Cox2 Daniel The evolutionarily recent transfer of the gene for cytochrome c oxidase subunit 2 (cox2) from the mitochondrion this presequence post-import, are considered to be essential adaptations for targeting of Cox2 to the mitochondrion

  14. COX2 Inhibition Combined with Radiation Reduces Orthotopic Glioma Outgrowth by Targeting the Tumor Vasculature1

    Microsoft Academic Search

    Michiel Wagemakers; Gesiena E. van der Wal; Rosa Cuberes; Inés Álvarez; Jordi Buxens; José M. Vela; Henk Moorlag; Jan Jakob; A. Mooij; Grietje Molema

    Cyclooxygenase 2 (COX-2) inhibitors have been shown to enhance tumor's response to radiation in several animal models. The strong association of COX-2 and angiogenesis suggests that the tumor vasculature may be involved in this process. The current study investigated whether treatment with the COX-2 inhibitor E-6087 could influence response to local radiation in orthotopically growing murine gliomas and aimed to

  15. Kinetics and docking studies of a COX-2 inhibitor isolated from Terminalia bellerica fruits.

    PubMed

    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

  16. Shape-preserving, multiscale interpolation by univariate curvature-based cubic L1 splines in Cartesian and polar coordinates

    Microsoft Academic Search

    John E. Lavery

    2002-01-01

    We investigate C1-smooth univariate curvature-based cubic L1 interpolating splines in Cartesian and polar coordinates. The coefficients of these splines are calculated by minimizing the L1 norm of curvature. We compare these curvature-based cubic L1 splines with second-derivative-based cubic L1 splines and with cubic L2 splines based on the L2 norm of curvature and of the second derivative. In computational experiments

  17. Design-adaptive Nonparametric Regression

    Microsoft Academic Search

    Jianqing Fan

    1992-01-01

    In this article we study the method of nonparametric regression based on a weighted local linear regression. This method has advantages over other popular kernel methods. Moreover, such a regression procedure has the ability of design adaptation: It adapts to both random and fixed designs, to both highly clustered and nearly uniform designs, and even to both interior and boundary

  18. Local Walsh-average regression

    Microsoft Academic Search

    Long Feng; Changliang Zou; Zhaojun Wang

    2012-01-01

    Local polynomial regression is widely used for nonparametric regression. However, the efficiency of least squares (LS) based methods is adversely affected by outlying observations and heavy tailed distributions. On the other hand, the least absolute deviation (LAD) estimator is more robust, but may be inefficient for many distributions of interest. Kai et al. (2010) [13] propose a nonparametric regression technique

  19. Cox rings, semigroups and automorphisms of affine algebraic varieties

    SciTech Connect

    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.

  20. Structural regression trees

    SciTech Connect

    Kramer, S. [Austrian Research Inst. for Artificial Intelligence, Vienna (Austria)

    1996-12-31

    In many real-world domains the task of machine learning algorithms is to learn a theory for predicting numerical values. In particular several standard test domains used in Inductive Logic Programming (ILP) are concerned with predicting numerical values from examples and relational and mostly non-determinate background knowledge. However, so far no ILP algorithm except one can predict numbers and cope with nondeterminate background knowledge. (The only exception is a covering algorithm called FORS.) In this paper we present Structural Regression Trees (SRT), a new algorithm which can be applied to the above class of problems. SRT integrates the statistical method of regression trees into ILP. It constructs a tree containing a literal (an atomic formula or its negation) or a conjunction of literals in each node, and assigns a numerical value to each leaf. SRT provides more comprehensible results than purely statistical methods, and can be applied to a class of problems most other ILP systems cannot handle. Experiments in several real-world domains demonstrate that the approach is competitive with existing methods, indicating that the advantages are not at the expense of predictive accuracy.

  1. Potential interaction of natural dietary bioactive compounds with COX2

    Microsoft Academic Search

    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

  2. Clinical use and pharmacological properties of selective COX2 inhibitors

    Microsoft Academic Search

    Shaojun Shi; Ulrich Klotz

    2008-01-01

    Selective COX-2 inhibitors (coxibs) are approved for the relief of acute pain and symptoms of chronic inflammatory conditions\\u000a such as osteoarthritis (OA) and rheumatoid arthritis (RA). They have similar pharmacological properties but a slightly improved\\u000a gastrointestinal (GI) safety profile if compared to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, long-term\\u000a use of coxibs can be associated with an increased risk for

  3. [New studies of COX-inhibitors, yet issues remain].

    PubMed

    Wollheim, Frank A

    2003-09-18

    Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized. PMID:14558211

  4. Linear regression applet

    NSDL National Science Digital Library

    Nicholas Exner

    2004-01-01

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

  5. Performance of univariate forecasting on seasonal diseases: the case of tuberculosis.

    PubMed

    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

  6. Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

    PubMed

    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

  7. A regularization corrected score method for nonlinear regression models with covariate error.

    PubMed

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

    2013-03-01

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

  8. Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning

    Microsoft Academic Search

    M R van Dijk; E W Steyerberg; S P Stenning; E Dusseldorp; J D F Habbema; van Dijk

    2004-01-01

    The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility.

  9. 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.

  10. Retargeted Least Squares Regression Algorithm.

    PubMed

    Zhang, Xu-Yao; Wang, Lingfeng; Xiang, Shiming; Liu, Cheng-Lin

    2014-12-01

    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

  11. Regression in Autistic Spectrum Disorders

    Microsoft Academic Search

    Gerry A. Stefanatos

    2008-01-01

    A significant proportion of children diagnosed with Autistic Spectrum Disorder experience a developmental regression characterized\\u000a by a loss of previously-acquired skills. This may involve a loss of speech or social responsitivity, but often entails both.\\u000a This paper critically reviews the phenomena of regression in autistic spectrum disorders, highlighting the characteristics\\u000a of regression, age of onset, temporal course, and long-term outcome.

  12. Regression analysis with longitudinal measurements

    E-print Network

    Ryu, Duchwan

    2005-08-29

    - tinuous response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3 Average fitted values (95% credible intervals) for 20 simulations when sigma2u = 1.0 and n = 200 with continuous response . . . . . . . . . 30 4 Continuous regression... simula- tions when sigma2u = 1.0 and n = 200 with binary response . . . . . . . . 42 7 Binary regression for the real data . . . . . . . . . . . . . . . . . . . 43 8 Directed acyclic graph for Bayesian nonparametric regression un- der Model-0...

  13. 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.

  14. Error bounds in cascading regressions

    USGS Publications Warehouse

    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.

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

    SciTech Connect

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

    2005-11-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Room temperature ferromagnetic (Fe?-xCox)?BO? nanorods.

    PubMed

    He, Shuli; Zhang, Hongwang; Xing, Hui; Li, Kai; Cui, Hongfei; Yang, Chenguang; Sun, Shouheng; Zeng, Hao

    2014-07-01

    Cobalt-doped ferroferriborate ((Fe1-xCox)3BO5) nanorods (NRs) are synthesized by a one-pot high-temperature organic-solution-phase method. The aspect ratios of the NRs are tuned by the heating rate. These NRs form via anisotropic growth along twin boundaries of the multiply twinned nuclei. Magnetic properties are dramatically modified by Co substitutional doping, changing from antiferromagnetic order at low temperatures to ferromagnetic above room temperature, with a greatly enhanced magnetic ordering temperature. These anisotropic ferromagnetic NRs with a high ordering temperature may provide a new platform for understanding nanomagnetism and for magnetic applications. PMID:24905634

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

    PubMed Central

    Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

    2014-01-01

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

  19. 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."

  20. Bayesian Multinomial Logistic Regression for Author Identification

    E-print Network

    Bayesian Multinomial Logistic Regression for Author Identification David Madigan, , Alexander logistic regression model together with an associated learning algorithm. Keywords: multinomial logistic regression, polytomous logistic regression, Bayesian estimation, classification, author identification

  1. COX-2 active agents in the chemoprevention of colorectal cancer.

    PubMed

    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

  2. myo-Inositol esters of indomethacin as COX-2 inhibitors.

    PubMed

    Kadirvel, Manikandan; Abudalal, Amna Salem; Rajendran, Ramkumar; Gbaj, Abdul; Demonacos, Constantinos; Freeman, Sally

    2012-07-01

    Ester prodrugs have the potential to eliminate the gastrotoxicity associated with the carboxylic acid group of indomethacin. 4,6-Bis-O-2'-[1'-(4?-chlorobenzoyl)-5'-methoxy-2'-methyl-1'H-indol-3'-acetyl]-myo-inositol-1,3,5-orthoacetate (2) was synthesised and evaluated as a COX-2 inhibitor. It adopts a conformationally restricted chair with two indomethacin groups in the sterically hindered 1,3-diaxial positions. Acid-induced cleavage of the orthoacetate lock of the prodrug leads to a ring flip of the myo-inositol ring with the two indomethacin groups now in 1,3-diequatorial positions. This increases the susceptibility of hydrolysis of the ester groups to release indomethacin under acidic conditions. The long half-life (152 min) of decomposition of (2) at ~pH 1-2 suggests that it may bypass the stomach with minimal hydrolysis upon oral administration. Indomethacin ester (2) was completely stable at pH 4.0-8.5 over 24h at 37°C and showed comparable activity to indomethacin in a COX-2 assay (pH 8.0). PMID:22578527

  3. A general regression neural network

    Microsoft Academic Search

    Donald F. Specht

    1991-01-01

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

  4. LOG HAZARD REGRESSION Huiying Sun

    E-print Network

    Heckman, Nancy E.

    of knots. The regression is applied to the data set of the Diabetic Retinopathy Study (Diabetic Retinopathy on b and fi . . . . . . . . . . . . . . . . . . . . . . . . 12 2.3 Consistency and Normality of â?? fi . . . . . . . . . . . . . . . . . . . . . . . . . 26 2.5.2 Consistency and Normality of â?? fi ¯ . . . . . . . . . . . . . . . . . . . 27 3 Regression

  5. Penalized Logistic Regression Stefanie Scheid

    E-print Network

    Spang, Rainer

    Penalized Logistic Regression Stefanie Scheid Max-Planck-Institute for Molecular Genetics, HC (2001): Classification of Microarray Data with Penalized Logistic Regression, Proceedings of SPIE volume 4266: progress in biomedical optics and imaging, 2, 187-198. Stefanie Scheid - Penalized Logistic

  6. Measuring overlap in binary regression

    Microsoft Academic Search

    Andreas Christmann; Peter J. Rousseeuw

    2001-01-01

    In this paper, we show that the recent notion of regression depth can be used as a data-analytic tool to measure the amount of separation between successes and failures in the binary response framework. Extending this algorithm, allows us to compute the overlap in data sets which are commonly fitted by logistic or probit regression models. The overlap is the

  7. 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…

  8. Regression Models with Interval Censoring

    Microsoft Academic Search

    Jian Huang; Jon A. Wellner

    In this paper we discuss estimation in semiparametric regression models with interval censoring, with emphasis on estimation of the regression parameter . The first section surveys some of the existing literature concerning these models and the various existing approaches to estimation, including a selected subset of the enormous literature on the binary choice model used in econometrics. In section 2

  9. 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…

  10. The issue of multiple univariate comparisons in the context of neuroelectric brain mapping: an application in a neuromarketing experiment.

    PubMed

    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

  11. Cox2 induces interleukin-11 production in human breast cancer cells

    Microsoft Academic Search

    J. Berry; B. Singh; A. Lucci

    2004-01-01

    Introduction. Cyclooxygenase-2 (COX-2) is overexpressed in 40% of human invasive breast cancers. Interleukin-11 (IL-11) is a potent mediator of osteoclastogenesis. Since breast cancers that overexpress COX-2 are known to be associated with a higher rate of metastasis to bone, we hypothesized that cancer cells that overexpress COX-2 would induce IL-11 production. Methods. We transfected MCF-7 (poorly metastatic) and MDA-231 (highly

  12. Probiotics Regulate the Expression of COX2 in Intestinal Epithelial Cells

    Microsoft Academic Search

    Jan-Michel Otte; Rudja Mahjurian-Namari; Stephan Brand; Ilka Werner; Wolfgang E. Schmidt; Frank Schmitz

    2008-01-01

    Cyclooxygenase-2 (COX) 2 promotes intestinal wound healing but elicits also proinflammatory effects and has been implicated in colorectal carcinogenesis. Thus, a balanced expression of COX-2 is essential for intestinal homeostasis. This study was designed to evaluate the regulation of COX-2 by probiotic organisms and to characterize ligands and receptors involved. Colo320 and SW480 intestinal epithelial cells (IEC) were stimulated with

  13. Gastrointestinal bleeding after the introduction of COX 2 inhibitors: ecological study

    Microsoft Academic Search

    Muhammad Mamdani; David N Juurlink; Alex Kopp; Gary Naglie; Peter C Austin; Andreas Laupacis

    2004-01-01

    Recent evidence suggests a lower risk of upper gastrointestinal haemorrhage for selective cyclo- oxygenase-2 (COX 2) inhibitors compared with non-selective non-steroidal anti-inflammatory drugs (NSAIDs) at the patient level, 1-3 although COX 2 inhibitors are likely not devoid of gastrointestinal toxicity. At the population level, however, the widespread proliferation of COX 2 inhibitors might lead to an increase in the overall

  14. Structural insight into DNA binding and oligomerization of the multifunctional Cox protein of bacteriophage P2

    PubMed Central

    Berntsson, Ronnie P.-A.; Odegrip, Richard; Sehlén, Wilhelmina; Skaar, Karin; Svensson, Linda M.; Massad, Tariq; Högbom, Martin; Haggård-Ljungquist, Elisabeth; Stenmark, Pål

    2014-01-01

    The Cox protein from bacteriophage P2 is a small multifunctional DNA-binding protein. It is involved in site-specific recombination leading to P2 prophage excision and functions as a transcriptional repressor of the P2 Pc promoter. Furthermore, it transcriptionally activates the unrelated, defective prophage P4 that depends on phage P2 late gene products for lytic growth. In this article, we have investigated the structural determinants to understand how P2 Cox performs these different functions. We have solved the structure of P2 Cox to 2.4 Å resolution. Interestingly, P2 Cox crystallized in a continuous oligomeric spiral with its DNA-binding helix and wing positioned outwards. The extended C-terminal part of P2 Cox is largely responsible for the oligomerization in the structure. The spacing between the repeating DNA-binding elements along the helical P2 Cox filament is consistent with DNA binding along the filament. Functional analyses of alanine mutants in P2 Cox argue for the importance of key residues for protein function. We here present the first structure from the Cox protein family and, together with previous biochemical observations, propose that P2 Cox achieves its various functions by specific binding of DNA while wrapping the DNA around its helical oligomer. PMID:24259428

  15. Distribution of COX-negative mitochondria in myofibers of rats intoxicated with Senna occidentalis seeds.

    PubMed

    Calore, N M P; Calore, E E; Sesso, A; Correia, H; Marcondes, M C S L; Vilela de Almeida, L

    2002-04-01

    We have described that administration of seeds or parts of the seed of Senna occidentalis (coffee senna) for long periods, induces histochemical changes in the skeletal muscles of hens and rats that are characteristic of a mitochondrial myopathy--as decrease of SDH and COX activity, with some COX negative fibers. In this experimental model of mitochondrial myopathy, as in many human mitochondrial diseases, there is a random distribution of COX negative fibers. Some fibers are completely COX negative while others are partially negative and others are completely positive. In the present work we have studied the distribution of COX negative mitochondria at transmission electron microscopy in skeletal muscle of rats in this experimental myopathy. In myofibers of intoxicated animals the expression of COX was heterogeneous. The histochemical reaction was observed in the internal membrane (more evident in mitochondrial cristae) of all mitochondria of some myofibers, while it was almost absent in other myofibers. In these myofibers the great part of the mitochondria were negative for COX reaction while other ones had a weak expression of this enzyme (dot or focal expression of COX). Our results indicated that the COX mitochondrial activity is heterogeneously impaired in myofibers of rats intoxicated with S. occidentalis. These abnormalities remember those observed in some types of human mitochondrial myopathies. PMID:12117285

  16. 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.

  17. MODULATION OF COX I AND COX II-MEDIATED FORMATION OF VARIOUS ARACHIDONIC ACID METABOLITES IN VITRO AND IN VIVO BY DIETARY POLYPHENOLS

    E-print Network

    Bai, Hyoungwoo

    2009-12-03

    Cyclooxygenase (COX) is a key enzyme required for the conversion of arachidonic acid (AA) to various prostaglandins (PGs), thromboxanes (TXs), and hydroxyeicosatetraenoic acids (HETEs), by which AA exert numerous biological ...

  18. Synthesis, biological evaluation, molecular docking and theoretical evaluation of ADMET properties of nepodin and chrysophanol derivatives as potential cyclooxygenase (COX-1, COX-2) inhibitors.

    PubMed

    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

  19. Interaction between NO and COX pathways modulating hepatic endothelial cells from control and cirrhotic rats

    PubMed Central

    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

  20. Reversible Suppression of Cyclooxygenase 2 (COX-2) Expression In Vivo by Inducible RNA Interference

    PubMed Central

    Zaiss, Anne K.; Zuber, Johannes; Chu, Chun; Machado, Hidevaldo B.; Jiao, Jing; Catapang, Arthur B.; Ishikawa, Tomo-o; Gil, Jose S.; Lowe, Scott W.; Herschman, Harvey R.

    2014-01-01

    Prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), plays a critical role in many normal physiological functions and modulates a variety of pathological conditions. The ability to turn endogenous COX-2 on and off in a reversible fashion, at specific times and in specific cell types, would be a powerful tool in determining its role in many contexts. To achieve this goal, we took advantage of a recently developed RNA interference system in mice. An shRNA targeting the Cox2 mRNA 3?untranslated region was inserted into a microRNA expression cassette, under the control of a tetracycline response element (TRE) promoter. Transgenic mice containing the COX-2-shRNA were crossed with mice encoding a CAG promoter-driven reverse tetracycline transactivator, which activates the TRE promoter in the presence of tetracycline/doxycycline. To facilitate testing the system, we generated a knockin reporter mouse in which the firefly luciferase gene replaces the Cox2 coding region. Cox2 promoter activation in cultured cells from triple transgenic mice containing the luciferase allele, the shRNA and the transactivator transgene resulted in robust luciferase and COX-2 expression that was reversibly down-regulated by doxycycline administration. In vivo, using a skin inflammation-model, both luciferase and COX-2 expression were inhibited over 80% in mice that received doxycycline in their diet, leading to a significant reduction of infiltrating leukocytes. In summary, using inducible RNA interference to target COX-2 expression, we demonstrate potent, reversible Cox2 gene silencing in vivo. This system should provide a valuable tool to analyze cell type-specific roles for COX-2. PMID:24988319

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  3. Regression quantiles for time series

    E-print Network

    Cai, Zongwu

    2002-02-01

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

  4. 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.

  5. Correlation and Regression Worksheet 1

    E-print Network

    Watkins, Joseph C.

    Correlation and Regression Worksheet 1 1. Global warming has many indirect effects on climate. As the climate warms and winter snow cover in Europe and Asia decreases, the land heats up more rapidly in summer

  6. Abstract Expression Grammar Symbolic Regression

    NASA Astrophysics Data System (ADS)

    Korns, Michael F.

    This chapter examines the use of Abstract Expression Grammars to perform the entire Symbolic Regression process without the use of Genetic Programming per se. The techniques explored produce a symbolic regression engine which has absolutely no bloat, which allows total user control of the search space and output formulas, which is faster, and more accurate than the engines produced in our previous papers using Genetic Programming. The genome is an all vector structure with four chromosomes plus additional epigenetic and constraint vectors, allowing total user control of the search space and the final output formulas. A combination of specialized compiler techniques, genetic algorithms, particle swarm, aged layered populations, plus discrete and continuous differential evolution are used to produce an improved symbolic regression sytem. Nine base test cases, from the literature, are used to test the improvement in speed and accuracy. The improved results indicate that these techniques move us a big step closer toward future industrial strength symbolic regression systems.

  7. Multiple Correlation versus Multiple Regression.

    ERIC Educational Resources Information Center

    Huberty, Carl J.

    2003-01-01

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

  8. Is the gasoline tax regressive?

    E-print Network

    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 ...

  9. Linear Regression of BMD Scanners

    NSDL National Science Digital Library

    VU Bioengineering RET Program,

    Students complete an exercise showing logarithmic relationships and examine how to find the linear regression of data that does not seem linear upon initial examination. They relate number of BMD scanners to time.

  10. Trend estimation and univariate forecast of the sunspot numbers: Development and comparison of ARMA, ARIMA and Autoregressive Neural Network models

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Surajit; Jhajharia, Deepak; Chattopadhyay, Goutami

    2011-07-01

    In the present study, a prominent 11-year cycle, supported by the pattern of the autocorrelation function and measures of Euclidean distances, in the mean annual sunspot number time series has been observed by considering the sunspot series for the duration of 1749 to 2007. The trend in the yearly sunspot series, which is found to be non-normally distributed, is examined through the Mann-Kendall non-parametric test. A statistically significant increasing trend is observed in the sunspot series in annual duration. The results indicate that the performance of the autoregressive neural network-based model is much better than the autoregressive moving average and autoregressive integrated moving average-based models for the univariate forecast of the yearly mean sunspot numbers.

  11. 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.

  12. Regression analysis with missing data

    E-print Network

    Michelli, Frank Anthony

    1968-01-01

    appreoiation to Dr. William B. Smith for his guidanoe and friendship. Also, appreciation is expressed to the other members of my committee, Dr. R. R. Rocking, Dr. R. J. Freund, and Mr. B. C. Moore. A special thanks is given to everyone who made this thesis... of the 'Rocking and Smith Technique. . . 2. 2 Extension to Estimation of Regression Coefficients. . . . . . . . . . . 10 2. 3 Alternate Method of Estimating the Regression Coefficients. . . . . . . . . . . . . 15 ChaPter I1I Evaluation of the Technique...

  13. 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.

  14. Regression Discontinuity Designs in Epidemiology

    PubMed Central

    Moscoe, Ellen; Mutevedzi, Portia; Newell, Marie-Louise; Bärnighausen, Till

    2014-01-01

    When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007–2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/?L CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45–0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology. PMID:25061922

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

    PubMed Central

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

    2012-01-01

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

  16. QSAR analysis of meclofenamic acid analogues as selective COX2 inhibitors

    Microsoft Academic Search

    Tamanna Narsinghani; S. C. Chaturvedi

    2006-01-01

    The use of quantitative structure–activity relationships, since its advent, has become increasingly helpful in understanding many aspects of biochemical interactions in drug research. This approach was utilized to explain the relationship of structure with biological activity of selective COX-2 inhibitors. The enormity of the COX-2 discovery is reflected in the unprecedented speed at which research laboratories have sought to validate

  17. The 2?-Trifluoromethyl Analogue of Indomethacin Is a Potent and Selective COX-2 Inhibitor

    PubMed Central

    2013-01-01

    Indomethacin is a potent, time-dependent, nonselective inhibitor of the cyclooxygenase enzymes (COX-1 and COX-2). Deletion of the 2?-methyl group of indomethacin produces a weak, reversible COX inhibitor, leading us to explore functionality at that position. Here, we report that substitution of the 2?-methyl group of indomethacin with trifluoromethyl produces CF3–indomethacin, a tight-binding inhibitor with kinetic properties similar to those of indomethacin and unexpected COX-2 selectivity (IC50 mCOX-2 = 267 nM; IC50 oCOX-1 > 100 ?M). Studies with site-directed mutants reveal that COX-2 selectivity results from insertion of the CF3 group into a small hydrophobic pocket formed by Ala-527, Val-349, Ser-530, and Leu-531 and projection of the methoxy group toward a side pocket bordered by Val-523. CF3–indomethacin inhibited COX-2 activity in human head and neck squamous cell carcinoma cells and exhibited in vivo anti-inflammatory activity in the carrageenan-induced rat paw edema model with similar potency to that of indomethacin. PMID:23687559

  18. ETUDE MULTICENTRIQUE DE LA SURVENUE D'ESCARRES PAR UN MODELE DE COX BASE

    E-print Network

    Boyer, Edmond

    Analysis of a multicenter clinical trial on pressure ulcer develop- ment by a marginal approach in the Cox approach. Cox model. Correlated survival times. pressure ulcer. 1 HALauthormanuscriptinserm-00138530 intervention on pressure ulcer development in critically ill older patients from a multicentric trial

  19. Mori dream spaces of Calabi-Yau type and the log canonicity of the Cox rings

    E-print Network

    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.

  20. Evidence suggesting multiple promoting roles of luteal group IVA phospholipase A(2) in prostaglandin F(2alpha)-induced regression in pseudopregnant rats.

    PubMed

    Kurusu, Shiro; Sonoda, Norifumi; Nakahara, Masato; Yonezawa, Tomohiro; Kawaminami, Mitsumori

    2010-09-01

    We evaluated effects of local administration of selective inhibitors of group IVA phospholipase A(2) (GIVA PLA(2)) and cyclooxygenase (COX) on exogenous prostaglandin (PG) F(2alpha)-induced luteal regression in pseudopregnant rats. Intra-bursal treatment with a GIVA PLA(2) inhibitor AACOCF(3) just prior to PGF(2alpha) (30microg, subcutaneously) on day 6 of pseudopregnancy (PSP6) prevented a decline in circulating progesterone and inhibited TUNEL-positive reactions of steroidogenic cell. Its treatment on PSP9 failed to inhibit functional regression, but reduced significantly apoptosis of steroidogenic cells and vascular endothelial cells, and suppressed the infiltration of macrophages. A COX-2-selective inhibitor NS398 inhibited the decline of progesterone and apoptosis of steroidogenic cells on PSP6 but not on PSP9. A COX-1 inhibitor SC560 exerted insignificant anti-luteolytic effects. Overall data suggest that luteal GIVA PLA(2) plays multiple promoting roles in PGF(2alpha)-induced luteal regression at least partly by a COX-2 activity-related mechanism in pseudopregnant rats. PMID:20601072

  1. PSHREG: a SAS macro for proportional and nonproportional subdistribution hazards regression.

    PubMed

    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

  2. A comparative analysis of the bifunctional Cox proteins of two heteroimmune P2-like phages with different host integration sites.

    PubMed

    Ahlgren-Berg, Alexandra; Cardoso-Palacios, Carlos; Eriksson, Jesper M; Mandali, Sridhar; Sehlén, Wilhelmina; Sylwan, Lina; Haggård-Ljungquist, Elisabeth

    2009-03-15

    The Cox protein of the coliphage P2 is multifunctional; it acts as a transcriptional repressor of the Pc promoter, as a transcriptional activator of the P(LL) promoter of satellite phage P4, and as a directionality factor for site-specific recombination. The Cox proteins constitute a unique group of directionality factors since they couple the developmental switch with the integration or excision of the phage genome. In this work, the DNA binding characteristics of the Cox protein of WPhi, a P2-related phage, are compared with those of P2 Cox. P2 Cox has been shown to recognize a 9 bp sequence, repeated at least 6 times in different targets. In contrast to P2 Cox, WPhi Cox binds with a strong affinity to the early control region that contains an imperfect direct repeat of 12 nucleotides. The removal of one of the repeats has drastic effects on the capacity of WPhi to bind to the Pe-Pc region. Again in contrast to P2 Cox, WPhi Cox has a lower affinity to attP compared to the Pe-Pc region, and a repeat of 9 bp can be found that has 5 bp in common with the repeat in the Pe-Pc region. WPhi Cox, however, is essential for excisive recombination in vitro. WPhi Cox, like P2 Cox, binds cooperatively with integrase to attP. Both Cox proteins induce a strong bend in their DNA targets upon binding. PMID:19150106

  3. The HMGA1-COX-2 axis: A key molecular pathway and potential target in pancreatic adenocarcinoma

    PubMed Central

    Hillion, Joelle; Smail, Shamayra S.; Di Cello, Francescopaolo; Belton, Amy; Shah, Sandeep; Huso, Tait; Schuldenfrei, Andrew; Nelson, Dwella Moton; Cope, Leslie; Campbell, Nathaniel; Karikari, Collins; Aderinto, Abimbola; Maitra, Anirban; Huso, David L.; Resar, Linda M. S.

    2012-01-01

    Context Although pancreatic cancer is a common, highly lethal malignancy, the molecular events that enable precursor lesions to become invasive carcinoma remain unclear. We previously reported that the high-mobility group A1 (HMGA1) protein is overexpressed in >90% of primary pancreatic cancers, with absent or low levels in early precursor lesions. Methods Here, we investigate the role of HMGA1 in reprogramming pancreatic epithelium into invasive cancer cells. We assessed oncogenic properties induced by HMGA1 in non-transformed pancreatic epithelial cells expressing activated K-RAS. We also explored the HMGA1-cyclooxygenase (COX-2) pathway in human pancreatic cancer cells and the therapeutic effects of COX-2 inhibitors in xenograft tumorigenesis. Results HMGA1 cooperates with activated K-RAS to induce migration, invasion, and anchorage-independent cell growth in a cell line derived from normal human pancreatic epithelium. Moreover, HMGA1 and COX-2 expression are positively correlated in pancreatic cancer cell lines (r2=0.93; p<0.001). HMGA1 binds directly to the COX-2 promoter at an AT-rich region in vivo in three pancreatic cancer cell lines. In addition, HMGA1 induces COX-2 expression in pancreatic epithelial cells, while knock-down of HMGA1 results in repression of COX-2 in pancreatic cancer cells. Strikingly, we also discovered that Sulindac (a COX-1/COX-2 inhibitor) or Celecoxib (a more specific COX-2 inhibitor) block xenograft tumorigenesis from pancreatic cancer cells expressing high levels of HMGA1. Conclusions Our studies identify for the first time an important role for the HMGA1-COX-2 pathway in pancreatic cancer and suggest that targeting this pathway could be effective to treat, or even prevent, pancreatic cancer. PMID:22898640

  4. Functional expression cloning identifies COX-2 as a suppressor of antigen-specific cancer immunity.

    PubMed

    Göbel, C; Breitenbuecher, F; Kalkavan, H; Hähnel, P S; Kasper, S; Hoffarth, S; Merches, K; Schild, H; Lang, K S; Schuler, M

    2014-01-01

    The efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation of a sustained immune response targeting cancer antigens and the susceptibility of cancer cells to immune effector mechanisms. Using functional expression cloning and T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against the cytotoxicity induced by activated, antigen-specific T cells. Expressing COX-2, but not a catalytically inactive COX-2 mutant, increased the clonogenic survival of E1A-transformed murine cancer cells when cocultured with lymphocytes from St42Rag2(-/-) mice harboring a transgenic TCR directed against an E1A epitope. COX-2 expressing tumors established in immune-deficient mice were less susceptible to adoptive immunotherapy with TCR transgenic lymphocytes in vivo. Also, immune surveillance of COX-2-positive tumor cells in TCR transgenic mice was less efficient. The growth of murine MC-GP tumors, which show high endogenous COX-2 expression, in immunocompetent mice was effectively suppressed by treatment with a selective COX-2 inhibitor, celecoxib. Mechanistically, COX-2 expression blunted the interferon-gamma release of antigen-specific T cells exposed to their respective cellular targets, and increased the expression of interleukin-4 and indoleamine 2,3-dioxygenase by tumor cells. Addition of interferon-gamma sensitized COX-2 expressing cancer cells to tumor suppression by antigen-specific T cells. In conclusion, COX-2, which is frequently induced in colorectal cancer, contributes to immune evasion and resistance to antigen-specific cancer immunotherapy by local suppression of T-cell effector functions. PMID:25501829

  5. Ensemble Logistic Regression for Feature Selection

    E-print Network

    Dupont, Pierre

    Ensemble Logistic Regression for Feature Selection Roman Zakharov and Pierre Dupont Machine algorithm em- bedded into logistic regression. It specifically addresses high dimensional data with few relevance is treated as a feature sampling prob- ability and a multivariate logistic regression

  6. Logistic regression for dichotomized counts.

    PubMed

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

    2014-05-26

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

  7. Diagnostics for multiple regression problems

    SciTech Connect

    Daly, J.C.

    1982-03-01

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

  8. 463. COX2Based Gene Therapy: Reduction of Intraocular Pressure in a Glaucoma Gene Therapy Animal Model with Lentiviral Vectors Expressing COX2, a Prostaglandin Synthase, or a Prostaglandin Receptor

    Microsoft Academic Search

    Roman A. Barraza; Eric M. Poeschla

    2006-01-01

    BACKGROUND: Cyclooxygenase-2 (COX-2), an inducible enzyme in the prostaglandin (PG) biosynthesis cascade, is important in medically significant disease states, including glaucoma and cancer. Most recently, COX-2 inhibitors have been implicated in adverse cardiovascular outcomes. Durable COX-2 expression by exogenous genes has not been previously achieved. We hypothesized that the inducible PG biosynthetic and response pathways could be manipulated via a

  9. Nonparametric regression to the mean

    PubMed Central

    Müller, Hans-Georg; Abramson, Ian; Azari, Rahman

    2003-01-01

    Available data may reflect a true but unknown random variable of interest plus an additive error, which is a nuisance. The problem in predicting the unknown random variable arises in many applied situations where measurements are contaminated with errors; it is known as the regression-to-the-mean problem. There exists a well known solution when both the distributions of the true underlying random variable and the contaminating errors are normal. This solution is given by the classical regression-to-the-mean formula, which has a data-shrinkage interpretation. We discuss the extension of this solution to cases where one or both of these distributions are unknown and demonstrate that the fully nonparametric case can be solved for the case of small contaminating errors. The resulting nonparametric regression-to-the-mean paradigm can be implemented by a straightforward data-sharpening algorithm that is based on local sample means. Asymptotic justifications and practical illustrations are provided. PMID:12902544

  10. Interquantile Shrinkage in Regression Models

    PubMed Central

    Jiang, Liewen; Wang, Huixia Judy; Bondell, Howard D.

    2012-01-01

    Conventional analysis using quantile regression typically focuses on fitting the regression model at different quantiles separately. However, in situations where the quantile coefficients share some common feature, joint modeling of multiple quantiles to accommodate the commonality often leads to more efficient estimation. One example of common features is that a predictor may have a constant effect over one region of quantile levels but varying effects in other regions. To automatically perform estimation and detection of the interquantile commonality, we develop two penalization methods. When the quantile slope coefficients indeed do not change across quantile levels, the proposed methods will shrink the slopes towards constant and thus improve the estimation efficiency. We establish the oracle properties of the two proposed penalization methods. Through numerical investigations, we demonstrate that the proposed methods lead to estimations with competitive or higher efficiency than the standard quantile regression estimation in finite samples. Supplemental materials for the article are available online. PMID:24363546

  11. Partial AUC estimation and regression.

    PubMed

    Dodd, Lori E; Pepe, Margaret S

    2003-09-01

    Accurate diagnosis of disease is a critical part of health care. New diagnostic and screening tests must be evaluated based on their abilities to discriminate diseased from nondiseased states. The partial area under the receiver operating characteristic (ROC) curve is a measure of diagnostic test accuracy. We present an interpretation of the partial area under the curve (AUC), which gives rise to a nonparametric estimator. This estimator is more robust than existing estimators, which make parametric assumptions. We show that the robustness is gained with only a moderate loss in efficiency. We describe a regression modeling framework for making inference about covariate effects on the partial AUC. Such models can refine knowledge about test accuracy. Model parameters can be estimated using binary regression methods. We use the regression framework to compare two prostate-specific antigen biomarkers and to evaluate the dependence of biomarker accuracy on the time prior to clinical diagnosis of prostate cancer. PMID:14601762

  12. 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.

  13. 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

  14. Regressive Evolution in Astyanax Cavefish

    PubMed Central

    Jeffery, William R.

    2013-01-01

    A diverse group of animals, including members of most major phyla, have adapted to life in the perpetual darkness of caves. These animals are united by the convergence of two regressive phenotypes, loss of eyes and pigmentation. The mechanisms of regressive evolution are poorly understood. The teleost Astyanax mexicanus is of special significance in studies of regressive evolution in cave animals. This species includes an ancestral surface dwelling form and many con-specific cave-dwelling forms, some of which have evolved their recessive phenotypes independently. Recent advances in Astyanax development and genetics have provided new information about how eyes and pigment are lost during cavefish evolution; namely, they have revealed some of the molecular and cellular mechanisms involved in trait modification, the number and identity of the underlying genes and mutations, the molecular basis of parallel evolution, and the evolutionary forces driving adaptation to the cave environment. PMID:19640230

  15. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation

    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.

  16. Noncrossing quantile regression curve estimation

    PubMed Central

    Bondell, Howard D.; Reich, Brian J.; Wang, Huixia

    2010-01-01

    Summary Since quantile regression curves are estimated individually, the quantile curves can cross, leading to an invalid distribution for the response. A simple constrained version of quantile regression is proposed to avoid the crossing problem for both linear and nonparametric quantile curves. A simulation study and a reanalysis of tropical cyclone intensity data shows the usefulness of the procedure. Asymptotic properties of the estimator are equivalent to the typical approach under standard conditions, and the proposed estimator reduces to the classical one if there is no crossing. The performance of the constrained estimator has shown significant improvement by adding smoothing and stability across the quantile levels. PMID:22822254

  17. Model Selection for Cox Models with Time-Varying Coefficients

    PubMed Central

    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

  18. Cox's Chair Revisited: Can Spinning Alter Mood States?

    PubMed

    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

  19. Chromatin and DNA methylation dynamics of Helicobacter pylori-induced COX-2 activation.

    PubMed

    Pero, Raffaela; Peluso, Silvia; Angrisano, Tiziana; Tuccillo, Concetta; Sacchetti, Silvana; Keller, Simona; Tomaiuolo, Rossella; Bruni, Carmelo B; Lembo, Francesca; Chiariotti, Lorenzo

    2011-02-01

    COX-2 expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in COX-2 disregulation. We undertook this study to investigate possible chromatin and DNA methylation changes occurring early during COX-2 gene activation as a direct consequence of Hp-gastric cells interaction. We show that Hp infection is followed by different expression, chromatin and DNA methylation changes including: (i) biphasic activation of COX-2 gene; (ii) rapid remodulation of HDACs expression and activity, increased acetylation and release of HDAC from COX-2 promoter; (iii) transient gradual increase of H3 acetylation and H3K4 dimethylation and decrease of H3K9 dimethylation; (iv) late and long-lasting increase of H3K27 trimethylation; (v) rapid cyclical DNA methylation/demethylation events at 8 specific CpG sites (-176, -136, +25, +36, +57, +82, +198, +231) surrounding the COX-2 gene transcriptional start site. Our data indicate that specific chromatin and DNA methylation changes occur at COX-2 gene in the first phases of Hp exposure in cultured gastric cells as a primary response to host-parasite interaction. PMID:20934379

  20. Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

    PubMed Central

    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

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

    PubMed Central

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

    2011-01-01

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

  2. Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model.

    PubMed

    Martin, Jonathan E; Young, Graeme P; LE Leu, Richard K; Hu, Ying

    2013-09-01

    The protection against colorectal cancer (CRC) by non-steroidal anti-inflammatory drugs (NSAIDs) is in part dependent on inhibition of cyclooxygenase (COX). We compared the efficacy of the non-COX-inhibiting R-flurbiprofen (R-FB) with COX-inhibiting sulindac and racemic flurbiprofen (Rac-FB), and determined their effects on apoptosis, in an azoxymethane (AOM)-induced rat CRC model. In experiment 1, groups of rats were given a daily drug gavage (R-FB 30 mg/kg, Rac-FB 10 mg/kg and Sulindac 20 mg/kg) for one week, followed by AOM treatment and were sacrificed eight hours later, colons were examined for apoptosis and cell proliferation. In experiment 2, groups of rats were given two AOM treatments, followed by a daily drug gavage until they were sacrificed ten weeks later, and colons were examined for aberrant crypt foci (ACF) and prostaglandin E2 production. All drugs significantly enhanced apoptosis and inhibited ACF, irrespective of their COX-inhibiting potency (p<0.01), but sulindac was more potent in inhibition of large ACF, p<0.05. COX-inhibiting sulindac achieved the greatest protective effect. The greater safety profile of Rac-FB should provide an advantage for chemoprevention. PMID:24023283

  3. Regression

    MedlinePLUS

    ... member A recent death Marital conflict or parents’ divorce An upcoming or recent move to a new house Such events—even when they are happy ones—can represent a real challenge to young children still struggling to master their own personal routines. ...

  4. Least Median of Squares Regression

    Microsoft Academic Search

    Peter J. Rousseeuw

    1984-01-01

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

  5. REGH: Stata module: heteroscedastic regression

    Microsoft Academic Search

    Jeroen Weesie

    1999-01-01

    regh computes maximum-likelihood estimates for the regression model with multiplicative heteroscedasticity. It also estimates a model in which the mean is included among the predictors for the log-variance. For those with Stata v6 on an internet-accessible machine, install by typing .net cd http:\\/\\/www.fss.uu.nl\\/soc\\/iscore\\/stata\\/ then .net install regh

  6. Convergence Failures in Logistic Regression

    Microsoft Academic Search

    Paul D. Allison

    2008-01-01

    A frequent problem in estimating logistic regression models is a failure of the likelihood maximization algorithm to converge. In most cases, this failure is a consequence of data patterns known as complete or quasi-complete separation. For these patterns, the maximum likelihood estimates simply do not exist. In this paper, I examine how and why complete or quasi-complete separation occur, and

  7. 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…

  8. 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…

  9. 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…

  10. Is the Gasoline Tax Regressive?

    Microsoft Academic Search

    James M. Poterba

    1991-01-01

    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 for middle or high-income households. This paper argues that annual expenditure provides a more reliable indicator of household well-being than annual income. It uses data from

  11. Linear Regression and Best Fit

    NSDL National Science Digital Library

    Patel, Amar

    This lesson, created by Amar Patel of the University of Illinois - Urbana-Champaign, introduces simple linear regression with several Excel spreadsheet examples such as temperature versus cricket chirps, height versus shoe size, and laziness versus amount of television watched. These activities require class participation. This would be a great interactive lesson for a classroom studying statistics.

  12. Regression Test Selection for C++ Software

    Microsoft Academic Search

    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

  13. Privacy-preserving logistic regression Kamalika Chaudhuri

    E-print Network

    Smith, Adam D.

    Privacy-preserving logistic regression Kamalika Chaudhuri Information Theory and Applications on privacy-preserving logistic regression. First we apply an idea of Dwork et al. [6] to design a privacy-preserving logistic regression algorithm. This involves bound- ing the sensitivity of regularized logistic regression

  14. Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors

    PubMed Central

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

    2013-01-01

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

  15. Predictive factors for the regression of canine transmissible venereal tumor during vincristine therapy.

    PubMed

    Scarpelli, Karime C; Valladão, Maria L; Metze, Konradin

    2010-03-01

    Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression. PMID:19109042

  16. Students Speak With Gary Cox, EPIC Project Manager - Duration: 19 minutes.

    NASA Video Gallery

    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...

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

    EPA Science Inventory

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

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

    SciTech Connect

    Castor, J.I.

    1997-10-02

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

  19. Regulated Expression of PTPRJ by COX-2/PGE2 Axis in Endothelial Cells

    PubMed Central

    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

  20. NDRG2 Controls COX-2/PGE2-Mediated Breast Cancer Cell Migration and Invasion

    PubMed Central

    Kim, Myung-Jin; Kim, Hak-Su; Lee, Soo-Hwan; Yang, Young; Lee, Myeong-Sok; Lim, Jong-Seok

    2014-01-01

    N-myc downstream-regulated gene 2 (NDRG2), which is known to have tumor suppressor functions, is frequently down-regulated in breast cancers and potentially involved in preventing the migration and invasion of malignant tumor cells. In the present study, we examined the inhibitory effects of NDRG2 overexpression, specifically focusing on the role of cyclooxygenase-2 (COX-2) in the migration of breast cancer cells. NDRG2 overexpression in MDA-MB-231 cells inhibited the expression of the COX-2 mRNA and protein, the transcriptional activity of COX-2, and prostaglandin E2 (PGE2) production, which were induced by a treatment with phorbol-12-myristate-13-acetate (PMA). Nuclear transcription factor-?B (NF-?B) signaling attenuated by NDRG2 expression resulted in a decrease in PMA-induced COX-2 expression. Interestingly, the inhibition of COX-2 strongly suppressed PMA-stimulated migration and invasion in MDA-MB-231-NDRG2 cells. Moreover, siRNA-mediated knockdown of NDRG2 in MCF7 cells increased the COX-2 mRNA and protein expression levels and the PMA-induced COX-2 expression levels. Consistent with these results, the migration and invasion of MCF7 cells treated with NDRG2 siRNA were significantly enhanced following treatment with PMA. Taken together, our data show that the inhibition of NF-?B signaling by NDRG2 expression is able to suppress cell migration and invasion through the down-regulation of COX-2 expression. PMID:25256221

  1. Methanandamide increases COX2 expression and tumor growth in murine lung cancer

    Microsoft Academic Search

    Brian Gardner; Li X. Zhu; Sherven Sharma; Donald P. Tashkin; Steven M. Dubinett

    2003-01-01

    Increased COX-2 expression and elevated PGE2 have been associated with a poor prognosis in lung cancer. Cannabinoids have been known to exert some of their biological effects via modulation of prostaglandin production. We evaluated the impact of methanandamide on COX-2 expression, PGE2 production, and tumor growth in murine lung cancer. Methanandamide administration (5 mg\\/kg, four times\\/wk i.p.) resulted in an

  2. Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.

    PubMed

    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

  3. ?9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    PubMed Central

    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

  4. ?9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

    PubMed

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-11-21

    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 downregulation 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, working, 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

  5. Estrogen protects the heart from ischemia-reperfusion injury via COX-2-derived PGI2.

    PubMed

    Booth, Erin Anne; Flint, RaShonda Renee; Lucas, Kathryn Louise; Knittel, Andrea Kathleen; Lucchesi, Benedict R

    2008-09-01

    There is an accumulating body of data to suggest that estrogen mediates its cardioprotective effects via cyclooxygenase activation and synthesis of prostaglandins (PG), specifically PGI2. We hypothesized that inhibition of COX-2 would prevent estrogen's cardioprotective effects after myocardial ischemia-reperfusion. Acute treatment with 17beta-estradiol (E2; 20 microg/rabbit) increased COX-2 protein expression and activity in the myocardium. To determine the effects of COX-2 inhibition on infarct size after E2 treatment, New Zealand white rabbits were anesthetized and administered the COX-2 inhibitor nimesulide (5 mg/kg) or vehicle intravenously 30 minutes before an intravenous injection of E2. Thirty minutes after estrogen treatment, the coronary artery was occluded for 30 minutes followed by 4 hours of reperfusion. E2 significantly decreased infarct size as a percent of area at risk when compared to vehicle (18.9 +/- 3.1 versus 47.0 +/- 4.1; P < 0.001). Pretreatment with nimesulide nullified the infarct size sparing effect of E2 (55.8 +/- 5.6). Treatment with the PGI2 receptor antagonist RO3244794 also abolished the protective effects of E2 (45.3 +/- 4.5). The results indicate that estrogen protects the myocardium from ischemia-reperfusion injury through increased production of COX-2-derived PGI2. The data indicate that selective COX-2 inhibitors might counteract the potential cytoprotective effects of estrogen in premenopausal or postmenopausal women. PMID:18806603

  6. Expression of COX-2 and bcl-2 in oral lichen planus lesions and lichenoid reactions

    PubMed Central

    Arreaza, Alven J; Rivera, Helen; Correnti, María

    2014-01-01

    Oral lichen planus and lichenoid reactions are autoimmune type inflammatory conditions of the oral mucosa with similar clinical and histological characteristics. Recent data suggest that oral lichenoid reactions (OLR) present a greater percentage of malignant transformation than oral lichen planus (OLP). Objective To compare the expression of bcl-2 and COX-2 in OLP and OLR. Methods The study population consisted of 65 cases; 34 cases diagnosed as OLR and 31 as OLP. A retrospective study was done, and bcl-2 and COX-2 expression was semiquantitatively analysed. Results Fifty-three per cent (18/34) of the ORL samples tested positive for COX-2, whereas in the OLP group, 81% of the samples (25/31) immunostained positive for COX-2. The Fisher’s exact test for the expression of COX-2 revealed that there are significant differences between the two groups, P = 0.035. With respect to the expression of the bcl-2 protein, 76% (26/34) of the samples were positive in OLR, while 97% (30/31) were positive in the group with OLP. The Fisher’s exact test for the expression of bcl-2 revealed that there are significant statistical differences between the two groups, P = 0.028. Conclusions The expression of bcl-2 and COX-2 was more commonly expressed in OLP when compared with OLR. PMID:24834112

  7. Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells

    PubMed Central

    Chen, Li; Sooranna, Suren R; Lei, Kaiyu; Kandola, Mandeep; Bennett, Phillip R; Liang, Zhiqing; Grammatopoulos, Dimitri; Johnson, Mark R

    2012-01-01

    Abstract Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contraction-associated protein expression in myometrial cells and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and further studies confirmed that this was associated with COX-2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP-effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP-effector PDZ-GEF1-2, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX-2 expression and that PGE2 acts through EP-2 to activate MAPK and increase COX-2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function. PMID:21854542

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

    E-print Network

    Gelman, Andrew

    Scaling regression inputs by dividing by 2 sd Prior distribution for logistic regression Comparing by dividing by 2 sd Prior distribution for logistic regression Comparing the upper third to the lower third simple to us): 0.5/ n, linear regression, logistic regression, ordered logit, mean and variance

  9. Inhibition of COX1 and COX2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol)

    Microsoft Academic Search

    Angelika Schäfer; Zuzana Chovanová; Jana Muchová; Katarína Sumegová; Anna Liptáková; Zde?ka ?ura?ková; Petra Högger

    2006-01-01

    There is evidence from several studies that supplementation with French maritime pine bark extract (Pycnogenol®) improves inflammatory symptoms in vivo. However, the molecular pharmacological basis for the observed effects has not been fully uncovered yet. Direct inhibitory effects of plant extracts or components upon cyclooxygenase (COX) activity have been repeatedly reported, but the question remained whether sufficiently high in vivo

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

    PubMed

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

    2015-03-01

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

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

    SciTech Connect

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

    2013-04-15

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

  12. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

    PubMed

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-09-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

  13. Quantification of burkholderia coxL genes in Hawaiian volcanic deposits.

    PubMed

    Weber, C F; King, G M

    2010-04-01

    Isolation of multiple carbon monoxide (CO)-oxidizing Burkholderia strains and detection by culture-independent approaches suggest that Burkholderia may be an important component of CO-oxidizing communities in Hawaiian volcanic deposits. The absolute and relative abundance of the bacteria in these communities remains unknown, however. In this study, a quantitative PCR (Q-PCR) approach has been developed to enumerate Burkholderia coxL genes (large subunit of carbon monoxide dehydrogenase). This represents the first attempt to enumerate coxL genes from CO oxidizers in environmental samples. coxL copy numbers have been determined for samples from three sites representing a vegetation gradient on a 1959 volcanic deposit that included unvegetated cinders (bare), edges of vegetated sites (edge), and sites within tree stands (canopy). Q-PCR has also been used to estimate copy numbers of Betaproteobacteria 16S rRNA gene copy numbers and total Bacteria 16S rRNA. coxL genes could not be detected in the bare site (detection limit, > or = 4.7 x 10(3) copies per reaction) but average 1.0 x 10(8) + or - 2.4 x 10(7) and 8.6 x 10(8) + or - 7.6 x 10(7) copies g(-1) (dry weight) in edge and canopy sites, respectively, which differ statistically (P = 0.0007). Average Burkholderia coxL gene copy numbers, expressed as a percentage of total Bacteria 16S rRNA gene copy numbers, are 6.2 and 0.7% for the edge and canopy sites, respectively. Although the percentage of Burkholderia coxL is lower in the canopy site, significantly greater gene copy numbers demonstrate that absolute abundance of coxL increases in vegetated sites and contributes to the expansion of CO oxidizer communities during biological succession on volcanic deposits. PMID:20139318

  14. Meloxicam Executes Its Antitumor Effects against Hepatocellular Carcinoma in COX-2- Dependent and -Independent Pathways

    PubMed Central

    Dong, Xiaofeng; Li, Rui; Xiu, Peng; Dong, Xuesong; Xu, Zongzhen; Zhai, Bo; Liu, Feng; Jiang, Hongchi; Sun, Xueying; Li, Jie; Qiao, Haiquan

    2014-01-01

    Background Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including hepatocellular carcinoma (HCC). Meloxicam, a selective COX-2 inhibitor, has shown potential therapeutic effects against HCC, but the mechanisms accounting for its anti-cancer activities remain unclear. Methods and Findings Meloxicam inhibited the ability of human HCC cells expressing higher levels of COX-2 to migrate, invade, adhere and form colonies through upregulating the expression of E-cadherin and downregulating the expression of matrix metalloproteinase (MMP) -2. Meloxicam induced cell apoptosis by upregulating pro-apoptotic proteins including Bax and Fas-L, and downregulating anti-apoptotic proteins including survivin and myeloid cell leukemia-1 (Mcl-1), through inhibiting phosphorylation of AKT. Addition of prostaglandin E2 (PGE2), the major product of COX-2, could abrogate the effects of meloxicam on the expression of survivin and myeloid cell leukemia-1 (Mcl-1), but not Bax and Fas-L, indicating that meloxicam induces cell apoptosis via both COX-2-dependent and -independent pathways. Meloxicam also induced cell autophagy by upregulating Beclin 1 and light chain 3-II. Specific inhibition of autophagy by 3-methyladenine and chloroquine had little effect on cell apoptosis but could enhance the pro-apoptotic effects of meloxicam by further upregulating the expression of Bax. Conclusions Meloxicam executes its antitumor effects by targeting the COX-2/MMP-2/E-cadherin, AKT, apoptotic and autophagic pathways in COX-2-dependent and -independent pathways, and inhibition of cell autophagy could help to overcome the resistance to meloxicam-induced apoptosis in HCC. PMID:24675684

  15. HTEST: Stata module: homoscedasticity tests after regress

    Microsoft Academic Search

    Jeroen Weesie

    1999-01-01

    htest is an enhancements of hettest that optionally displays all univariate tests as well. szroeter performs the semi-parametric Szroeter\\/King test of homoscedasticy against a monotonic alternative. white performs White's homoscedasticity test again a general alternative. For those with Stata v6 on an internet-accessible machine, install by typing .net cd http:\\/\\/www.fss.uu.nl\\/soc\\/iscore\\/stata\\/ then .net install htest

  16. Semiparametric regression during 2003–2007*

    PubMed Central

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

    2010-01-01

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

  17. A Study of Fuzzy Linear Regression

    Microsoft Academic Search

    Jann-Huei Jinn; J. C. Chao

    We often use regression analysis to model the relationship between dependent (response) and independent (explanatory) variables. In traditional regression analysis, residuals are assumed to be due to random errors. Thus, statistical techniques are applied to perform estimation and inference in regression analysis. However, the residuals are sometimes due to the indefiniteness of the model structure or imprecise observations. The uncertainty

  18. Regression test selection for Java software

    Microsoft Academic Search

    Mary Jean Harrold; James A. Jones; Tongyu Li; Donglin Liang; Alessandro Orso; Maikel Pennings; Saurabh Sinha; S. Alexander Spoon; Ashish Gujarathi

    2001-01-01

    Regression testing is applied to modified software to provide confidence that the changed parts behave as intended and that the unchanged parts have not been adversely affected by the modifications. To reduce the cost of regression testing, test cases are selected from the test suite that was used to test the original version of the software---this process is called regression

  19. Estimation of a semiparametric contaminated regression model

    E-print Network

    Vandekerkhove, Pierre

    Estimation of a semiparametric contaminated regression model Vandekerkhove Pierre LAMA-CNRS UMR.vandek@univ-mlv.fr Abstract: We consider in this paper a contaminated regression model where the distribution of the contaminating component is known while the Euclidean parameters of the regression model, the error distribution

  20. Partial least-squares regression: a tutorial

    Microsoft Academic Search

    PAUL GELADI; BRUCE R. KOWALSKI

    1986-01-01

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

  1. Regression on feature projections H. Altay Guvenir

    E-print Network

    Güvenir, H. Altay

    -based regression algorithms. # Elsevier Science B.V. rights reserved. Keywords: Regression; Function approximation, whereas clas- si®cation t is strictly categorical. From perspective, classi®cation considered weighted regression produces local parametric functions according to the query instances, KNN [1

  2. A neural network approach to ordinal regression

    Microsoft Academic Search

    Jianlin Cheng

    2007-01-01

    Ordinal regression is an important type of learning, which has properties of both clas- sication and regression. Here we describe a simple and eective approach to adapt a traditional neural network to learn ordinal categories. Our approach is a generaliza- tion of the perceptron method for ordinal regression. On several benchmark datasets, our method (NNRank) outperforms a neural network classication

  3. 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,…

  4. Penalized Logistic Regression for Detecting Gene Interactions

    E-print Network

    Hastie, Trevor

    Penalized Logistic Regression for Detecting Gene Interactions Mee Young Park Trevor Hastie February 3, 2007 Abstract We propose using a variant of logistic regression with L2 regularization to fit are influenced by interaction of certain genes. Logistic regression models with quadratic penalization not only

  5. Graphical Methods for Assessing Logistic Regression Models

    Microsoft Academic Search

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

    1984-01-01

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

  6. 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…

  7. Multivariate versus classical univariate calibration methods for spectrofluorimetric data: application to simultaneous determination of olmesartan medoxamil and amlodipine besylate in their combined dosage form.

    PubMed

    Darwish, Hany W; Backeit, Ahmed H

    2013-01-01

    Olmesartan medoxamil (OLM, an angiotensin II receptor blocker) and amlodipine besylate (AML, a dihydropyridine calcium channel blocker), are co-formulated in a single-dose combination for the treatment of hypertensive patients whose blood pressure is not adequately controlled on either component monotherapy. In this work, four multivariate and two univariate calibration methods were applied for simultaneous spectrofluorimetric determination of OLM and AML in their combined pharmaceutical tablets in all ratios approved by FDA. The four multivariate methods are partial least squares (PLS), genetic algorithm PLS (GA-PLS), principal component ANN (PC-ANN) and GA-ANN. The two proposed univariate calibration methods are, direct spectrofluorimetric method for OLM and isoabsorpitive method for determination of total concentration of OLM and AML and hence AML by subtraction. The results showed the superiority of multivariate calibration methods over univariate ones for the analysis of the binary mixture. The optimum assay conditions were established and the proposed multivariate calibration methods were successfully applied for the assay of the two drugs in validation set and combined pharmaceutical tablets with excellent recoveries. No interference was observed from common pharmaceutical additives. The results were favorably compared with those obtained by a reference spectrophotometric method. PMID:22895851

  8. Variable Selection in ROC Regression

    PubMed Central

    2013-01-01

    Regression models are introduced into the receiver operating characteristic (ROC) analysis to accommodate effects of covariates, such as genes. If many covariates are available, the variable selection issue arises. The traditional induced methodology separately models outcomes of diseased and nondiseased groups; thus, separate application of variable selections to two models will bring barriers in interpretation, due to differences in selected models. Furthermore, in the ROC regression, the accuracy of area under the curve (AUC) should be the focus instead of aiming at the consistency of model selection or the good prediction performance. In this paper, we obtain one single objective function with the group SCAD to select grouped variables, which adapts to popular criteria of model selection, and propose a two-stage framework to apply the focused information criterion (FIC). Some asymptotic properties of the proposed methods are derived. Simulation studies show that the grouped variable selection is superior to separate model selections. Furthermore, the FIC improves the accuracy of the estimated AUC compared with other criteria. PMID:24312135

  9. Celecoxib exerts antitumor effects in canine mammary tumor cells via COX?2?independent mechanisms.

    PubMed

    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

  10. A Minimally Invasive Cox-Maze Procedure: Operative Technique and Results

    PubMed Central

    Lee, Anson M.; Clark, Kal; Bailey, Marci S.; Aziz, Abdulhameed; Schuessler, Richard B.; Damiano, Ralph J.

    2010-01-01

    Summary Objective The Cox-Maze procedure for the surgical treatment of atrial fibrillation traditionally has required a median sternotomy and cardiopulmonary bypass. This study describes a method using ablation technologies to create the full Cox-Maze lesion set through a 5–6 cm right mini-thoracotomy. Methods Twenty-two consecutive patients underwent a Cox-Maze procedure via a right mini-thoracotomy and cardiopulmonary bypass. All patients were followed prospectively with ECG and 24 hour Holter monitoring at 3, 6, and 12 months. The Cox-Maze procedure lesion set was created using bipolar radiofrequency energy and cryothermy. Results There was no operative mortality or major complications. Two patients required a permanent pacemaker. Five patients (23%) had early atrial tachyarrhythmias. At last follow-up (mean 18 ± 12 months), all of the patients (n=22) were free from atrial dysrhythmias. At 3 months (n=19), 84% of patients were off antiarrhythmic drugs. By 6 months (n=18), 94% of patients were free from AF and off antiarrhythmic medications. At 12 months (n=16), 81% of patients were free from AF and off antiarrhythmic drugs and three patients remained on warfarin for a mechanical mitral valve. Conclusions A full Cox-Maze procedure can be performed through a right mini-thoracotomy with outstanding short term results. This less invasive procedure can be offered to patients without compromising efficacy. PMID:21057605

  11. Differential accumulation of Phytophthora cambivora cox II gene transcripts in infected chestnut tissue.

    PubMed

    Vannini, Andrea; Tomassini, Alessia; Bruni, Natalia; Vettraino, Anna M

    2014-04-01

    This study provides a novel qRT-PCR protocol for specific detection and proof of viability of Phytophthora in environmental samples based on differential accumulation of cox II transcripts. Chemical and physical treatments were tested for their ability to induce in vitro the accumulation of cytochrome oxidase genes encoding subunits II (cox II) transcripts in Phytophthora cambivora. Glucose 170 mM, KNO3 0.25 mM and K3 PO3 0.5 and 0.8 mM induced the transcription of cox II in P. cambivora living mycelium while no transcription was observed in mycelium previously killed with 0.5% (p/v) RidomilGold(®) R WG. Living chestnut tissue was artificially infected with P. cambivora and treated with inducers. In vivo experiments confirmed the ability of glucose to induce the accumulation of P. cambivora cox II transcripts. Based on these results, pretreatment of environmental samples with glucose prior to nucleic acid extraction increased the accumulation of specific cox II transcripts, and therefore the sensitivity of qRT-PCR assay for detection of P. cambivora in living tissues. Furthermore, differential accumulation of transcripts between treated and untreated samples represents an unequivocal proof of inoculum viability. PMID:24527950

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

    PubMed Central

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

    2011-01-01

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

  13. Antiinflammatory and neuroprotective actions of COX2 inhibitors in the injured brain

    PubMed Central

    Strauss, Kenneth I.

    2008-01-01

    Overexpression of COX2 appears to be both a marker and an effector of neural damage after a variety of acquired brain injuries, and in natural or pathological aging of the brain. COX2 inhibitors may be neuroprotective in the brain by reducing prostanoid and free radical synthesis, or by directing arachidonic acid down alternate metabolic pathways. The arachidonic acid shunting hypothesis proposes that COX2 inhibitors' neuroprotective effects may be mediated by increased formation of potentially beneficial eicosanoids. Under conditions where COX2 activity is inhibited, arachidonic acid accumulates or is converted to eicosanoids via lipoxygenases and cytochrome P450 (CYP) epoxygenases. Several P450 eicosanoids have been demonstrated to have beneficial effects in the brain and/or periphery. We suspect that arachidonic acid shunting may be as important to functional recovery after brain injuries as altered prostanoid formation per se. Thus, COX2 inhibition and arachidonic acid shunting have therapeutic implications beyond the suppression of prostaglandin synthesis and free radical formation. PMID:17996418

  14. COX2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic fmolecular markers

    Microsoft Academic Search

    F. Millanta; S. Citi; D. Della Santa; M. Porciani; A. Poli

    2006-01-01

    Summary  Cyclooxygenase (COX)-2 is an inducible enzyme linked to tumor growth and angiogenesis. Its expression occurs in a wide range of preneoplastic and neoplastic conditions in humans, including colon and breast carcinomas. We evaluated the role of COX-2 as a mediator of angiogenesis in feline and canine invasive carcinomas (IMCs) and its role as a prognostic indicator. COX-2 expression was assessed

  15. Review: Logistic regression, Gaussian nave Bayes, linear regression, and their connections

    E-print Network

    Mitchell, Tom

    Review: Logistic regression, Gaussian naïve Bayes, linear regression, and their connections Yi, and feature selection #12;Outline Logistic regression Decision surface (boundary) of classifiers Generative Overfitting and regularization Feature selection 2 #12;Outline Logistic regression Model assumptions: P

  16. Avalos, M Penalized additive logistic regression PENALIZED ADDITIVE LOGISTIC REGRESSION FOR

    E-print Network

    Boyer, Edmond

    Avalos, M Penalized additive logistic regression PENALIZED ADDITIVE LOGISTIC REGRESSION of statistical models inferred from cohort data with methods such as logistic regression. Logistic regression statis- tics. Although attractively simple, the logistic model fails in some situations. 1) If the number

  17. 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).

  18. On Model Specification and Selection of the Cox Proportional Hazards Model*

    PubMed Central

    Lin, Chen-Yen; Halabi, Susan

    2013-01-01

    Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox’s model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing traditional linear assumption, flexible modeling techniques have been proposed to accommodate the nonlinear effect. We first review several existing nonparametric estimation and selection procedures and then present a numerical study to compare the performance between parametric and nonparametric procedures. We demonstrate the impact of model misspecification on variable selection and model prediction using a simulation study and a example from a phase III trial in prostate cancer. PMID:23784939

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2014-12-10

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

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

    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.

  2. Toxicity assessment of organic pollutants: reliability of bioluminescence inhibition assay and univariate QSAR models using freshly prepared Vibrio fischeri.

    PubMed

    Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

    2008-10-01

    The toxicity of 14 industrially relevant organic chemicals was determined using freshly grown Vibrio fischeri bioluminescence inhibition assay. The results were compared to lyophilized V. fischeri, 96h fish, 48h Daphnia magna and 95h green algae bioassays. Reliability of octanol-water partition coefficient (K(ow)), and first order simple and valence molecular connectivity index ((1)chi, (1)chi(v)) based regression models for predicting toxicity to V. fischeri was studied. Correlations were obtained between freshly grown V. fischeri data (Log(EC50)) and Log(K(ow)), molecular connectivity indices ((1)chi, (1)chi(v)), energy of the highest occupied (E(HOMO)) and lowest unoccupied (E(LUMO)) molecular orbitals, and their difference (E(LUMO)-E(HOMO)). A good match was observed between V. fischeri assay conducted with freshly grown and lyophilized culture (r2=0.90). Good correlations (r2>0.95) were obtained with all the other bioassays after excluding compounds with Log(K(ow)) less than 2.0. Available regression models based on Log(K(ow)) and (1)chi(v) yielded lower toxicity values. V. fischeri bioassay showed fairly good correlation with Log(K(ow)), (1)chi and (1)chi(v) (r2>0.75) but poor correlation with E(HOMO), E(LUMO) and (E(LUMO)-E(HOMO)) in presence of polar compounds. E(HOMO) and E(LUMO) values are affected by polarity and can be used along with Log(K(ow)) and (1)chi(v) for generating better predictive models. PMID:18701087

  3. COX1 and COX2 contribute differentially to the LPS-induced release of PGE 2 and TxA 2 in liver macrophages

    Microsoft Academic Search

    Yevgeniya Bezugla; Angelika Kolada; Sabine Kamionka; Brigitte Bernard; Roland Scheibe; Peter Dieter

    2006-01-01

    LPS induces an immediate release of thromboxane TxA2 and a delayed release of PGE2. Dexamethasone suppresses the LPS-induced release of TxA2 and PGE2. In the first 8h after LPS addition, the specific COX-2 inhibitor SC236 inhibits the PGE2 and TxA2 release by about 80% and 20%, whereas the release of PGE2 and TxA2 between 8 and 24h is inhibited by

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

    PubMed Central

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

    2014-01-01

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

  5. Involvement of COX-2/PGE2 signalling in hypoxia-induced angiogenic response in endothelial cells

    PubMed Central

    Zhao, Lixing; Wu, Yeke; Xu, Zhenrui; Wang, Hui; Zhao, Zhihe; Li, Yu; Yang, Pu; Wei, Xing

    2012-01-01

    Abstract To evaluate the impact of hypoxia on the angiogenic capability of endothelial cells (ECs), and further investigate whether the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signalling is involved in the angiogenic response of ECs to hypoxia. We explored the impact of various periods (1, 3, 6, 12, 24 hrs) of hypoxia (2% O2) on human umbilical vein endothelial cells (HUVECs) in vitro. We observed cell viability, migration, tube formation, analysed COX-2, vascular endothelial growth factor (VEGF), AQP1 mRNA transcription, protein expression and measured PGE2, VEGF protein concentration in cell supernatants. Then we treated HUVECs with COX-2 selective inhibitor NS398, EP1/2 combined antagonist AH6809 and exogenous PGE2 to investigate the role of COX-2/PGE2 signalling in the angiogenic response of ECs to hypoxia. The results demonstrated that short-term hypoxic treatment enhanced HUVECs proliferation, migration, tube formation, significantly up-regulated COX-2, VEGF, AQP1 mRNA level, protein expression and promoted PGE2, VEGF release. The pharmacological inhibition study revealed that exposure of HUVEC to NS398 and AH6809 under hypoxia impaired the biological responses of ECs to hypoxia. Exogenous PGE2 augments the effects of hypoxia on HUVECs, and partially reversed the inhibitory effects of NS398 on HUVECs proliferation and angiogenic capability. Short-term hypoxic treatment enhanced angiogenic capability of ECs, and COX-2/PGE2 signalling may play a critical role in the biological response of ECs to hypoxia. PMID:22050691

  6. Molecular docking and analgesic studies of Erythrina variegata?s derived phytochemicals with COX enzymes

    PubMed Central

    Uddin, Mir Muhammad Nasir; Emran, Talha Bin; Mahib, Muhammad Mamunur Rashid; Dash, Raju

    2014-01-01

    Secondary metabolites from plants are a good source for the NSAID drug development. We studied the analgesic activity of ethanolic extract of Erythrina variegata L. (Fabaceae) followed by molecular docking analysis. The analgesic activity of Erythrina variegata L. is evaluated by various methods viz., acetic acid-induced writhing test, hot plate and tail immersion test. Subsequently, molecular docking analysis has been performed to identify compounds having activity against COX-1 and COX-2 enzymes by using GOLD docking fitness. The result of preliminary phytochemical screening revealed that the extract contains alkaloids and flavonoids. In analgesic activity tests, the extract at the doses of 50, 100 and 200 mg/kg body weight (b.w.) produced a increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was similar to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). Docking studies shows that phaseollin of Erythrina variegata L. has the best fitness score against the COX-1 which is 56.64 and 59.63 for COX- 2 enzyme. Phaseollin of Erythrina variegata L. detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 is reported for further validation. PMID:25489172

  7. COX-2 dependent regulation of mechanotransduction in human breast cancer cells.

    PubMed

    Yoon, A-Rum; Stasinopoulos, Ioannis; Kim, Jae Hun; Yong, Hwan Mee; Kilic, Onur; Wirtz, Denis; Bhujwalla, Zaver M; An, Steven S

    2015-03-01

    The ability of living cells to exert physical forces upon their surrounding is a necessary prerequisite for diverse biological processes, such as local cellular migrations in wound healing to metastatic-invasion of cancer. How forces are coopted in metastasis has remained unclear, however, because the mechanical interplay between cancer cells and the various stromal components has not been experimentally accessible. Current dogma implicates inflammation in these mechanical processes. Using Fourier transform traction microscopy, we measured the force-generating capacity of human breast cancer cells occupying a spectrum of invasiveness as well as basal and inducible COX-2 expression (MCF-7COX-2. Both COX-2-silenced and COX-2-expressing cells expressed EP2 and EP4 receptors, but not EP1 and EP3. Exogenous addition of PGE2 increased cell tractions and stiffened the underlying cytoskeletal network. To our knowledge this is the first report linking the expression of COX-2 with mechanotransduction of human breast cancer cells, and the regulation of COX-2-PGE2-EP signaling with physical properties of the tumor microenvironment. Drug treatments aimed at reducing this mechanical interplay may have therapeutic potential in the treatment of breast cancer. PMID:25701047

  8. Transgenic Insulin-like Growth Factor-1 stimulates activation of COX-2 signaling in mammary glands

    PubMed Central

    Tian, Jie; Lambertz, Isabel; Berton, Thomas R.; Rundhaug, Joyce E.; Kiguchi, Kaoru; Shirley, Stephanie H.; DiGiovanni, John; Conti, Claudio J.; Fischer, Susan M.; Fuchs-Young, Robin

    2011-01-01

    Studies show that elevated IGF-1 levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF-1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX-2 signaling in the protumorigenic effects of IGF-1 in mammary glands, we used the unique BK5.IGF-1 mouse model in which transgenic (Tg) mice have significantly increased incidence of spontaneous and DMBA–induced mammary cancer compared to wild type (WT) littermates. Studies revealed that COX-2 expression was significantly increased in Tg mammary glands and tumors, compared to age-matched WTs. Consistent with this, PGE2 levels were also increased in Tg mammary glands. Analysis of expression of the EP receptors that mediate the effects of PGE2 showed that among the four G-protein-coupled receptors, EP3 expression was elevated in Tg glands. Up-regulation of the COX-2/PGE2/EP3 pathway was accompanied by increased expression of VEGF and a striking enhancement of angiogenesis in IGF-1 Tg mammary glands. Treatment with celecoxib, a selective COX-2 inhibitor, caused a 45% reduction in mammary PGE2 levels, attenuated the influx of mast cells and reduced vascularization in Tg glands. These findings indicate that the COX-2/PGE2/EP3 signaling pathway is involved in IGF-1–stimulated mammary tumorigenesis and that COX-2–selective inhibitors may be useful in the prevention or treatment of breast cancer associated with elevated IGF-1 levels in humans. PMID:22006370

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

    PubMed Central

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

    2009-01-01

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

  10. Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations to exercise.

    PubMed

    Trappe, Todd A; Liu, Sophia Z

    2013-09-01

    It has been ?40 yr since the discovery that PGs are produced by exercising skeletal muscle and since the discovery that inhibition of PG synthesis is the mechanism of action of what are now known as cyclooxygenase (COX)-inhibiting drugs. Since that time, it has been established that PGs are made during and after aerobic and resistance exercise and have a potent paracrine and autocrine effect on muscle metabolism. Consequently, it has also been determined that orally consumed doses of COX inhibitors can profoundly influence muscle PG synthesis, muscle protein metabolism, and numerous other cellular processes that regulate muscle adaptations to exercise loading. Although data from acute human exercise studies, as well as animal and cell-culture data, would predict that regular consumption of a COX inhibitor during exercise training would dampen the typical muscle adaptations, the chronic data do not support this conjecture. From the studies in young and older individuals, lasting from 1.5 to 4 mo, no interfering effects of COX inhibitors on muscle adaptations to resistance-exercise training have been noted. In fact, in older individuals, a substantial enhancement of muscle mass and strength has been observed. The collective findings of the PG/COX-pathway regulation of skeletal muscle responses and adaptations to exercise are compelling. Considering the discoveries in other areas of COX regulation of health and disease, there is certainly an interesting future of investigation in this re-emerging area, especially as it pertains to older individuals and the condition of sarcopenia, as well as exercise training and performance of individuals of all ages. PMID:23539318

  11. COX-2-Derived PGE2 Promotes Injury-induced Vascular Neointimal Hyperplasia through the EP3 Receptor

    PubMed Central

    Zhang, Jian; Zou, Fangfang; Tang, Juan; Zhang, Qianqian; Gong, Yanjun; Wang, Qingsong; Shen, Yujun; Xiong, Lixia; Breyer, Richard; Lararus, Michael; Funk, Colin D.; Yu, Ying

    2014-01-01

    Rationale Vascular smooth muscle cell (VSMC) migration and proliferation are the hallmarks of restenosis pathogenesis after angioplasty. Cyclooxygenase (COX)-derived prostaglandin (PG)E2 is implicated in the vascular remodeling response to injury. However, its precise molecular role remains unknown. Objective This study investigates the impact of COX-2-derived PGE2 on neointima formation after injury. Methods and Results Vascular remodeling was induced by wire-injury in femoral arteries of mice. Both neointima formation and the restenosis ratio were diminished in COX-2 KO mice as compared to controls, whereas these parameters were enhanced in COX-1>COX-2 mice where COX-1 is governed by COX-2 regulatory elements. PG profile analysis revealed that the reduced PGE2 by COX-2 deficiency, but not PGI2, could be rescued by COX-1 replacement, indicating COX-2-derived PGE2 enhanced neointima formation. Through multiple approaches, the EP3 receptor was identified to mediate the VSMC migration response to various stimuli. Disruption of EP3 impaired VSMC polarity for directional migration by depressing small GTPase activity and retarded vascular neointimal hyperplasia while overexpression of EP3? and EP3? aggravated neointima formation. Inhibition or deletion of EP3?/?, a G?s protein-coupled receptor, activated thecAMP/PKA pathway and depressed activation of RhoA in VSMCs. PGE2 could stimulate PI3K/Akt/GSK3? signaling in VSMCs through G?? subunits upon EP3?/? activation. Abolition of EP3 suppressed PI3K signaling and reduced GTPase activity in VSMCs, and altered cell polarity and directional migration. Conclusions COX-2-derived PGE2 facilitated the neointimal hyperplasia response to injury through EP3?/?-mediated cAMP/PKA and PI3K pathways, indicating EP3 inhibition maybe a promising therapeutic strategy for percutaneous transluminal coronary angioplasty. PMID:23595951

  12. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    SciTech Connect

    Zhu, Yingting, E-mail: yitizhu@yahoo.com [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States) [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States); Tissue Tech Inc., Miami, FL 33173 (United States); Zhu, Min; Lance, Peter [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States)] [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

  13. Insulin resistance: regression and clustering.

    PubMed

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

    2014-01-01

    In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression. Defining data come from measurements that play major roles in medical practice. A precise statement of what the data are is in Section 1. Their family structures are described in detail. They concern levels of lipids and the results of an oral glucose tolerance test (OGTT). We apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and lipids on functions of age and BMI that are inferred from the data. A bootstrap procedure developed for our family data supplemented by insights from other approaches leads us to believe that two clusters are appropriate for defining IR precisely. One cluster consists of women who are IR, and the other of women who seem not to be. Genes and other features are used to predict cluster membership. We argue that prediction with "main effects" is not satisfactory, but prediction that includes interactions may be. PMID:24887437

  14. Estimating equivalence with quantile regression

    USGS Publications Warehouse

    Cade, B.S.

    2011-01-01

    Equivalence testing and corresponding confidence interval estimates are used to provide more enlightened statistical statements about parameter estimates by relating them to intervals of effect sizes deemed to be of scientific or practical importance rather than just to an effect size of zero. Equivalence tests and confidence interval estimates are based on a null hypothesis that a parameter estimate is either outside (inequivalence hypothesis) or inside (equivalence hypothesis) an equivalence region, depending on the question of interest and assignment of risk. The former approach, often referred to as bioequivalence testing, is often used in regulatory settings because it reverses the burden of proof compared to a standard test of significance, following a precautionary principle for environmental protection. Unfortunately, many applications of equivalence testing focus on establishing average equivalence by estimating differences in means of distributions that do not have homogeneous variances. I discuss how to compare equivalence across quantiles of distributions using confidence intervals on quantile regression estimates that detect differences in heterogeneous distributions missed by focusing on means. I used one-tailed confidence intervals based on inequivalence hypotheses in a two-group treatment-control design for estimating bioequivalence of arsenic concentrations in soils at an old ammunition testing site and bioequivalence of vegetation biomass at a reclaimed mining site. Two-tailed confidence intervals based both on inequivalence and equivalence hypotheses were used to examine quantile equivalence for negligible trends over time for a continuous exponential model of amphibian abundance. ?? 2011 by the Ecological Society of America.

  15. Quantile regression applied to spectral distance decay

    USGS Publications Warehouse

    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.

  16. Hybrid fuzzy regression with trapezoidal fuzzy data

    NASA Astrophysics Data System (ADS)

    Razzaghnia, T.; Danesh, S.; Maleki, A.

    2012-01-01

    In this regard, this research deals with a method for hybrid fuzzy least-squares regression. The extension of symmetric triangular fuzzy coefficients to asymmetric trapezoidal fuzzy coefficients is considered as an effective measure for removing unnecessary fuzziness of the linear fuzzy model. First, trapezoidal fuzzy variable is applied to derive a bivariate regression model. In the following, normal equations are formulated to solve the four parts of hybrid regression coefficients. Also the model is extended to multiple regression analysis. Eventually, method is compared with Y-H.O. chang's model.

  17. Hybrid fuzzy regression with trapezoidal fuzzy data

    NASA Astrophysics Data System (ADS)

    Razzaghnia, T.; Danesh, S.; Maleki, A.

    2011-12-01

    In this regard, this research deals with a method for hybrid fuzzy least-squares regression. The extension of symmetric triangular fuzzy coefficients to asymmetric trapezoidal fuzzy coefficients is considered as an effective measure for removing unnecessary fuzziness of the linear fuzzy model. First, trapezoidal fuzzy variable is applied to derive a bivariate regression model. In the following, normal equations are formulated to solve the four parts of hybrid regression coefficients. Also the model is extended to multiple regression analysis. Eventually, method is compared with Y-H.O. chang's model.

  18. 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.

  19. Detection of independent associations in a large epidemiologic dataset: a comparison of random forests, boosted regression trees, conventional and penalized logistic regression for identifying independent factors associated with H1N1pdm influenza infections

    PubMed Central

    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

  20. ZN2+ INDUCES COX-2 EXPRESSION THROUGH DOWNREGULATION OF LIPID PHOSPHATASE PTEN

    EPA Science Inventory

    Zn2+ Induces COX-2 Expression through Downregulation of Lipid Phosphatase PTEN Weidong Wu*, James M. Samet, Philip A. Bromberg*?, Young E. Whang?, and Lee M. Graves* ? *CEMALB, ?Department of Medicine, and ?Department of Pharmacology, UNC-Chapel Hill, NC27599; Human Studie...

  1. Selective COX2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease

    Microsoft Academic Search

    Rosario Sánchez-Pernaute; Andrew Ferree; Oliver Cooper; Meixiang Yu; Anna-Liisa Brownell; Ole Isacson

    2004-01-01

    Several lines of evidence point to a significant role of neuroinflammation in Parkinson's disease (PD) and other neurodegenerative disorders. In the present study we examined the protective effect of celecoxib, a selective inhibitor of the inducible form of cyclooxygenase (COX-2), on dopamine (DA) cell loss in a rat model of PD. We used the intrastriatal administration of 6-hydroxydopamine (6-OHDA) that

  2. Current approaches to prevent NSAID-induced gastropathy – COX selectivity and beyond

    PubMed Central

    Becker, Jan C; Domschke, Wolfram; Pohle, Thorsten

    2004-01-01

    Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem – despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori. Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of NSAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative properties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the GI safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COX-inhibitors are currently evaluated in clinical studies with very promising results: NSAIDs combined with a nitric oxide releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa. PMID:15563357

  3. Modified Golgi-Cox method for micrometer scale sectioning of the whole mouse brain

    Microsoft Academic Search

    Bin Zhang; Anan Li; Zhongqin Yang; Jingpeng Wu; Qingming Luo; Hui Gong

    2011-01-01

    One of the major challenges of connectomics is obtaining a physical map of the neurons that comprise a circuit and the sites within the whole mouse brain. However, there is no report that addresses the preparation of whole mouse brain tissue for microsectioning. In this paper, such tissue is prepared by a modified Golgi-Cox method in which the staining time

  4. Fluorescence discrimination of cancer from inflammation by molecular response to COX-2 enzymes.

    PubMed

    Zhang, Hua; Fan, Jiangli; Wang, Jingyun; Dou, Bairui; Zhou, Fan; Cao, Jianfang; Qu, Junle; Cao, Zhi; Zhao, Weijie; Peng, Xiaojun

    2013-11-20

    Accurate identification of cancer from inflammation and normal tissue in a rapid, sensitive, and quantitative fashion is important for cancer diagnosis and resection during surgery. Here we report the use of cyclooxygenase-2 as a marker for identification of cancer from inflammation and the design of a novel smart COX-2-specific fluorogenic probe (NANQ-IMC6). The probe's fluorescence is "turned on" in both inflammations and cancers where COX-2 is overexpressed. Intriguingly, the fluorescent emission is quite different at these two sites with different expression level of COX-2. Hence, NANQ-IMC6 can not only distinguish normal cells/tissues from cancer cells/tissues but also distinguish the latter from sites of inflammation lesions by the different fluorescence recognition of NANQ-IMC6 for COX-2 enzymes. Following spraying with the NANQ-IMC6 solution, cancerous tissue, inflamed tissues, and normal tissues can be accurately discriminated in vivo by the unaided eye using a hand-held ultraviolet lamp emitting at 365 nm. So the probe may have potential application varying from cancer inflammation diagnosis to guiding tumor resection during surgery. PMID:24200121

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

    Microsoft Academic Search

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

    2001-01-01

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

  6. Direct-to-consumer advertising of COX-2 inhibitors: effect on appropriateness of prescribing.

    PubMed

    Spence, Michele M; Teleki, Stephanie S; Cheetham, T Craig; Schweitzer, Stuart O; Millares, Mirta

    2005-10-01

    Spending on direct-to-consumer advertising (DTCA) of prescription drugs has increased dramatically in the past several years. An unresolved question is whether such advertising leads to inappropriate prescribing. In this study, the authors use survey and administrative data to determine the association of DTCA with the appropriate prescribing of cyclooxygenase-2 (COX-2) inhibitors for 1,382 patients. Treatment with either a COX-2 or a traditional nonsteroidal anti-inflammatory drug (NSAID) was defined as appropriate or not according to three different definitions of gastrointestinal risk. Patients who saw or heard a COX-2 advertisement and asked their physician about the advertised drug were significantly more likely to be prescribed a COX-2 (versus a NSAID, as recommended by evidence-based guidelines) than all other patients. Findings also suggest that some patients may benefit from DTCA. The authors discuss the need for balanced drug information for consumers, increased physician vigilance in prescribing appropriately, and further study of DTCA. PMID:16177457

  7. Larry Cox, ljcox@lanl.gov, (505) 665-7344 Monte Carlo mini-App --

    E-print Network

    Larry Cox, ljcox@lanl.gov, (505) 665-7344 Monte Carlo mini-App -- It's a wrap... Next Steps) materials and cross sec.ons ­ For distribu.on with the miniApp ­ For use with MCNP6 for comparisons or in trying out these MC miniApp concepts, please get in touch. References: [1] MCNP website: h

  8. YIELD OPTION PRICING IN THE GENERALIZED COX-INGERSOLL-ROSS MODEL

    E-print Network

    Deelstra, Griselda

    1 YIELD OPTION PRICING IN THE GENERALIZED COX-INGERSOLL-ROSS MODEL Griselda Deelstra CREST, ENSAE, Malakoff, France Abstract : In this paper, we provide pricing formulae for both European and American yield. Keywords : Extended CIR model, European and American yield option pricing, forward- neutral probability

  9. Advantages and inconveniences of the Cox model compared with the logistic model: application

    E-print Network

    Paris-Sud XI, Université de

    Advantages and inconveniences of the Cox model compared with the logistic model: application and the logistic model were compared on a data set obtained from an ecopathological survey relative to the risk rather limited. ecopathology I survival model 1 logistic model Résumé - Avantages et inconvénients du

  10. Intramolecular Catalysis of Amide Isomerization Christopher Cox, Victor G. Young, Jr., and

    E-print Network

    Lectka, Thomas

    In this Communication, we report the first experimental study of intramolecular catalysis of AI in model systemsIntramolecular Catalysis of Amide Isomerization Christopher Cox, Victor G. Young, Jr., and Thomas The catalysis of amide bond isomerization (AI) by Bro¨nsted acids is a well-documented reaction that proceeds

  11. Vx32: Lightweight User-level Sandboxing on the x86 Bryan Ford and Russ Cox

    E-print Network

    Ford, Bryan

    Vx32: Lightweight User-level Sandboxing on the x86 Bryan Ford and Russ Cox Massachusetts Institute of Technology {baford,rsc}@pdos.csail.mit.edu Abstract Code sandboxing is useful for many purposes, but most sandboxing techniques require kernel modifications, do not completely isolate guest code, or incur

  12. The effects of calcium and other minerals on incidence of bitter pit in Cox's orange apples

    Microsoft Academic Search

    D. I. Jackson

    1962-01-01

    Sprays containing calcium, magnesium, potassium, phosphorus, nitrogen, boron, iron, strontium, tungsten, and vanadium were tested for their effect upon bitter pit development in stored apples (Cox's Orange). Only calcium nitrate significantly altered the incidence of pit, both tree sprays and post-harvest fruit sprays of this compound reducing incidence of bitter pit consistently. Later sprays tended to be more effective than

  13. Spike Sorting This example was modified from: Gabbiani & Cox, Mathematics for Neuroscientists

    E-print Network

    Born, Richard

    Spike Sorting This example was modified from: Gabbiani & Cox, Mathematics for Neuroscientists SpikeSort.m: Sorting spikes from noisy multi-unit extracellular recordings. MATLAB concepts covered: 1. thresholding an extracellular electrode: load SpikeSortData; This file contains 3 variables: 'Time' is the time-base, from 0

  14. The Source of Anthropogenic Heavy Metals in Fluvial Sediments of a Rural Catchment: Coxs River, Australia

    Microsoft Academic Search

    Gavin Birch; Made Siaka; Christopher Owens

    2001-01-01

    A serious health scare involving thesupply of drinking water to Sydney, Australia hasrecently focussed attention on the environmentalstatus of river catchments of the main reservoir, LakeBurragorang. Although the Coxs River – a majorcatchment of Lake Burragorang – comprises mainlyforests and grazing land, it supports a moderate sizedtown, power stations and coal mines. The heavy metal content of stream-bed sedimentscharacterises environmental

  15. TESSA, a system to aid communication with deaf people Stephen Cox, Michael

    E-print Network

    Edinburgh, University of

    TESSA, a system to aid communication with deaf people Stephen Cox, Michael Lincoln and Judy Royal National Institute for Deaf People, 19­23 Featherstone Street, London EC1Y 8SL U.K. Mark Wells.K. ABSTRACT TESSA is an experimental system that aims to aid transactions between a deaf person and a clerk

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

    SciTech Connect

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

    2013-10-11

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

  17. Extraendothelial and constitutive COX-2 expression is involved in the contractile effect of angiotensin II in the rat aorta.

    PubMed

    Castillo-Hernández, M C; Martinez-Godinez, M A; Guevara-Balcazar, G; Miliar-Garcia, A; Mancilla, J; Lopez-Mayorga, R M; Castillo-Henkel, E F; Castillo-Henkel, C

    2010-10-01

    1 The role of the extraendothelial and constitutive isoforms of cyclo-oxygenase-2 (COX-2) in the contractile effect of angiotensin II (Ang II) was investigated using thoracic and abdominal aortic rings without endothelium from young Wistar rats. 2 Ang II elicited similar contractions in both aortic segments, and the effect was inhibited by pretreatment with NS398 (a selective COX-2 inhibitor) but not SC-560 [selective cyclo-oxygenase-1 (COX-1) inhibitor]. 3 COX-2 mRNA was expressed under basal conditions in both aortic segments. Additionally, Ang II increased COX-2 mRNA expression in the abdominal but not the thoracic segment, while cycloheximide (a protein synthesis inhibitor) did not affect the contractile response to Ang II in either of the two segments; this suggests that the effect is not associated with de novo COX-2 synthesis. 4 In conclusion, the basal amount of COX-2 found in aortic smooth muscle cells is sufficient to explain the production of the prostanoids related to the contractile effect of Ang II. The production of these prostanoids, which are derived from constitutive COX-2, occurs independently of the endothelium vascular system. PMID:20626388

  18. 1,2-Diaryl-2-hydroxyiminoethanones as Dual COX-1 and ?-Amyloid Aggregation Inhibitors: Biological Evaluation and In Silico Study.

    PubMed

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

    2015-04-01

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

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

    E-print Network

    Leary, Scot

    ,2 Nancy G. Kennaway,4 and Eric A. Shoubridge1,2 1 Montreal Neurological Institute and 2 Department of heme A, the heme prosthetic group for COX, can functionally complement the isolated COX deficiency. Address for correspondence and reprints: Dr. Eric A. Shoubridge, Montreal Neurological Institute, 3801

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

    E-print Network

    Goodman, Wayne

    Chemical Engineering Journal 93 (2003) 69­80 Production of COx-free hydrogen for fuel cells via Abstract The stringent COx-free hydrogen requirement for the current low temperature fuel cells has-wise reforming; Model catalysts 1. Introduction Fuel cells represent an exciting technology for converting fuel

  1. The challenge of multispeaker lip-reading Stephen Cox, Richard Harvey, Yuxuan Lan, Jacob Newman, Barry-John Theobald

    E-print Network

    Theobald, Barry-John

    The challenge of multispeaker lip-reading Stephen Cox, Richard Harvey, Yuxuan Lan, Jacob Newman, Barry-John Theobald School of Computing Sciences, University of East Anglia, Norwich, NR4 7TJ, UK. {s.j.cox,r.w.harvey,y.lan,jacob.newman,b.theobald}@uea.ac.uk Abstract In speech recognition, the problem

  2. A comparative analysis of the bifunctional Cox proteins of two heteroimmune P2-like phages with different host integration sites

    Microsoft Academic Search

    Alexandra Ahlgren-Berg; Carlos Cardoso-Palacios; Jesper M. Eriksson; Sridhar Mandali; Wilhelmina Sehlén; Lina Sylwan; Elisabeth Haggård-Ljungquist

    2009-01-01

    The Cox protein of the coliphage P2 is multifunctional; it acts as a transcriptional repressor of the Pc promoter, as a transcriptional activator of the PLL promoter of satellite phage P4, and as a directionality factor for site-specific recombination. The Cox proteins constitute a unique group of directionality factors since they couple the developmental switch with the integration or excision

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

    ERIC Educational Resources Information Center

    Albrecht, Doris

    2007-01-01

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

  4. Abnormal COX2 Protein Expression May Be Correlated with Poor Prognosis in Oral Cancer: A Meta-Analysis

    PubMed Central

    Wang, Zhi-Ming; Liu, Jie; Liu, Hong-Bo; Ye, Ming; Zhang, Yu-Fei; Yang, Dong-Sheng

    2014-01-01

    Background. The prognostic significance of COX2 for survival of patients with oral cancer remains controversial. Thus, the meta-analysis was performed in order to identify COX2 expression impact on prognosis of oral cancer. Method. Relevant literatures were searched using the following electronic databases without any language restrictions: Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and CBM. Version 12.0 STATA software (Stata Corporation, College Station, Texas, USA) was used for the current meta-analysis. Odds ratios (ORs) and hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between COX2 expression and prognosis of oral cancer. Results. Final analysis of 979 oral cancer patients from 12 clinical cohort studies was performed. The meta-analysis results show that COX2 expression in cancer tissues was significantly higher than those in normal and benign tissues (all P < 0.05). Combined HR of COX2 suggests that positive COX2 expression has a shorter overall survival (OS) than those of negative COX2 expression (P < 0.05). Conclusion. The meta-analysis study shows that elevated COX2 expression may be associated with the pathogenesis of oral cancer and with a worse prognosis in oral cancer patients. PMID:25028647

  5. Geoadditive hazard regression for interval censored survival times

    Microsoft Academic Search

    Thomas Kneib

    The Cox proportional hazards model is the most commonly used method when analyzing the impact of covariates on continuous survival times. In its classical form, the Cox model was introduced in the setting of right-censored observations. However, in practice other sampling schemes are frequently encountered and there- fore extensions allowing for interval and left censoring or left truncation are clearly

  6. Bias correction for the proportional odds logistic regression model with application to a study of surgical complications

    PubMed Central

    Lipsitz, Stuart R.; Fitzmaurice, Garrett M.; Regenbogen, Scott E.; Sinha, Debajyoti; Ibrahim, Joseph G.; Gawande, Atul A.

    2013-01-01

    Summary The proportional odds logistic regression model is widely used for relating an ordinal outcome to a set of covariates. When the number of outcome categories is relatively large, the sample size is relatively small, and/or certain outcome categories are rare, maximum likelihood can yield biased estimates of the regression parameters. Firth (1993) and Kosmidis and Firth (2009) proposed a procedure to remove the leading term in the asymptotic bias of the maximum likelihood estimator. Their approach is most easily implemented for univariate outcomes. In this paper, we derive a bias correction that exploits the proportionality between Poisson and multinomial likelihoods for multinomial regression models. Specifically, we describe a bias correction for the proportional odds logistic regression model, based on the likelihood from a collection of independent Poisson random variables whose means are constrained to sum to 1, that is straightforward to implement. The proposed method is motivated by a study of predictors of post-operative complications in patients undergoing colon or rectal surgery (Gawande et al., 2007). PMID:23913986

  7. Increased dietary sodium induces COX2 expression by activating NF?B in renal medullary interstitial cells.

    PubMed

    He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming

    2014-02-01

    High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NF?B in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NF?B reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NF?B-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NF?B-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective I?B kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NF?B plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806

  8. Increased Dietary Sodium Induces COX2 Expression by activating NF?B in Renal Medullary Interstitial Cells

    PubMed Central

    Zhao, Min; Davis, Linda S.; Blackwell, Timothy S.; Yull, Fiona; Breyer, Matthew D.; Hao, Chuan-Ming

    2013-01-01

    High salt diet induces renal medullary COX2 expression. Selective blockade of renal medullary COX2 activity in rats causes salt sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NF?B in mediating this COX2 induction in response to increased dietary salt. High salt diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co-immunofluorescence using a COX2 antibody and antibodies against AQP2, ClC-K, AQP1 and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NF?B reporter transgenic mice, we observed a 7 fold increase of luciferase activity in the renal medulla of the NF?B-luciferase reporter mice following high salt diet, and a robust induction of EGFP expression mainly in renal medullary interstitial cells of the NF?B-EGFP reporter mice following high salt diet. Treating high salt diet fed C57Bl/6J mice with selective I?B kinase inhibitor IMD-0354 (8mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary PGE2. These data therefore suggest that renal medullary interstitial cell NF?B plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806

  9. IL1{beta}-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

    SciTech Connect

    Zhu, Yingting, E-mail: yitizhu@yahoo.com [University of Arizona Arizona Cancer Center Tissue Tech Inc, 7000 SW 97th Avenue Suite 212, Miami, FL 33173 (United States) [University of Arizona Arizona Cancer Center Tissue Tech Inc, 7000 SW 97th Avenue Suite 212, Miami, FL 33173 (United States); Tissue Tech Inc, Miami, FL 33173 (United States); Zhu, Min; Lance, Peter [University of Arizona Arizona Cancer Center Tissue Tech Inc, 7000 SW 97th Avenue Suite 212, Miami, FL 33173 (United States)] [University of Arizona Arizona Cancer Center Tissue Tech Inc, 7000 SW 97th Avenue Suite 212, Miami, FL 33173 (United States)

    2012-11-15

    COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1{beta} in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1{beta}, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1{beta}. Further analysis indicated that the major COX-2 product, prostaglandin E{sub 2}, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1{beta}. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1{beta} in the fibroblasts.

  10. Deriving the Regression Equation without Using Calculus

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.; Gordon, Florence S.

    2004-01-01

    Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

  11. Ridge Regression: Applications to Nonorthogonal Problems

    Microsoft Academic Search

    Arthur E. Hoerl; Robert W. Kennard

    1970-01-01

    This paper is an exposition of the use of ridge regression methods. Two examples from the literature are used as a base. Attention is focused on the RIDGE TRACE which is a two-dimensional graphical procedure for portraying the complex relationships in multifactor data. Recommendations are made for obtaining a better regression equation than that given by ordinary least squares estimation.

  12. WINKS Statistics Software - Simple Linear Regression

    NSDL National Science Digital Library

    This tutorial on Simple Linear Regression includes its definition, assumptions, and characteristics as well as related statistics and hypothesis test procedures. One section instructs users to perform simple linear regression in the WINKS software, but those without the software can still use the tutorial. An exercise is given at the end that can be done with any statistical software package.

  13. ContentsContents4343Regression and correlation

    E-print Network

    Vickers, James

    of the relationship(s) between two or more variables. The technique of regression analysis is very useful and well-used in this situation. This Section will look at the basics of regression analysis and should enable you to apply between two variables does not necessarily imply that the relationship is causal. You might find

  14. Covariate Measurement Error in Logistic Regression

    Microsoft Academic Search

    Leonard A. Stefanski; Raymond J. Carroll

    1985-01-01

    In a logistic regression model when covariates are subject to measurement error the naive estimator, obtained by regressing on the observed covariates, is asymptotically biased. We introduce a bias-adjusted estimator and two estimators appropriate for normally distributed measurement errors -a functional maximum likelihood estimator and an estimator which exploits the consequences of sufficiency. The four proposals are studied asymptotically under

  15. Variational Logistic Regression Sunday, October 12, 2008

    E-print Network

    Cevher, Volkan

    Variational Logistic Regression Sunday, October 12, 2008 Rice University STAT 631 / ELEC 639 this to variational logistic regression governed by the logistic sigmoid function. This document is organized as follows: Section 2 details the bounding of the logistic sigmoid function which will be used in the final

  16. WhartonDepartment of Statistics Logistic Regression &

    E-print Network

    Stine, Robert A.

    WhartonDepartment of Statistics Logistic Regression & Classification Bob Stine Dept of Statistics #12;WhartonDepartment of Statistics Logistic Regression · Model · Assumes latent factor = x11 + ... + xkk for which the log of the odds ratio is · Logistic curve resembles normal CDF · Estimation uses

  17. Choosing between Logistic Regression and Discriminant Analysis

    Microsoft Academic Search

    Sandra Wilson

    1978-01-01

    Classifying an observation into one of several populations is discriminant analysis, or classification. Relating qualitative variables to other variables through a logistic cdf functional form is logistic regression. Estimators generated for one of these problems are often used in the other. If the populations are normal with identical covariance matrices, discriminant analysis estimators are preferred to logistic regression estimators for

  18. Regression Analysis and the Sociological Imagination

    ERIC Educational Resources Information Center

    De Maio, Fernando

    2014-01-01

    Regression analysis is an important aspect of most introductory statistics courses in sociology but is often presented in contexts divorced from the central concerns that bring students into the discipline. Consequently, we present five lesson ideas that emerge from a regression analysis of income inequality and mortality in the USA and Canada.

  19. A measure to identify regression outliers

    NASA Astrophysics Data System (ADS)

    Ramaboa, Kutlwano K. K. M.; Underhill, Les G.

    2014-12-01

    In this paper we describe a measure that can be used to detect regression outliers. Observations that deviate from the bulk of the data can easily influence the fit of the least squares regression line, and the residuals, which take the response variable,y, into account, are often examined to determine the observations that may have influenced the fit of the least squares regression line, hence affecting other regression estimates. One drawback of using transformed residuals such as the Studentized residuals is that they may fail to identify the regression outliers when these observations are being accommodated by the least squares fit, thus we propose a measure that is based on the role that each observation plays in the displacement of other observations from the fitted least squares regression line. The proposed measure is based on the off-diagonal values of the hat matrix, and illustrated on three data sets that have appeared in the literature on regression diagnostics. A comparison is also made using popular MM estimator used to obtain robust regression estimates to illustrate the value of the proposed measure.

  20. Head pose estimation: Classification or regression?

    Microsoft Academic Search

    Guodong Guo; Yun Fu; Charles R. Dyer; Thomas S. Huang

    2008-01-01

    Head pose estimation has many useful applications in practice. How to estimate the head pose automat- ically and robustly is still a challenging problem. In pose estimation, different pose angles can be used as regression values or viewed as different class labels. Thus a question is raised in our study: which is proper for pose estimation - classification or regression?

  1. Bayesian nonparametric regression with varying residual density

    E-print Network

    West, Mike

    the mean and variance to change with predictors using thin plate splines. In certain applications conditions to ensure strong posterior consistency in estimating the regression function under the sPSB prior Gaussian processes in the stick-breaking components. This leads to a robust Bayesian regression procedure

  2. REFORMAT: Stata module to reformat regression output

    Microsoft Academic Search

    Tony Brady

    2002-01-01

    The output from the last regression command is re-displayed in a more readable format using variable and value labels for clarity. The columns to be displayed can be controlled by the user and extra options to show the number of observations or likelihood ratio P-value associated with each covariate is provided. The command is particularly suited to regression output containing

  3. Hidden Markov Model Regression Moshe Fridman \\Lambda

    E-print Network

    Hidden Markov Model Regression Moshe Fridman \\Lambda Institute for Mathematics and its Applications, 1993 Abstract Hidden Markov Model Regression (HMMR) is an extension of the Hid­ den Markov Model (HMM. Key words: Hidden Markov model, Forward­Backward proce­ dure, Baum­Welch algorithm, Switching

  4. Hidden Markov Model Regression Moshe Fridman

    E-print Network

    Hidden Markov Model Regression Moshe Fridman Institute for Mathematics and its Applications, 1993 Abstract Hidden Markov Model Regression (HMMR) is an extension of the Hid- den Markov Model (HMM. Key words: Hidden Markov model, Forward-Backward proce- dure, Baum-Welch algorithm, Switching

  5. THE PARTIAL REGRESSION COEFFICIENTS IN PEDIGREE EVALUATION

    E-print Network

    Paris-Sud XI, Université de

    of the same size were first discussed. In sex- limited characters where the number of partial regression regression coefficients for traits expressed on both sexes and for sex-limited characters. The regular cases arithmetic. A solution for the irregular cases in which the ancestors provide information of different

  6. Principles of Quantile Regression and an Application

    ERIC Educational Resources Information Center

    Chen, Fang; Chalhoub-Deville, Micheline

    2014-01-01

    Newer statistical procedures are typically introduced to help address the limitations of those already in practice or to deal with emerging research needs. Quantile regression (QR) is introduced in this paper as a relatively new methodology, which is intended to overcome some of the limitations of least squares mean regression (LMR). QR is more…

  7. Time Series Regression with a Unit Root

    Microsoft Academic Search

    P. C. B. Phillips

    1987-01-01

    This paper studies the random walk in a general time series setting that allows for weakly dependent and heterogeneously distributed innovations. It is shown that simple least squares regression consistently estimates a unit root under very general conditions in spite of the presence of autocorrelated errors. The limiting distribution of the standardized estimator and the associated regression t statistic are

  8. Assumptions of Multiple Regression: Correcting Two Misconceptions

    ERIC Educational Resources Information Center

    Williams, Matt N.; Gomez Grajales, Carlos Alberto; Kurkiewicz, Dason

    2013-01-01

    In 2002, an article entitled "Four assumptions of multiple regression that researchers should always test" by Osborne and Waters was published in "PARE." This article has gone on to be viewed more than 275,000 times (as of August 2013), and it is one of the first results displayed in a Google search for "regression

  9. Using Regression Analysis to Project Pumpage

    Microsoft Academic Search

    Stephen D. Rhoades; Thomas M. Walski

    1991-01-01

    The city of Austin, Texas, Water and Wastewater Utility has used regression analysis to project water pumpage. It is a reasonably accurate, easy to learn and use, and inexpensive technique; it does not require an unusual amount of data; the explanatory variables and regression results can be quickly checked for statistical significance; and the input data can be easily modified.

  10. Adaptive Local Hyperplane for regression tasks

    Microsoft Academic Search

    Vojislav Kecman; Tao Yang

    2009-01-01

    The paper introduces novel machine learning (data mining) algorithm called Adaptive Local Hyperplane (ALH) and it presents its application in solving regression problems. ALH algorithm has recently shown extremely good results in classification, and it is adopted for solving regression tasks here. It is a local margin maximizing algorithm in the original, weighted, input space blending a Nearest Neighbors (NN)

  11. Illustration of Regression towards the Means

    ERIC Educational Resources Information Center

    Govindaraju, K.; Haslett, S. J.

    2008-01-01

    This article presents a procedure for generating a sequence of data sets which will yield exactly the same fitted simple linear regression equation y = a + bx. Unless rescaled, the generated data sets will have progressively smaller variability for the two variables, and the associated response and covariate will "regress" towards their…

  12. LS-SVM REGRESSION WITH AUTOCORRELATED ERRORS

    E-print Network

    LS-SVM REGRESSION WITH AUTOCORRELATED ERRORS Marcelo Espinoza, Johan A.K. Suykens, Bart De Moor K. Using LS-SVM regression as a nonlinear black-box tech- nique, it is illustrated that neglecting of black-box NAR(X) system identification using Least Squares Support Vector Machines (LS-SVM) (Suykens et

  13. Regression of Environmental Noise in LIGO Data

    E-print Network

    Vaibhav Tiwari; Marco Drago; Valery Frolov; Sergey Klimenko; Guenakh Mitselmakher; Valentin Necula; Giovanni Prodi; Virginia Re; Francesco Salemi; Gabriele Vedovato; Igor Yakushin

    2015-03-25

    We address the problem of noise regression in the output of gravitational-wave (GW) interferometers, using data from the physical environmental monitors (PEM). The objective of the regression analysis is to predict environmental noise in the gravitational-wave channel from the PEM measurements. One of the most promising regression method is based on the construction of Wiener-Kolmogorov filters. Using this method, the seismic noise cancellation from the LIGO GW channel has already been performed. In the presented approach the Wiener-Kolmogorov method has been extended, incorporating banks of Wiener filters in the time-frequency domain, multi-channel analysis and regulation schemes, which greatly enhance the versatility of the regression analysis. Also we presents the first results on regression of the bi-coherent noise in the LIGO data.

  14. On the misuse of residuals in ecology: regression of residuals vs. multiple regression

    Microsoft Academic Search

    Robert P. Freckleton

    2002-01-01

    Summary 1. Residuals from linear regressions are used frequently in statistical analysis, often for the purpose of controlling for unwanted effects in multivariable datasets. This paper criticizes the practice, building upon recent critiques. 2. Regression of residuals is often used as an alternative to multiple regression, often with the aim of controlling for confounding variables. When correlations exist between independent

  15. Locally-Weighted Regression: An Approach to Regression Analysis by Local Fitting

    Microsoft Academic Search

    William S. Cleveland; Susan J. Devlin; J. B. Wagenaar

    1988-01-01

    Locally weighted regression, or loess, is a way of estimating a regression surface through a multivariate smoothing procedure, fitting a function of the independent variables locally and in a moving fashion analogous to how a moving average is computed for a time series. With local fitting we can estimate a much wider class of regression surfaces than with the usual

  16. A comparison of regression and regression-kriging for soil characterization using remote sensing imagery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In precision agriculture regression has been used widely to quality the relationship between soil attributes and other environmental variables. However, spatial correlation existing in soil samples usually makes the regression model suboptimal. In this study, a regression-kriging method was attemp...

  17. Discovering genetic associations with high-dimensional neuroimaging phenotypes: A sparse reduced-rank regression approach.

    PubMed

    Vounou, Maria; Nichols, Thomas E; Montana, Giovanni

    2010-11-15

    There is growing interest in performing genome-wide searches for associations between genetic variants and brain imaging phenotypes. While much work has focused on single scalar valued summaries of brain phenotype, accounting for the richness of imaging data requires a brain-wide, genome-wide search. In particular, the standard approach based on mass-univariate linear modelling (MULM) does not account for the structured patterns of correlations present in each domain. In this work, we propose sparse reduced rank regression (sRRR), a strategy for multivariate modelling of high-dimensional imaging responses (measurements taken over regions of interest or individual voxels) and genetic covariates (single nucleotide polymorphisms or copy number variations), which enforces sparsity in the regression coefficients. Such sparsity constraints ensure that the model performs simultaneous genotype and phenotype selection. Using simulation procedures that accurately reflect realistic human genetic variation and imaging correlations, we present detailed evaluations of the sRRR method in comparison with the more traditional MULM approach. In all settings considered, sRRR has better power to detect deleterious genetic variants compared to MULM. Important issues concerning model selection and connections to existing latent variable models are also discussed. This work shows that sRRR offers a promising alternative for detecting brain-wide, genome-wide associations. PMID:20624472

  18. Modulation of redox switches of copper chaperone Cox17 by Zn(II) ions determined by new ESI MS-based approach.

    PubMed

    Zovo, Kairit; Palumaa, Peep

    2009-05-01

    Cox17, a copper chaperone for cytochrome-c oxidase, contains six conserved Cys residues and exists in three oxidative states, linked with two thiol-based redox switches. The first switch leads to formation of two disulfides and occurs upon transport of Cox17 into mitochondrial intermembrane space (IMS). Cox17(2S-S) is retained in the IMS and is also a functional form of the protein, which can be further oxidized to Cox17(3S-S). According to the midpoint redox potential values, Cox17 can be partially oxidized in the cytosol, which might hinder its transport into IMS. We hypothesize that Zn(II) ions might protect cytosolic Cox17 from oxidation. In order to get quantitative information about the modulatory effect of Zn(II) ions on redox switches in Cox17, we have used ESI MS for determination of the midpoint potentials for redox couples of Cox17: Cox17(3S-S) <--> Cox17(2S-S) (E(m1)) and Cox17(2S-S) <--> Cox17(0S-S) (E(m2)) in the presence of Zn(II). 10 microM Zn(II) ions shift the E(m2) by 21 mV and E(m1) by 15 mV to more positive values. Apparent dissociation constants for Zn(II) complexes of Cox17(0S-S) and Cox17(2S-S), are 0.067 and 0.29 nM, respectively. The high affinity shows that metallation of Cox17(0S-S) by Zn(II) might be significant in cellular conditions, which might protect Cox17 from oxidation and enable its transport into IMS. PMID:19018666

  19. Expression of STAT5, COX-2 and PIAS3 in Correlation with NSCLC Histhopathological Features

    PubMed Central

    Czarnecka, Karolina H.; Kordiak, Jacek; Migdalska-S?k, Monika; Nawrot, Ewa; Kisza?kiewicz, Justyna; Antczak, Adam; Górski, Pawe?; Brzezia?ska, Ewa

    2014-01-01

    Signal transducers and activators of transcription (STATs), their inhibitors and cyclooxygenase-2 (COX-2) participate in transformations of many various types of cancers. The aim of the present study was to evaluate the relationship between STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status, and histopathological subtype in 71 patients with confirmed non-small cell lung cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and the expression of the studied genes was assessed using TaqMan probes in real-time PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression was decreased in the majority (69%) of the studied tissues. Statistically significant differences were observed between STAT5 isoforms (P?=?0.0008), with higher expression of STAT5B. We found statistically significant positive correlation between STAT5B and COX-2 (rho?=?0.045), and significant negative correlation between STAT5B and PIAS3 (rho?=??0.049). The negative correlation between STAT5B and PIAS3 (rho?=??0.43) was also observed in T2a+T2b tumor group. Additionally, STAT5B and COX-2 expression levels were significantly different between T1a+T1b and T2a+T2b tumors (P?=?0.002 and P?=?0.041, respectively), with higher expression of both genes in T2 tumor stage. PIAS3 expression was significantly lower in NSCC subtype as compared with SCC subtype (P?=?0.017). Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated significantly higher protein levels in NSCLC patients as compared with controls (P?=?0.048 and P?=?0.034, respectively). High STAT5B immunoexpression was positively correlated with STAT5B gene expression in tumors (rho?=?0.755). STAT5B protein level was also significantly higher in T2a+T2b tumors, reflecting high STAT5B gene expression in this group. There was no statistically significant association between mRNA and protein expression levels of the studied genes and patients' characteristics: age, gender, smoking. The obtained results highlight the importance of the genes STAT5B and COX-2 in lung cancer progression. PMID:25137041

  20. Parallel evolution of cox genes in H2S-tolerant fish as key adaptation to a toxic environment.

    PubMed

    Pfenninger, Markus; Lerp, Hannes; Tobler, Michael; Passow, Courtney; Kelley, Joanna L; Funke, Elisabeth; Greshake, Bastian; Erkoc, Umut Kaan; Berberich, Thomas; Plath, Martin

    2014-01-01

    Populations that repeatedly adapt to the same environmental stressor offer a unique opportunity to study adaptation, especially if there are a priori predictions about the genetic basis underlying phenotypic evolution. Hydrogen sulphide (H2S) blocks the cytochrome-c oxidase complex (COX), predicting the evolution of decreased H2S susceptibility of the COX in three populations in the Poecilia mexicana complex that have colonized H2S-containing springs. Here, we demonstrate that decreased H2S susceptibility of COX evolved in parallel in two sulphide lineages, as evidenced by shared amino acid substitutions in cox1 and cox3 genes. One of the shared substitutions likely triggers conformational changes in COX1 blocking the access of H2S. In a third sulphide population, we detect no decreased H2S susceptibility of COX, suggesting that H2S resistance is achieved through another mechanism. Our study thus demonstrates that even closely related lineages follow both parallel and disparate molecular evolutionary paths to adaptation in response to the same selection pressure. PMID:24815812

  1. Prognostic factors for metachronous contralateral breast cancer: A comparison of the linear Cox regression model and its artificial neural network extension

    Microsoft Academic Search

    L. Mariani; D. Coradini; E. Biganzoli; P. Boracchi; E. Marubini; S. Pilotti; B. Salvadori; R. Silvestrini; U. Veronesi; R. Zucali; F. Rilke

    1997-01-01

    The purpose of the present study was toassess prognostic factors for metachronous contralateral recurrence ofbreast cancer (CBC). Two factors were of particularinterest, namely estrogen (ER) and progesterone (PgR) receptorsassayed with the biochemical method in primary tumortissue. Information was obtained from a prospective clinicaldatabase for 1763 axillary node-negative women who hadreceived curative surgery, mostly of the conservative type,and followed-up for a

  2. Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.

    PubMed

    Kohannim, Omid; Hibar, Derrek P; Stein, Jason L; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; de Zubicaray, Greig I; McMahon, Katie L; Hansell, Narelle K; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

    2012-01-01

    We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8?±?2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. PMID:22888310

  3. Assessing multivariate gene-metabolome associations with rare variants using Bayesian reduced rank regression

    PubMed Central

    Marttinen, Pekka; Pirinen, Matti; Sarin, Antti-Pekka; Gillberg, Jussi; Kettunen, Johannes; Surakka, Ida; Kangas, Antti J.; Soininen, Pasi; O’Reilly, Paul; Kaakinen, Marika; Kähönen, Mika; Lehtimäki, Terho; Ala-Korpela, Mika; Raitakari, Olli T.; Salomaa, Veikko; Järvelin, Marjo-Riitta; Ripatti, Samuli; Kaski, Samuel

    2014-01-01

    Motivation: A typical genome-wide association study searches for associations between single nucleotide polymorphisms (SNPs) and a univariate phenotype. However, there is a growing interest to investigate associations between genomics data and multivariate phenotypes, for example, in gene expression or metabolomics studies. A common approach is to perform a univariate test between each genotype–phenotype pair, and then to apply a stringent significance cutoff to account for the large number of tests performed. However, this approach has limited ability to uncover dependencies involving multiple variables. Another trend in the current genetics is the investigation of the impact of rare variants on the phenotype, where the standard methods often fail owing to lack of power when the minor allele is present in only a limited number of individuals. Results: We propose a new statistical approach based on Bayesian reduced rank regression to assess the impact of multiple SNPs on a high-dimensional phenotype. Because of the method’s ability to combine information over multiple SNPs and phenotypes, it is particularly suitable for detecting associations involving rare variants. We demonstrate the potential of our method and compare it with alternatives using the Northern Finland Birth Cohort with 4702 individuals, for whom genome-wide SNP data along with lipoprotein profiles comprising 74 traits are available. We discovered two genes (XRCC4 and MTHFD2L) without previously reported associations, which replicated in a combined analysis of two additional cohorts: 2390 individuals from the Cardiovascular Risk in Young Finns study and 3659 individuals from the FINRISK study. Availability and implementation: R-code freely available for download at http://users.ics.aalto.fi/pemartti/gene_metabolome/. Contact: samuli.ripatti@helsinki.fi; samuel.kaski@aalto.fi Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24665129

  4. Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo

    PubMed Central

    Hao, Yubin; Gu, Xinbin; Zhao, Yuan; Greene, Stephen; Sha, Wei; Smoot, Duane T.; Califano, Joseph; Wu, T.-C.; Pang, Xiaowu

    2012-01-01

    It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2-associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3?-untranslated region (3?-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression. PMID:21430074

  5. Enforced expression of miR-101 inhibits prostate cancer cell growth by modulating the COX-2 pathway in vivo.

    PubMed

    Hao, Yubin; Gu, Xinbin; Zhao, Yuan; Greene, Stephen; Sha, Wei; Smoot, Duane T; Califano, Joseph; Wu, T-C; Pang, Xiaowu

    2011-07-01

    It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2-associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1(CmiR101)) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3'-untranslated region (3'-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1(CmiR101) group (0.22 g) than the BPH1(Cvec) group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression. PMID:21430074

  6. BMP-2 induces ATF4 phosphorylation in chondrocytes through a COX-2/PGE2 dependent signaling pathway

    PubMed Central

    Li, Tian-Fang; Yukata, Kiminori; Yin, Guoyong; Sheu, Tzongjen; Maruyama, Takamitsu; Jonason, Jennifer H.; Hsu, Wei; Zhang, Xinping; Xiao, Guozhi; Konttinen, Yrjo T.; Chen, Di; O’Keefe, Regis J.

    2014-01-01

    Objective BMP-2 is approved for fracture non-union and spine fusion. We aimed to further dissect its downstream signaling events in chondrocytes with the ultimate goal to develop novel therapeutics that can mimic BMP-2 effect but have less complications. Methods BMP-2 effect on COX-2 expression was examined using RT-PCR and Western blot analysis. Genetic approach was used to identify the signaling pathway mediating the BMP-2 effect. Similarly, the pathway transducing the PGE2 effect on ATF4 was investigated. Immunoprecipitation was performed to assess the complex formation after PGE2 binding. Results BMP-2 increased COX-2 expression in primary mouse costosternal chondrocytes (PMCSC). The results from the C9 Tet-off system demonstrated that endogenous BMP-2 also upregulated COX-2 expression. Genetic approaches using PMCSC from ALK2fx/fx, ALK3fx/fx, ALK6?/?, and Smad1fx/fx mice established that BMP-2 regulated COX-2 through activation of ALK3-Smad1 signaling. PGE-2 EIA showed that BMP-2 increased PGE2 production in PMCSC. ATF4 is a transcription factor that regulates bone formation. While PGE2 did not have significant effect on ATF4 expression, it induced ATF4 phosphorylation. In addition to stimulating COX-2 expression, BMP-2 also induced phosphorylation of ATF4. Using COX-2 deficient chondrocytes, we demonstrated that the BMP-2 effect on ATF4 was COX-2-dependent. Tibial fracture samples from COX-2?/? mice showed reduced phospho-ATF4 immunoreactivity compared to WT ones. PGE2 mediated ATF4 phosphorylation involved signaling primarily through the EP2 and EP4 receptors and PGE2 induced an EP4-ERK1/2-RSK2 complex formation. Conclusions BMP-2 regulates COX-2 expression through ALK3-Smad1 signaling, and PGE2 induces ATF4 phosphorylation via EP4-ERK1/2-RSK2 axis. PMID:24418675

  7. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by ?CT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  8. Cyclooxygenase-2 (COX-2) Mediates Arsenite Inhibition of UVB-Induced Cellular Apoptosis in Mouse Epidermal Cl41 Cells

    PubMed Central

    Zuo, Z.; Ouyang, W.; Li, J.; Costa, M.; Huang, C.

    2013-01-01

    Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 ?M) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a co-inductive effect on COX-2 expression and nuclear factor-?B (NF?B) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NF?B pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown Cl41 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NF?B-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis. PMID:22463588

  9. Regression of altitude-produced cardiac hypertrophy.

    NASA Technical Reports Server (NTRS)

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  10. Sparse Multivariate Regression With Covariance Estimation

    PubMed Central

    Rothman, Adam J.; Levina, Elizaveta; Zhu, Ji

    2014-01-01

    We propose a procedure for constructing a sparse estimator of a multivariate regression coefficient matrix that accounts for correlation of the response variables. This method, which we call multivariate regression with covariance estimation (MRCE), involves penalized likelihood with simultaneous estimation of the regression coefficients and the covariance structure. An efficient optimization algorithm and a fast approximation are developed for computing MRCE. Using simulation studies, we show that the proposed method outperforms relevant competitors when the responses are highly correlated. We also apply the new method to a finance example on predicting asset returns. An R-package containing this dataset and code for computing MRCE and its approximation are available online. PMID:24963268

  11. Design and synthesis of 4-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF? production.

    PubMed

    Lee, Bit; Kwak, Jae-Hwan; Huang, Shin-Won; Jang, Jae-Yong; Lim, Sanglae; Kwak, Young-Shin; Lee, Kiho; Kim, Hyung Sook; Han, Sang-Bae; Hong, Jin-Tae; Lee, Heesoon; Song, Sukgil; Seo, Seung-Yong; Jung, Jae-Kyung

    2012-05-01

    A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production. PMID:22494844

  12. Molecular identification of Taenia tapeworms by Cox1 gene in Koh Kong, Cambodia.

    PubMed

    Jeon, Hyeong-Kyu; Yong, Tai-Soon; Sohn, Woon-Mok; Chai, Jong-Yil; Hong, Sung-Jong; Han, Eun-Taek; Jeong, Hoo-Gn; Chhakda, Tep; Sinuon, Muth; Socheat, Duong; Eom, Keeseon S

    2011-06-01

    We collected fecal samples from 21 individuals infected with Taenia tapeworms in Koh Kong Province, Cambodia, and performed nucleotide sequencing of the cox1 gene and multiplex PCR on the eggs for DNA differential diagnosis of human Taenia tapeworms. Genomic DNA was extracted from the eggs of a minimum number of 10 isolated from fecal samples. Using oligonucleotide primers Ta7126F, Ts7313F, Tso7466F, and Rev7915, the multiplex PCR assay proved useful for differentially diagnosing Taenia solium, Taenia saginata, and Taenia asiatica based on 706, 629, and 474 bp bands, respectively. All of the Taenia specimens from Kho Kong, Cambodia, were identified as either T. saginata (n=19) or T. solium (n=2) by cox1 sequencing and multiplex PCR. PMID:21738280

  13. Role of COX-2/mPGES-1/Prostaglandin E2 Cascade in Kidney Injury

    PubMed Central

    Jia, Zhanjun; Zhang, Yue; Ding, Guixia; Heiney, Kristina Marie; Huang, Songming; Zhang, Aihua

    2015-01-01

    COX-2/mPGES-1/PGE2 cascade plays critical roles in modulating many physiological and pathological actions in different organs. In the kidney, this cascade is of high importance in regulating fluid metabolism, blood pressure, and renal hemodynamics. Under some disease conditions, this cascade displays various actions in response to the different pathological insults. In the present review, the roles of this cascade in the pathogenesis of kidney injuries including diabetic and nondiabetic kidney diseases and acute kidney injuries were introduced and discussed. The new insights from this review not only increase the understanding of the pathological role of the COX-2/mPGES-1/PGE2 pathway in kidney injuries, but also shed new light on the innovation of the strategies for the treatment of kidney diseases. PMID:25729216

  14. Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia

    PubMed Central

    Altavilla, D; Minutoli, L; Polito, F; Irrera, N; Arena, S; Magno, C; Rinaldi, M; Burnett, BP; Squadrito, F; Bitto, A

    2012-01-01

    BACKGROUND AND PURPOSE Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid–based ‘dual inhibitor’ of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL APPROACH Rats were treated daily with testosterone propionate (3 mg·kg?1 s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg?1, i.p.) or flavocoxid (20 mg·kg?1, i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. KEY RESULTS Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE2 and leukotriene B4 (LTB4), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS Our results show that a ‘dual inhibitor’ of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism. PMID:22471974

  15. Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms.

    PubMed

    Chignalia, Andreia Z; Oliveira, Maria Aparecida; Debbas, Victor; Dull, Randal O; Laurindo, Francisco R M; Touyz, Rhian M; Carvalho, Maria Helena C; Fortes, Zuleica B; Tostes, Rita C

    2015-07-01

    The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinants. Herein, we sought to determine whether exogenous testosterone, at physiological levels, induces leucocyte migration, a central feature in immune and inflammatory responses and the mediating mechanisms. We hypothesized that testosterone induces leucocyte migration via NADPH oxidase (NADPHox)-driven reactive oxygen species (ROS) and cyclooxygenase (COX)-dependent mechanisms. Sixteen-week-old Wistar rats received an intraperitoneal injection (5 ml) of either testosterone (10-7 mol/l) or saline. Rats were pre-treated with 5 ml of sodium salicylate (SS, non-selective COX inhibitor, 1.25×10-3 mol/l, 1 h prior to testosterone or saline), flutamide (androgen receptor antagonist, 10-5 mol/l), apocynin (NADPHox inhibitor, 3×10-4 mol/l), N-[2-Cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS398, COX2 inhibitor, 10-4 mol/l) or saline, 4 h before testosterone or saline administration. Leucocyte migration was assessed 24 h after testosterone administration by intravital microscopy of the mesenteric bed. Serum levels of testosterone were measured by radioimmunoassay. NADPHox activity was assessed in membrane fractions of the mesenteric bed by dihydroethidium (DHE) fluorescence and in isolated vascular smooth muscle cells (VSMC) by HPLC. NADPHox subunits and VCAM (vascular cell adhesion molecule) expression were determined by immunoblotting. Testosterone administration did not change serum levels of endogenous testosterone, but increased venular leucocyte migration to the adventia, NADPHox activity and expression (P<0.05). These effects were blocked by flutamide. SS inhibited testosterone-induced leucocyte migration (P<0.05). Apocynin and NS398 abolished testosterone-induced leucocyte migration and NADPHox activity (P<0.05). Testosterone induces leucocyte migration via NADPHox- and COX2-dependent mechanisms and may contribute to inflammatory processes and oxidative stress in the vasculature potentially increasing cardiovascular risk. PMID:25700020

  16. Structure and photoluminescence of arrayed Zn1-xCoxO nanorods grown via hydrothermal method

    Microsoft Academic Search

    Yanmei Liu; Qingqing Fang; Mingzai Wu; Yan Li; Qingrong Lv; Jun Zhou; Baoming Wang

    2007-01-01

    High density arrays of Zn1-xCoxO (x = 0.05, 0.10, 0.15, denoted by ZnCoO) nanorods were vertically grown on glass coated ZnO films via hydrothermal reaction at 70 °. The structures and morphology of the arrays were studied by x-ray diffraction, photoluminescence (PL) spectroscopy and field emission scanning electron microscopy, which show that the nanorods of 150 nm diameter and 4.5

  17. Frequent, Phylogenetically Local Horizontal Transfer of the cox1 Group I Intron in Flowering Plant Mitochondria

    PubMed Central

    Cho, Yangrae; Mower, Jeffrey P.; Alverson, Andrew J.; Palmer, Jeffrey D.

    2008-01-01

    Horizontal gene transfer is surprisingly common among plant mitochondrial genomes. The first well-established case involves a homing group I intron in the mitochondrial cox1 gene shown to have been frequently acquired via horizontal transfer in angiosperms. Here, we report extensive additional sampling of angiosperms, including 85 newly sequenced introns from 30 families. Analysis of all available data leads us to conclude that, among the 640 angiosperms (from 212 families) whose cox1 intron status has been characterized thus far, the intron has been acquired via roughly 70 separate horizontal transfer events. We propose that the intron was originally seeded into angiosperms by a single transfer from fungi, with all subsequent inferred transfers occurring from one angiosperm to another. The pattern of angiosperm-to-angiosperm transfer is biased toward exchanges between plants belonging to the same family. Illegitimate pollination is proposed as one potential factor responsible for this pattern, given that aberrant, cross-species pollination is more likely between close relatives. Other potential factors include shared vectoring agents or common geographic locations. We report the first apparent cases of loss of the cox1 intron; losses are accompanied by retention of the exonic coconversion tract, which is located immediately downstream of the intron and which is a product of the intron's self-insertion mechanism. We discuss the many reasons why the cox1 intron is so frequently and detectably transferred, and rarely lost, and conclude that it should be regarded as the “canary in the coal mine” with respect to horizontal transfer in angiosperm mitochondria. PMID:18524785

  18. Citral, a component of lemongrass oil, activates PPAR? and ? and suppresses COX2 expression

    Microsoft Academic Search

    Michiko Katsukawa; Rieko Nakata; Yoshie Takizawa; Kazuyuki Hori; Saori Takahashi; Hiroyasu Inoue

    2010-01-01

    Lemongrass is a widely used herb as a food flavoring, as a perfume, and for its analgesic and anti-inflammatory purposes; however, the molecular mechanisms of these effects have not been elucidated. Previously, we identified carvacrol from the essential oil of thyme as a suppressor of cyclooxygenase (COX)-2, a key enzyme for prostaglandin synthesis, and also an activator of peroxisome proliferator-activated

  19. Frequent, phylogenetically local horizontal transfer of the cox1 group I Intron in flowering plant mitochondria.

    PubMed

    Sanchez-Puerta, M Virginia; Cho, Yangrae; Mower, Jeffrey P; Alverson, Andrew J; Palmer, Jeffrey D

    2008-08-01

    Horizontal gene transfer is surprisingly common among plant mitochondrial genomes. The first well-established case involves a homing group I intron in the mitochondrial cox1 gene shown to have been frequently acquired via horizontal transfer in angiosperms. Here, we report extensive additional sampling of angiosperms, including 85 newly sequenced introns from 30 families. Analysis of all available data leads us to conclude that, among the 640 angiosperms (from 212 families) whose cox1 intron status has been characterized thus far, the intron has been acquired via roughly 70 separate horizontal transfer events. We propose that the intron was originally seeded into angiosperms by a single transfer from fungi, with all subsequent inferred transfers occurring from one angiosperm to another. The pattern of angiosperm-to-angiosperm transfer is biased toward exchanges between plants belonging to the same family. Illegitimate pollination is proposed as one potential factor responsible for this pattern, given that aberrant, cross-species pollination is more likely between close relatives. Other potential factors include shared vectoring agents or common geographic locations. We report the first apparent cases of loss of the cox1 intron; losses are accompanied by retention of the exonic coconversion tract, which is located immediately downstream of the intron and which is a product of the intron's self-insertion mechanism. We discuss the many reasons why the cox1 intron is so frequently and detectably transferred, and rarely lost, and conclude that it should be regarded as the "canary in the coal mine" with respect to horizontal transfer in angiosperm mitochondria. PMID:18524785

  20. Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer

    PubMed Central

    Weinberg, Vivian; Magbanua, Mark J.; Sosa, Eduardo; Simko, Jeffry; Shinohara, Katsuto; Federman, Scot; Mattie, Mike; Hughes-Fulford, Millie; Haqq, Christopher; Carroll, Peter R.

    2010-01-01

    Background Nutritional factors are associated with reduced risk of prostate cancer progression, yet mechanisms remain unclear. We examined the effects of lycopene and fish oil supplements versus placebo on the normal prostate microenvironment, among men pursuing active surveillance for low-burden prostate cancer. We hypothesized that lycopene or fish oil supplements would down-regulate insulin-like growth factor-1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression, respectively, reflecting putative proliferation (IGF-1) and inflammatory (COX-2) pathways relevant to carcinogenesis. Methods We conducted a 3-month randomized, double-blinded, clinical trial comparing prostate tissue gene expression profiles (assessed by qRT–PCR) among men with favorable-risk prostate cancer receiving either 30 mg/day lycopene, 3 g/day fish oil (including 1,098 mg eicosapentaenoic and 549 mg docosahexaenoic fatty acids) or placebo. Results Among 69 men (22 assigned to lycopene, 21 to fish, and 26 to placebo), there was no difference in the change from baseline to the 3 months in IGF-1 expression level between the placebo and lycopene arms (p = 0.93) nor in COX-2 expression between the placebo and fish arms (p = 0.99). Conclusion Compared to placebo, 3-month intervention with lycopene or fish oil did not significantly change IGF-1 and COX-2 gene expression in the normal prostate microenvironment in men with low-burden prostate cancer. Further analysis of global gene expression profiles may shed light on the bioactivity and relevance of these nutrients in prostate cancer. PMID:21103921

  1. The Cox-Maze III procedure for atrial fibrillation associated with rheumatic mitral valve disease

    Microsoft Academic Search

    Ki-Bong Kim; Kwang Ree Cho; Dae-Won Sohn; Hyuk Ahn; Joon Ryang Rho

    1999-01-01

    Background. The surgical results of the Cox-Maze III procedure (CM-III) for atrial fibrillation (AF) associated with rheumatic mitral valve (MV) disease are not as good as the results from surgery for AF alone.Methods. To assess the efficacy and safety of the CM-III in AF associated with rheumatic MV disease, we retrospectively analyzed 75 patients who underwent the CM-III combined with

  2. Cox decompression chiropractic manipulation of a patient with postsurgical lumbar fusion: a case report

    PubMed Central

    Kruse, Ralph A.; Cambron, Jerrilyn A.

    2011-01-01

    Objective The purpose of this case report is to describe a patient with an L5/S1 posterior surgical fusion who presented to a chiropractic clinic with subsequent low back and leg pain and was treated with Cox decompression manipulation. Clinical Features A 55-year-old male postal clerk presented to a private chiropractic practice with complaints of pain and spasms in his low back radiating down the right buttock and leg. His pain was a 5 of 10, and Oswestry Disability Index score was 18%. The patient reported a previous surgical fusion at L5/S1 for a grade 2 spondylolytic spondylolisthesis. Radiographs revealed surgical hardware extending through the pedicles of L5 and S1, fusing the posterior arches. Intervention and Outcome Treatment consisted of ultrasound, electric stimulation, and Cox decompression manipulation (flexion distraction) to the low back. After 13 treatments, the patient had a complete resolution of his symptoms with a pain score of 0 of 10 and an Oswestry score of 2%. A 2-year follow-up revealed continued resolution of the patient's symptoms. Conclusions Cox chiropractic decompression manipulation may be an option for patients with back pain subsequent to spinal fusion. More research is needed to verify these results. PMID:22654683

  3. Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway.

    PubMed

    Markworth, James F; Cameron-Smith, David

    2013-01-01

    Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF(2?) and PGE(2); however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway. PMID:23076795

  4. The Respiratory Chain Supercomplex Organization Is Independent of COX7a2l Isoforms

    PubMed Central

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-01-01

    Summary The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research. PMID:25470551

  5. Leishmania donovani secretory serine protease alters macrophage inflammatory response via COX-2 mediated PGE-2 production.

    PubMed

    Das, Partha; De, Tripti; Chakraborti, Tapati

    2014-12-01

    Leishmania parasites determine the outcome of the infection by inducing inflammatory response that suppresses macrophage's activation. Defense against Leishmania is dependent on Th1 inflammatory response by turning off macrophages' microbicidal property by upregulation of COX-2, as well as immunosuppressive PGE-2 production. To understand the role of L. donovani secretory serine protease (pSP) in these phenomena, pSP was inhibited by its antibody and serine protease inhibitor, aprotinin. Western blot and TAME assay demonstrated that pSP antibody and aprotinin significantly inhibited protease activity in the live Leishmania cells and reduced infection index of L. donovani-infected macrophages. Additionally, ELISA and RT-PCR analysis showed that treatment with pSP antibody or aprotinin hold back COX-2-mediated immunosuppressive PGE-2 secretion with enhancement of Th1 cytokine like IL-12 expression. This was also supported in Griess test and NBT assay, where inhibition of pSP with its inhibitors elevated ROS and NO production. Overall, our study implies the pSP is involved in down-regulation of macrophage microbicidal activity by inducing host inflammatory responses in terms of COX-2-mediated PGE-2 release with diminished reactive oxygen species generation and thus suggests its importance as a novel drug target of visceral leishmaniasis. PMID:25823228

  6. Cooperative interactions between bacteriophage P2 integrase and its accessory factors IHF and Cox.

    PubMed

    Frumerie, Clara; Sylwan, Lina; Ahlgren-Berg, Alexandra; Haggård-Ljungquist, Elisabeth

    2005-02-01

    Bacteriophage P2 integrase (Int) mediates site-specific recombination leading to integration or excision of the phage genome in or out of the bacterial chromosome. Int belongs to the large family of tyrosine recombinases that have two different DNA recognition motifs binding to the arm and core sites, respectively, which are located within the phage attachment sites (attP). In addition to the P2 integrase, the accessory proteins Escherichia coli IHF and P2 Cox are needed for recombination. IHF is a structural protein needed for integration and excision by bending the DNA. As opposed to lambda, only one IHF site is found in P2 attP. P2 Cox controls the direction of recombination by inhibiting integration but being required for excision. In this work, the effects of accessory proteins on the capacity of Int to bind to its DNA recognition sequences are analyzed using electromobility shifts. P2 Int binds with low affinity to the arm site, and this binding is greatly enhanced by IHF. The arm binding domain of Int is located at the N-terminus. P2 Int binds with high affinity to the core site, and this binding is also enhanced by IHF. The fact that the cooperative binding of Int and IHF is strongly reduced by lengthening the distance between the IHF and core binding sites indicates that the distance between these sites may be important for cooperative binding. The Int and Cox proteins also bind cooperatively to attP. PMID:15661160

  7. A new bivariate negative binomial regression model

    NASA Astrophysics Data System (ADS)

    Faroughi, Pouya; Ismail, Noriszura

    2014-12-01

    This paper introduces a new form of bivariate negative binomial (BNB-1) regression which can be fitted to bivariate and correlated count data with covariates. The BNB regression discussed in this study can be fitted to bivariate and overdispersed count data with positive, zero or negative correlations. The joint p.m.f. of the BNB1 distribution is derived from the product of two negative binomial marginals with a multiplicative factor parameter. Several testing methods were used to check overdispersion and goodness-of-fit of the model. Application of BNB-1 regression is illustrated on Malaysian motor insurance dataset. The results indicated that BNB-1 regression has better fit than bivariate Poisson and BNB-2 models with regards to Akaike information criterion.

  8. Bayesian Selection of Geostatistical Regression Models

    E-print Network

    of Mathematics and Statistics and Institute of Arctic Biology University of Alaska Fairbanks WNAR/IMS June 21 GIS layers) Failing to take spatial correlation into account can affect regression model selection

  9. REGRESSION ESTIMATES FOR TOPOLOGICAL-HYDROGRAPH INPUT.

    USGS Publications Warehouse

    Karlinger, Michael R.; Guertin, D. Phillip; Troutman, Brent M.

    1988-01-01

    Physiographic, hydrologic, and rainfall data from 18 small drainage basins in semiarid, central Wyoming were used to calibrate topological, unit-hydrograph models for celerity, the average rate of travel of a flood wave through the basin. The data set consisted of basin characteristics and hydrologic data for the 18 basins and rainfall data for 68 storms. Calibrated values of celerity and peak discharges subsequently were regressed as a function of the basin characteristics and excess rainfall volume. Predicted values obtained in this way can be used as input for estimating hydrographs in ungaged basins. The regression models included ordinary least-squares and seemingly unrelated regression. This latter regression model jointly estimated the celerity and peak discharge.

  10. Model checking for ROC regression analysis.

    PubMed

    Cai, Tianxi; Zheng, Yingye

    2007-03-01

    The receiver operating characteristic (ROC) curve is a prominent tool for characterizing the accuracy of a continuous diagnostic test. To account for factors that might influence the test accuracy, various ROC regression methods have been proposed. However, as in any regression analysis, when the assumed models do not fit the data well, these methods may render invalid and misleading results. To date, practical model-checking techniques suitable for validating existing ROC regression models are not yet available. In this article, we develop cumulative residual-based procedures to graphically and numerically assess the goodness of fit for some commonly used ROC regression models, and show how specific components of these models can be examined within this framework. We derive asymptotic null distributions for the residual processes and discuss resampling procedures to approximate these distributions in practice. We illustrate our methods with a dataset from the cystic fibrosis registry. PMID:17447940

  11. Thresholding Multivariate Regression and Generalized Principal Components

    E-print Network

    Sun, Ranye

    2014-03-17

    reduced rank multivariate regression and the generalized principal component analysis/singular value decomposition (SVD). The following two para- graphs give brief introductions to each of the two topics, respectively. Uncovering a meaningful relationship...

  12. Introducing Evolutionary Computing in Regression Analysis

    NSDL National Science Digital Library

    Olcay Akman

    A typical upper level undergraduate or first year graduate level regression course syllabus treats model selection with various stepwise regression methods. Here we implement evolutionary computing for subset model selection and accomplish two goals: i) introduce students to the powerful optimization method of genetic algorithms, and ii) transform a regression analysis course to a regression and modeling without requiring any additional time or software commitment.Furthermore we also employed Akaike Information Criterion (AIC) as a measure of model fitness instead of another commonly used measure of R-square. The model selection tool uses Excel which makes the procedure accessible to a very wide spectrum of interdisciplinary students with no specialized software requirement. An Excel macro, to be used as an instructional tool is freely available through the author's website.

  13. Understanding the Least-Squares Regression Line

    NSDL National Science Digital Library

    This applet, created by the National Council of Teachers of Mathematics, allows students to explore three methods for measuring "goodness of fit" of a linear model. Users can manipulate both the data and the regression line to see changes in the square error, the absolute error, and the shortest distance from the data point to the regression line. The page outlines different tasks that students to strive to learn. It then asks questions that facilitate discussion based upon these concepts.

  14. Multivariate Locally Weighted Least Squares Regression

    Microsoft Academic Search

    D. Ruppert; M. P. Wand

    1994-01-01

    Nonparametric regression using locally weighted least squares was first discussed by Stone and by Cleveland. Recently, it was shown by Fan and by Fan and Gijbels that the local linear kernel-weighted least squares regression estimator has asymptotic properties making it superior, in certain senses, to the Nadaraya-Watson and Gasser-Muller kernel estimators. In this paper we extend their results on asymptotic

  15. Conditional Logistic Regression with Sandwich Estimators

    Cancer.gov

    This IBM PC program performs conditional logistic regression on clustered data and calculates a sandwich ("robust") estimator of the covariance of the regression coefficients. Use of the sandwich estimator allows appropriate inferences for either fixed or random effects across clusters. The program uses two modifications to the usual Wald test to adjust for cases where some parameters are estimated from a small number of clusters.

  16. In situ calibration using univariate analyses based on the onboard ChemCam targets: first prediction of Martian rock and soil compositions

    NASA Astrophysics Data System (ADS)

    Fabre, C.; Cousin, A.; Wiens, R. C.; Ollila, A.; Gasnault, O.; Maurice, S.; Sautter, V.; Forni, O.; Lasue, J.; Tokar, R.; Vaniman, D.; Melikechi, N.

    2014-09-01

    Curiosity rover landed on August 6th, 2012 in Gale Crater, Mars and it possesses unique analytical capabilities to investigate the chemistry and mineralogy of the Martian soil. In particular, the LIBS technique is being used for the first time on another planet with the ChemCam instrument, and more than 75,000 spectra have been returned in the first year on Mars. Curiosity carries body-mounted calibration targets specially designed for the ChemCam instrument, some of which are homgeneous glasses and others that are fine-grained glass-ceramics. We present direct calibrations, using these onboard standards to infer elements and element ratios by ratioing relative peak areas. As the laser spot size is around 300 ?m, the LIBS technique provides measurements of the silicate glass compositions representing homogeneous material and measurements of the ceramic targets that are comparable to fine-grained rock or soil. The laser energy and the auto-focus are controlled for all sequences used for calibration. The univariate calibration curves present relatively to very good correlation coefficients with low RSDs for major and ratio calibrations. Trace element calibration curves (Li, Sr, and Mn), down to several ppm, can be used as a rapid tool to draw attention to remarkable rocks and soils along the traverse. First comparisons to alpha-particle X-ray spectroscopy (APXS) data, on selected targets, show good agreement for most elements and for Mg# and Al/Si estimates. SiO2 estimates using univariate cannot be yet used. Na2O and K2O estimates are relevant for high alkali contents, but probably under estimated due to the CCCT initial compositions. Very good results for CaO and Al2O3 estimates and satisfactory results for FeO are obtained.

  17. A note on "Einstein's special relativity beyond the speed of light by James M. Hill and Barry J. Cox"

    E-print Network

    Hajnal Andréka; Judit X. Madarász; István Németi; Gergely Székely

    2013-02-17

    We show that the transformations J. M. Hill and B. J. Cox introduce between inertial observers moving faster than light with respect to each other are consistent with Einstein's principle of relativity only if the spacetime is 2 dimensional.

  18. Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion

    PubMed Central

    Sharma-Walia, Neelam; Sadagopan, Sathish; Veettil, Mohanan Valiya; Kerur, Nagaraj; Chandran, Bala

    2010-01-01

    Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS. PMID:20169190

  19. PIM2 Induced COX-2 and MMP-9 Expression in Macrophages Requires PI3K and Notch1 Signaling

    PubMed Central

    Narayana, Yeddula; Puzo, Germain; Gilleron, Martine; Balaji, Kithiganahalli Narayanaswamy

    2009-01-01

    Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor -?B (NF-?B) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of Suppressor of Hairless (CSL) and NF-?B to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages. PMID:19290049

  20. Specific inhibition of cyclooxygenase-2 (COX2) expression by dietary curcumin in HT29 human colon cancer cells

    Microsoft Academic Search

    Ajay Goel; C. Richard Boland; Dharam P Chauhan

    2001-01-01

    Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration-

  1. Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX\\/COX inhibitors: an expression profiling study

    Microsoft Academic Search

    Petr Chlapek; Martina Redova; Karel Zitterbart; Marketa Hermanova; Jaroslav Sterba; Renata Veselska

    2010-01-01

    BACKGROUND: We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA) and inhibitors of lipoxygenases (LOX) and cyclooxygenases (COX). This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX\\/COX inhibitors and brings more detailed

  2. NS-398, Ibuprofen and COX-2 RNAi produce significantly different gene expression profiles in prostate cancer cells

    PubMed Central

    John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Falduto, Michael T.; Magnuson, Scott R.; Coleman, C. Norman

    2010-01-01

    Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit potent anticancer effects in vitro and in vivo by COX-2 dependent and independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2 specific NSAID NS-398 (0.01 and 0.1mM), a non-specific NSAID ibuprofen (0.1 and 1.5mM) and RNA interference-mediated COX-2 inhibition (COX-2 RNAi) in PC3 prostate cancer cells. A total of 3,362 differentially expressed genes with 2 fold change, and p<0.05 were identified. Low concentrations of NSAIDs and COX-2 RNAi altered very few genes (1-3%) compared to the higher concentration of NS-398 (17%) and ibuprofen (80%). Ingenuity Pathway Analysis (IPA) was used for distributing the differentially expressed genes into biological networks and for evaluation of functional significance. The top 3 networks for the both NSAIDs included functional categories DNA replication, recombination and repair, and gastrointestinal disease. Immune response function was specific to NS-398, and cell cycle, cellular movement were among the top functions for ibuprofen. IPA also identified renal and urological disease as a function specific for ibuprofen. This comprehensive study identified several COX-2 independent targets of NSAIDs which may help explain the antitumor and radiosensitizing effects of NSAIDs. However, none of these categories were reflected in the identified networks in PC3 cells treated with clinically relevant low concentrations of NS-398 and ibuprofen or with COX-2 RNAi suggesting the benefit to fingerprinting pre-clinical drug concentrations to improve their relevance to the clinical setting. PMID:19139136

  3. Phylogenetic analysis of diatom coxI genes and implications of a fluctuating GC content on mitochondrial genetic code evolution

    Microsoft Academic Search

    Megumi Ehara; Yuji Inagaki; Kazuo I. Watanabe; Takeshi Ohama

    2000-01-01

    In order to address the relationships among diatom groups and to investigate possible changes in their mitochondrial (mt)\\u000a genetic codes, we have analyzed a 1.1-kb region of the cytochrome c oxidase subunit I (coxI) gene from eight diverse diatom species. A phylogenetic analysis of these coxI sequences including representative species of the Phaeophyta, Xanthophyta, Eustigmatophyta and Haptophyta showed that the

  4. Cordyceps militaris (Hypocreales: Cordycipitaceae): transcriptional analysis and molecular characterization of cox1 and group I intron with putative LAGLIDADG endonuclease

    Microsoft Academic Search

    Zhuangli Zheng; Keqing Jiang; Chunhua Huang; Caiying Mei; Richou Han

    The full-length cytochrome c oxidase subunit I gene (cox1) containing a group I intron was isolated from an important medical fungus Cordyceps militaris (Cordycipitaceae). The open reading frame (ORF) of 1,593 nucleotides encoded a predicted protein COX1 of 530 amino acids.\\u000a The group I intron encoded a putative homing endonuclease (HE) with two LAGLIDADG motifs. RT-PCR and Northern analysis showed

  5. Nuclear co-localization and functional interaction of COX2 and HIF-1? characterize bone metastasis of human breast carcinoma

    Microsoft Academic Search

    Paola Maroni; Emanuela Matteucci; Alessandro Luzzati; Giuseppe Perrucchini; Paola Bendinelli; Maria Alfonsina Desiderio

    2011-01-01

    The aim of this article is to identify nuclear co-localization of COX-2 and HIF-1? in human-bone metastasis of breast cancer,\\u000a index of transcriptionally activated cells and functional for gene expression. In particular, we verified whether hypoxia\\u000a exerted a direct role on metastasis-gene expression or through COX-2 signaling, due to the relevance for clinical implications\\u000a to individuate molecular targets for diagnosis

  6. The role of anti-LeY antibody in the downregulation of MAPKs/COX-2 pathway in gastric cancer.

    PubMed

    Aziz, Faisal; Qiu, Yan

    2014-04-01

    Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. Lewis Y (LeY) is overexpressed on tumor cells surface either as glycoproteins or glycolipids. LeY is difucosylated oligosaccharide with the chemical structure [Fuc?1,2Gal?1?4(Fuc?1,3)GlcNAc?1?R], which is catalyzed by fucosyltransferases, such as FUT1 (?1,2) and FUT4 (?1,3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase- 2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway. PMID:24533777

  7. Direct Sequencing of Cyclooxygenase-2 (COX-2) Revealed an Intronic Variant rs201231411 in Iranian Patients with Pancreatic Cancer

    PubMed Central

    Mohamadkhani, Ashraf; Akbari, Mohammad Reza; Ghanbari, Reza; Naderi, Elnaz; Rezanejad-Asl, Parisa; Pourshams, Akram

    2015-01-01

    BACKGROUND There are hoarding documents for the biological importance of cyclooxygenase-2 (COX-2) in pancreatic carcinogenesis. We aimed to thoroughly investigate the DNA sequence variations of whole COX-2 exons in a large case-control study of pancreatic cancer by direct sequencing. METHODS The entire exonic regions of COX-2 including 10 exons were sequenced in the germline DNA of 96 patients with pancreatic cancer. Selected variants within exons six to seven (E6E7) amplicon from the test panel were genotyped in 96 controls. RESULTS The COX-2 gene was demonstrated to be genetically conserved. Four missense mutations were found in three cases. However the common variant c.724-10_724-7delATTT (rs201231411) that is located in intron 6, showed significant difference between cases and controls (21 [21.9%] vs 11 [%11.5], p=0.05). CONCLUSION This study determined that COX-2 has a conservative sequence, which is required for its enzymatic activity and supports the important role of this enzyme’s expression in pancreatic cancer rather than any changes in its activity. The effect of intronic variant rs201231411 on COX-2 expression could be analyzed in future studies. PMID:25628848

  8. Quantitative Assessment of the Association of COX-2 (Cyclooxygenase-2) Immunoexpression with Prognosis in Human Osteosarcoma: A Meta-Analysis

    PubMed Central

    Xiao, Zengming; Wu, Hao; Wu, Yang

    2013-01-01

    Background Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2) immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. Methods We accordingly conducted a meta-analysis of 9 studies (442 patients) that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death). Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using the random-effects or fixed-effects model. Results Meta–analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10–3.74; P=0.009) and disease-free survival rate (RR=1.63; 95% CI: 1.17–2.28; P=0.004) at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. Conclusions COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma. PMID:24358237

  9. Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway

    PubMed Central

    Lee, Jaetae; Lee, Young Sup

    2015-01-01

    The COX-2/PGE2 pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, PGE2, in cancer survival remain unknown. Herein, we investigated PGE2-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with PGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. PGE2 not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of PGE2, and restored the menadione-induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the PGE2-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that PGE2 signaling acts in an autocrine manner, and specific inhibition of PGE2 will provide a novel approach for the treatment of leukemia. [BMB Reports 2015; 48(2): 109-114] PMID:24965577

  10. Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway.

    PubMed

    Shehzad, Adeeb; Lee, Jaetae; Lee, Young Sup

    2015-02-01

    The COX-2/PGE2 pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, PGE2, in cancer survival remain unknown. Herein, we investigated PGE2-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with PGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. PGE2 not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of PGE2, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the PGE2-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that PGE2 signaling acts in an autocrine manner, and specific inhibition of PGE2 will provide a novel approach for the treatment of leukemia. [BMB Reports 2015; 48(2): 109-114]. PMID:24965577

  11. Involvement of NF-kappaB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein.

    PubMed

    Kim, Su-Hyeong; Oh, Jung-Min; No, Jae-Hong; Bang, Yung-Jue; Juhnn, Yong-Sung; Song, Yong-Sang

    2009-05-01

    The human papillomavirus (HPV) E6 and E7 oncoproteins play important roles in cervical carcinogenesis through multiple mechanisms, including upregulation of cyclooxygenase-2 (COX-2), which has been shown to be involved in both carcinogenesis and cancer progression. To explore the role of E5 in cervical carcinogenesis, we herein investigated the effect of HPV 16 E5 on COX-2 expression. Our results revealed that E5 induced COX-2 expression through the epidermal growth factor receptor-signaling pathway, with nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) acting as critical factors in E5-induced COX-2 expression. NF-kappaB inhibition blocked COX-2 expression more potently than inhibition of AP-1. Our findings collectively suggest that the HPV 16 E5 oncoprotein mediates cervical carcinogenesis at least in part via upregulation of COX-2 expression through NF-kappaB and AP-1, with NF-kappaB playing a larger role. PMID:19321801

  12. Low-level laser therapy in IL-1?, COX-2, and PGE2 modulation in partially injured Achilles tendon.

    PubMed

    de Jesus, Julio Fernandes; Spadacci-Morena, Diva Denelle; dos Anjos Rabelo, Nayra Deise; Pinfildi, Carlos Eduardo; Fukuda, Thiago Yukio; Plapler, Helio

    2015-01-01

    This study evaluated IL-1?, COX-2, and PGE2 modulation in partially injured Achilles tendons treated with low-level laser therapy (LLLT). Sixty-five male Wistar rats were used. Sixty were submitted to a direct injury on Achilles tendon and then distributed into six groups: LASER 1 (a single LLLT application), LASER 3 (three LLLT applications), and LASER 7 (seven LLLT applications) and Sham 1, 3, and 7 (the same injury but LLLT applications were simulated). The five remaining animals were allocated at control group (no procedure performed). LLLT (780 nm) was applied with 70 mW of mean power and 17.5 J/cm(2) of fluency for 10 s, once a day. The tendons were surgically removed and assessed immunohistochemically for IL-1?, COX-2, and PGE2. In comparisons with control (IL-1?: 100.5?±?92.5 / COX-2: 180.1?±?97.1 / PGE2: 187.8?±?128.8) IL-1? exhibited (mean?±?SD) near-normal level (p?>?0.05) at LASER 3 (142.0?±?162.4). COX-2 and PGE2 exhibited near-normal levels (p?>?0.05) at LASER 3 (COX-2: 176.9?±?75.4 / PGE2: 297.2?±?259.6) and LASER 7 (COX-2: 259.2?±?190.4 / PGE2: 587.1?±?409.7). LLLT decreased Achilles tendon's inflammatory process. PMID:25070591

  13. Celecoxib and acetylbritannilactone interact synergistically to suppress breast cancer cell growth via COX-2-dependent and -independent mechanisms

    PubMed Central

    Liu, B; Wen, J K; Li, B H; Fang, X M; Wang, J J; Zhang, Y P; Shi, C J; Zhang, D Q; Han, M

    2011-01-01

    The use of celecoxib is associated with a significant decrease in breast cancer risk. However, the long-term use of high-dose celecoxib might be limited owing to cardiovascular side effects. In this study, we found that acetylbritannilactone (ABL), extract from a Chinese medicinal herb, could reduce celecoxib dose and potentiate the growth-inhibitory effect in breast cancer cells. ABL enhanced the apoptotic effect of celecoxib in COX-2-expressing cells, but had little effect in COX-2-negative cells. The apoptosis induced by the combination treatment disappeared when COX-2 was knocked down, whereas the lack of apoptotic effects in COX-2-negative cells was reversed after COX-2 transfection. However, the combination treatment induced a G0/G1 phase arrest independent of whether or not the cells expressed COX-2. The G0/G1 arrest was attributed to a decreased expression of cyclinD1, cyclinE, CDK2 and CDK6, especially the upregulation of p21. In addition, inhibition of Akt and p38 signaling pathways was required by the synergism, as the constitutively active Akt and p38 protected cells against apoptosis and cell cycle arrest induced by the combination treatment. In vivo, administration of celecoxib and ABL were more effective than the individual agents against xenograft tumor growth. Thus, our data suggested that the combinatorial approach of celecoxib and ABL might be helpful for breast cancer treatment. PMID:21796157

  14. Anti-inflammatory potential of alpha-linolenic acid mediated through selective COX inhibition: computational and experimental data.

    PubMed

    Anand, Richa; Kaithwas, Gaurav

    2014-08-01

    The present work investigates the anti-inflammatory activity of alpha-linolenic acid (ALA) and linoleic acid (LA) using computational and experimental analysis. The binding affinity of ALA and LA was appraised for cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), and 5-lipoxygenase (5-LOX) using AutoDock 4.2 and AutoDock Vina 1.1.2. Anti-inflammatory activity of ALA (2 and 4 ml/kg, i.p.) (55.65 %?v/v) and LA (2 and 4 ml/kg, i.p.) (55 %?v/v) was further assayed using the rat paw edema test against a variety of phlogistic agents including carrageenan, arachidonic acid, prostaglandin, and leukotriene, respectively. ALA (2 and 4 ml/kg, i.p.) and LA (2 and 4 ml/kg, i.p.) were further tested for their efficacy against complete Freund's adjuvant (CFA)-induced (0.05 ml) arthritis in albino rats. Following CFA-induced arthritis, ALA and LA were tested for their inhibitory proficiency against COX-1, COX-2, and 5-LOX in vitro. The present study commends that the anti-inflammatory potential of ALA could be attributed to COX inhibition, in particular, COX-2. PMID:24639012

  15. Logistic regression for longitudinal case-control Thierry Duchesne1

    E-print Network

    Duchesne, Thierry

    Logistic regression for longitudinal case-control studies Thierry Duchesne1 Department supported by NSERC and FQRNT #12;Outline Introduction GEE GEE for conditional logistic regression Application Conclusion Outline 1 Introduction Conditional logistic regression Problem: What if several matched

  16. A Multiple Logistic Regression Model for Predicting the Development of

    E-print Network

    Standiford, Richard B.

    A Multiple Logistic Regression Model for Predicting the Development of Phytophthora ramorum of insect, fungal infection or disease symptoms for significance in multiple logistic regression analysis logistic regression, Phytophthora ramorum, tanoak Introduction Phytophthora ramorum has emerged as a major

  17. Sparse Multinomial Logistic Regression: Fast Algorithms and Generalization Bounds

    E-print Network

    Hartemink, Alexander

    Sparse Multinomial Logistic Regression: Fast Algorithms and Generalization Bounds Balaji on multinomial logistic regression. Second, by combining a bound optimization approach with a component algorithms to perform exact multinomial logistic regression with a sparsity-promoting prior. Third, we show

  18. Nonstationary Logistic Regression William D. Penny and Stephen J. Roberts

    E-print Network

    Roberts, Stephen

    Nonstationary Logistic Regression William D. Penny and Stephen J. Roberts Technical Report, Neural propose an online learning algorithm for training a logistic regression model on nonstationary classification problems. The nonstationarity is captured by modelling the weights in a logistic regression

  19. Proportional hazards regression in epidemiologic follow-up studies: an intuitive consideration of primary time scale.

    PubMed

    Cologne, John; Hsu, Wan-Ling; Abbott, Robert D; Ohishi, Waka; Grant, Eric J; Fujiwara, Saeko; Cullings, Harry M

    2012-07-01

    In epidemiologic cohort studies of chronic diseases, such as heart disease or cancer, confounding by age can bias the estimated effects of risk factors under study. With Cox proportional-hazards regression modeling in such studies, it would generally be recommended that chronological age be handled nonparametrically as the primary time scale. However, studies involving baseline measurements of biomarkers or other factors frequently use follow-up time since measurement as the primary time scale, with no explicit justification. The effects of age are adjusted for by modeling age at entry as a parametric covariate. Parametric adjustment raises the question of model adequacy, in that it assumes a known functional relationship between age and disease, whereas using age as the primary time scale does not. We illustrate this graphically and show intuitively why the parametric approach to age adjustment using follow-up time as the primary time scale provides a poor approximation to age-specific incidence. Adequate parametric adjustment for age could require extensive modeling, which is wasteful, given the simplicity of using age as the primary time scale. Furthermore, the underlying hazard with follow-up time based on arbitrary timing of study initiation may have no inherent meaning in terms of risk. Given the potential for biased risk estimates, age should be considered as the preferred time scale for proportional-hazards regression with epidemiologic follow-up data when confounding by age is a concern. PMID:22517300

  20. Non-Iterative, Regression-Based Estimation of Haplotype Associations with Censored Survival Outcomes

    PubMed Central

    French, Benjamin; Lumley, Thomas; Cappola, Thomas P.; Mitra, Nandita

    2012-01-01

    The general availability of reliable and affordable genotyping technology has enabled genetic association studies to move beyond small case-control studies to large prospective studies. For prospective studies, genetic information can be integrated into the analysis via haplotypes, with focus on their association with a censored survival outcome. We develop non-iterative, regression-based methods to estimate associations between common haplotypes and a censored survival outcome in large cohort studies. Our non-iterative methods—weighted estimation and weighted haplotype combination—are both based on the Cox regression model, but differ in how the imputed haplotypes are integrated into the model. Our approaches enable haplotype imputation to be performed once as a simple data-processing step, and thus avoid implementation based on sophisticated algorithms that iterate between haplotype imputation and risk estimation. We show that non-iterative weighted estimation and weighted haplotype combination provide valid tests for genetic associations and reliable estimates of moderate associations between common haplotypes and a censored survival outcome, and are straightforward to implement in standard statistical software. We apply the methods to an analysis of HSPB7-CLCNKA haplotypes and risk of adverse outcomes in a prospective cohort study of outpatients with chronic heart failure. PMID:22499703

  1. Discrete mixture modeling to address genetic heterogeneity in time-to-event regression

    PubMed Central

    Eng, Kevin H.; Hanlon, Bret M.

    2014-01-01

    Motivation:?Time-to-event regression models are a critical tool for associating survival time outcomes with molecular data. Despite mounting evidence that genetic subgroups of the same clinical disease exist, little attention has been given to exploring how this heterogeneity affects time-to-event model building and how to accommodate it. Methods able to diagnose and model heterogeneity should be valuable additions to the biomarker discovery toolset. Results:?We propose a mixture of survival functions that classifies subjects with similar relationships to a time-to-event response. This model incorporates multivariate regression and model selection and can be fit with an expectation maximization algorithm, we call Cox-assisted clustering. We illustrate a likely manifestation of genetic heterogeneity and demonstrate how it may affect survival models with little warning. An application to gene expression in ovarian cancer DNA repair pathways illustrates how the model may be used to learn new genetic subsets for risk stratification. We explore the implications of this model for censored observations and the effect on genomic predictors and diagnostic analysis. Availability and implementation:?R implementation of CAC using standard packages is available at https://gist.github.com/programeng/8620b85146b14b6edf8f Data used in the analysis are publicly available. Contact:?kevin.eng@roswellpark.org Supplementary information:?Supplementary data are available at Bioinformatics online. PMID:24532723

  2. 25-Hydroxycholesterol exerts both a cox-2-dependent transient proliferative effect and cox-2-independent cytotoxic effect on bovine endothelial cells in a time- and cell-type-dependent manner

    PubMed Central

    2010-01-01

    Background 25-hydroxycholesterol (25-OHC) is a product of oxidation of dietary cholesterol present in human plasma. 25-OHC and other oxidized forms of cholesterol are implicated in modulating inflammatory responses involved in development of atherosclerosis and colon carcinogenesis. Methods Primary lymphatic, venous and arterial endothelial cells isolated from bovine mesentery (bmLEC, bmVEC, bmAEC) were treated with 25-OHC and tested for several different cellular parameters. Results We found 25-OHC to be a potent inducer of cyclooxygenase-2 (Cox-2, prostaglandin G-H synthase-2) expression in bovine mesenteric lymphatic, venous, and arterial endothelial cells. The induction of Cox-2 expression in endothelial cells by 25-OHC led to an initial increase in cellular proliferation that was inhibited by the Cox-2 selective inhibitor celecoxib (Celebrex). Prolonged exposure to 25-OHC was cytotoxic. Furthermore, endothelial cells induced to express Cox-2 by 25-OHC were more sensitive to the effects of the Cox-2 selective inhibitor celecoxib (Celebrex). These results suggest that some effects of 25-OHC on cells may be dependent on Cox-2 enzymatic activity. Conclusions Cox-2 dependent elevating effects of 25-OHC on endothelial cell proliferation was transient. Prolonged exposure to 25-OHC caused cell death and enhanced celecoxib-induced cell death in a cell-type dependent manner. The lack of uniform response by the three endothelial cell types examined suggests that our model system of primary cultures of bmLECs, bmVECs, and bmAECs may aid the evaluation of celecoxib in inhibiting proliferation of different types of tumour-associated endothelial cells. PMID:21070649

  3. Expression of integrin ?3?1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    PubMed Central

    2014-01-01

    Background Expression of integrin ?3?1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin ?3?1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin ?3?1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Methods Immunohistochemistry was performed to assess co-expression of ?3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n?=?59 samples) or obtained from Albany Medical Center archives (n?=?68 samples). Immunostaining intensity for the integrin ?3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Results Although expression of integrin ?3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between ?3 and COX2 in both tissue microarrays (rs?=?0.49, p?COX2 and ?3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin ?3?1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of ?3?1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target ?3?1, and that ?3 expression might serve as an independent prognostic biomarker. PMID:24950714

  4. Multiple recent horizontal transfers of the cox1 intron in Solanaceae and extended co-conversion of flanking exons

    PubMed Central

    2011-01-01

    Background The most frequent case of horizontal transfer in plants involves a group I intron in the mitochondrial gene cox1, which has been acquired via some 80 separate plant-to-plant transfer events among 833 diverse angiosperms examined. This homing intron encodes an endonuclease thought to promote the intron's promiscuous behavior. A promising experimental approach to study endonuclease activity and intron transmission involves somatic cell hybridization, which in plants leads to mitochondrial fusion and genome recombination. However, the cox1 intron has not yet been found in the ideal group for plant somatic genetics - the Solanaceae. We therefore undertook an extensive survey of this family to find members with the intron and to learn more about the evolutionary history of this exceptionally mobile genetic element. Results Although 409 of the 426 species of Solanaceae examined lack the cox1 intron, it is uniformly present in three phylogenetically disjunct clades. Despite strong overall incongruence of cox1 intron phylogeny with angiosperm phylogeny, two of these clades possess nearly identical intron sequences and are monophyletic in intron phylogeny. These two clades, and possibly the third also, contain a co-conversion tract (CCT) downstream of the intron that is extended relative to all previously recognized CCTs in angiosperm cox1. Re-examination of all published cox1 genes uncovered additional cases of extended co-conversion and identified a rare case of putative intron loss, accompanied by full retention of the CCT. Conclusions We infer that the cox1 intron was separately and recently acquired by at least three different lineages of Solanaceae. The striking identity of the intron and CCT from two of these lineages suggests that one of these three intron captures may have occurred by a within-family transfer event. This is consistent with previous evidence that horizontal transfer in plants is biased towards phylogenetically local events. The discovery of extended co-conversion suggests that other cox1 conversions may be longer than realized but obscured by the exceptional conservation of plant mitochondrial sequences. Our findings provide further support for the rampant-transfer model of cox1 intron evolution and recommend the Solanaceae as a model system for the experimental analysis of cox1 intron transfer in plants. PMID:21943226

  5. Efficient Regressions via Optimally Combining Quantile Information.

    PubMed

    Zhao, Zhibiao; Xiao, Zhijie

    2014-12-01

    We develop a generally applicable framework for constructing efficient estimators of regression models via quantile regressions. The proposed method is based on optimally combining information over multiple quantiles and can be applied to a broad range of parametric and nonparametric settings. When combining information over a fixed number of quantiles, we derive an upper bound on the distance between the efficiency of the proposed estimator and the Fisher information. As the number of quantiles increases, this upper bound decreases and the asymptotic variance of the proposed estimator approaches the Cramér-Rao lower bound under appropriate conditions. In the case of non-regular statistical estimation, the proposed estimator leads to super-efficient estimation. We illustrate the proposed method for several widely used regression models. Both asymptotic theory and Monte Carlo experiments show the superior performance over existing methods. PMID:25484481

  6. The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning

    PubMed Central

    Guo, Yiru; Tukaye, Deepali Nivas; Wu, Wen-Jian; Zhu, Xiaoping; Book, Michael; Tan, Wei; Jones, Steven P.; Rokosh, Gregg; Narumiya, Shuh; Li, Qianhong; Bolli, Roberto

    2012-01-01

    Background Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear. Objective To determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion. Methods COX-2 knockout (KO) mice (COX-2?/?), prostacyclin receptor KO (IP?/?) mice, and respective wildtype (WT, COX-2+/+ and IP+/+) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30-min O/24 h R. Results There were no significant differences in infarct size (IS) between non-preconditioned (non-PC) COX-2+/+, COX-2?/?, IP+/+, and IP?/? mice, indicating that neither COX-2 nor IP modulates IS in the absence of PC. When COX-2?/? or IP?/? mice were preconditioned, IS was not reduced, indicating that the protection of late PC was completely abrogated by deletion of either the COX-2 or the IP gene. Administration of the IP selective antagonist, RO3244794 to C57BL6/J (B6) mice 30 min prior to the 30-min O had no effect on IS. When B6 mice were preconditioned 24 h prior to the 30-min O, IS was markedly reduced; however, the protection of late PC was completely abrogated by pretreatment of RO3244794. Conclusions This is the first study to demonstrate that targeted disruption of the COX-2 gene completely abrogates the infarct-sparing effect of late PC, and that the IP, downstream of the COX-2/prostanoid pathway, is a key mediator of the late PC. These results provide unequivocal molecular genetic evidence for an essential role of the COX-2/PGI2 receptor axis in the cardioprotection afforded by the late PC. PMID:22844439

  7. The impact of CHADS2 score on late stroke after the Cox maze procedure

    PubMed Central

    Pet, Mitchell; Robertson, Jason O.; Bailey, Marci; Guthrie, Tracey J.; Moon, Marc R.; Lawton, Jennifer S.; Rinne, Andrew; Damiano, Ralph J.; Maniar, Hersh S.

    2015-01-01

    Objective The Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society jointly recommend indefinite warfarin anticoagulation in patients with CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke) score of at least 2 who have undergone ablation for atrial fibrillation. This study determined the impact of CHADS2 score on risk of late stroke or transient ischemic attack after the performance of a surgical Cox maze procedure. Methods A retrospective review of 433 patients who underwent a Cox maze procedure at our institution was conducted. Three months after surgery, warfarin was discontinued regardless of CHADS2 score if the patient showed no evidence of atrial fibrillation, was off antiarrhythmic medications, and had no other indication for anticoagulation. A follow-up questionnaire was used to determine whether any neurologic event had occurred since surgery. Results Follow-up was obtained for 90% of the study group (389/433) at a mean of 6.6 ± 5.0 years. Among these patients, 32% (125/389) had a CHADS2 score of at least 2, of whom only 40% (51/125) remained on long-term warfarin after surgery. Six patients had late neurologic events (annualized risk of 0.2%). Neither CHADS2 score nor warfarin anticoagulation was significantly associated with the occurrence of late neurologic events. Among the individual CHADS2 criteria, both diabetes mellitus and previous stroke or transient ischemic attack were predictive of late neurologic events. Conclusions The risk of stroke or transient ischemic attack in patients after a surgical Cox maze procedure was low and not associated with CHADS2 score or warfarin use. Given the known risks of warfarin, we recommend discontinuation of anticoagulation 3 months after the procedure if the patient has no evidence of atrial fibrillation, has discontinued antiarrhythmic medications, and is without any other indication for systemic anticoagulation. PMID:22818126

  8. Differential expression of biphenyl synthase gene family members in fire-blight-infected apple 'Holsteiner Cox'.

    PubMed

    Chizzali, Cornelia; Gaid, Mariam M; Belkheir, Asma K; Hänsch, Robert; Richter, Klaus; Flachowsky, Henryk; Peil, Andreas; Hanke, Magda-Viola; Liu, Benye; Beerhues, Ludger

    2012-02-01

    Fire blight, caused by the bacterium Erwinia amylovora, is a devastating disease of apple (Malus × domestica). The phytoalexins of apple are biphenyls and dibenzofurans, whose carbon skeleton is formed by biphenyl synthase (BIS), a type III polyketide synthase. In the recently published genome sequence of apple 'Golden Delicious', nine BIS genes and four BIS gene fragments were detected. The nine genes fall into four subfamilies, referred to as MdBIS1 to MdBIS4. In a phylogenetic tree, the BIS amino acid sequences from apple and Sorbus aucuparia formed an individual cluster within the clade of the functionally diverse type III polyketide synthases. cDNAs encoding MdBIS1 to MdBIS4 were cloned from fire-blight-infected shoots of apple 'Holsteiner Cox,' heterologously expressed in Escherichia coli, and functionally analyzed. Benzoyl-coenzyme A and salicoyl-coenzyme A were the preferred starter substrates. In response to inoculation with E. amylovora, the BIS3 gene was expressed in stems of cv Holsteiner Cox, with highest transcript levels in the transition zone between necrotic and healthy tissues. The transition zone was the accumulation site of biphenyl and dibenzofuran phytoalexins. Leaves contained transcripts for BIS2 but failed to form immunodetectable amounts of BIS protein. In cell cultures of apple 'Cox Orange,' expression of the BIS1 to BIS3 genes was observed after the addition of an autoclaved E. amylovora suspension. Using immunofluorescence localization under a confocal laser-scanning microscope, the BIS3 protein in the transition zone of stems was detected in the parenchyma of the bark. Dot-shaped immunofluorescence was confined to the junctions between neighboring cortical parenchyma cells. PMID:22158676

  9. KRAS, EGFR, PDGFR-?, KIT and COX-2 status in carcinoma showing thymus-like elements (CASTLE)

    PubMed Central

    2014-01-01

    Background CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid. Methods We retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-? and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets. Results Diagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-? gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene. Conclusions All tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-? gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1658499296115016 PMID:24934485

  10. Increased endoplasmic reticulum stress in mouse osteocytes with aging alters cox-2 response to mechanical stimuli.

    PubMed

    Chalil, Sreeda; Jaspers, Richard T; Manders, Ralph J; Klein-Nulend, Jenneke; Bakker, Astrid D; Deldicque, Louise

    2015-02-01

    Aging reduces bone mass as well as the anabolic response of bone to mechanical stimuli, resulting in osteopenia. Endoplasmic reticulum (ER) stress impairs the response of myogenic cells to anabolic stimuli, and is involved in sarcopenia, but whether ER stress also contributes to osteopenia is unknown. Therefore, we tested whether ER stress exists in bones of aged mice, and whether this impairs the osteocyte response to mechanical stimulation. Primary osteocytes were obtained from long bones of adult (8 months) and old (24-26 months) mice, treated with or without the pharmacological ER stress inducer tunicamycin, and either or not subjected to mechanical loading by pulsating fluid flow (PFF). The osteocyte response to PFF was assessed by measuring cyclooxygenase-2 (Cox-2) mRNA levels and nitric oxide (NO) production. mRNA levels of ER stress markers were higher in old versus adult osteocytes (+40 % for activating transcription factor-4, +120 % for C/EBP homologous protein, and +120 % for spliced X-box binding protein-1, p < 0.05). The Cox-2 response to PFF was fourfold decreased in cells from old bones (p < 0.001), while tunicamycin decreased PFF-induced Cox-2 expression by threefold in cells from adult bones (p < 0.01). PFF increased NO production by 50 % at 60 min in osteocytes from old versus adult bones (p < 0.01). In conclusion, our data indicate that the expression of several ER stress markers was higher in osteocytes from bones of old compared to adult mice. Since ER stress altered the response of osteocytes to mechanical loading, it could be a novel factor contributing to osteopenia. PMID:25539857

  11. An Improved Sequential Procedure for Estimating the Regression Parameter in Regression Models with Symmetric Errors

    Microsoft Academic Search

    T. N. Sriram

    1992-01-01

    A sequential procedure for estimating the regression parameter $\\\\beta \\\\in R^k$ in a regression model with symmetric errors is proposed. This procedure is shown to have asymptotically smaller regret than the procedure analyzed by Martinsek when $\\\\mathbf{\\\\beta} = \\\\mathbf{0}$, and the same asymptotic regret as that procedure when $\\\\mathbf{\\\\beta} \\\

  12. Comparison of multinomial logistic regression and logistic regression: which is more efficient in allocating land use?

    NASA Astrophysics Data System (ADS)

    Lin, Yingzhi; Deng, Xiangzheng; Li, Xing; Ma, Enjun

    2014-12-01

    Spatially explicit simulation of land use change is the basis for estimating the effects of land use and cover change on energy fluxes, ecology and the environment. At the pixel level, logistic regression is one of the most common approaches used in spatially explicit land use allocation models to determine the relationship between land use and its causal factors in driving land use change, and thereby to evaluate land use suitability. However, these models have a drawback in that they do not determine/allocate land use based on the direct relationship between land use change and its driving factors. Consequently, a multinomial logistic regression method was introduced to address this flaw, and thereby, judge the suitability of a type of land use in any given pixel in a case study area of the Jiangxi Province, China. A comparison of the two regression methods indicated that the proportion of correctly allocated pixels using multinomial logistic regression was 92.98%, which was 8.47% higher than that obtained using logistic regression. Paired t-test results also showed that pixels were more clearly distinguished by multinomial logistic regression than by logistic regression. In conclusion, multinomial logistic regression is a more efficient and accurate method for the spatial allocation of land use changes. The application of this method in future land use change studies may improve the accuracy of predicting the effects of land use and cover change on energy fluxes, ecology, and environment.

  13. Generalized approach to the problem of regression

    NASA Astrophysics Data System (ADS)

    Partyka, Dariusz; Zaja¸c, Józef

    2015-01-01

    As a result of studying and solving certain extremal problems defined on the basis of finite and infinite dimensional pseudo-Hilbert space, the authors present a generalization of the classical regression idea. Given discrete or continuous empiric data, the class of solutions is uniquely determined and expressed in a new form of the regression function sequences, both within the asynchronous and synchronous type in a given pseudo-Hilbert space. With the help of this new technique, a large variety of observed phenomena in different areas of practical and theoretical sciences can be precisely described and investigated.

  14. Weibull regression for lifetimes measured with error.

    PubMed

    Skinner, C J; Humphreys, K

    1999-01-01

    Models are considered in which 'true' lifetimes are generated by a Weibull regression model and measured lifetimes are determined from the true times by certain measurement error models. Adjusted estimators are obtained under one parametric specification. The bias properties of these estimators and standard estimators are compared both theoretically, using small measurement error asymptotics, and by simulation. The standard estimators of regression coefficients, other than the intercept, are bias-robust. The adjusted estimator of the shape parameter removes the bias of the standard estimator. PMID:10214000

  15. Removing Malmquist bias from linear regressions

    NASA Technical Reports Server (NTRS)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  16. Topics in route-regression analysis

    USGS Publications Warehouse

    Geissler, P.H.; Sauer, J.R.

    1990-01-01

    The route-regression method has been used in recent years to analyze data from roadside surveys. With this method, a population trend is estimated for each route in a region, then regional trends are estimated as a weighted mean of the individual route trends. This method can accurately incorporate data that is unbalanced by changes in years surveyed and observer differences. We suggest that route-regression methodology is most efficient in the estimation of long-term (>5 year) trends, and tends to provide conservative results for low-density species.

  17. Nèel temperature variation of CoxNi1-xFe2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Niu, Ziping; Li, Fashen

    2015-04-01

    CoxNi1-xFe2O4 (x=0.1, 0.3, 0.5) nanoparticles were synthesized by the PVA Sol-Gel method, and all the samples were found to be single phase spinel by powder X-ray diffraction measurements. High temperature Mössbauer spectra were recorded by a Mössbauer spectrometer. Temperature dependence of hyperfine magnetic fields of two magnetic sextets indicates a "two Nèel temperatures" phenomenon in Co0.3Ni0.7Fe2O4 and Co0.5Ni0.5Fe2O4, which has been further demonstrated by the magnetic thermo-gravimetric analysis (MTGA).

  18. Racemic and chiral sulfoxides as potential prodrugs of the COX-2 inhibitors Vioxx and Arcoxia.

    PubMed

    Caturla, Francisco; Amat, Mercè; Reinoso, Raquel F; Córdoba, Mónica; Warrellow, Graham

    2006-06-15

    The preparation of the sulfoxide analogues 2 and 4, and their enantiomeric pure forms is discussed as well as their potential to act as prodrugs to the potent and selective sulfone-containing COX-2 inhibitors rofecoxib and etoricoxib. Sulfoxides 2 and 4 were shown to be effectively transformed in vivo into rofecoxib and etoricoxib, respectively, after oral administration in rats. In the case of sulfoxide 2, both a slightly improved pharmacokinetic profile and a better pharmacological activity in an arthritis model were seen when compared with rofecoxib. PMID:16616494

  19. Mixed-Phase Icing Simulation and Testing at the Cox Icing Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Al-Khalil, Kamel; Irani, Eddie; Miller, Dean

    2003-01-01

    A new capability was developed for indoor simulation of snow and mixed-phase icing conditions. This capability is useful for year-round testing in the Cox closed-loop Icing Wind Tunnel. Certification of aircraft for flight into these types of icing conditions is only required by the JAA in Europe. In an effort to harmonize certification requirements, the FAA in the US sponsored a preliminary program to study the effects of mixed-phase and fully glaciated icing conditions on the performance requirements of thermal ice protection systems. This paper describes the test program and the associated results.

  20. Infrared Faraday measurements on Ba(Fe1-xCox)2As2 superconductors

    NASA Astrophysics Data System (ADS)

    Mukherjee, Alok; Ellis, Chase T.; Murat Arik, M.; Cerne, John; Sato, Hikaru; Hiramatsu, Hidenori; Hosono, Hideo

    2013-03-01

    We report infrared Faraday measurements on electron-doped Ba(Fe1-xCox)2As2 superconducting films, which are grown by pulsed laser deposition. The complex Faraday angle ?F is proportional to the difference of the sample's response to right and left circularly polarized light, making it a highly sensitive tool to probe electronic structure, electron-electron correlations, and magnetic ordering. We measure ?F for normal and superconducting states in the 110-1400 meV range at temperatures down to 10K and magnetic fields up to 7T. This work is supported by NSF-DMR1006078.