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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. Univariate Nonparametric Analysis of Variance Through Multiple Linear Regression

    ERIC Educational Resources Information Center

    Huitema, Bradley E.

    1978-01-01

    Many methodologists are aware that parametric tests associated with the analysis of variance and the analysis of covariance can be computed using regression procedures. It is shown that multiple linear regression can also be employed to compute the Kruskal-Wallis nonparametric analysis of variance. (Author)

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

    ERIC Educational Resources Information Center

    Chen, Chau-Kuang

    2005-01-01

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

  4. 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

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

    PubMed

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

    2015-01-01

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

  6. Modeling and predicting the popularity of online contents with Cox proportional hazard regression model

    E-print Network

    Moon, Sue B.

    Modeling and predicting the popularity of online contents with Cox proportional hazard regression model Jong Gun Lee a,�, Sue Moon b , Kave´ Salamatian c a SENSE (Sociology and Economics of Networks i n f o Available online 3 August 2011 Keywords: Popularity of online contents Survival analysis Cox

  7. 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…

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

    PubMed Central

    Kong, Shengchun; Nan, Bin

    2013-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses. PMID:24516328

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

    PubMed

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses. PMID:24516328

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

    E-print Network

    Kong, Shengchun

    2012-01-01

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

  11. The Gaussian process latent variable model with Cox regression James Barrett

    E-print Network

    Hennig, Christian

    The Gaussian process latent variable model with Cox regression James Barrett Institute for Mathematical and Molecular Biomedicine (IMMB), King's College London James Barrett (IMMB, KCL) GP Latent model James Barrett (IMMB, KCL) GP Latent Variable Model 2 / 19 #12;Integrating Multiple Data Sources

  12. Univariate calibration by reversed regression of heteroscedastic data: a case study.

    PubMed

    Zeng, Qiaoling Charlene; Zhang, Elizabeth; Tellinghuisen, Joel

    2008-12-01

    In a study of calibration with HPLC data for acetaldehyde-DNPH, we have collected replicate data (5-11 points each) for 33 samples spanning the range 0.0004-3 microg of detected analyte. Over most of this range, the data uncertainty is proportional to the signal, implying that weighted least squares is required to obtain the calibration function, since minimum-variance estimation requires weights inversely proportional to the data variance. When a variance function derived from an analysis of the replicate statistics is used to assign weights, w(i) = 1/sigma(i)(2), the resulting values of chi(2) for the calibration fit are too large by a factor of 400. This implies that the method error is dominated by sample preparation rather than measurement uncertainty, and it means that in the calibration fit, the peak area should be taken as the independent variable and the amount as the dependent. In this reversed regression, the generalized LS method (GLS) is used to estimate the total method variance function from the residuals. The resulting method variance function resembles the instrumental variance, in containing constant and proportional error terms. The calibration data demand at least a cubic polynomial for adequate representation, but other response functions are statistically equivalent, with the result that this model uncertainty is comparable to the directly computed statistical uncertainty of the calibration function. In these computations, emphasis is placed on the virtues of chi(2) as a statistical figure of merit over the widely used R. PMID:19082066

  13. Network regularised Cox regression and multiplex network models to predict disease comorbidities and survival of cancer.

    PubMed

    Xu, Haoming; Moni, Mohammad Ali; Liò, Pietro

    2015-12-01

    In cancer genomics, gene expression levels provide important molecular signatures for all types of cancer, and this could be very useful for predicting the survival of cancer patients. However, the main challenge of gene expression data analysis is high dimensionality, and microarray is characterised by few number of samples with large number of genes. To overcome this problem, a variety of penalised Cox proportional hazard models have been proposed. We introduce a novel network regularised Cox proportional hazard model and a novel multiplex network model to measure the disease comorbidities and to predict survival of the cancer patient. Our methods are applied to analyse seven microarray cancer gene expression datasets: breast cancer, ovarian cancer, lung cancer, liver cancer, renal cancer and osteosarcoma. Firstly, we applied a principal component analysis to reduce the dimensionality of original gene expression data. Secondly, we applied a network regularised Cox regression model on the reduced gene expression datasets. By using normalised mutual information method and multiplex network model, we predict the comorbidities for the liver cancer based on the integration of diverse set of omics and clinical data, and we find the diseasome associations (disease-gene association) among different cancers based on the identified common significant genes. Finally, we evaluated the precision of the approach with respect to the accuracy of survival prediction using ROC curves. We report that colon cancer, liver cancer and renal cancer share the CXCL5 gene, and breast cancer, ovarian cancer and renal cancer share the CCND2 gene. Our methods are useful to predict survival of the patient and disease comorbidities more accurately and helpful for improvement of the care of patients with comorbidity. Software in Matlab and R is available on our GitHub page: https://github.com/ssnhcom/NetworkRegularisedCox.git. PMID:26611766

  14. Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression

    PubMed Central

    2014-01-01

    Background Recent global genomic analyses identified 69 gene sets and 12 core signaling pathways genetically altered in pancreatic cancer, which is a highly malignant disease. A comprehensive understanding of the genetic signatures and signaling pathways that are directly correlated to pancreatic cancer survival will help cancer researchers to develop effective multi-gene targeted, personalized therapies for the pancreatic cancer patients at different stages. A previous work that applied a LASSO penalized regression method, which only considered individual genetic effects, identified 12 genes associated with pancreatic cancer survival. Results In this work, we integrate pathway information into pancreatic cancer survival analysis. We introduce and apply a doubly regularized Cox regression model to identify both genes and signaling pathways related to pancreatic cancer survival. Conclusions Four signaling pathways, including Ion transport, immune phagocytosis, TGF? (spermatogenesis), regulation of DNA-dependent transcription pathways, and 15 genes within the four pathways are identified and verified to be directly correlated to pancreatic cancer survival. Our findings can help cancer researchers design new strategies for the early detection and diagnosis of pancreatic cancer. PMID:24565114

  15. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    PubMed

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method. PMID:26434910

  16. 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.

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

    PubMed

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

    2009-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

  19. The Covariance Adjustment Approaches for Combining Incomparable Cox Regressions Caused by Unbalanced Covariates Adjustment: A Multivariate Meta-Analysis Study

    PubMed Central

    Dehesh, Tania; Zare, Najaf; Ayatollahi, Seyyed Mohammad Taghi

    2015-01-01

    Background. Univariate meta-analysis (UM) procedure, as a technique that provides a single overall result, has become increasingly popular. Neglecting the existence of other concomitant covariates in the models leads to loss of treatment efficiency. Our aim was proposing four new approximation approaches for the covariance matrix of the coefficients, which is not readily available for the multivariate generalized least square (MGLS) method as a multivariate meta-analysis approach. Methods. We evaluated the efficiency of four new approaches including zero correlation (ZC), common correlation (CC), estimated correlation (EC), and multivariate multilevel correlation (MMC) on the estimation bias, mean square error (MSE), and 95% probability coverage of the confidence interval (CI) in the synthesis of Cox proportional hazard models coefficients in a simulation study. Result. Comparing the results of the simulation study on the MSE, bias, and CI of the estimated coefficients indicated that MMC approach was the most accurate procedure compared to EC, CC, and ZC procedures. The precision ranking of the four approaches according to all above settings was MMC ? EC ? CC ? ZC. Conclusion. This study highlights advantages of MGLS meta-analysis on UM approach. The results suggested the use of MMC procedure to overcome the lack of information for having a complete covariance matrix of the coefficients. PMID:26413142

  20. Prediction of Early Breast Cancer Metastasis from DNA Microarray Data Using High-Dimensional Cox Regression Models

    PubMed Central

    Zemmour, Christophe; Bertucci, François; Finetti, Pascal; Chetrit, Bernard; Birnbaum, Daniel; Filleron, Thomas; Boher, Jean-Marie

    2015-01-01

    BACKGROUND DNA microarray studies identified gene expression signatures predictive of metastatic relapse in early breast cancer. Standard feature selection procedures applied to reduce the set of predictive genes did not take into account the correlation between genes. In this paper, we studied the performances of three high-dimensional regression methods – CoxBoost, LASSO (Least Absolute Shrinkage and Selection Operator), and Elastic net – to identify prognostic signatures in patients with early breast cancer. METHODS We analyzed three public retrospective datasets, including a total of 384 patients with axillary lymph node-negative breast cancer. The Amsterdam van’t Veer’s training set of 78 patients was used to determine the optimal gene sets and classifiers using sensitivity thresholds resulting in mis-classification of no more than 10% of the poor-prognosis group. To ensure the comparability between different methods, an automatic selection procedure was used to determine the number of genes included in each model. The van de Vijver’s and Desmedt’s datasets were used as validation sets to evaluate separately the prognostic performances of our classifiers. The results were compared to the original Amsterdam 70-gene classifier. RESULTS The automatic selection procedure reduced the number of predictive genes up to a minimum of six genes. In the two validation sets, the three models (Elastic net, LASSO, and CoxBoost) led to the definition of genomic classifiers predicting the 5-year metastatic status with similar performances, with respective 59, 56, and 54% accuracy, 83, 75, and 83% sensitivity, and 53, 52, and 48% specificity in the Desmedt’s dataset. In comparison, the Amsterdam 70-gene signature showed 45% accuracy, 97% sensitivity, and 34% specificity. The gene overlap and the classification concordance between the three classifiers were high. All the classifiers added significant prognostic information to that provided by the traditional prognostic factors and showed a very high overlap with respect to gene ontologies (GOs) associated with genes overexpressed in the predicted poor-prognosis vs. good-prognosis classes and centred on cell proliferation. Interestingly, all classifiers reported high sensitivity to predict the 4-year status of metastatic disease. CONCLUSIONS High-dimensional regression methods are attractive in prognostic studies because finding a small subset of genes may facilitate the transfer to the clinic, and also because they strengthen the robustness of the model by limiting the selection of false-positive predictive genes. With only six genes, the CoxBoost classifier predicted the 4-year status of metastatic disease with 93% sensitivity. Selecting a few genes related to ontologies other than cell proliferation might further improve the overall sensitivity performance. PMID:25983547

  1. Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables.

    PubMed

    Christensen, E; Schlichting, P; Andersen, P K; Fauerholdt, L; Schou, G; Pedersen, B V; Juhl, E; Poulsen, H; Tygstrup, N

    1986-03-01

    A multivariate Cox regression analysis with time-dependent variables has been performed on the data of 415 patients with cirrhosis included in a controlled clinical trial of 10-15 mg prednisone daily versus placebo. The analysis showed that a poor prognosis was associated with a low prothrombin index, marked ascites, GI bleeding, high age, high daily alcohol consumption, high bilirubin and alkaline phosphatase and low albumin values, little liver connective tissue inflammation, and poor nutritional status. Prothrombin index and ascites showed significant interaction with the treatment in such a manner that high prothrombin index and absence of ascites were associated with a beneficial effect of prednisone, whereas low prothrombin index and presence of ascites were associated with a harmful effect of prednisone treatment. The final model was validated in independent patients by comparing their actual survival with that predicted from the model, using a split-sample testing technique. The prognostic factors were combined with an index that can be used to update prognosis whenever changes occur in the clinical status of a patient during the course of the disease. The probability of surviving the next 3 or 6 months can be estimated from the prognostic index at any time during the course. The index may be of value for the correct timing of special therapeutic procedures such as liver transplantation. PMID:3520795

  2. Five Years Survival of Patients After Liver Transplantation and Its Effective Factors by Neural Network and Cox Poroportional Hazard Regression Models

    PubMed Central

    Khosravi, Bahareh; Pourahmad, Saeedeh; Bahreini, Amin; Nikeghbalian, Saman; Mehrdad, Goli

    2015-01-01

    Background: Transplantation is the only treatment for patients with liver failure. Since the therapy imposes high expenses to the patients and community, identification of effective factors on survival of such patients after transplantation is valuable. Objectives: The current study attempted to model the survival of patients (two years old and above) after liver transplantation using neural network and Cox Proportional Hazards (Cox PH) regression models. The event is defined as death due to complications of liver transplantation. Patients and Methods: In a historical cohort study, the clinical findings of 1168 patients who underwent liver transplant surgery (from March 2008 to march 2013) at Shiraz Namazee Hospital Organ Transplantation Center, Shiraz, Southern Iran, were used. To model the one to five years survival of such patients, Cox PH regression model accompanied by three layers feed forward artificial neural network (ANN) method were applied on data separately and their prediction accuracy was compared using the area under the receiver operating characteristic curve (ROC). Furthermore, Kaplan-Meier method was used to estimate the survival probabilities in different years. Results: The estimated survival probability of one to five years for the patients were 91%, 89%, 85%, 84%, and 83%, respectively. The areas under the ROC were 86.4% and 80.7% for ANN and Cox PH models, respectively. In addition, the accuracy of prediction rate for ANN and Cox PH methods was equally 92.73%. Conclusions: The present study detected more accurate results for ANN method compared to those of Cox PH model to analyze the survival of patients with liver transplantation. Furthermore, the order of effective factors in patients’ survival after transplantation was clinically more acceptable. The large dataset with a few missing data was the advantage of this study, the fact which makes the results more reliable. PMID:26500682

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  4. 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

  5. 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…

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

    PubMed

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

    2011-12-10

    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 nondiabetic 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

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

    PubMed Central

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

    2013-01-01

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

  9. 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. ...

  10. Properties of Generalized Univariate Hypergeometric Functions

    NASA Astrophysics Data System (ADS)

    van de Bult, F. J.; Rains, E. M.; Stokman, J. V.

    2007-10-01

    Based on Spiridonov’s analysis of elliptic generalizations of the Gauss hypergeometric function, we develop a common framework for 7-parameter families of generalized elliptic, hyperbolic and trigonometric univariate hypergeometric functions. In each case we derive the symmetries of the generalized hypergeometric function under the Weyl group of type E 7 (elliptic, hyperbolic) and of type E 6 (trigonometric) using the appropriate versions of the Nassrallah-Rahman beta integral, and we derive contiguous relations using fundamental addition formulas for theta and sine functions. The top level degenerations of the hyperbolic and trigonometric hypergeometric functions are identified with Ruijsenaars’ relativistic hypergeometric function and the Askey-Wilson function, respectively. We show that the degeneration process yields various new and known identities for hyperbolic and trigonometric special functions. We also describe an intimate connection between the hyperbolic and trigonometric theory, which yields an expression of the hyperbolic hypergeometric function as an explicit bilinear sum in trigonometric hypergeometric functions.

  11. Univariant assessment of the quality of images

    NASA Astrophysics Data System (ADS)

    Jung, Mathieu; Leger, Dominique; Gazalet, Marc G.

    2002-07-01

    To evaluate the quality of images, most methods compare a degraded image to a perfect reference. Nevertheless in many cases, a reference does not exist. We propose an original univariant (i.e., without a reference) method based on the use of artificial neural networks. The principle behind it is to first teach a neural network to assess image quality using images taken from a pool of known examples, then use it to assess the quality of unknown images. The defects considered are compression artifacts, ringing, local singularities, etc. To simplify, only images with defects that are not mixed with one another were first used. Two illustrative examples are presented: assessment of the quality of JPEG compressed images and detection of local defects. The quality of the images is assessed without a reference and with error less than 6% - 7% compared to the bivariant method that was learned. Our method can even be used to model some very simple visual comportment.

  12. The Moxie of Kathy Cox

    ERIC Educational Resources Information Center

    Johns, Stephanie

    2010-01-01

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

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

    PubMed Central

    Schaubel, Douglas E.; Kalbeisch, John D.

    2015-01-01

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

  14. Bayesian random threshold estimation in a Cox proportional hazards cure model.

    PubMed

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

    2014-02-20

    In this paper, we develop a Bayesian approach to estimate a Cox proportional hazards model that allows a threshold in the regression coefficient, when some fraction of subjects are not susceptible to the event of interest. A data augmentation scheme with latent binary cure indicators is adopted to simplify the Markov chain Monte Carlo implementation. Given the binary cure indicators, the Cox cure model reduces to a standard Cox model and a logistic regression model. Furthermore, the threshold detection problem reverts to a threshold problem in a regular Cox model. The baseline cumulative hazard for the Cox model is formulated non-parametrically using counting processes with a gamma process prior. Simulation studies demonstrate that the method provides accurate point and interval estimates. Application to a data set of oropharynx cancer patients suggests a significant threshold in age at diagnosis such that the effect of gender on disease-specific survival changes after the threshold. PMID:24009083

  15. Univariate statistical analysis of environmental (compositional) data: Problems and possibilities

    E-print Network

    Filzmoser, Peter

    Univariate statistical analysis of environmental (compositional) data: Problems and possibilities 2009 Accepted 5 August 2009 Available online xxxx Keywords: Compositional data Closure problem known that compositional (closed) data have special geometrical properties. In environmental sciences

  16. 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...

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  18. Comparison of Univariate and Multivariate Models of (13)C SSNMR and XRPD Techniques for Quantification of Nimodipine Polymorphs.

    PubMed

    Rahman, Ziyaur; Mohammad, Adil; Siddiqui, Akhtar; Khan, Mansoor A

    2015-12-01

    The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance ((13)C ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) crystallized in a cosolvent formulation. The cosolvent formulation composed of polyethylene glycol 400, glycerin, water, and 2.5% drug, and was stored at 5°C for the drug crystallization. The (13)C ssNMR and XRPD data of the sample matrices containing varying percentages of nimodipine form I and form II were collected. Univariate and multivariate models were developed using the data. Least square method was used for the univariate model generation. Partial least square and principle component regressions were used for the multivariate models development. The univariate models of the (13)C ssNMR were better than the XRPD as indicated by statistical parameters such as correlation coefficient, R (2), root mean square error, and standard error. On the other hand, the XRPD multivariate models were better than the (13)C ssNMR as indicated by precision and accuracy parameters. Similar values were predicted by the univariate and multivariate models for independent samples. In conclusion, the univariate and multivariate models of (13)C ssNMR and XRPD can be used to quantitate nimodipine polymorphs. PMID:25956485

  19. Characterization of Paracoccidioides brasiliensis COX9, COX12, and COX16 respiratory genes.

    PubMed

    Bandeira, Simone C B; Nóbrega, Marina P

    2008-12-01

    Paracoccidioides brasiliensis is a thermo-dimorphic fungus that is the causative agent of paracoccidioidomyicosis (PCM), a human systemic granulomatous mycosis found in Latin America. Dimorphic transition from mycelium to yeast is required for establishing pathogenicity. Dimorphism is marked by changes in mitochondrial physiology, including modulation of respiration rate. In this work, we present the identification of three P. brasiliensis nuclear genes PbCOX9, PbCOX12, and PbCOX16 that code for structural subunits and a putative assembly facilitator (PbCOX16) of the mitochondrial cytochrome c oxidase (COX), the terminal enzyme complex of the respiratory chain. We measured their expression pattern during the dimorphic transition from mycelium to yeast and back by real-time reverse transcription quantitative polymerase chain reaction (real-time RT-qPCR). Our results show that messages from these genes increase during the mycelium to yeast transition and decrease during the opposite conversion. This result supports active mitochondrial participation in the transition. Heterologous complementation of the corresponding Saccharomyces cerevisiae null mutant with the PbCOX9 gene was successfully obtained. PMID:18672058

  20. Efficient Regression in Metric Spaces via Approximate Lipschitz Extension

    E-print Network

    Krauthgamer, Robert

    the target function are made, the regression problem is termed nonparametric. Informally, the main objective in the study of nonparametric regression is to understand the relationship between the reg- ularity conditions is the computational efficiency of constructing the regression function. The general (univariate) nonparametric

  1. ESTIMATING ILLUMINATION CHROMATICITY via KERNEL REGRESSION Vivek Agarwal, Andrei V. Gribok, Andreas Koschan, and Mongi A. Abidi

    E-print Network

    Koschan, Andreas

    regression is a locally weighted polynomial and nonparametric regression technique [1] [16]. There are two forms of local regression models, namely: univariate regression and multivariate regression. We useESTIMATING ILLUMINATION CHROMATICITY via KERNEL REGRESSION Vivek Agarwal, Andrei V. Gribok, Andreas

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

    PubMed

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

    2015-02-01

    Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg(-1) over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach. PMID:26064595

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

    PubMed Central

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

    2015-01-01

    Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg?1 over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach. PMID:26064595

  4. Univariable Optimal Discriminant Analysis: One-Tailed Hypotheses.

    ERIC Educational Resources Information Center

    Soltysik, Robert C.; Yarnold, Paul R.

    1994-01-01

    This article describes the theoretical distribution of optima arising from two-category univariable optimal discriminant analysis (UniODA) of continuous random data for a one-tailed (directional) hypothesis. Directional UniODA is illustrated through an investigation of the relationship between depression and brain monoamine turnover. (SLD)

  5. 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…

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

    ERIC Educational Resources Information Center

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

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

  7. Color Sequences for Univariate Maps: Theory, Experiments, and Principles

    E-print Network

    New Hampshire, University of

    Color Sequences for Univariate Maps: Theory, Experiments, and Principles Colin Ware University which color sequences will be effective at conveying value and form information respectively. According experiment which test five color sequences. The results show that simultaneous contrast can be a major source

  8. Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

    E-print Network

    Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease Christian Habeck Medical Center, PH18, 622 West 168th Street, New York, NY 10032, USA b Center for Alzheimer's Care analysis of FDG­PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG­PET scans

  9. 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

  10. Nonparametric Regression Analysis of Multivariate Longitudinal Data

    E-print Network

    Qiu, Peihua

    Nonparametric Regression Analysis of Multivariate Longitudinal Data Dongdong Xiang1, Peihua Qiu2 models are invalid. On the other hand, all existing nonparametric methods for analyzing longitudinal data are for univariate cases only. When longitudinal data are multivariate, nonparametric modeling becomes challenging

  11. 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

  12. RENCI Engagement Steven Cox: http://osglog.wordpress.com

    E-print Network

    Deelman, Ewa

    High Throughput Parallel Molecular Dynamics HTPMD Steve Cox RENCI Engagement #12;Steven Cox: http://osglog.wordpress Workflow and Hybrid Computing #12;Steven Cox: http://osglog.wordpress.comSteven Cox: http://osglog.wordpress configuration High Throughput Parallel Computing (HTPC) #12;Steven Cox: http://osglog.wordpress.comSteven Cox

  13. Towards a universal barcode of oomycetes - a comparison of the cox1 and cox2 loci.

    PubMed

    Choi, Young-Joon; Beakes, Gordon; Glockling, Sally; Kruse, Julia; Nam, Bora; Nigrelli, Lisa; Ploch, Sebastian; Shin, Hyeon-Dong; Shivas, Roger G; Telle, Sabine; Voglmayr, Hermann; Thines, Marco

    2015-11-01

    Oomycetes are a diverse group of eukaryotes in terrestrial, limnic and marine habitats worldwide and include several devastating plant pathogens, for example Phytophthora infestans (potato late blight). The cytochrome c oxidase subunit 2 gene (cox2) has been widely used for identification, taxonomy and phylogeny of various oomycete groups. However, recently the cox1 gene was proposed as a DNA barcode marker instead, together with ITS rDNA. The cox1 locus has been used in some studies of Pythium and Phytophthora, but has rarely been used for other oomycetes, as amplification success of cox1 varies with different lineages and sample ages. To determine which out of cox1 or cox2 is best suited as a universal oomycete barcode, we compared these two genes in terms of (i) PCR efficiency for 31 representative genera, as well as for historic herbarium specimens, and (ii) sequence polymorphism, intra- and interspecific divergence. The primer sets for cox2 successfully amplified all oomycete genera tested, while cox1 failed to amplify three genera. In addition, cox2 exhibited higher PCR efficiency for historic herbarium specimens, providing easier access to barcoding-type material. Sequence data for several historic type specimens exist for cox2, but there are none for cox1. In addition, cox2 yielded higher species identification success, with higher interspecific and lower intraspecific divergences than cox1. Therefore, cox2 is suggested as a partner DNA barcode along with ITS rDNA instead of cox1. The cox2-1 spacer could be a useful marker below species level. Improved protocols and universal primers are presented for all genes to facilitate future barcoding efforts. PMID:25728598

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

    E-print Network

    Osborn, Pamela

    2014-01-17

    The relative contributions of cyclooxygenase-1 (COX-1) versus COX-2 to vascular biosynthesis of prostacyclin (PGI_(2)) and thromboxane (TxA_(2)) and the role of estrogen in the regulation of COX function were studied in the thoracic aorta of age...

  15. 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

  16. Nonparametric Regression Using Local Kernel Estimating Equations for Correlated Failure Time Data

    E-print Network

    Lin, Xihong

    Nonparametric Regression Using Local Kernel Estimating Equations for Correlated Failure Time Data@hsph.harvard.edu August 22, 2006 Summary We study nonparametric regression for correlated failure time data. Kernel effect nonparametrically. Considerable work has been done on nonparametric regression for univariate

  17. A Note on Local Scoring and Weighted Local Polynomial Regression in Generalized Additive

    E-print Network

    Opsomer, Jean

    A Note on Local Scoring and Weighted Local Polynomial Regression in Generalized Additive Models1 J This article describes the asymptotic properties of local polynomial regression esti- mators for univariate additive models using local polynomial regression, a widely used non-projection smoother, and Opsomer (2000

  18. DAVID R. COX PRIZE FOR RARE COMPASSION

    E-print Network

    Emmons, Scott

    . In preparation, students are required to build a relationship with a patient, family, or advocate affected David R. Cox Prize for Rare Compassion, in recognition of the inspiring essays of student doctors who, like Dr. Cox, have most identified with and understood a rare or neglected patient community they have

  19. Forecasting electricity usage using univariate time series models

    NASA Astrophysics Data System (ADS)

    Hock-Eam, Lim; Chee-Yin, Yip

    2014-12-01

    Electricity is one of the important energy sources. A sufficient supply of electricity is vital to support a country's development and growth. Due to the changing of socio-economic characteristics, increasing competition and deregulation of electricity supply industry, the electricity demand forecasting is even more important than before. It is imperative to evaluate and compare the predictive performance of various forecasting methods. This will provide further insights on the weakness and strengths of each method. In literature, there are mixed evidences on the best forecasting methods of electricity demand. This paper aims to compare the predictive performance of univariate time series models for forecasting the electricity demand using a monthly data of maximum electricity load in Malaysia from January 2003 to December 2013. Results reveal that the Box-Jenkins method produces the best out-of-sample predictive performance. On the other hand, Holt-Winters exponential smoothing method is a good forecasting method for in-sample predictive performance.

  20. Certified counting of roots of random univariate polynomials

    E-print Network

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

    2014-12-04

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

  1. 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

  2. Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer

    PubMed Central

    CHEN, JUN; WU, FANG; PEI, HONG-LEI; GU, WEN-DONG; NING, ZHONG-HUA; SHAO, YING-JIE; HUANG, JIN

    2015-01-01

    The present study aimed to explore the importance of P53 and Cox-2 protein expression in esophageal cancer and assess their influence on prognosis. The expression of P53 and Cox-2 was assessed in esophageal cancer samples from 195 patients subjected to radical surgery at Changzhou First People's Hospital (Changzhou, China) between May 2010 and December 2011. Expression of P53 and Cox-2 proteins were detected in 60.5% (118/195) and 69.7% (136/195) of the samples, respectively, and were co-expressed in 43.1% (84/195) of the samples. A correlation was identified between P53 expression and overall survival (OS) (P=0.0351) as well as disease-free survival (DFS) (P=0.0307). In addition, the co-expression of P53 and Cox-2 also correlated with OS (P=0.0040) and DFS (P=0.0042). P53 expression (P=0.023), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.009) were identified as independent factors affecting OS in patients with esophageal cancer via a Cox multivariate regression model analysis. A similar analysis also identified P53 expression (P=0.020), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.008) as independent prognostic factors influencing DFS in these patients. Binary logistic regression analysis demonstrated a correlation between P53 expression (P=0.012), TNM staging (P<0.001), tumor differentiation level (P=0.023) and P53/Cox-2 co-expression (P=0.021), and local recurrence or distant esophageal cancer metastasis. The results of the present study indicate that P53 and Cox-2 proteins may act synergistically in the development of esophageal cancer, and the assessment of P53/Cox-2 co-expression status in esophageal cancer biopsies may become an important diagnostic criterion to evaluate the prognosis of patients with esophageal cancer.

  3. 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

  4. 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…

  5. 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.

  6. Univariant assessment of the visual quality of images

    NASA Astrophysics Data System (ADS)

    Jung, Mathieu; Leger, Dominique

    2000-06-01

    In order to evaluate the visual quality of images, most methods compare a degraded image to a perfect reference. We propose an original univariant (i.e. without reference) method based on the use of artificial neural networks. The principle is first to use a neural network to learn the quality of images taken from a pool of known examples, then use it to assess the quality of unknown images. The considered defects are compression artefacts, ringing or local singularities. To simplify, only images with defects that are not mixed with each other were first used. The method follows four steps. Observers are first required to mark degraded images to establish a pool of examples. Then, a characterization of the defect is extracted mathematically from the image. Then, the neural network learns how to establish a relation between the mathematical characterization of the defect and the visual mark. Finally, it can be used to assess the visual quality of an unknown image from the mathematical characterization of its defects. Two illustrative examples are presented: the assessment of the quality of JPEG compressed images and the detection of local defects.

  7. 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

  8. Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.

    PubMed

    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

  9. Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides.

    PubMed Central

    Gatell, J M; Ferran, F; Araujo, V; Bonet, M; Soriano, E; Traserra, J; SanMiguel, J G

    1987-01-01

    Risk factors predisposing to auditory toxicity of aminoglycosides were analyzed from records of 187 patients enrolled in three prospective randomized trials comparing the toxicity of netilmicin, tobramycin, and amikacin. Patients were eligible if they received three or more days of therapy and at least two serial audiograms were available. The overall auditory toxicity rate was 9.6% (18 of 187). Auditory toxicity was detected in 4.4, 10.8, and 23.5% of patients given netilmicin, tobramycin, and amikacin, respectively (P = 0.05). In the univariate analysis, patients who developed auditory toxicity were significantly older (P = 0.01) and had a significantly higher (P = 0.04) percentage of trough levels of netilmicin or tobramycin above 2 mg/liter or amikacin above 5 mg/liter. In the final logistic regression model, only age was retained as independently influencing the development of auditory toxicity (P less than 0.00001). Conversely, factors that did not add significantly to the prediction of auditory toxicity were aminoglycoside serum levels, total aminoglycoside dose, duration of therapy, sex, peak temperature, presence of bacteremia, shock, liver cirrhosis, dehydration, previous otic pathology or renal failure, and development of renal toxicity. At least in certain populations, age is the most important predisposing factor for the development of auditory toxicity in patients receiving aminoglycosides. PMID:3674849

  10. Moment Based Dimension Reduction for Multivariate Response Regression

    E-print Network

    Bura, Efstathia

    . In this article, the covariance- based method developed by Yin and Cook (2002) for univariate regressions is ex in (1). They have wide applicability in fields such as chemometrics (Frank and Friedman 1993, Ch. 4). Bura and Cook (2003) developed a theory for estimating the rank of the subspace spanned

  11. A counterexample to theorems of Cox and Fine

    SciTech Connect

    Halpern, J.Y.

    1996-12-31

    Cox`s well-known theorem justifying the use of probability is shown not to hold in finite domains. The counterexample also suggests that Cox`s assumptions are insufficient to prove the result even in infinite domains. The same counterexample is used to disprove a result of Fine on comparative conditional probability.

  12. 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

  13. Bootstrapping to Test for Nonzero Population Correlation Coefficients Using Univariate Sampling

    ERIC Educational Resources Information Center

    Beasley, William Howard; DeShea, Lise; Toothaker, Larry E.; Mendoza, Jorge L.; Bard, David E.; Rodgers, Joseph Lee

    2007-01-01

    This article proposes 2 new approaches to test a nonzero population correlation ([rho]): the hypothesis-imposed univariate sampling bootstrap (HI) and the observed-imposed univariate sampling bootstrap (OI). The authors simulated correlated populations with various combinations of normal and skewed variates. With [alpha[subscript "set"

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

    PubMed

    Berger, Ursula; Schäfer, Juliane; Ulm, Kurt

    2003-04-15

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

  15. Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator.

    PubMed

    Almada, M; Piscitelli, F; Fonseca, B M; Di Marzo, V; Correia-da-Silva, G; Teixeira, N

    2015-11-01

    Recently, endocannabinoids have emerged as signalling mediators in reproduction. It is widely accepted that anandamide (AEA) levels must be tightly regulated, and that a disturbance in AEA levels may impact decidual stability and regression. We have previously characterized the endocannabinoid machinery in rat decidual tissue and reported the pro-apoptotic action of AEA on rat decidual cells. Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays a crucial role in early pregnancy, and is also a key modulator in the crosstalk between endocannabinoids and prostaglandins. On the other hand, AEA-oxidative metabolism by COX-2 is not merely a mean to inactivate its action, but it yields the formation of a new class of mediators, named prostaglandin-ethanolamides, or prostamides. In this study we found that AEA-induced apoptosis in decidual cells involves COX-2 metabolic pathway. AEA induced COX-2 expression through p38 MAPK, resulting in the formation of prostamide E2 (PME2). Our findings also suggest that AEA-induced effect is associated with NF-kB activation. Finally, we describe the involvement of PME2 in the induction of the intrinsic apoptotic pathway in rat decidual cells. Altogether, our findings highlight the role of COX-2 as a gatekeeper in the uterine environment and clarify the impact of the deregulation of AEA levels on the decidual remodelling process. PMID:26335727

  16. Covariate analysis of survival data: a small-sample study of Cox's model

    SciTech Connect

    Johnson, M.E.; Tolley, H.D.; Bryson, M.C.; Goldman, A.S.

    1982-09-01

    Cox's proportional-hazards model is frequently used to adjust for covariate effects in survival-data analysis. The small-sample performances of the maximum partial likelihood estimators of the regression parameters in a two-covariate hazard function model are evaluated with respect to bias, variance, and power in hypothesis tests. Previous Monte Carlo work on the two-sample problem is reviewed.

  17. Biological parametric mapping accounting for random regressors with regression calibration and model II regression.

    PubMed

    Yang, Xue; Lauzon, Carolyn B; Crainiceanu, Ciprian; Caffo, Brian; Resnick, Susan M; Landman, Bennett A

    2012-09-01

    Massively univariate regression and inference in the form of statistical parametric mapping have transformed the way in which multi-dimensional imaging data are studied. In functional and structural neuroimaging, the de facto standard "design matrix"-based general linear regression model and its multi-level cousins have enabled investigation of the biological basis of the human brain. With modern study designs, it is possible to acquire multi-modal three-dimensional assessments of the same individuals--e.g., structural, functional and quantitative magnetic resonance imaging, alongside functional and ligand binding maps with positron emission tomography. Largely, current statistical methods in the imaging community assume that the regressors are non-random. For more realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional consideration of all observations is appropriate. Herein, we discuss two unified regression and inference approaches, model II regression and regression calibration, for use in massively univariate inference with imaging data. These methods use the design matrix paradigm and account for both random and non-random imaging regressors. We characterize these methods in simulation and illustrate their use on an empirical dataset. Both methods have been made readily available as a toolbox plug-in for the SPM software. PMID:22609453

  18. Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells.

    PubMed

    Agarwal, B; Swaroop, P; Protiva, P; Raj, S V; Shirin, H; Holt, P R

    2003-12-01

    The role of Cox-2 in NSAID-induced apoptosis is debated. We studied the role of Cox-2 inhibition in apoptosis induced by a selective Cox-2 inhibitor, SC236 (a structural analogue of celecoxib) in two colon cancer cell lines, HT29 (expressing Cox-2 protein) and HCT116 (not expressing Cox-2 protein). Apoptosis was quantified by flow cytometry. SC236 0-75 microM decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC236, concentrations >75 microM reduced Cox-2 protein expression in HT29 cells and induced greater levels of apoptosis in HT29 than in HCT116 cells. In contrast, sulindac sulfide (SSD) (which inhibits Cox-1 and Cox-2) 0-200 microM or sulindac sulfone (SSN) 0-500 microM (without significant activity against Cox-1 or Cox-2) caused identical decreases in cell number and increases in apoptosis in HT29 and HCT116 cells. Neither SSD nor SSN altered the expression of Cox-2 in HT29 cells. To determine that the higher levels of apoptosis in HT29 cells with SC236 >75 microM were related to decreased Cox-2 protein levels, we decreased Cox-2 protein expression in HT29 cells with curcumin (diferuloylmethane) and studied its effect on SC236-induced apoptosis. Curcumin augmented apoptosis induced by SC236 in HT29 cells but not in Cox-2 lacking HCT116 cells. In conclusion, selective Cox-2 inhibitors can induce apoptosis independent of Cox-2 expression. However they may selectively target cells that express Cox-2 by decreasing their Cox-2 protein expression. PMID:14739610

  19. Nested Reachability Approximation for Discrete-Time Markov Chains with Univariate Parameters

    E-print Network

    Stephan, Frank

    Nested Reachability Approximation for Discrete-Time Markov Chains with Univariate Parameters Guoxin (PMCs), and probabilistic reachability properties with nested PCTL probabilistic operators. In particular, for reachability functions involving only single- nested probabilistic operators, we provide

  20. Censored Regression Trend Analyses for Ambient Water Quality Data

    E-print Network

    Smyth, Gordon K.

    Censored Regression Trend Analyses for Ambient Water Quality Data Gordon K. Smyth 1 , Melanie Cox 2 environments requires an understanding of the im- pacts on water quality and an understanding of the e#11;ectiveness of man- agement actions. Monitoring programs to assess water quality typically aim to assess

  1. 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.…

  2. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products

    PubMed Central

    Félétou, Michel; Huang, Yu; Vanhoutte, Paul M

    2011-01-01

    Endothelium-dependent contractions contribute to endothelial dysfunction in various animal models of aging, diabetes and cardiovascular diseases. In the spontaneously hypertensive rat, the archetypal model for endothelium-dependent contractions, the production of the endothelium-derived contractile factors (EDCF) involves an increase in endothelial intracellular calcium concentration, the production of reactive oxygen species, the predominant activation of cyclooxygenase-1 (COX-1) and to a lesser extent that of COX-2, the diffusion of EDCF towards the smooth muscle cells and the subsequent stimulation of their thromboxane A2-endoperoxide TP receptors. Endothelium-dependent contractions are also observed in various models of hypertension, aging and diabetes. They generally also involve the generation of COX-1- and/or COX-2-derived products and the activation of smooth muscle TP receptors. Depending on the model, thromboxane A2, PGH2, PGF2?, PGE2 and paradoxically PGI2 can all act as EDCFs. In human, the production of COX-derived EDCF is a characteristic of the aging and diseased blood vessels, with essential hypertension causing an earlier onset and an acceleration of this endothelial dysfunction. As it has been observed in animal models, COX-1, COX-2 or both isoforms can contribute to these endothelial dysfunctions. Since in most cases, the activation of TP receptors is the common downstream effector, selective antagonists of this receptor should curtail endothelial dysfunction and be of therapeutic interest in the treatment of cardiovascular disorders. LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3 PMID:21323907

  3. COX-2 Expression and Survival in Patients with Locally Advanced Cervical Cancer Treated with Chemoradiotherapy and Celecoxib: A Quantitative Immunohistochemical Analysis of RTOG C0128

    PubMed Central

    Doll, Corinne M; Winter, Kathryn; Gaffney, David K; Ryu, Janice K; Jhingran, Anuja; Dicker, Adam P; Weidhaas, Joanne B; Miller, Brigitte E; Magliocco, Anthony M

    2015-01-01

    Purpose To measure expression of COX-2 and CD34 in pre-treatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry (IHC), with clinical outcome parameters. Methods and Materials Pre-treatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative IHC (AQUA®). Cox regression models and Fisher's exact test were used to explore associations between expression of the biomarkers and clinical endpoints. Results 84 patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data was available, 6 of 37 (16%) patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA® score median [HR=0.39; 95%CI= (0.07, 2.16); p=0.28]. Of the 8 patients with DFS failures, 5 had tumors with COX-2 levels below the median [HR=0.49; 95%CI= (0.12, 2.04); p=0.32]. The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher's p=0.046). There was no statistically significant association between CD34 status and clinical outcome. Conclusions Low COX-2 expression measured by AQUA® was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA® technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer. PMID:23221733

  4. Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation

    SciTech Connect

    Colleselli, Daniela; Bijuklic, Klaudija; Mosheimer, Birgit A.; Kaehler, Christian M. . E-mail: C.M.Kaehler@uibk.ac.at

    2006-09-10

    Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in the pathogenesis of inflammatory disorders and various types of cancer. Endothelial progenitor cells recruited from the bone marrow have been shown to be involved in the formation of new vessels in malignancies and discussed for being a key point in tumour progression and metastasis. However, until now, nothing is known about an interaction between COX and endothelial progenitor cells (EPC). Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were analysed by MTT test and FACS analysis. Further analyses revealed an implication of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2 inhibition leads to a significant reduction in proliferation of endothelial progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2 inhibition leads further to an increased cleavage of caspase-3 protein and inversely to inhibition of Akt activation. Highly proliferating endothelial progenitor cells can be targeted by selective COX-2 inhibition in vitro. These results indicate that upcoming therapy strategies in cancer patients targeting COX-2 may be effective in inhibiting tumour vasculogenesis as well as angiogenic processes.

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

    PubMed Central

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

    2009-01-01

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

  6. 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 regression (2) Generalization to choquistic regression (3) First experimental results 2 #12;Logistic

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Moses, Tim; Holland, Paul W.

    2009-01-01

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

  9. Epileptic Seizure Prediction based on Ratio and Differential Linear Univariate Features

    PubMed Central

    Rasekhi, Jalil; Mollaei, Mohammad Reza Karami; Bandarabadi, Mojtaba; Teixeira, César A.; Dourado, António

    2015-01-01

    Bivariate features, obtained from multichannel electroencephalogram recordings, quantify the relation between different brain regions. Studies based on bivariate features have shown optimistic results for tackling epileptic seizure prediction problem in patients suffering from refractory epilepsy. A new bivariate approach using univariate features is proposed here. Differences and ratios of 22 linear univariate features were calculated using pairwise combination of 6 electroencephalograms channels, to create 330 differential, and 330 relative features. The feature subsets were classified using support vector machines separately, as one of the two classes of preictal and nonpreictal. Furthermore, minimum Redundancy Maximum Relevance feature reduction method is employed to improve the predictions and reduce the number of false alarms. The studies were carried out on features obtained from 10 patients. For reduced subset of 30 features and using differential approach, the seizures were on average predicted in 60.9% of the cases (28 out of 46 in 737.9 h of test data), with a low false prediction rate of 0.11 h?1. Results of bivariate approaches were compared with those achieved from original linear univariate features, extracted from 6 channels. The advantage of proposed bivariate features is the smaller number of false predictions in comparison to the original 22 univariate features. In addition, reduction in feature dimension could provide a less complex and the more cost-effective algorithm. Results indicate that applying machine learning methods on a multidimensional feature space resulting from relative/differential pairwise combination of 22 univariate features could predict seizure onsets with high performance. PMID:25709936

  10. Box-Cox Transformation and Random Regression Models for Fecal Egg Count Data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. Sometimes these phenotypes are measured several times over the life of the animal, so called longitudinal data. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematode...

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

    E-print Network

    Wolfe, Patrick J.

    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

  12. Worth the Weight: Using Inverse Probability Weighted Cox Models in AIDS Research

    PubMed Central

    Buchanan, Ashley L.; Cole, Stephen R.; Lau, Bryan; Adimora, Adaora A.

    2014-01-01

    Abstract In an observational study with a time-to-event outcome, the standard analytical approach is the Cox proportional hazards regression model. As an alternative to the standard Cox model, in this article we present a method that uses inverse probability (IP) weights to estimate the effect of a baseline exposure on a time-to-event outcome. IP weighting can be used to adjust for multiple measured confounders of a baseline exposure in order to estimate marginal effects, which compare the distribution of outcomes when the entire population is exposed versus when the entire population is unexposed. For example, IP-weighted Cox models allow for estimation of the marginal hazard ratio and marginal survival curves. IP weights can also be employed to adjust for selection bias due to loss to follow-up. This approach is illustrated using an example that estimates the effect of injection drug use on time until AIDS or death among HIV-infected women. PMID:25183195

  13. An approach to the estimation of growth standards: the univariate case.

    PubMed

    Fryer, J G; Karlberg, J; Hayes, M

    1989-01-01

    This paper shows how reference values can be determined when the underlying characteristic (say, weight) follows a distribution that is not too distant from the Gaussian. Application of the normalizing Box-Cox power transformation is the basis of our approach. This transformation is monotonic and hence invertible, so offering the choice of two scales of measurement on which to work--the original and the Gaussian. Modified versions of the procedure are provided allowing use of the basic transformation in the presence of certain deficiencies in the data, principally measurement error and misclassification. It is shown that application of Box-Cox to a cohort at several points in time can be quite revealing. When the data are already symmetrical the Box-Cox transformation has no effect: in this case the John-Draper modulus transformation and modifications of it are shown to be helpful. All of this is illustrated by using data from the Swedish Longitudinal Growth Study. PMID:2801103

  14. 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.

  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. 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.

  17. NCCS Regression Test Harness

    SciTech Connect

    2015-09-09

    The NCCS Regression Test Harness is a software package that provides a framework to perform regression and acceptance testing on NCCS High Performance Computers. The package is written in Python and has only the dependency of a Subversion repository to store the regression tests.

  18. Projection pursuit regression

    SciTech Connect

    Friedman, J.H.; Jacobson, M.; Stuetzle, W.

    1980-02-01

    A new method for nonparametric multiple regression is presented. The procedure models the regression surface as a sum of general smooth functions of linear combinations of the predictor variables in an iterative manner. This procedure is more general than standard stepwise and stagewise regression procedures, is affine invariant, does not require the definition of a metric, and lends itself to graphical interpretation. 3 figures.

  19. Projection pursuit regression

    SciTech Connect

    Friedman, J.H.; Stuetzle, W.

    1981-12-01

    A new method for nonparametric multiple regression is presented. The procedure models the regression surface as a sum of general smooth functions of linear combinations of the predictor variables in an iterative manner. It is more general than standard stepwise and stagewise regression procedures, does not require the definition of a metric in the predictor space, and lends itself to graphical interpretation.

  20. The pharmacology of selective inhibition of COX-2.

    PubMed

    Grosser, Tilo

    2006-10-01

    Selective inhibitors of cyclooxygenase (COX)-2 were developed to improve the safety of anti-inflammatory therapy in patients at elevated risk for gastrointestinal complications which are thought to be caused primarily by depression of COX-1 derived mucosal prostanoids. They were not expected to be more efficacious analgesics than compounds acting on both cyclooxygenases, the traditional (t) non-steroidal antiinflammatory drugs (NSAIDs). While these predictions were generally supported by clinical evidence, an elevated rate of severe cardiovascular complications was observed in randomized controlled trials of three chemically distinct COX-2 selective compounds. The cardiovascular hazard is plausibly explained by the depression of COX-2 dependent prostanoids formed in vasculature and kidney; vascular prostacyclin (PGI2) constrains the effect of prothrombotic and atherogenic stimuli, and renal medullary prostacyclin and prostaglandin (PG) E(2) formed by COX-2 contribute to arterial pressure homeostasis. A drug development strategy more closely linking research into the biology of the drug target with clinical drug development may have allowed earlier recognition of these mechanisms and the cardiovascular risk of COX-2 inhibition. Open questions are i) whether the gastrointestinal benefit of COX-2 selective compounds drugs can be conserved by identifying individuals at risk and excluding them from treatment; ii) whether the risk extends to tNSAIDs; iii) and whether alternative strategies to anti-inflammatory therapy with a more advantageous risk-benefit profile can be developed. PMID:17003913

  1. Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity.

    PubMed

    Lazer, E S; Miao, C K; Cywin, C L; Sorcek, R; Wong, H C; Meng, Z; Potocki, I; Hoermann, M; Snow, R J; Tschantz, M A; Kelly, T A; McNeil, D W; Coutts, S J; Churchill, L; Graham, A G; David, E; Grob, P M; Engel, W; Meier, H; Trummlitz, G

    1997-03-14

    Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothizines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5. PMID:9083488

  2. 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

  3. COX-2 selective nonsteroidal anti-inflammatory drugs: current status.

    PubMed

    Mahajan, A; Sharma, Rashmi

    2005-03-01

    Since, their introduction, COX (cyclooxygenase enzyme)-2 specific inhibitors have become a rapidly growing segment of the prescription drug market. Researchers have recently focused on the potentially lethal side effects associated with their. FDA has banned the use of nimesulide (hepatotoxic) in pediatric patients and rofecoxib (cardiovascular complications) in both adults and children. COX-2 inhibitors may decrease vascular prostacyclin production and may tip the balance in favour of prothrombotic eicosanoids (thromboxane A2) and lead to increased cardiovascular thrombotic events. COX-2 inhibitors can also result into increase blood pressure, macular eruptions, urticaria, pseudoporphyria, erythema multiforme, oedema, worsening of heart failure, fatal allergic vasculitis and aggravation of doxorubicin-mediated cardiac injury. The COX-2 enzyme is also involved in the development of many organ systems, and its inhibition may lead to various congenital defects in neonates. It has been reported that COX-2 inhibitors also interfere with implantation, hence their use should be avoided in sexually active women at risk of pregnancy. However, presently the choice of COX-2 selective inhibitors for a particular patient should be based upon their relative efficacy, toxicity, concomitant drug use, concurrent disease states, hepatic and renal function and relative cost. PMID:15926604

  4. COX-2 inhibitor reduces skeletal muscle hypertrophy in mice.

    PubMed

    Novak, Margaret L; Billich, William; Smith, Sierra M; Sukhija, Kunal B; McLoughlin, Thomas J; Hornberger, Troy A; Koh, Timothy J

    2009-04-01

    Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation. PMID:19176887

  5. 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...

  6. 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

  7. Evaluation dam overtopping risk based on univariate and bivariate flood frequency analysis

    NASA Astrophysics Data System (ADS)

    Goodarzi, E.; Mirzaei, M.; Shui, L. T.; Ziaei, M.

    2011-11-01

    There is a growing tendency to assess the safety levels of existing dams based on risk and uncertainty analysis using mathematical and statistical methods. This research presents the application of risk and uncertainty analysis to dam overtopping based on univariate and bivariate flood frequency analyses by applying Gumbel logistic distribution for the Doroudzan earth-fill dam in south of Iran. The bivariate frequency analysis resulted in six inflow hydrographs with a joint return period of 100-yr. The overtopping risks were computed for all of those hydrographs considering quantile of flood peak discharge (in particular 100-yr), initial depth of water in the reservoir, and discharge coefficient of spillway as uncertain variables. The maximum height of the water, as most important factor in the overtopping analysis, was evaluated using reservoir routing and the Monte Carlo and Latin hypercube techniques were applied for uncertainty analysis. Finally, the achieved results using both univariate and bivariate frequency analysis have been compared to show the significance of bivariate analyses on dam overtopping.

  8. 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.

  9. Automatic procedures for river reach delineation: Univariate and multivariate approaches in a fluvial context

    NASA Astrophysics Data System (ADS)

    Martínez-Fernández, V.; Solana-Gutiérrez, J.; González del Tánago, M.; García de Jalón, D.

    2016-01-01

    Segmenting the continuum of rivers into homogeneous reaches is an important issue in river research and management. Automatic procedures provide significance, objectivity, and repeatability. Although univariate techniques are frequently used to identify river reaches, multivariate approaches offer a more integrative context. Three nonparametric methods (multi-response permutation procedures (MRPP) with an advance in the significance level estimation, the Pettitt and Mann-Kendall tests) are applied for segmenting the river based on three geomorphic variables (valley width, active channel width, and channel slope) systematically measured in a GIS environment. The cited techniques have been applied to the Curueño River (NW Spain) to illustrate the methods, we analyse reach distribution along the river longitudinal profile. The methods successfully characterize the evident transitions along fluvial systems and also others less noticeable. The three methods provide more reaches according to valley width and less reaches according to channel slope (18.0 and 3.7 reaches on average, respectively). In contrast to the Mann-Kendall test, MRPP and Pettitt tests provide more stable segmentations when significance level varies. However, the Pettitt test provides irregular segmentations for regular patterns. The MRPP both univariate and multivariate applications enables a wider scope for the segmentation issue, which is useful in diverse aspects of fluvial domain.

  10. Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models.

    PubMed

    Zucknick, Manuela; Saadati, Maral; Benner, Axel

    2015-11-01

    One important task in translational cancer research is the search for new prognostic biomarkers to improve survival prognosis for patients. The use of high-throughput technologies allows simultaneous measurement of genome-wide gene expression or other genomic data for all patients in a clinical trial. Penalized likelihood methods such as lasso regression can be applied to such high-dimensional data, where the number of (genomic) covariables is usually much larger than the sample size. There is a connection between the lasso and the Bayesian regression model with independent Laplace priors on the regression parameters, and understanding this connection has been useful for understanding the properties of lasso estimates in linear models (e.g. Park and Casella, ). In this paper, we study the lasso in the frequentist and Bayesian frameworks in the context of Cox models. For the Bayesian lasso we extend the approach by Lee et al. (). In particular, we impose the lasso penalty only on the genome features, but not on relevant clinical covariates, to allow the mandatory inclusion of important established factors. We investigate the models in high- and low-dimensional simulation settings and in an application to chronic lymphocytic leukemia. PMID:26417963

  11. In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

    PubMed

    Ramírez-Cisneros, M Ángeles; Rios, María Yolanda; Aguilar-Guadarrama, A Berenice; Rao, Praveen P N; Aburto-Amar, Rola; Rodríguez-López, Verónica

    2015-10-15

    A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0±0.6%) and COX-2 (80.8±4.0%) inhibition at 10?M. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition. PMID:26351040

  12. Failure time regression with continuous informative auxiliary covariates

    PubMed Central

    Ghosh, Lipika; Jiang, Jiancheng; Sun, Yanqing; Zhou, Haibo

    2015-01-01

    In this paper we use Cox’s regression model to fit failure time data with continuous informative auxiliary variables in the presence of a validation subsample. We first estimate the induced relative risk function by kernel smoothing based on the validation subsample, and then improve the estimation by utilizing the information on the incomplete observations from non-validation subsample and the auxiliary observations from the primary sample. Asymptotic normality of the proposed estimator is derived. The proposed method allows one to robustly model the failure time data with an informative multivariate auxiliary covariate. Comparison of the proposed approach with several existing methods is made via simulations. Two real datasets are analyzed to illustrate the proposed method.

  13. Myoglobinuria and COX deficiency in a patient taking cerivastatin and gemfibrozil.

    PubMed

    Arenas, J; Fernández-Moreno, M A; Molina, J A; Fernández, V; del Hoyo, P; Campos, Y; Calvo, P; Martín, M A; García, A; Moreno, T; Martínez-Salio, A; Börnstein, B; Bermejo, F; Cabello, A; Garesse, R

    2003-01-14

    The authors describe a patient who presented with myoglobinuria after starting cerivastatin-gemfibrozil therapy. Muscle histochemistry revealed ragged-red fibers and cytochrome c oxidase negative (COX) fibers, and biochemistry showed a defect of COX activity. Immunoblot analysis showed a 60% reduction of COX I and COX II polypeptides. Cerivastatin myotoxicity might be related to a depletion of essential metabolites needed to anchor COX subunit I to mitochondrial membrane. PMID:12525734

  14. Investigating univariate temporal patterns for intrinsic connectivity networks based on complexity and low-frequency oscillation: a test-retest reliability study.

    PubMed

    Wang, X; Jiao, Y; Tang, T; Wang, H; Lu, Z

    2013-12-19

    Intrinsic connectivity networks (ICNs) are composed of spatial components and time courses. The spatial components of ICNs were discovered with moderate-to-high reliability. So far as we know, few studies focused on the reliability of the temporal patterns for ICNs based their individual time courses. The goals of this study were twofold: to investigate the test-retest reliability of temporal patterns for ICNs, and to analyze these informative univariate metrics. Additionally, a correlation analysis was performed to enhance interpretability. Our study included three datasets: (a) short- and long-term scans, (b) multi-band echo-planar imaging (mEPI), and (c) eyes open or closed. Using dual regression, we obtained the time courses of ICNs for each subject. To produce temporal patterns for ICNs, we applied two categories of univariate metrics: network-wise complexity and network-wise low-frequency oscillation. Furthermore, we validated the test-retest reliability for each metric. The network-wise temporal patterns for most ICNs (especially for default mode network, DMN) exhibited moderate-to-high reliability and reproducibility under different scan conditions. Network-wise complexity for DMN exhibited fair reliability (ICC<0.5) based on eyes-closed sessions. Specially, our results supported that mEPI could be a useful method with high reliability and reproducibility. In addition, these temporal patterns were with physiological meanings, and certain temporal patterns were correlated to the node strength of the corresponding ICN. Overall, network-wise temporal patterns of ICNs were reliable and informative and could be complementary to spatial patterns of ICNs for further study. PMID:24042040

  15. 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.

  16. 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.

  17. Redox-regulated dynamic interplay between Cox19 and the copper-binding protein Cox11 in the intermembrane space of mitochondria facilitates biogenesis of cytochrome c oxidase

    PubMed Central

    Bode, Manuela; Woellhaf, Michael W.; Bohnert, Maria; van der Laan, Martin; Sommer, Frederik; Jung, Martin; Zimmermann, Richard; Schroda, Michael; Herrmann, Johannes M.

    2015-01-01

    Members of the twin Cx9C protein family constitute the largest group of proteins in the intermembrane space (IMS) of mitochondria. Despite their conserved nature and their essential role in the biogenesis of the respiratory chain, the molecular function of twin Cx9C proteins is largely unknown. We performed a SILAC-based quantitative proteomic analysis to identify interaction partners of the conserved twin Cx9C protein Cox19. We found that Cox19 interacts in a dynamic manner with Cox11, a copper transfer protein that facilitates metalation of the Cu(B) center of subunit 1 of cytochrome c oxidase. The interaction with Cox11 is critical for the stable accumulation of Cox19 in mitochondria. Cox19 consists of a helical hairpin structure that forms a hydrophobic surface characterized by two highly conserved tyrosine-leucine dipeptides. These residues are essential for Cox19 function and its specific binding to a cysteine-containing sequence in Cox11. Our observations suggest that an oxidative modification of this cysteine residue of Cox11 stimulates Cox19 binding, pointing to a redox-regulated interplay of Cox19 and Cox11 that is critical for copper transfer in the IMS and thus for biogenesis of cytochrome c oxidase. PMID:25926683

  18. George: Gaussian Process regression

    NASA Astrophysics Data System (ADS)

    Foreman-Mackey, Dan

    2015-11-01

    George is a fast and flexible library, implemented in C++ with Python bindings, for Gaussian Process regression useful for accounting for correlated noise in astronomical datasets, including those for transiting exoplanet discovery and characterization and stellar population modeling.

  19. Detection of biomarkers for Hepatocellular Carcinoma using a hybrid univariate gene selection methods

    PubMed Central

    2012-01-01

    Background Discovering new biomarkers has a great role in improving early diagnosis of Hepatocellular carcinoma (HCC). The experimental determination of biomarkers needs a lot of time and money. This motivates this work to use in-silico prediction of biomarkers to reduce the number of experiments required for detecting new ones. This is achieved by extracting the most representative genes in microarrays of HCC. Results In this work, we provide a method for extracting the differential expressed genes, up regulated ones, that can be considered candidate biomarkers in high throughput microarrays of HCC. We examine the power of several gene selection methods (such as Pearson’s correlation coefficient, Cosine coefficient, Euclidean distance, Mutual information and Entropy with different estimators) in selecting informative genes. A biological interpretation of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and Integrated Discovery) databases. The top ten genes selected using Pearson’s correlation coefficient and Cosine coefficient contained six genes that have been implicated in cancer (often multiple cancers) genesis in previous studies. A fewer number of genes were obtained by the other methods (4 genes using Mutual information, 3genes using Euclidean distance and only one gene using Entropy). A better result was obtained by the utilization of a hybrid approach based on intersecting the highly ranked genes in the output of all investigated methods. This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in different types of cancer) in the top ten genes of the list of intersected genes. Conclusions To strengthen the effectiveness of the univariate selection methods, we propose a hybrid approach by intersecting several of these methods in a cascaded manner. This approach surpasses all of univariate selection methods when used individually according to biological interpretation and the examination of gene expression signal profiles. PMID:22867264

  20. Cox methodology applied to interlaboratory comparison program for flow measurement

    NASA Astrophysics Data System (ADS)

    Taira, N. M.; Yoshida, O. S.; Avelino, M. R.

    2015-10-01

    This paper presents an application of the methodology developed by Cox in Interlaboratory Comparison on water flow measurement. As no reference laboratory wouldn't be chosen, the comparison was carried out using a reference value by consensus estimated from measurements reported by participating laboratories.

  1. On nonsingular potentials of Cox-Thompson inversion scheme

    SciTech Connect

    Palmai, Tamas; Apagyi, Barnabas

    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.

  2. Natural information measures in Cox' approach for contextual probabilistic theories

    E-print Network

    F. Holik; A. Plastino; M. Sáenz

    2015-09-30

    In this article we provide, from a novel perspective, arguments that support the idea that, in the wake of Cox' approach to probability theory, von Neumann's entropy should be the natural one in Quantum Mechanics. We also generalize the pertinent reasoning to more general orthomodular lattices, which reveals the structure of a general non-Boolean information theory.

  3. Principles of Statistical Inference Nancy Reid and David Cox

    E-print Network

    Reid, Nancy

    structure must be continually tested against new applications Principles of Statistical Inference Reid & Cox of statistical work Equally important are aspects of study design types of measurement formulation of research of the challenges of statistical work We must also consider study design various aspects of measurement formulation

  4. Cox Models Survival Analysis Based on Breast Cancer Treatments

    PubMed Central

    Abadi, Alireza; Yavari, Parvin; Dehghani-Arani, Monireh; Alavi-Majd, Hamid; Ghasemi, Erfan; Amanpour, Farzaneh; Bajdik, Chris

    2014-01-01

    Background The aim of this study is to evaluate the association between different treatments and survival time of breast cancer patients using either standard Cox model or stratified Cox model. Methods The study was conducted on 15830 women diagnosed with breast cancer in British Columbia, Canada. They were divided into eight groups according to patients’ ages and stage of disease Either Cox’s PH model or stratified Cox model was fitted to each group according to the PH assumption and tested using Schoenfeld residuals. Results The data show that in the group of patients under age 50 years old and over age 50 with stage I cancer, the highest hazard was related to radiotherapy (HR= 3.15, CI: 1.85-5.35) and chemotherapy (HR= 3, CI: 2.29- 3.93) respectively. For both groups of patients with stage II cancer, the highest risk was related to radiotherapy (HR=3.02, CI: 2.26-4.03) (HR=2.16, CI:1.85-2.52). For both groups of patients with stage III cancer, the highest risk was for surgery (HR=0.49, CI: 0.33-0.73), (HR=0.45, CI: 0.36-0.57). For patients of age 50 years or less with stage IV cancer, none of the treatments were statistically significant. In group of patients over age 50 years old with stage IV cancer, the highest hazard was related to surgery (HR=0.64, CI: 0.53-0.78). Conclusion The results of this study show that for patients with stage I and II breast cancer, radiotherapy and chemotherapy had the highest hazard; for patients with stage III and IV breast cancer, the highest hazard was associated with treatment surgery. PMID:25250162

  5. Sequential Nonparametric Regression

    E-print Network

    Gu, Haijie

    2012-01-01

    We present algorithms for nonparametric regression in settings where the data are obtained sequentially. While traditional estimators select bandwidths that depend upon the sample size, for sequential data the effective sample size is dynamically changing. We propose a linear time algorithm that adjusts the bandwidth for each new data point, and show that the estimator achieves the optimal minimax rate of convergence. We also propose the use of online expert mixing algorithms to adapt to unknown smoothness of the regression function. We provide simulations that confirm the theoretical results, and demonstrate the effectiveness of the methods.

  6. 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.

  7. Risk Factors of Graft Survival After Diagnosis of Post-kidney Transplant Malignancy: Using Cox Proportional Hazard Model

    PubMed Central

    Rahimi Foroushani, Abbas; Salesi, Mahmoud; Rostami, Zohreh; Mehrazmay, Ali Reza; Mohammadi, Jamile; Einollahi, Behzad; Eshraghian, Mohammad Reza

    2015-01-01

    Background: All recipients of kidney transplantation, especially those with posttransplant malignancy, are at risk of long-term graft failure. Objectives: The purpose of our study was to evaluate the risk factors associated with graft survival after diagnosis of malignancy. Patients and Methods: To reach this purpose, we conducted a historical cohort study in Iran and 266 cases with posttransplant malignancy were followed up from diagnosis of malignancy until long-term graft loss or the date of last visit. These patients were taken as a census from 16 Transplant Centers in Iran during 22 years follow-up period since October 1984 to December 2008. A Cox proportional hazards model was performed to determine the important independent predictors of graft survival after malignancy. Results: At the end of the study, long-term graft failure was seen in 27 (10.2%) cases. One-year and 2-year graft survival after diagnosis of cancer were 93.6% and 91.7%, respectively. The univariate analysis showed that the incidence of chronic graft loss was significantly higher in male patients with solid cancers, withdrawal of immunosuppressant regimen, no response to treatment, and tumor metastasis. In continuation, the Cox model indicated that the significant risk factors associated with graft survival were type of cancer (P < 0.0001), response to treatment (P < 0.0001, HR = 0.14, 95% CI: 0.06 - 0.32), metastasis (P < 0.0001, HR = 5.68, 95% CI: 2.24 - 14.42), and treatment modality (P = 0.0001). Conclusions: By controlling the modifiable risk factors and modality of treatment in our study, physicians can reach more effective treatment.

  8. The Arabidopsis COX11 Homolog is Essential for Cytochrome c Oxidase Activity

    PubMed Central

    Radin, Ivan; Mansilla, Natanael; Rödel, Gerhard; Steinebrunner, Iris

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  10. Applications of multivariate modeling to neuroimaging group analysis: a comprehensive alternative to univariate general linear model.

    PubMed

    Chen, Gang; Adleman, Nancy E; Saad, Ziad S; Leibenluft, Ellen; Cox, Robert W

    2014-10-01

    All neuroimaging packages can handle group analysis with t-tests or general linear modeling (GLM). However, they are quite hamstrung when there are multiple within-subject factors or when quantitative covariates are involved in the presence of a within-subject factor. In addition, sphericity is typically assumed for the variance-covariance structure when there are more than two levels in a within-subject factor. To overcome such limitations in the traditional AN(C)OVA and GLM, we adopt a multivariate modeling (MVM) approach to analyzing neuroimaging data at the group level with the following advantages: a) there is no limit on the number of factors as long as sample sizes are deemed appropriate; b) quantitative covariates can be analyzed together with within-subject factors; c) when a within-subject factor is involved, three testing methodologies are provided: traditional univariate testing (UVT) with sphericity assumption (UVT-UC) and with correction when the assumption is violated (UVT-SC), and within-subject multivariate testing (MVT-WS); d) to correct for sphericity violation at the voxel level, we propose a hybrid testing (HT) approach that achieves equal or higher power via combining traditional sphericity correction methods (Greenhouse-Geisser and Huynh-Feldt) with MVT-WS. To validate the MVM methodology, we performed simulations to assess the controllability for false positives and power achievement. A real FMRI dataset was analyzed to demonstrate the capability of the MVM approach. The methodology has been implemented into an open source program 3dMVM in AFNI, and all the statistical tests can be performed through symbolic coding with variable names instead of the tedious process of dummy coding. Our data indicates that the severity of sphericity violation varies substantially across brain regions. The differences among various modeling methodologies were addressed through direct comparisons between the MVM approach and some of the GLM implementations in the field, and the following two issues were raised: a) the improper formulation of test statistics in some univariate GLM implementations when a within-subject factor is involved in a data structure with two or more factors, and b) the unjustified presumption of uniform sphericity violation and the practice of estimating the variance-covariance structure through pooling across brain regions. PMID:24954281

  11. 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

  12. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

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

  13. Introduction Linear Regression

    E-print Network

    Lega, Joceline

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

  14. Partial covariate adjusted regression.

    PubMed

    Sentürk, Damla; Nguyen, Danh V

    2009-02-01

    Covariate adjusted regression (CAR) is a recently proposed adjustment method for regression analysis where both the response and predictors are not directly observed (?entürk and Müller, 2005). The available data has been distorted by unknown functions of an observable confounding covariate. CAR provides consistent estimators for the coefficients of the regression between the variables of interest, adjusted for the confounder. We develop a broader class of partial covariate adjusted regression (PCAR) models to accommodate both distorted and undistorted (adjusted/unadjusted) predictors. The PCAR model allows for unadjusted predictors, such as age, gender and demographic variables, which are common in the analysis of biomedical and epidemiological data. The available estimation and inference procedures for CAR are shown to be invalid for the proposed PCAR model. We propose new estimators and develop new inference tools for the more general PCAR setting. In particular, we establish the asymptotic normality of the proposed estimators and propose consistent estimators of their asymptotic variances. Finite sample properties of the proposed estimators are investigated using simulation studies and the method is also illustrated with a Pima Indians diabetes data set. PMID:20126296

  15. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

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

  16. Local Modal Regression.

    PubMed

    Yao, Weixin; Lindsay, Bruce G; Li, Runze

    2012-01-01

    A local modal estimation procedure is proposed for the regression function in a non-parametric regression model. A distinguishing characteristic of the proposed procedure is that it introduces an additional tuning parameter that is automatically selected using the observed data in order to achieve both robustness and efficiency of the resulting estimate. We demonstrate both theoretically and empirically that the resulting estimator is more efficient than the ordinary local polynomial regression estimator in the presence of outliers or heavy tail error distribution (such as t-distribution). Furthermore, we show that the proposed procedure is as asymptotically efficient as the local polynomial regression estimator when there are no outliers and the error distribution is a Gaussian distribution. We propose an EM type algorithm for the proposed estimation procedure. A Monte Carlo simulation study is conducted to examine the finite sample performance of the proposed method. The simulation results confirm the theoretical findings. The proposed methodology is further illustrated via an analysis of a real data example. PMID:23049230

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

    PubMed

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

    2015-07-01

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

  18. Applications of multivariate modeling to neuroimaging group analysis: A comprehensive alternative to univariate general linear model

    PubMed Central

    Chen, Gang; Adleman, Nancy E.; Saad, Ziad S.; Leibenluft, Ellen; Cox, RobertW.

    2014-01-01

    All neuroimaging packages can handle group analysis with t-tests or general linear modeling (GLM). However, they are quite hamstrung when there are multiple within-subject factors or when quantitative covariates are involved in the presence of a within-subject factor. In addition, sphericity is typically assumed for the variance–covariance structure when there are more than two levels in a within-subject factor. To overcome such limitations in the traditional AN(C)OVA and GLM, we adopt a multivariate modeling (MVM) approach to analyzing neuroimaging data at the group level with the following advantages: a) there is no limit on the number of factors as long as sample sizes are deemed appropriate; b) quantitative covariates can be analyzed together with within- subject factors; c) when a within-subject factor is involved, three testing methodologies are provided: traditional univariate testing (UVT)with sphericity assumption (UVT-UC) and with correction when the assumption is violated (UVT-SC), and within-subject multivariate testing (MVT-WS); d) to correct for sphericity violation at the voxel level, we propose a hybrid testing (HT) approach that achieves equal or higher power via combining traditional sphericity correction methods (Greenhouse–Geisser and Huynh–Feldt) with MVT-WS. PMID:24954281

  19. 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

  20. 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 - Penalized Logistic Regression - October 7, 2002 2 #12;Linear vs. logistic regression · Task: Find a model

  1. 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…

  2. 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

  3. 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.

  4. Association Between COX-2 Polymorphisms and Lung Cancer Risk.

    PubMed

    Wang, Weiwei; Fan, Xinyun; Zhang, Yong; Yang, Yi; Yang, Siyuan; Li, Gaofeng

    2015-01-01

    BACKGROUND Multiple relevant risk factors for lung cancer have been reported in different populations, but results of previous studies were not consistent. Therefore, a meta-analysis is necessary to summarize these outcomes and reach a relatively comprehensive conclusion. MATERIAL AND METHODS STATA 12.0 software was used for all statistical of the relationship between COX-2 polymorphisms and lung cancer risk. Inter-study heterogeneity was examined with the Q statistic (significance level at P<0.1). The publication bias among studies in the meta-analysis was analyzed with Begg's funnel plot and Egger's test. Hardy-Weinberg equilibrium was tested in all controls of the studies. RESULTS COX-2 rs20417 polymorphism had a significant association with reduced risk of lung cancer under homozygous and recessive models, and similar results were observed in white and population-based subgroups under 2 and 3 contrasts, respectively. Additionally, rs2066826 polymorphism manifested a strong correlation with increased risk of lung cancer under 5 genetic models. CONCLUSIONS In COX-2 gene, rs20417 may have a certain relationship with reduced risk of lung cancer, while rs2066826 may increase the risk of lung cancer. PMID:26624903

  5. Association Between COX-2 Polymorphisms and Lung Cancer Risk

    PubMed Central

    Wang, Weiwei; Fan, Xinyun; Zhang, Yong; Yang, Yi; Yang, Siyuan; Li, Gaofeng

    2015-01-01

    Background Multiple relevant risk factors for lung cancer have been reported in different populations, but results of previous studies were not consistent. Therefore, a meta-analysis is necessary to summarize these outcomes and reach a relatively comprehensive conclusion. Material/Methods STATA 12.0 software was used for all statistical of the relationship between COX-2 polymorphisms and lung cancer risk. Inter-study heterogeneity was examined with the Q statistic (significance level at P<0.1). The publication bias among studies in the meta-analysis was analyzed with Begg’s funnel plot and Egger’s test. Hardy-Weinberg equilibrium was tested in all controls of the studies. Results COX-2 rs20417 polymorphism had a significant association with reduced risk of lung cancer under homozygous and recessive models, and similar results were observed in white and population-based subgroups under 2 and 3 contrasts, respectively. Additionally, rs2066826 polymorphism manifested a strong correlation with increased risk of lung cancer under 5 genetic models. Conclusions In COX-2 gene, rs20417 may have a certain relationship with reduced risk of lung cancer, while rs2066826 may increase the risk of lung cancer. PMID:26624903

  6. 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

  7. Univariate frontoparietal BOLD does not track the magnitude of attentional modulations in visual cortex.

    PubMed

    Smith, Mary; Sprague, Thomas; Serences, John

    2015-09-01

    Directing attention to a region of visual space facilitates the processing of relevant sensory information, resulting in increased neural and BOLD activity in areas of the brain that process this sensory information. This process is thought to be mediated by a frontoparietal "attentional control" network that biases processing in visual cortex. Electrical microstimulation of frontal area FEF in macaques selectively enhances responses in area V4, and also leads to improved behavior (Moore, Fallah 2001, 2004; Armstrong, Moore 2007). If frontoparietal regions such as the FEF are responsible for the differential modulations in early visual cortex across time, then the magnitude of frontoparietal activity should track the magnitude of attentional modulations in early visual cortex on a trial-by-trial basis. Here, we attempted to test this hypothesis using fMRI. Participants directed spatial attention to either the left or right visual field on each trial while performing a demanding spatial attention task. Consistent with previous data, we found that frontoparietal responses were high when early visual responses were high across trials (i.e. an overall yoking between frontoparietal and occipital regions). In addition, visual areas in the hemisphere contralateral to the attended stimulus showed reliably larger BOLD responses compared to areas in the ipsilateral hemisphere. We compared the magnitude of frontoparietal activity and the differential activity in visual areas contra and ipsilateral to the attended stimulus. However, we found no evidence that the overall magnitude of responses in frontoparietal regions track the magnitude of differential attentional responses in early visual cortex. These findings indicate that the univariate magnitude in frontoparietal ROIs is not related to the magnitude of attention effects in visual cortex, at least as measured with the BOLD signal. Meeting abstract presented at VSS 2015. PMID:26326739

  8. Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function

    PubMed Central

    Chen, Edward P.; Markosyan, Nune; Connolly, Emma; Lawson, John A.; Li, Xuanwen; Grant, Gregory R.; Grosser, Tilo; FitzGerald, Garret A.; Smyth, Emer M.

    2014-01-01

    Cyclooxygenase-2 (COX-2) expression is associated with poor prognosis across a range of human cancers, including breast cancer. The contribution of tumor cell-derived COX-2 to tumorigenesis has been examined in numerous studies; however, the role of stromal-derived COX-2 is ill-defined. Here, we examined how COX-2 in myeloid cells, an immune cell subset that includes macrophages, influences mammary tumor progression. In mice engineered to selectively lack myeloid cell COX-2 [myeloid-COX-2 knockout (KO) mice], spontaneous neu oncogene-induced tumor onset was delayed, tumor burden reduced, and tumor growth slowed compared with wild-type (WT). Similarly, growth of neu-transformed mammary tumor cells as orthotopic tumors in immune competent syngeneic myeloid-COX-2 KO host mice was reduced compared with WT. By flow cytometric analysis, orthotopic myeloid-COX-2 KO tumors had lower tumor-associated macrophage (TAM) infiltration consistent with impaired colony stimulating factor-1-dependent chemotaxis by COX-2 deficient macrophages in vitro. Further, in both spontaneous and orthotopic tumors, COX-2-deficient TAM displayed lower immunosuppressive M2 markers and this was coincident with less suppression of CD8+ cytotoxic T lymphocytes (CTLs) in myeloid-COX-2 KO tumors. These studies suggest that reduced tumor growth in myeloid-COX-2 KO mice resulted from disruption of M2-like TAM function, thereby enhancing T-cell survival and immune surveillance. Antibody-mediated depletion of CD8+, but not CD4+ cells, restored tumor growth in myeloid-COX-2 KO to WT levels, indicating that CD8+ CTLs are dominant antitumor effectors in myeloid-COX-2 KO mice. Our studies suggest that inhibition of myeloid cell COX-2 can potentiate CTL-mediated tumor cytotoxicity and may provide a novel therapeutic approach in breast cancer therapy. PMID:24590894

  9. Nonparametric regression in exponential families

    E-print Network

    Brown, Lawrence D; Zhou, Harrison H; 10.1214/09-AOS762

    2010-01-01

    Most results in nonparametric regression theory are developed only for the case of additive noise. In such a setting many smoothing techniques including wavelet thresholding methods have been developed and shown to be highly adaptive. In this paper we consider nonparametric regression in exponential families with the main focus on the natural exponential families with a quadratic variance function, which include, for example, Poisson regression, binomial regression and gamma regression. We propose a unified approach of using a mean-matching variance stabilizing transformation to turn the relatively complicated problem of nonparametric regression in exponential families into a standard homoscedastic Gaussian regression problem. Then in principle any good nonparametric Gaussian regression procedure can be applied to the transformed data. To illustrate our general methodology, in this paper we use wavelet block thresholding to construct the final estimators of the regression function. The procedures are easily i...

  10. caret: Classification and Regression Training

    NASA Astrophysics Data System (ADS)

    Kuhn, Max

    2015-05-01

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

  11. Logistic Regression Sargur N. Srihari

    E-print Network

    Logistic Regression Sargur N. Srihari University at Buffalo, State University of New York USA #12 2. Nonlinear basis funcs in linear classification 3. Logistic Regression ­ Two-class, Multi)/p(C2|x)] C. Derivative d/da=(1-) 2. Logistic Regression · Feature vector , two-classes C1 and C2

  12. COX-2 inhibition in schizophrenia and major depression.

    PubMed

    Müller, Norbert; Schwarz, Markus J

    2008-01-01

    In schizophrenia and depression, opposite patterns of type-1 - type-2 immune response seem to be associated with differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan - kynurenine metabolism resulting in increased production of kynurenic acid in schizophrenia and decreased production of kynurenic acid in depression. These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an overweight of N-methyl-D-aspartate (NMDA) agonism in depression and of NMDA antagonism in schizophrenia. The differential activation of microglia cells and astrocytes may be an additional mechanism contributing to this imbalance. The immunological imbalance results both in schizophrenia and in depression in an increased Prostaglandin E(2) (PGE(2)) production and probably also in an increased Cyclo-oxygenase-2 (COX-2) expression. Although there is strong evidence for the view, that the interactions of the immune system, IDO, the serotonergic system, and the glutamatergic neurotransmission play a key role in schizophrenia and in depression, several gaps, e.g. the roles of genetics, disease course, sex, different psychopathological states, etc. have to be bridged by intense further research. There are already hints that anti-inflammatory therapy may have beneficial effects in schizophrenia and major depression. COX-2 inhibititors have been tested in animal models of depression and in preliminary clinical trials, the latter showing favourable effects compared to placebo, both, in schizophrenia and in major depression. The effects of COX-2 inhibition in the central nervous system (CNS) as well as the different components of the inflammatory system, the kynurenine-metabolism and the glutamatergic neurotransmission, however, still need careful further validation including clinical studies with sufficient sample size. PMID:18537668

  13. Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.

    PubMed

    Cusan, Claudia; Spalluto, Giampiero; Prato, Maurizio; Adams, Michael; Bodensieck, Antje; Bauer, Rudolf; Tubaro, Aurelia; Bernardi, Paolo; Da Ros, Tatiana

    2005-01-01

    A new series of potential human 5-LOX inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 2) has been synthesized and the activity against COX-1, COX-2, and human 5-LOX enzymes has been evaluated. In contrast with literature data, we observed that phenidone resulted to be inactive against human 5-LOX, while retains its activity against cyclooxygenases in a micromolar range. The present results suggest that the substitution of the amino function at the 4-position is detrimental in terms of activity toward COX-1 and COX-2, while the presence of a double bond at the 4,5-position does not alter the biological profile against COX. The absence of activity vs. human 5-LOX strongly suggests a re-consideration of phenidone and its analogs as 5-LOX inhibitors in humans. PMID:15652362

  14. Revisiting the role of COX-2 inhibitor for non-small cell lung cancer

    PubMed Central

    Kanazawa, Kenya

    2015-01-01

    Accumulating preclinical and clinical studies have shown that cyclooxygenase-2 (COX-2) inhibitor has some efficacy for non-small cell lung cancer (NSCLC). However, two phase III clinical trials using COX-2 inhibitor in combination with platinum-based chemotherapy showed no survival benefit for “unselected” patients with advanced NSCLC. Thus, exploratory analyses of the association between biomarker and clinical outcome of NSCLC patients treated with COX-2 inhibitors have been warranted. A report by Edelman recently published in the Journal of Clinical Oncology demonstrated the results of a prospective randomized trial using a combination of chemotherapy (docetaxel or pemetrexed) and either COX-2 inhibitor or a placebo for patients with advanced NSCLC. The remarkable point of this study was that it adopted the eligible criteria requiring decreased urinary levels of prostaglandin E metabolite (PGE-M) after administration of COX-2 inhibitor in a run-in period, as a possible predictive marker for the COX-2 inhibitor. The primary endpoint was progression-free survival (PFS). However, no improvement in PFS was observed between the patients treated with COX-2 inhibitor and those with placebo. A number of efforts from various investigators, including this report, have failed to demonstrate the meaningful clinical effect of COX-2 inhibitor for NSCLC. Is COX-2 inhibitor useless anymore? Here, we address the “difficult” character of this COX-2 inhibitor from various viewpoints and discuss potential future strategy using this drug. PMID:26629442

  15. Characterization of the Cytochrome C Oxidase Assembly Factor Cox19 of 'Saccharomyces Cerevisiae'

    SciTech Connect

    Rigby, K.; Zhang, L.; Cobine, P.A.; George, G.N.; Winge, D.R.; /Utah U. /Saskatchewan U.

    2007-07-12

    Cox19 is an important accessory protein in the assembly of cytochrome c oxidase in yeast. The protein is functional when tethered to the mitochondrial inner membrane, suggesting its functional role within the intermembrane space. Cox19 resembles Cox17 in having a twin CX{sub 9}C sequence motif that adopts a helical hairpin in Cox17. The function of Cox17 appears to be a Cu(I) donor protein in the assembly of the copper centers in cytochrome c oxidase. Cox19 also resembles Cox17 in its ability to coordinate Cu(I). Recombinant Cox19 binds 1 mol eq of Cu(I) per monomer and exists as a dimeric protein. Cox19 isolated from the mitochondrial intermembrane space contains variable quantities of copper, suggesting that Cu(I) binding may be a transient property. Cysteinyl residues important for Cu(I) binding are also shown to be important for the in vivo function of Cox19. Thus, a correlation exists in the ability to bind Cu(I) and in vivo function.

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Otis, Jeffrey S.; Burkholder, Thomas J.; Pavlath, Grace K. . E-mail: gpavlat@emory.edu

    2005-11-01

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

  18. Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

    PubMed Central

    Wilson, Andrew J.; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md. Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D.; Pietenpol, Jennifer A.; Crispens, Marta A.; Marnett, Lawrence J.; Khabele, Dineo

    2015-01-01

    Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors. PMID:25972361

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  1. Ridge regression processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

    Current navigation requirements depend on a geometric dilution of precision (GDOP) criterion. As long as the GDOP stays below a specific value, navigation requirements are met. The GDOP will exceed the specified value when the measurement geometry becomes too collinear. A new signal processing technique, called Ridge Regression Processing, can reduce the effects of nearly collinear measurement geometry; thereby reducing the inflation of the measurement errors. It is shown that the Ridge signal processor gives a consistently better mean squared error (MSE) in position than the Ordinary Least Mean Squares (OLS) estimator. The applicability of this technique is currently being investigated to improve the following areas: receiver autonomous integrity monitoring (RAIM), coverage requirements, availability requirements, and precision approaches.

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

    PubMed Central

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

    1989-01-01

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

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

    PubMed Central

    Cornett, Ashley L.

    2014-01-01

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

  4. Exposure to diesel exhaust upregulates COX-2 expression in ApoE knockout mice

    PubMed Central

    Bai, Ni; Tranfield, Erin M.; Kavanagh, Terrance J.; Kaufman, Joel D.; Rosenfeld, Michael E.; van Eeden, Stephan F.

    2015-01-01

    Introduction We have shown that diesel exhaust (DE) inhalation caused progression of atherosclerosis; however, the mechanisms are not fully understood. We hypothesize that exposure to DE upregulates cyclooxygenase (COX) expression and activity, which could play a role in DE-induced atherosclerosis. Methods ApoE knockout mice (30-week old) fed with regular chow were exposed to DE (at 200 ?g/m3 of particulate matter) or filtered air (control) for 7 weeks (6 h/day, 5 days/week). The protein and mRNA expression of COX-1 and COX-2 were evaluated by immunohistochemistry analysis and quantitative real-time PCR, respectively. To examine COX activity, thoracic aortae were mounted in a wire myograph, and phenylephrine (PE)-stimulated vasoconstriction was measured with and without the presence of COX antagonists (indomethacin). COX-2 activity was further assessed by urine 2,3-dinor-6-keto PGF1? level, a major metabolite of prostacyclin I2 (PGI2). Results Immunohistochemistry analysis demonstrates that DE exposure enhanced COX-2 expression in both thoracic aorta (p < 0.01) and aortic root (p < 0.03), with no modification of COX-1 expression. The increased COX-2 expression was positively correlated with smooth muscle cell content in aortic lesions (R2 = 0.4081, p < 0.008). The fractional changes of maximal vasoconstriction in the presence of indomethacin was attenuated by 3-fold after DE exposure (p < 0.02). Urine 2,3-dinor-6-keto PGF1? level was 15-fold higher in DE group than the control (p < 0.007). The mRNA expression of COX-2 (p < 0.006) and PGI synthase (p < 0.02), but not COX-1, was significantly augmented after DE exposure. Conclusion We show that DE inhalation enhanced COX-2 expression, which is also associated with phenotypic changes of aortic lesion. PMID:22746401

  5. COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

    PubMed Central

    Timoshenko, A V; Chakraborty, C; Wagner, G F; Lala, P K

    2006-01-01

    Increased expression of COX-2 or VEGF-C has been correlated with progressive disease in certain cancers. Present study utilized several human breast cancer cell lines (MCF-7, T-47D, Hs578T and MDA-MB-231, varying in COX-2 expression) as well as 10 human breast cancer specimens to examine the roles of COX-2 and prostaglandin E (EP) receptors in VEGF-C expression or secretion, and the relationship of COX-2 or VEGF-C expression to lymphangiogenesis. We found a strong correlation between COX-2 mRNA expression and VEGF-C expression or secretion levels in breast cancer cell lines and VEGF-C expression in breast cancer tissues. Expression of LYVE-1, a selective marker for lymphatic endothelium, was also positively correlated with COX-2 or VEGF-C expression in breast cancer tissues. Inhibition of VEGF-C expression and secretion in the presence of COX-1/2 or COX-2 inhibitors or following downregulation of COX-2 with COX-2 siRNA established a stimulatory role COX-2 in VEGF-C synthesis by breast cancer cells. EP1 as well as EP4 receptor antagonists inhibited VEGF-C production indicating the roles of EP1 and EP4 in VEGF-C upregulation by endogenous PGE2. Finally, VEGF-C secretion by MDA-MB-231 cells was inhibited in the presence of kinase inhibitors for Her-2/neu, Src and p38 MAPK, indicating a requirement of these kinases for VEGF-C synthesis. These results, for the first time, demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby lymphangiogenesis) in human breast cancer, which is mediated at least in part by EP1/EP4 receptors. PMID:16570043

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

    SciTech Connect

    Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar; Jarlsfelt, Ingvar; Sun Xiaofeng . E-mail: xiao-feng.sun@ibk.liu.se

    2005-11-01

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

  7. 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.

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

    PubMed

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

    2010-10-01

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

  9. 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.

  10. Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

    ERIC Educational Resources Information Center

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

  11. Regression trees Summary of regression models so far

    E-print Network

    Reich, Brian J.

    of the tree is fit separately. · The tree essentially reduces the predictors into one categorical variable algorithms use both forward and backward steps. (4) Nonlinear regression - Part 4 Page 3 #12;MARS · Multivariate Adaptive Regression Splines (MARS) is a popular extension. · MARS shares features with both trees

  12. Additive Hazard Regression Models: An Application to the Natural History of Human Papillomavirus

    PubMed Central

    Xie, Xianhong; Strickler, Howard D.; Xue, Xiaonan

    2013-01-01

    There are several statistical methods for time-to-event analysis, among which is the Cox proportional hazards model that is most commonly used. However, when the absolute change in risk, instead of the risk ratio, is of primary interest or when the proportional hazard assumption for the Cox proportional hazards model is violated, an additive hazard regression model may be more appropriate. In this paper, we give an overview of this approach and then apply a semiparametric as well as a nonparametric additive model to a data set from a study of the natural history of human papillomavirus (HPV) in HIV-positive and HIV-negative women. The results from the semiparametric model indicated on average an additional 14 oncogenic HPV infections per 100 woman-years related to CD4 count < 200 relative to HIV-negative women, and those from the nonparametric additive model showed an additional 40 oncogenic HPV infections per 100 women over 5 years of followup, while the estimated hazard ratio in the Cox model was 3.82. Although the Cox model can provide a better understanding of the exposure disease association, the additive model is often more useful for public health planning and intervention. PMID:23424606

  13. 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

  14. Semiparametric Binary Regression Models under Shape Constraints

    E-print Network

    Banerjee, Moulinath

    , 2008)) on monotone binary regression models considered in a fully nonparametric setting. This paperSemiparametric Binary Regression Models under Shape Constraints Moulinath Banerjee 1 , Debasri Abstract We consider estimation of the regression function in a semiparametric binary regression model

  15. 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

  16. Estimating Regression Parameters in an Extended Proportional Odds Model

    PubMed Central

    Chen, Ying Qing; Hu, Nan; Cheng, Su-Chun; Musoke, Philippa; Zhao, Lue Ping

    2012-01-01

    The proportional odds model may serve as a useful alternative to the Cox proportional hazards model to study association between covariates and their survival functions in medical studies. In this article, we study an extended proportional odds model that incorporates the so-called “external” time-varying covariates. In the extended model, regression parameters have a direct interpretation of comparing survival functions, without specifying the baseline survival odds function. Semiparametric and maximum likelihood estimation procedures are proposed to estimate the extended model. Our methods are demonstrated by Monte-Carlo simulations, and applied to a landmark randomized clinical trial of a short course Nevirapine (NVP) for mother-to-child transmission (MTCT) of human immunodeficiency virus type-1 (HIV-1). Additional application includes analysis of the well-known Veterans Administration (VA) Lung Cancer Trial. PMID:22904583

  17. Reading Expectancy and Regression Formulas.

    ERIC Educational Resources Information Center

    Brown, Robert M.; Byrd, Carol C.

    To determine the most accurate means of estimating the expected grade or reading level of 61 sixth grade students, three expectancy formulas were compared to a custom regression equation from a user friendly microcomputer program. The expectancy formulas, based in part on student I.Q. and chronological age, and the regression equations were…

  18. Precision Efficacy Analysis for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.

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

  19. 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…

  20. 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…

  1. 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

  2. Suppressing the charged coupled device noise in univariate thin-layer videoscans: a comparison of several algorithms.

    PubMed

    Komsta, Lukasz

    2009-03-20

    The digital processing of chromatographic thin-layer plate images has increasing popularity among last years. When using a camera instead of flatbed scanner, the charged coupled device (CCD) noise is a well-known problem-especially when scanning dark plates with weakly fluorescing spots. Various techniques are proposed to denoise (smooth) univariate signals in chemometric processing, but the choice could be difficult. In the current paper the classical filters (Savitzky-Golay, adaptive degree polynomial filter, Fourier denoising, Butterworth and Chebyshev infinite impulse response filters) were compared with the wavelet shrinkage (31 mother wavelets, 3 thresholding techniques and 8 decomposition levels). The signal obtained from 256 averaged videoscans was treated as the reference signal (with noise naturally suppressed, which was found to be almost white one). The best choice for denoising was the Haar mother wavelet with soft denoising and any decomposition level larger than 1. Satisfying similarity to reference signal was also observed in the case of Butterworth filter, Savitzky-Golay smoothing, ADPF filter, Fourier denoising and soft-thresholded wavelet shrinkage with any mother wavelet and middle to high decomposition level. The Chebyshev filters, Whittaker smoother and wavelet shrinkage with hard thresholding were found to be less efficient. The results obtained can be used as general recommendations for univariate denoising of such signals. PMID:19187937

  3. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    PubMed

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1?)/COX-2 in invasive pathways in breast cancer. PMID:26193871

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

    PubMed

    Dennerlein, Sven; Rehling, Peter

    2015-03-01

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

  5. 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.

  6. Glutathione selectively modulates the binding of platinum drugs to human copper chaperone Cox17.

    PubMed

    Zhao, Linhong; Wang, Zhen; Wu, Han; Xi, Zhaoyong; Liu, Yangzhong

    2015-12-01

    The copper chaperone Cox17 (cytochrome c oxidase copper chaperone) has been shown to facilitate the delivery of cisplatin to mitochondria, which contributes to the overall cytotoxicity of the drug [Zhao et al. (2014) Chem. Commun. 50: , 2667-2669]. Kinetic data indicate that Cox17 has reactivity similar to glutathione (GSH), the most abundant thiol-rich molecule in the cytoplasm. In the present study, we found that GSH significantly modulates the reaction of platinum complexes with Cox17. GSH enhances the reactivity of three anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to Cox17, but suppresses the reaction of transplatin. Surprisingly, the pre-formed cisplatin-GSH adducts are highly reactive to Cox17; over 90% platinum transfers from GSH to Cox17. On the other hand, transplatin-GSH adducts are inert to Cox17. These different effects are consistent with the drug activity of these platinum complexes. In addition, GSH attenuates the protein aggregation of Cox17 induced by platination. These results indicate that the platinum-protein interactions could be substantially influenced by the cellular environment. PMID:26399480

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

    E-print Network

    Olmstead, Richard

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

  8. A novel iNOS and COX-2 inhibitor from the aerial parts of Rodgersia podophylla

    E-print Network

    Suh, Young-Ger

    Ltd. All rights reserved. Inducible nitric oxide synthase (iNOS) and cyclooxgen- ase-2 (COX-2 effects on protein expression of iNOS and COX-2 in vitro using Raw 246.7 cells. The air-dried aerial parts to fractionation using Sephadex LH-20, fol- lowed by silica gel column chromatography, and re- versed-phase HPLC

  9. Improving Your Data Transformations: Applying the Box-Cox Transformation

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2010-01-01

    Many of us in the social sciences deal with data that do not conform to assumptions of normality and/or homoscedasticity/homogeneity of variance. Some research has shown that parametric tests (e.g., multiple regression, ANOVA) can be robust to modest violations of these assumptions. Yet the reality is that almost all analyses (even nonparametric…

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

    PubMed Central

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

    2015-01-01

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

  11. Wnt/?-Catenin Signaling Enhances Cyclooxygenase-2 (COX2) Transcriptional Activity in Gastric Cancer Cells

    PubMed Central

    Nuñez, Felipe; Bravo, Soraya; Cruzat, Fernando; Montecino, Martín; De Ferrari, Giancarlo V.

    2011-01-01

    Background Increased expression of the cyclooxygenase-2 enzyme (COX2) is one of the main characteristics of gastric cancer (GC), which is a leading cause of death in the world, particularly in Asia and South America. Although the Wnt/?-catenin signaling pathway has been involved in the transcriptional activation of the COX2 gene, the precise mechanism modulating this response is still unknown. Methodology/Principal Findings Here we studied the transcriptional regulation of the COX2 gene in GC cell lines and assessed whether this phenomenon is modulated by Wnt/?-catenin signaling. We first examined the expression of COX2 mRNA in GC cells and found that there is a differential expression pattern consistent with high levels of nuclear-localized ?-catenin. Pharmacological treatment with either lithium or valproic acid and molecular induction with purified canonical Wnt3a significantly enhanced COX2 mRNA expression in a dose- and time-dependent manner. Serial deletion of a 1.6 Kbp COX2 promoter fragment and gain- or loss-of-function experiments allowed us to identify a minimal Wnt/?-catenin responsive region consisting of 0.8 Kbp of the COX2 promoter (pCOX2-0.8), which showed maximal response in gene-reporter assays. The activity of this pCOX2-0.8 promoter region was further confirmed by site-directed mutagenesis and DNA-protein binding assays. Conclusions/Significance We conclude that the pCOX2-0.8 minimal promoter contains a novel functional T-cell factor/lymphoid enhancer factor (TCF/LEF)-response element (TBE Site II; -689/-684) that responds directly to enhanced Wnt/?-catenin signaling and which may be important for the onset/progression of GC. PMID:21494638

  12. 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

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

    PubMed Central

    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

  14. Post-irradiation regression of choroidal melanomas as a risk factor for death from metastatic disease

    SciTech Connect

    Augsburger, J.J.; Gamel, J.W.; Shields, J.A.; Markoe, A.M.; Brady, L.W.

    1987-09-01

    To determine the prognostic value of the regression rate of choroidal melanomas after cobalt-60 plaque radiotherapy, the authors performed a multivariate analysis on 159 patients treated with a cobalt plaque during the interval from 1976 through 1980. Thirty-three of the 159 patients had died as of the survey date; 29 of metastatic melanoma and 4 of other causes. Multivariate Cox proportional hazards modeling identified a two-term regression incorporating maximal basal tumor diameter at treatment and tumor thickness at 12 months posttreatment as the best model (P less than 0.005 for both parameters) for predicting length of tumor-free survival. These results are consistent with the hypothesis that rapid regression of a choroidal melanoma after cobalt-60 plaque radiotherapy is an unfavorable prognostic sign for prolonged metastasis-free survival.

  15. 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.

  16. Practical Session: Simple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-01-01

    Two exercises are proposed to illustrate the simple linear regression. The first one is based on the famous Galton's data set on heredity. We use the lm R command and get coefficients estimates, standard error of the error, R2, residuals …In the second example, devoted to data related to the vapor tension of mercury, we fit a simple linear regression, predict values, and anticipate on multiple linear regression. This pratical session is an excerpt from practical exercises proposed by A. Dalalyan at EPNC (see Exercises 1 and 2 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_4.pdf).

  17. The role of COX-2/PGE2 in gossypol-induced apoptosis of colorectal carcinoma cells.

    PubMed

    Chien, Chih-Chiang; Ko, Ching-Huai; Shen, Shing-Chuan; Yang, Liang-Yo; Chen, Yen-Chou

    2012-08-01

    Our previous study showed that gossypol (GOS) exhibits potent cytotoxic effects via apoptosis induction against human colorectal carcinoma cells; however, the role of cyclooxygenase (COX)-2/prostaglandin (PG)E(2) on GOS-induced apoptosis is still unknown. In the present study, 12-O-tetradecanoylphorbol-13-acetate (TPA) addition significantly inhibited GOS-induced apoptosis in human colorectal carcinoma HT-29 cells in accordance with inducing COX-2 protein/PGE(2) production. TPA inhibition of GOS-induced apoptosis was blocked by adding protein kinase (PK)C inhibitors including staurosporine (ST), GF109203X (GF), and H7, characterized by the occurrence of cleaved caspase 3 proteins and a decrease in COX-2 protein/PGE(2) production in HT-29 cells. The addition of COX activity inhibitors, including NS398 (NS), aspirin (AS), diclofenac (DI), and indomethacin (IN), suppressed TPA protection of GOS-induced apoptosis with decreased PGE(2) production in HT-29 cells. Application of PGE(2), but not it analogs PGD(2), PGJ(2), or PGF(2?), protected HT-29 cells from GOS-induced DNA ladders, and the E-prostanoid (EP(1)) receptor agonist, 17PT-PGE(2), mimicked the protection induced by PGE(2), whereas the selective EP(2) receptor agonist, butaprostol (BUT), the EP(3) receptor agonist, sulprostol (SUL), and the EP(4) receptor agonist, PGE(1) alcohol (PGE(1)), showed no significant effects on GOS-induced apoptosis in HT-29 cells. PGE(2) 's protection against GOS-induced apoptosis was reversed by adding the selective EP(1) receptor antagonist, SC-19220. Furthermore, GOS had an effective apoptotic effect on COLO205 colorectal carcinoma cells which expressed undetectable level of endogenous COX-2 protein than HT-29 cells, and the decreased COX-2 protein level via COX-2 siRNA or addition of COX-2 activity inhibitor NS significantly elevated GOS-induced cell death in HT-29 cells. COLO205-T cells were established through sustained TPA incubation of COLO205 cells, and COLO205-T cells showed a lower sensitivity to GOS-induced cell death with increased COX-2 (not Bcl-2 and Mcl-1) protein than parental COLO-205 cells. A decrease in COX-2 protein expression in COLO205-T cells by COX-2 siRNA transfection or enhanced GOS-induced cell death according to MTT assay and DNA integrity assay. The notion of COX-2/PGE(2) activation against GOS-induced apoptosis in colon carcinoma cells was demonstrated, and the combination of GOS and COX-2 inhibitors to treat colon carcinoma possesses clinical potential worthy of further investigation. PMID:22170686

  18. 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.

  19. Regression analysis with longitudinal measurements 

    E-print Network

    Ryu, Duchwan

    2005-08-29

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

  20. 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 ...

  1. The relative importance of imaging markers for the prediction of Alzheimer's disease dementia in mild cognitive impairment — Beyond classical regression

    PubMed Central

    Teipel, Stefan J.; Kurth, Jens; Krause, Bernd; Grothe, Michel J.

    2015-01-01

    Selecting a set of relevant markers to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) has become a challenging task given the wealth of regional pathologic information that can be extracted from multimodal imaging data. Here, we used regularized regression approaches with an elastic net penalty for best subset selection of multiregional information from AV45-PET, FDG-PET and volumetric MRI data to predict conversion from MCI to AD. The study sample consisted of 127 MCI subjects from ADNI-2 who had a clinical follow-up between 6 and 31 months. Additional analyses assessed the effect of partial volume correction on predictive performance of AV45- and FDG-PET data. Predictor variables were highly collinear within and across imaging modalities. Penalized Cox regression yielded more parsimonious prediction models compared to unpenalized Cox regression. Within single modalities, time to conversion was best predicted by increased AV45-PET signal in posterior medial and lateral cortical regions, decreased FDG-PET signal in medial temporal and temporobasal regions, and reduced gray matter volume in medial, basal, and lateral temporal regions. Logistic regression models reached up to 72% cross-validated accuracy for prediction of conversion status, which was comparable to cross-validated accuracy of non-linear support vector machine classification. Regularized regression outperformed unpenalized stepwise regression when number of parameters approached or exceeded the number of training cases. Partial volume correction had a negative effect on the predictive performance of AV45-PET, but slightly improved the predictive value of FDG-PET data. Penalized regression yielded more parsimonious models than unpenalized stepwise regression for the integration of multiregional and multimodal imaging information. The advantage of penalized regression was particularly strong with a high number of collinear predictors. PMID:26199870

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

    PubMed

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

    2012-05-01

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

  3. 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.

  4. 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.

  5. Correlating carbon monoxide oxidation with cox genes in the abundant Marine Roseobacter Clade

    PubMed Central

    Cunliffe, Michael

    2011-01-01

    The Marine Roseobacter Clade (MRC) is a numerically and biogeochemically significant component of the bacterioplankton. Annotation of multiple MRC genomes has revealed that an abundance of carbon monoxide dehydrogenase (CODH) cox genes are present, subsequently implying a role for the MRC in marine CO cycling. The cox genes fall into two distinct forms based on sequence analysis of the coxL gene; forms I and II. The two forms are unevenly distributed across the MRC genomes. Most (18/29) of the MRC genomes contain only the putative form II coxL gene. Only 10 of the 29 MRC genomes analysed have both the putative form II and the definitive form I coxL. None have only the form I coxL. Genes previously shown to be required for post-translational maturation of the form I CODH enzyme are absent from the MRC genomes containing only form II. Subsequent analyses of a subset of nine MRC strains revealed that only MRC strains with both coxL forms are able to oxidise CO. PMID:21068776

  6. Bayesian Logistic Regression Sargur N. Srihari

    E-print Network

    Bayesian Logistic Regression Sargur N. Srihari University at Buffalo, State University of New York USA #12;Topics · Recap of Logistic Regression · Roadmap of Bayesian Logistic Regression · Laplace Regression Machine Learning Srihari 2 #12;Recap of Logistic Regression · Feature vector , two-classes C1

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

    PubMed

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

    2010-12-01

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

  8. Multiple Origins of Eukaryotic cox15 Suggest Horizontal Gene Transfer from Bacteria to Jakobid Mitochondrial DNA.

    PubMed

    He, Ding; Fu, Cheng-Jie; Baldauf, Sandra L

    2016-01-01

    The most gene-rich and bacterial-like mitochondrial genomes known are those of Jakobida (Excavata). Of these, the most extreme example to date is the Andalucia godoyi mitochondrial DNA (mtDNA), including a cox15 gene encoding the respiratory enzyme heme A synthase (HAS), which is nuclear-encoded in nearly all other mitochondriate eukaryotes. Thus cox15 in eukaryotes appears to be a classic example of mitochondrion-to-nucleus (endosymbiotic) gene transfer, with A. godoyi uniquely retaining the ancestral state. However, our analyses reveal two highly distinct HAS types (encoded by cox15-1 and cox15-2 genes) and identify A. godoyi mitochondrial cox15-encoded HAS as type-1 and all other eukaryotic cox15-encoded HAS as type-2. Molecular phylogeny places the two HAS types in widely separated clades with eukaryotic type-2 HAS clustering with the bulk of ?-proteobacteria (>670 sequences), whereas A. godoyi type-1 HAS clusters with an eclectic set of bacteria and archaea including two ?-proteobacteria missing from the type-2 clade. This wide phylogenetic separation of the two HAS types is reinforced by unique features of their predicted protein structures. Meanwhile, RNA-sequencing and genomic analyses fail to detect either cox15 type in the nuclear genome of any jakobid including A. godoyi. This suggests that not only is cox15-1 a relatively recent acquisition unique to the Andalucia lineage but also the jakobid last common ancestor probably lacked both cox15 types. These results indicate that uptake of foreign genes by mtDNA is more taxonomically widespread than previously thought. They also caution against the assumption that all ?-proteobacterial-like features of eukaryotes are ancient remnants of endosymbiosis. PMID:26412445

  9. Albumin-induced podocyte injury and protection are associated with regulation of COX-2.

    PubMed

    Agrawal, Shipra; Guess, Adam J; Chanley, Melinda A; Smoyer, William E

    2014-12-01

    Albuminuria is both a hallmark and a risk factor for progressive glomerular disease, and results in increased exposure of podocytes to serum albumin with its associated factors. Here in vivo and in vitro models of serum albumin-overload were used to test the hypothesis that albumin-induced proteinuria and podocyte injury directly correlate with COX-2 induction. Albumin induced COX-2, MCP-1, CXCL1, and the stress protein HSP25 in both rat glomeruli and cultured podocytes, whereas B7-1 and HSP70i were also induced in podocytes. Podocyte exposure to albumin induced both mRNA and protein and enhanced the mRNA stability of COX-2, a key regulator of renal hemodynamics and inflammation, which renders podocytes susceptible to injury. Podocyte exposure to albumin also stimulated several kinases (p38 MAPK, MK2, JNK/SAPK, and ERK1/2), inhibitors of which (except JNK/SAPK) downregulated albumin-induced COX-2. Inhibition of AMPK, PKC, and NF?B also downregulated albumin-induced COX-2. Critically, albumin-induced COX-2 was also inhibited by glucocorticoids and thiazolidinediones, both of which directly protect podocytes against injury. Furthermore, specific albumin-associated fatty acids were identified as important contributors to COX-2 induction, podocyte injury, and proteinuria. Thus, COX-2 is associated with podocyte injury during albuminuria, as well as with the known podocyte protection imparted by glucocorticoids and thiazolidinediones. Moreover, COX-2 induction, podocyte damage, and albuminuria appear mediated largely by serum albumin-associated fatty acids. PMID:24918154

  10. 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

  11. PSHREG: A SAS macro for proportional and nonproportional subdistribution hazards regression

    PubMed Central

    Kohl, Maria; Plischke, Max; Leffondré, Karen; Heinze, Georg

    2015-01-01

    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

  12. 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

  13. Kernel Regression in the Presence of Correlated Errors Kernel Regression in the Presence of Correlated Errors

    E-print Network

    in nonparametric regression is difficult in the presence of correlated errors. There exist a wide variety vector machines for regression. Keywords: nonparametric regression, correlated errors, bandwidth choice, cross-validation, short-range dependence, bimodal kernel 1. Introduction Nonparametric regression

  14. 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...

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

    E-print Network

    November 1999 / Accepted: 15 December 1999 Abstract Pollutant degradation in biotrickling ®lters for waste . On day 0, 0.35 l of a mineral medium (Cox and Deshusses 1999) and 10 ml of a seed culture from

  16. Recent Methodologies toward the Synthesis of Valdecoxib: A Potential 3,4-diarylisoxazolyl COX-2 Inhibitor

    PubMed Central

    Dadiboyena, Sureshbabu; Nefzi, Adel

    2011-01-01

    Non-steroidal anti-inflammatory drugs are widely used therapeutic agents in the treatment of inflammation, pain and fever. Cyclooxygenase catalyzes the initial step of biotransformation of arachidonic acid to prostanoids, and exist as three distinct isozymes; COX-I, COX-II and COX-III. Selective COX-II inhibitors are a class of potential anti-inflammatory, analgesic, and antipyretic drugs with reduced gastrointestinal (GI) side effects compared to nonselective inhibitors. 3,4-diarylisoxazole scaffold is recurrently found in a wide variety of NSAIDs, protein kinase inhibitors, hypertensive agents, and estrogen receptor (ER) modulators. In the present review, we document on the recent synthetic strategies of 3,4-diarylisoxazolyl scaffolds of valdecoxib and its relevant structural analogues. PMID:20724040

  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. 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

  19. Regressive evolution in Astyanax cavefish.

    PubMed

    Jeffery, William R

    2009-01-01

    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

  20. In Computational Statistics and Data Analysis 53 (2008), pp. 289297 Unimodal Regression via Prefix Isotonic Regression

    E-print Network

    Stout, Quentin F.

    2008-01-01

    of applications. They are shape-constrained nonparametric regressions, closely re- lated to isotonic regression isotonic regression and unimodal regression are ex- amples of nonparametric shape-constrained regressionIn Computational Statistics and Data Analysis 53 (2008), pp. 289­297 Unimodal Regression via Prefix

  1. Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation.

    PubMed

    Teather, Lisa A; Packard, Mark G; Bazan, Nicolas G

    2002-01-01

    Evidence indicates that prostanoids, such as prostaglandins, play a regulatory role in several forms of neural plasticity, including long-term potentiation, a cellular model for certain forms of learning and memory. In these experiments, the significance of the COX isoforms cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in post-training memory processes was assessed. Adult male Long-Evans rats underwent an eight-trial (30-sec intertrial interval) training session on a hippocampus-dependent (hidden platform) or dorsal striatal-dependent (visible platform) tasks in a water maze. After the completion of training, rats received an intraperitoneal injection of the nonselective COX inhibitor indomethacin, the COX-1-specific inhibitor piroxicam, the COX-2-specific inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]-methanesulfonamide (NS-398), vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water), or saline. On a two-trial retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In the hidden platform task, the retention test escape latencies of rats administered indomethacin (5 and 10 mg/kg) or NS-398 (2 and 5 mg/kg) were significantly higher than those of vehicle-treated rats, indicating an impairment in retention. Injections of indomethacin or NS-398 that were delayed 2 h post-training had no effect on retention. Post-training indomethacin or NS-398 had no influence on retention of the visible platform version of the water maze at any of the doses administered. Furthermore, selective inhibition of COX-1 via post-training piroxicam administration had no effect on retention of either task. These findings indicate that COX-2 is a required biochemical component mediating the consolidation of hippocampal-dependent memory. PMID:11917005

  2. Nonparametric regression with filtered data

    E-print Network

    Linton, Oliver; Nielsen, Jens Perch; Van Keilegom, Ingrid; 10.3150/10-BEJ260

    2011-01-01

    We present a general principle for estimating a regression function nonparametrically, allowing for a wide variety of data filtering, for example, repeated left truncation and right censoring. Both the mean and the median regression cases are considered. The method works by first estimating the conditional hazard function or conditional survivor function and then integrating. We also investigate improved methods that take account of model structure such as independent errors and show that such methods can improve performance when the model structure is true. We establish the pointwise asymptotic normality of our estimators.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. From prostaglandin replacement to specific COX-2 inhibition: a critical appraisal.

    PubMed

    Kremer, J

    2000-10-01

    Nonsteroidal antiinflammatory drugs (NSAID) are among the most widely prescribed medications worldwide. While these agents are efficacious for the relief of both pain and the signs and symptoms of inflammation, the use of traditional NSAID is associated with a high prevalence of toxic events. It is estimated that 2-4% of traditional NSAID users will have a serious adverse gastrointestinal (GI) event per year, with a point prevalence of GI ulcers at any given time of 10-30%. The mortality rate associated with these NSAID is one of the highest attributed to the use of any agent. Prostaglandin replacement with misoprostol has been shown to significantly reduce the incidence of serious GI toxicity related to the use of conventional NSAID. All conventional NSAID inhibit both cyclooxygenase-1 (COX-1) and COX-2 enzymes. As COX-1 is constitutively expressed in many tissues and contributes to the maintenance of the normal physiologic state in the GI tract, the kidney, and platelets, an agent that specifically inhibits COX-2, an inducible enzyme associated with the inflammatory response, would be highly desirable. Specific COX-2 inhibition would have the advantage of improving the signs and symptoms of inflammation, while avoiding the possibly significant toxicity of traditional NSAID. This article describes the biology of eicosanoids and the effects of NSAID, the toxicity profile of conventional NSAID, and the rationale for the use of gastroprotective agents or agents that specifically inhibit the COX-2 isozyme. PMID:11032096

  7. 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…

  8. Linear regression issues in astronomy

    E-print Network

    Babu, G. Jogesh

    Linear regression issues in astronomy Eric Feigelson Summer School in astrostatistics References-dependent & Quantitative Variables in Econometrics 1983) Astronomy: Malmquist bias in Hubble diagram (Deeming, Vistas Astr) Schmitt (ApJ 1985) Presented for astronomy by Isobe, Feigelson & Nelson (ApJ 1986) Implemented

  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. 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…

  11. Cluster-based computational methods for mass univariate analyses of event-related brain potentials/fields: A simulation study

    PubMed Central

    Pernet, C.R.; Latinus, M.; Nichols, T.E.; Rousselet, G.A.

    2015-01-01

    Background In recent years, analyses of event related potentials/fields have moved from the selection of a few components and peaks to a mass-univariate approach in which the whole data space is analyzed. Such extensive testing increases the number of false positives and correction for multiple comparisons is needed. Method Here we review all cluster-based correction for multiple comparison methods (cluster-height, cluster-size, cluster-mass, and threshold free cluster enhancement – TFCE), in conjunction with two computational approaches (permutation and bootstrap). Results Data driven Monte-Carlo simulations comparing two conditions within subjects (two sample Student's t-test) showed that, on average, all cluster-based methods using permutation or bootstrap alike control well the family-wise error rate (FWER), with a few caveats. Conclusions (i) A minimum of 800 iterations are necessary to obtain stable results; (ii) below 50 trials, bootstrap methods are too conservative; (iii) for low critical family-wise error rates (e.g. p = 1%), permutations can be too liberal; (iv) TFCE controls best the type 1 error rate with an attenuated extent parameter (i.e. power < 1). PMID:25128255

  12. Table 1: Classification of EGIL signatures (assumed univariate---see text). CLASS Pho Vac Awcs H2O Cab Prp Wcs Tps Rcr Gal Novel

    E-print Network

    Fisher, Douglas H.

    Table 1: Classification of EGIL signatures (assumed univariate---see text). CLASS Pho Vac Awcs H2O H2O 1 2\\Sigma9 98\\Sigma9 8 100\\Sigma0 Cab 1 79\\Sigma17 22\\Sigma17 8 90\\Sigma16 10\\Sigma16 Prp 1 98

  13. Small Area Estimation Using Penalized Spline Regression

    E-print Network

    ;2/28 Back Close Outline 1. Introduction: Northeastern Lakes Survey 2. Methods (a) Nonparametric regression model #12;7/28 Back Close 2.1) Methods: Nonparametric Regression Using Penalized Splines Regression1/28 Back Close Small Area Estimation Using Penalized Spline Regression Jean Opsomer Iowa State

  14. Asymmetric -tube Support Vector Regression Xiaolin Huanga,

    E-print Network

    Regression (-SVR) has become a standard tool in nonparametric regression tasks. The -SVRs extend standardAsymmetric -tube Support Vector Regression Xiaolin Huanga, , Lei Shia,c , Kristiaan Pelckmansb-known -tube Support Vector Regression (-SVR) is an effective method for implementing this idea in the context

  15. Small Area Estimation Using Penalized Spline Regression

    E-print Network

    ;2/31 Back Close Outline 1. Introduction: Northeastern Lakes Survey 2. Methods (a) Nonparametric regression Close 2.1) Methods: Nonparametric Regression Using Penalized Splines Regression model yi = m(xi) + i1/31 Back Close Small Area Estimation Using Penalized Spline Regression Jean Opsomer Iowa State

  16. Jon Wakefield: Bayesian and Frequentist Regression Methods

    E-print Network

    Wakefield, Jon

    attention could have been devoted to Bayesian nonparametric regression models. These are discussedJon Wakefield: Bayesian and Frequentist Regression Methods Taeryon CHOI Regression analysis in the development of research, textbooks, and software for regression analysis in theory and methods as well as real

  17. Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

    PubMed Central

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A.; Wilensky, Robert L.; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A.

    2012-01-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD2 receptor DP1. NSAID-mediated suppression of COX-2–derived PGI2 has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD2 was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD2, like PGI2, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy. PMID:22406532

  18. Staurosporine synergistically potentiates the deoxycholate?mediated induction of COX?2 expression

    PubMed Central

    Saeki, Tohru; Inui, Haruka; Fujioka, Saya; Fukuda, Suguru; Nomura, Ayumi; Nakamura, Yasushi; Park, Eun Young; Sato, Kenji; Kanamoto, Ryuhei

    2014-01-01

    Abstract Colorectal cancer is a major cause of cancer?related death in western countries, and thus there is an urgent need to elucidate the mechanism of colorectal tumorigenesis. A diet that is rich in fat increases the risk of colorectal tumorigenesis. Bile acids, which are secreted in response to the ingestion of fat, have been shown to increase the risk of colorectal tumors. The expression of cyclooxygenase (COX)?2, an inducible isozyme of cyclooxygenase, is induced by bile acids and correlates with the incidence and progression of cancers. In this study, we investigated the signal transduction pathways involved in the bile?acid?mediated induction of COX?2 expression. We found that staurosporine (sts), a potent protein kinase C (PKC) inhibitor, synergistically potentiated the deoxycholate?mediated induction of COX?2 expression. Sts did not increase the stabilization of COX?2 mRNA. The sts? and deoxycholate?mediated synergistic induction of COX?2 expression was suppressed by a membrane?permeable Ca2+ chelator, a phosphoinositide 3?kinase inhibitor, a nuclear factor??B pathway inhibitor, and inhibitors of canonical and stress?inducible mitogen?activated protein kinase pathways. Inhibition was also observed using PKC inhibitors, suggesting the involvement of certain PKC isozymes (?, ?, ?, ?, or ?). Our results indicate that sts exerts its potentiating effects via the phosphorylation of p38. However, the effects of anisomycin did not mimic those of sts, indicating that although p38 activation is required, it does not enhance deoxycholate?induced COX?2 expression. We conclude that staurosporine synergistically enhances deoxycholate?induced COX?2 expression in RCM?1 colon cancer cells. PMID:25168879

  19. Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

    PubMed Central

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington

    2013-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further investigation. PMID:23316477

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

    PubMed

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

    2014-11-01

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

  1. Role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients’ prognosis

    PubMed Central

    Wu, Ai-Wen; Gu, Jin; Ji, Jia-Fu; Li, Zhen-Fu; Xu, Guang-Wei

    2003-01-01

    AIM: Recent clinical epidemiological studies have demonstrated the preventive effect of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer. The underlying mechanism might be the inhibition of rate-limiting enzyme cyclooxygenase-2 (COX-2) in metabolism of arachidonic acid. The role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients’ prognosis still remain unclear. This study was to investigate the role of COX-2 expression in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients’ prognosis. METHODS: A total of 139 colorectal cancers and 19 adenomas surgically treated in School of Oncology, Peking University, from January 1993 to September 2001 were retrospectively studied. COX-2 expression was detected with tissue microarray (TMA) and immunohistochemistry (IHC) procedure. The association between COX-2 expression and clinicopathological features and its influence on patients’ prognosis were studied. RESULTS: COX-2 expression was strong in colorectal cancer, moderate in adenoma and weak in normal mucosa, which demonstrated statistically significant difference (?2 = 46.997, P < 0.001). COX-2 expression had no association with clinicopathological features such as gross type, differentiation, invasion depth, vessel emboli and TNM staging. Cox proportional hazards modeling analysis and Log rank test revealed no prognostic role of COX-2 expression in colorectal cancer patients. CONCLUSION: COX-2 may play an important role in the early stage of carcinogenesis, and its expression in colorectal cancer is not associated with clinicopathological features and patients’ prognosis. PMID:12970891

  2. Prostaglandin E2 produced by late induced COX-2 stimulates hippocampal neuron loss after seizure in the CA3 region.

    PubMed

    Takemiya, Takako; Maehara, Michiyo; Matsumura, Kiyoshi; Yasuda, Shin; Sugiura, Hiroko; Yamagata, Kanato

    2006-09-01

    Injection of kainic acid (KA) into the brain causes severe seizures with hippocampal neuron loss. KA has been shown to immediately induce cyclooxygenase-2 (COX-2) expression in hippocampal neurons, indicating that neuronal COX-2 might be involved in neuronal death. In this study, however, we reveal that the delayed COX-2 induction in non-neuronal cells after KA injection plays an important role in hippocampal neuron loss rather than early COX-2 expression in neurons. We find that KA microinjection into the hemilateral hippocampus shows a later induction of COX-2 expression in non-neuronal cells, such as endothelial cells and astrocytes. In the KA-injected side, PGE2 concentration gradually increases and peaks at 24 h after injection, when non-neuronal COX-2 expression also peaks. When this delayed PGE2 elevation is prevented by selective COX-2 inhibitor NS398, it can block hippocampal cell death. Moreover, COX-2 knockout mice are also resistant to neuronal death after KA treatment. These findings indicate that delayed PGE2 production by non-neuronal COX-2 may facilitate neuronal death after seizure. Inhibition of COX-2 to an extent similar to PGE2 elevation after onset of seizure may be useful to prevent neuronal death. PMID:16837093

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

    PubMed Central

    Huang, Jian; Zhang, Di; Xie, Fuqiang

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs. PMID:26124697

  4. 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

  5. Patient-specific meta-analysis for risk assessment using multivariate proportional hazards regression

    PubMed Central

    Crager, Michael R.; Tang, Gong

    2015-01-01

    We propose a method for assessing an individual patient’s risk of a future clinical event using clinical trial or cohort data and Cox proportional hazards regression, combining the information from several studies using meta-analysis techniques. The method combines patient-specific estimates of the log cumulative hazard across studies, weighting by the relative precision of the estimates, using either fixed- or random-effects meta-analysis calculations. Risk assessment can be done for any future patient using a few key summary statistics determined once and for all from each study. Generalizations of the method to logistic regression and linear models are immediate. We evaluate the methods using simulation studies and illustrate their application using real data.

  6. 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; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-04-15

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

  7. 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

  8. Efficient methods for estimating constrained parameters with applications to lasso logistic regression

    PubMed Central

    Tian, Guo-Liang; Tang, Man-Lai; Fang, Hong-Bin; Tan, Ming

    2008-01-01

    Fitting logistic regression models is challenging when their parameters are restricted. In this article, we first develop a quadratic lower-bound (QLB) algorithm for optimization with box or linear inequality constraints and derive the fastest QLB algorithm corresponding to the smallest global majorization matrix. The proposed QLB algorithm is particularly suited to problems to which EM-type algorithms are not applicable (e.g., logistic, multinomial logistic, and Cox’s proportional hazards models) while it retains the same EM ascent property and thus assures the monotonic convergence. Secondly, we generalize the QLB algorithm to penalized problems in which the penalty functions may not be totally differentiable. The proposed method thus provides an alternative algorithm for estimation in lasso logistic regression, where the convergence of the existing lasso algorithm is not generally ensured. Finally, by relaxing the ascent requirement, convergence speed can be further accelerated. We introduce a pseudo-Newton method that retains the simplicity of the QLB algorithm and the fast convergence of the Newton method. Theoretical justification and numerical examples show that the pseudo-Newton method is up to 71 (in terms of CPU time) or 107 (in terms of number of iterations) times faster than the fastest QLB algorithm and thus makes bootstrap variance estimation feasible. Simulations and comparisons are performed and three real examples (Down syndrome data, kyphosis data, and colon microarray data) are analyzed to illustrate the proposed methods. PMID:18443660

  9. 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

  10. Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program

    PubMed Central

    Perreault, Leigh; Kahn, Steven E.; Christophi, Costas A.; Knowler, William C.; Hamman, Richard F.

    2009-01-01

    OBJECTIVE Participants in the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS) or metformin had a significantly reduced incidence of diabetes compared with those randomized to placebo, yet most were still at risk because they had pre-diabetes. We explored the effect of baseline characteristics, weight change, ILS, and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation (NGR) defined by American Diabetes Association criteria. RESEARCH DESIGN AND METHODS The DPP was a prospective randomized trial. Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up. RESULTS Lower baseline fasting (hazard ratio 1.52, P < 0.01) and 2-h (1.24, P < 0.01) glucose predicted regression to NGR, as did younger age (1.07, P < 0.01) and greater insulin secretion (1.09, P = 0.04). ILS (2.05, P < 0.01) and weight loss (1.34, P < 0.01) had significant and independent effects on regression. A nonsignificant trend for regression was also observed for metformin (1.25, P = 0.06), male sex (1.17, P = 0.08), and insulin sensitivity (1.07, P = 0.09). In those entering the study with both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), male sex and insulin sensitivity predicted regression to isolated IFG, whereas ILS, metformin, female sex, and greater insulin secretion predicted regression to isolated IGT. CONCLUSIONS Insulin secretion, and other biologic processes retained with younger age, are key in restoring NGR in people with pre-diabetes. However, NGR may also be attained through weight loss and additional aspects of ILS. PMID:19587364

  11. CoxFey@C Composites with Tunable Atomic Ratios for Excellent Electromagnetic Absorption Properties.

    PubMed

    Lv, Hualiang; Ji, Guangbin; Zhang, Haiqian; Li, Meng; Zuo, Zhongzheng; Zhao, Yue; Zhang, Baoshan; Tang, Dongming; Du, Youwei

    2015-01-01

    The shell on the nano-magnetic absorber can prevent oxidation, which is very important for its practical utilization. Generally, the nonmagnetic shell will decrease the integral magnetic loss and thus weaken the electromagnetic absorption. However, maintaining the original absorption properties of the magnetic core is a major challenge. Here, we designed novel and facile CoxFey@C composites by reducing CoxFe3-xO4@phenolic resin (x?=?1, 0.5 and 0.25). High saturation magnetization value (Ms) of CoxFey particle, as a core, shows the interesting magnetic loss ability. Meanwhile, the carbon shell may increase the integral dielectric loss. The resulting composite shows excellent electromagnetic absorption properties. For example, at a coating thickness of 2?mm, the RLmin value can reach to -23?dB with an effective frequency range of 7?GHz (11-18?GHz). The mechanisms of the improved microwave absorption properties are discussed. PMID:26659124

  12. Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation.

    PubMed

    Hermanson, Daniel J; Gamble-George, Joyonna C; Marnett, Lawrence J; Patel, Sachin

    2014-07-01

    Pharmacologic augmentation of endogenous cannabinoid (eCB) signaling is an emerging therapeutic approach for the treatment of a broad range of pathophysiological conditions. Thus far, pharmacological approaches have focused on inhibition of the canonical eCB inactivation pathways - fatty acid amide hydrolase (FAAH) for anandamide and monoacylglycerol lipase (MAGL) for 2-arachidonoylglycerol. We review here the experimental evidence that cyclooxygenase-2 (COX-2)-mediated eCB oxygenation represents a third mechanism for terminating eCB action at cannabinoid receptors. We describe the development, molecular mechanisms, and in vivo validation of 'substrate-selective' COX-2 inhibitors (SSCIs) that prevent eCB inactivation by COX-2 without affecting prostaglandin (PG) generation from arachidonic acid (AA). Lastly, we review recent data on the potential therapeutic applications of SSCIs with a focus on neuropsychiatric disorders. PMID:24845457

  13. CoxFey@C Composites with Tunable Atomic Ratios for Excellent Electromagnetic Absorption Properties

    PubMed Central

    Lv, Hualiang; Ji, Guangbin; Zhang, Haiqian; Li, Meng; Zuo, Zhongzheng; Zhao, Yue; Zhang, Baoshan; Tang, Dongming; Du, Youwei

    2015-01-01

    The shell on the nano-magnetic absorber can prevent oxidation, which is very important for its practical utilization. Generally, the nonmagnetic shell will decrease the integral magnetic loss and thus weaken the electromagnetic absorption. However, maintaining the original absorption properties of the magnetic core is a major challenge. Here, we designed novel and facile CoxFey@C composites by reducing CoxFe3?xO4@phenolic resin (x?=?1, 0.5 and 0.25). High saturation magnetization value (Ms) of CoxFey particle, as a core, shows the interesting magnetic loss ability. Meanwhile, the carbon shell may increase the integral dielectric loss. The resulting composite shows excellent electromagnetic absorption properties. For example, at a coating thickness of 2?mm, the RLmin value can reach to ?23?dB with an effective frequency range of 7?GHz (11–18?GHz). The mechanisms of the improved microwave absorption properties are discussed. PMID:26659124

  14. Robust inhibitory effects of conjugated linolenic acids on a cyclooxygenase-related linoleate 10S-dioxygenase: Comparison with COX-1 and COX-2.

    PubMed

    Mashhadi, Zahra; Boeglin, William E; Brash, Alan R

    2015-10-01

    There are many reports of the anti-inflammatory, anti-cancer, and anti-atherosclerotic activities of conjugated linolenic acids (cLNA). They constitute a small percentage of fatty acids in the typical human diet, although up to 80% of the fatty acids in certain fruits such as pomegranate. In the course of studying a bacterial fatty acid dioxygenase (Nostoc linoleate 10S-DOX, an ancient relative of mammalian cyclooxygenases), we detected strong inhibitory activity in a commercial sample of linoleic acid. We identified two cLNA isomers, ?-eleostearic (9E,11E,13E-18:3) and ?-calendic acid (8E,10E,12E-18:3), as responsible for that striking inhibition with a Ki of ~49nM and ~125nM, respectively, the most potent among eight cLNA tested. We also examined the effects of all eight cLNA on the activity of COX-1 and COX-2. Jacaric acid (8Z,10E,12Z-18:3) and its 12E isomer, 8Z,10E,12E-18:3, strongly inhibit the activity of COX-1 with a Ki of ~1.7 and ~1.1?M, respectively. By contrast, COX-2 was ?30% inhibited at 10?M concentrations of the cLNA. Identifying the activities of the naturally occurring fatty acids is of interest in terms of understanding their interaction with the enzymes, and for explaining the mechanistic basis of their biological effects. The study also highlights the potential presence of inhibitory fatty acids in commercial lipids prepared from natural sources. Analysis of seven commercial samples of linoleic acid by HPLC and UV spectroscopy is illustrated as supplementary data. PMID:26209563

  15. The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice

    PubMed Central

    Maurer, Stefanie F.; Fromme, Tobias; Grossman, Lawrence I.; Hüttemann, Maik; Klingenspor, Martin

    2015-01-01

    The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1. PMID:26635001

  16. The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice.

    PubMed

    Maurer, Stefanie F; Fromme, Tobias; Grossman, Lawrence I; Hüttemann, Maik; Klingenspor, Martin

    2015-01-01

    The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1. PMID:26635001

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

    PubMed Central

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

    2014-01-01

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

  18. 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

  19. 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

  20. 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

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

    PubMed

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

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

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

    PubMed Central

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

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

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

    SciTech Connect

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

    2012-03-09

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

  4. Regression analysis of cytopathological data

    SciTech Connect

    Whittemore, A.S.; McLarty, J.W.; Fortson, N.; Anderson, K.

    1982-12-01

    Epithelial cells from the human body are frequently labelled according to one of several ordered levels of abnormality, ranging from normal to malignant. The label of the most abnormal cell in a specimen determines the score for the specimen. This paper presents a model for the regression of specimen scores against continuous and discrete variables, as in host exposure to carcinogens. Application to data and tests for adequacy of model fit are illustrated using sputum specimens obtained from a cohort of former asbestos workers.

  5. A Formulation for Minimax Probability Machine Regression

    E-print Network

    Grudic, Greg

    problem as one of maximizing the mini- mum probability, symbolized by , that future predicted outputs trivial regression problems. As with the minimax probability machine classification (MPMC) frameworkA Formulation for Minimax Probability Machine Regression Thomas Strohmann Department of Computer

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

    NASA Astrophysics Data System (ADS)

    Larrinaga, Asier R.

    2010-01-01

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

  7. 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

  8. Assessment of brown trout habitat suitability in the Jucar River Basin (SPAIN): comparison of data-driven approaches with fuzzy-logic models and univariate suitability curves.

    PubMed

    Muñoz-Mas, Rafael; Martínez-Capel, Francisco; Schneider, Matthias; Mouton, Ans M

    2012-12-01

    The implementation of the Water Framework Directive implies the determination of an environmental flow (E-flow) in each running water body. In Spain, many of the minimum flow assessments were determined with the physical habitat simulation system based on univariate habitat suitability curves. Multivariate habitat suitability models, widely applied in habitat assessment, are potentially more accurate than univariate suitability models. This article analyses the microhabitat selection by medium-sized (10-20 cm) brown trout (Salmo trutta fario) in three streams of the Jucar River Basin District (eastern Iberian Peninsula). The data were collected with an equal effort sampling approach. Univariate habitat suitability curves were built with a data-driven process for depth, mean velocity and substrate classes; three types of data-driven fuzzy models were generated with the FISH software: two models of presence-absence and a model of abundance. FISH applies a hill-climbing algorithm to optimize the fuzzy rules. A hydraulic model was calibrated with the tool River-2D in a segment of the Cabriel River (Jucar River Basin). The fuzzy-logic models and three methods to produce a suitability index from the three univariate curves were applied to evaluate the river habitat in the tool CASiMiR©. The comparison of results was based on the spatial arrangement of habitat suitability and the curves of weighted usable area versus discharge. The differences were relevant in different aspects, e.g. in the estimated minimum environmental flow according to the Spanish legal norm for hydrological planning. This work demonstrates the impact of the model's selection on the habitat suitability modelling and the assessment of environmental flows, based on an objective data-driven procedure; the conclusions are important for the water management in the Jucar River Basin and other river systems in Europe, where the environmental flows are a keystone for the achievement of the goals established in the European Water Framework Directive. PMID:22909786

  9. Penalized Logistic Regression for Detecting Gene Interactions

    E-print Network

    Hastie, Trevor

    Penalized Logistic Regression for Detecting Gene Interactions Mee Young Park Trevor Hastie May 25, 2006 Abstract We propose using a variant of logistic regression with L2 regularization to fit gene are influenced by interaction of certain genes. Logistic regression models with quadratic penalization not only

  10. 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

  11. 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 on the logistic sigmoid derived in Section 2. Section 4 will develop the regression model for computing

  12. 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 · Calibrate · Compare to logistic regression · Data · 4,404 voters in ANES 2012 · Response is Presidential

  13. Logistic Regression with Missing Haplotypes Kelly Burkett

    E-print Network

    Brennand, Tracy

    Logistic Regression with Missing Haplotypes by Kelly Burkett B.Sc., University of Guelph, 2000 of project: Logistic Regression with Missing Haplotypes Examining Committee: Dr. Richard Lockhart Chair Dr maximiza- tion (EM) algorithm is used to handle the missing haplotype information in a logistic regression

  14. 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,…

  15. 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…

  16. Comparing Methods for Multivariate Nonparametric Regression

    E-print Network

    Comparing Methods for Multivariate Nonparametric Regression David L. Banks Robert T. Olszewskiy Roy, of the National Science Foundation or the U.S. government. #12;Keywords: multivariate nonparametric regression-wave method- ologies for high-dimensional nonparametric regression has exploded over the last decade

  17. Nonparametric Regression with Correlated Errors Jean Opsomer

    E-print Network

    Wang, Yuedong

    Nonparametric Regression with Correlated Errors Jean Opsomer Iowa State University Yuedong Wang Nonparametric regression techniques are often sensitive to the presence of correlation in the errors Nonparametric regression is a rapidly growing and exciting branch of statistics, both because of recent

  18. Small Area Estimation Using Penalized Spline Regression

    E-print Network

    ;2/29 Back Close Outline 1. Introduction: Northeastern Lakes Survey 2. Methods (a) Nonparametric regression for parametric shape #12;7/29 Back Close 2.1) Methods: Nonparametric Regression Using Penalized Splines1/29 Back Close Small Area Estimation Using Penalized Spline Regression Jean Opsomer Iowa State

  19. Rodeo: Sparse Nonparametric Regression in High Dimensions

    E-print Network

    Rodeo: Sparse Nonparametric Regression in High Dimensions John Lafferty1 Larry Wasserman2 Computer and variable selection in nonparametric regression. The method starts with a local linear estimator with large: Nonparametric regression, sparsity, local linear smoothing, adaptive estimation, band- width estimation

  20. Rodeo: Sparse Nonparametric Regression in High Dimensions

    E-print Network

    Rodeo: Sparse Nonparametric Regression in High Dimensions John La#11;erty 1 Larry Wasserman 2 bandwidth selection and variable selection in nonparametric regression. The method starts with a local the locally optimal bandwidth. Keywords: Nonparametric regression, sparsity, local linear smoothing, adaptive

  1. NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION

    E-print Network

    Drummond, Tom

    NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION J. E. Lindop, G. M. Treece, A. H. Gee and R; NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION Joel E. Lindop, Graham M. Treece, Andrew H. Gee bearing on overall performance. We introduce a nonparametric regression method. Comparing with other

  2. Comparing Methods for Multivariate Nonparametric Regression

    E-print Network

    Comparing Methods for Multivariate Nonparametric Regression David L. Banks \\Lambda Robert T, of the National Science Foundation or the U.S. government. #12; Keywords: multivariate nonparametric regression­wave method­ ologies for high­dimensional nonparametric regression has exploded over the last decade

  3. NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION

    E-print Network

    Drummond, Tom

    NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION J. E. Lindop, G. M. Treece, A. H. Gee and R;NONPARAMETRIC SURFACE REGRESSION FOR STRAIN ESTIMATION Joel E. Lindop, Graham M. Treece, Andrew H. Gee bearing on overall performance. We introduce a nonparametric regression method. Comparing with other

  4. Structural Nonparametric Cointegrating Regression Qiying Wang

    E-print Network

    Jin, Jiashun

    Structural Nonparametric Cointegrating Regression by Qiying Wang The University of Sydney School Nonparametric estimation of a structural cointegrating regression model is studied. As in the standard linear in nonparametric regression but there is an asymptotic gain in variance reduction. The results provide a convenient

  5. Nonparametric Survey Regression Estimation in Spatial Sampling

    E-print Network

    0 since no auxiliary information is used · Generalized Regression: ^µi = xi ^ · Local Polynomial. ­ Non-diagonal matrices change the orientation of the smoothing weights. #12;Local Linear Regression is Wsi = Diag 1 jhxhy K xj - xi hx , yj - yi hy js . · Local linear regression estimate

  6. Developmental Regression in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rogers, Sally J.

    2004-01-01

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

  7. Bayesian nonparametric multivariate convex regression

    E-print Network

    Hannah, Lauren A

    2011-01-01

    In many applications, such as economics, operations research and reinforcement learning, one often needs to estimate a multivariate regression function f subject to a convexity constraint. For example, in sequential decision processes the value of a state under optimal subsequent decisions may be known to be convex or concave. We propose a new Bayesian nonparametric multivariate approach based on characterizing the unknown regression function as the max of a random collection of unknown hyperplanes. This specification induces a prior with large support in a Kullback-Leibler sense on the space of convex functions, while also leading to strong posterior consistency. Although we assume that f is defined over R^p, we show that this model has a convergence rate of log(n)^{-1} n^{-1/(d+2)} under the empirical L2 norm when f actually maps a d dimensional linear subspace to R. We design an efficient reversible jump MCMC algorithm for posterior computation and demonstrate the methods through application to value funct...

  8. COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial

    PubMed Central

    Khor, Li-Yan; Bae, Kyounghwa; Pollack, Alan; Hammond, M Elizabeth; Grignon, David J; Venkatesan, Varagur M; Rosenthal, Seth A; Ritter, Mark A; Sandler, Howard M; Hanks, Gerald E; Shipley, William U; Dicker, Adam P

    2007-01-01

    Summary Background COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy. Methods Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality, overall mortality, and any failure. Findings 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1.181 [95% CI 1.077–1.295], p=0.0004); biochemical failure by two definitions (ASTRO HR 1.073 [1.018–1.131], p=0.008; Phoenix HR 1.073 [1.014–1.134], p=0.014); and any failure (HR 1.068 [1.015–1.124], p=0.011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD. Interpretation To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD. PMID:17881290

  9. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells

    SciTech Connect

    Sun, Lixin; Zhang, Shuang; Jiang, Zhenzhou; Huang, Xin; Wang, Tao; Huang, Xiao; Li, Han; Zhang, Luyong

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased. Black-Right-Pointing-Pointer The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide. Black-Right-Pointing-Pointer Triptolide inhibited 3 Prime -UTR fluorescence reporter gene activity. Black-Right-Pointing-Pointer COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments. -- Abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-{alpha}-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3 Prime -untranslated region (3 Prime -UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer.

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

    SciTech Connect

    Zhu, Yingting; Tissue Tech Inc., Miami, FL 33173 ; Zhu, Min; Lance, Peter

    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.

  11. The Tpl2 Kinase Regulates the COX-2/Prostaglandin E2 Axis in Adipocytes in Inflammatory Conditions.

    PubMed

    Berthou, Flavien; Ceppo, Franck; Dumas, Karine; Massa, Fabienne; Vergoni, Bastien; Alemany, Susana; Cormont, Mireille; Tanti, Jean-François

    2015-07-01

    Bioactive lipid mediators such as prostaglandin E2 (PGE2) have emerged as potent regulator of obese adipocyte inflammation and functions. PGE2 is produced by cyclooxygenases (COXs) from arachidonic acid, but inflammatory signaling pathways controlling COX-2 expression and PGE2 production in adipocytes remain ill-defined. Here, we demonstrated that the MAP kinase kinase kinase tumor progression locus 2 (Tpl2) controls COX-2 expression and PGE2 secretion in adipocytes in response to different inflammatory mediators. We found that pharmacological- or small interfering RNA-mediated Tpl2 inhibition in 3T3-L1 adipocytes decreased by 50% COX-2 induction in response to IL-1?, TNF-?, or a mix of the 2 cytokines. PGE2 secretion induced by the cytokine mix was also markedly blunted. At the molecular level, nuclear factor ?B was required for Tpl2-induced COX-2 expression in response to IL-1? but was inhibitory for the TNF-? or cytokine mix response. In a coculture between adipocytes and macrophages, COX-2 was mainly increased in adipocytes and pharmacological inhibition of Tpl2 or its silencing in adipocytes markedly reduced COX-2 expression and PGE2 secretion. Further, Tpl2 inhibition in adipocytes reduces by 60% COX-2 expression induced by a conditioned medium from lipopolysaccharide (LPS)-treated macrophages. Importantly, LPS was less efficient to induce COX-2 mRNA in adipose tissue explants of Tpl2 null mice compared with wild-type and Tpl2 null mice displayed low COX-2 mRNA induction in adipose tissue in response to LPS injection. Collectively, these data established that activation of Tpl2 by inflammatory stimuli in adipocytes and adipose tissue contributes to increase COX-2 expression and production of PGE2 that could participate in the modulation of adipose tissue inflammation during obesity. PMID:26020725

  12. Angiotensin-(1-7)-induced plasticity changes in the lateral amygdala are mediated by COX-2 and NO

    PubMed Central

    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 demonstrated that the selective COX-2 inhibitor NS-398 significantly reduced the probability of long-term potentiation (LTP) induction in the lateral nucleus of the amygdala. Similarly, in COX-2?/? mice, LTP induced by external capsule (EC) stimulation was impaired. Second, we evaluated the action of angiotensin-(1-7) in the amygdala. In wild-type mice, angiotensin-(1-7) increased LTP. This LTP-enhancing effect of Ang-(1-7) was not observed in COX-2+/? mice. However, in COX-2?/? mice, Ang-(1-7) caused an enhancement of LTP similar to that in wild-type mice. The NO synthetase inhibitor L-NAME blocked this angiotensin-(1-7)-induced increase in LTP in COX-2?/? mice. Low-frequency stimulation of external capsule fibers did not cause long-term depression (LTD) in drug-free and angiotensin-(1-7)-treated brain slices in wild-type mice. In contrast, in COX-2?/? mice, angiotensin-(1-7) caused stable LTD. Increasing NO concentration by the NO-donor SNAP also caused LTD in wild-type mice. Our study shows for the first time that LTP in the amygdala is dependent on COX-2 activity. Moreover, COX-2 is involved in the mediation of angiotensin-(1-7) effects on LTP. Finally, it is recognized that there is a molecular cross-talk between COX-2 and NO that may regulate synaptic plasticity. PMID:17351141

  13. 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...

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

    SciTech Connect

    Chen, Huimin; Ma, Feng; Hu, Xiaona; Jin, Ting; Xiong, Chuhui; Teng, Xiaochun

    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.

  15. A COX2 PHYLOGENETIC HYPOTHESIS FOR THE DOWNY MILDEWS AND WHITE RUSTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mitochondrially encoded cox2 sequences were used to infer evolutionary relationships of downy mildew and white rust taxa in a data set of 36 peronosporomycete isolates. The data set of 599 aligned nucleotides was analyzed using neighbor joining, maximum parsimony, and maximum likelihood. These phylo...

  16. Case-Based Plan Recognition with Incomplete Plan Libraries Boris Kerkez and Michael T. Cox

    E-print Network

    Kerkez, Boris

    of a simple planning episode from the blocksworld planning domain. b) Two different views of the observed planCase-Based Plan Recognition with Incomplete Plan Libraries Boris Kerkez and Michael T. Cox-based keyhole plan recognition dealing with incomplete plan libraries. Most traditional plan recognition systems

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

    E-print Network

    Agmon, Noam

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

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

    E-print Network

    Nasipuri, Asis

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

  19. Liquid Foams D. Weaire, S.J. Cox and K. Brakke

    E-print Network

    Cox, Simon

    Liquid Foams D. Weaire, S.J. Cox §and K. Brakke ¶ Department of Physics, Trinity College, Dublin. Abstract The elegant structure of a liquid foam and its constituent parts have fascinated scientists, particularly for wet foams. 1 The structure of a liquid foam In 1873 the blind Belgian physicist Joseph Plateau

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

    E-print Network

    Cox, Landon

    to prevent confidential data from leaking. Un- fortunately, sensitive data is increasingly stored on per challenge for individuals and organizations on the Internet: inadvertent data leaks. GlobalRedFlag: Reducing Inadvertent Leaks by Personal Machines Landon P. Cox and Peter Gilbert Duke

  1. A Safety-Oriented Platform for Web Applications Richard S. Cox

    E-print Network

    Gribble, Steve

    A Safety-Oriented Platform for Web Applications Richard S. Cox , Jacob Gorm Hansen , Steven D and safety. 1 Introduction The 1993 release of the Mosaic browser sparked the on- set of the modern Web, archival file storage, multime- dia, and e-commerce services of all types. Users transfer funds, purchase

  2. SDO: A Statistical Method for Global Optimization \\Lambda Dennis D. Cox y Susan John z

    E-print Network

    Neumaier, Arnold

    SDO: A Statistical Method for Global Optimization \\Lambda Dennis D. Cox y Susan John z Abstract. 1 Introduction There has been considerable interest in the problem of global optimization, the problem involves finding the global optimal point x \\Lambda of a general function f(x). There is no dearth

  3. Microstructure, ferromagnetism, and magnetic transport of Ti1-xCoxO2 amorphous magnetic semiconductor

    E-print Network

    Liu, J. Ping

    semiconductor Hong-Qiang Song,a Liang-Mo Mei, and Shi-Shen Yan School of Physics and Microelectronics, Shandong-based magnetic semiconductors with high Co doping concentrations Ti1-xCoxO2 were synthesized under semiconductor. The electrical transport in a low temperature range was explained by spin-dependent Efros

  4. Simplified solutions of the Cox-Thompson inverse scattering method at fixed energy

    E-print Network

    Tamas Palmai; Miklos Horvath; Barnabas Apagyi

    2011-11-25

    Simplified solutions of the Cox-Thompson inverse quantum scattering method at fixed energy are derived if a finite number of partial waves with only even or odd angular momenta contribute to the scattering process. Based on new formulae various approximate methods are introduced which also prove applicable to the generic scattering events.

  5. Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance

    PubMed Central

    Hoang, Bao; Zhu, Li; Shi, Yijiang; Frost, Patrick; Yan, Huajun; Sharma, Sanjai; Sharma, Sherven; Goodglick, Lee; Dubinett, Steven; Lichtenstein, Alan

    2006-01-01

    Oncogenic RAS expression occurs in up to 40% of multiple myeloma (MM) cases and correlates with aggressive disease. Since activated RAS induces cyclooxygenase-2 (cox-2) expression in other tumor models, we tested a role for cox-2 in mutant RAS–containing MM cells. We used the ANBL-6 isogenic MM cell lines in which the IL-6–dependent parental line becomes cytokine independent following transfection with mutated N-RAS or K-RAS. Both mutated N-RAS– and K-RAS–expressing ANBL-6 cells demonstrated a selective up-regulation of cox-2 expression and enhanced secretion of PGE2, a product of cox-2. Furthermore, in 3 primary marrow specimens, which contained MM cells expressing mutated RAS, 15% to 40% of tumor cells were positive for cox-2 expression by immunohistochemistry. We used cox-2 inhibitors, NS398 and celecoxib, and neutralizing anti-PGE2 antibody to test whether cox-2/PGE2 was involved in the aggressive phenotype of MM ANBL-6 cells containing mutated RAS. Although these interventions had no effect on IL-6–independent growth or adhesion to marrow stromal cells, they significantly inhibited the enhanced binding of mutant RAS– containing MM cells to fibronectin and the enhanced resistance to melphalan. These results indicate a selective induction of cox-2 in MM cells containing RAS mutations, which results in heightened binding to extracellular matrix protein and chemotherapeutic drug resistance. PMID:16497971

  6. 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…

  7. Logistic Regression Multiple linear regression is used when the response variable is quantitative,

    E-print Network

    Olive, David

    Chapter 10 Logistic Regression Multiple linear regression is used when the response variable random variables with Yi binomial(1, (xi)). The binary logistic regression (LR) model is the special that = Cov(x|Y ) = Cov(x). Then as for the binary logistic regression model, P(Y = 1|x) = (x) = exp( + T x) 1

  8. The cytosol-synthesized subunit II (Cox2) precursor with the point mutation W56R is correctly processed in yeast mitochondria to rescue cytochrome oxidase.

    PubMed

    Cruz-Torres, Valentín; Vázquez-Acevedo, Miriam; García-Villegas, Rodolfo; Pérez-Martínez, Xochitl; Mendoza-Hernández, Guillermo; González-Halphen, Diego

    2012-12-01

    Deletion of the yeast mitochondrial gene COX2 encoding subunit 2 (Cox2) of cytochrome c oxidase (CcO) results in loss of respiration (?cox2 strain). Supekova et al. (2010) [1] transformed a ?cox2 strain with a vector expressing Cox2 with a mitochondrial targeting sequence (MTS) and the point mutation W56R (Cox2(W56R)), restoring respiratory growth. Here, the CcO carrying the allotopically-expressed Cox2(W56R) was characterized. Yeast mitochondria from the wild-type (WT) and the ?cox2+Cox2(W56R) strains were subjected to Blue Native electrophoresis. In-gel activity of CcO and spectroscopic quantitation of cytochromes revealed that only 60% of CcO is present in the complemented strain, and that less CcO is found associated in supercomplexes as compared to WT. CcOs from the WT and the mutant exhibited similar subunit composition, although activity was 20-25% lower in the enzyme containing Cox2(W56R) than in the one with Cox2(WT). Tandem mass spectrometry confirmed that W(56) was substituted by R(56) in Cox2(W56R). In addition, Cox2(W56R) exhibited the same N-terminus than Cox2(WT), indicating that the MTS of Oxa1 and the leader sequence of 15 residues were removed from Cox2(W56R) during maturation. Thus, Cox2(W56R) is identical to Cox2(WT) except for the point mutation W56R. Mitochondrial Cox1 synthesis is strongly reduced in ?cox2 mutants, but the Cox2(W56R) complemented strain led to full restoration of Cox1 synthesis. We conclude that the cytosol-synthesized Cox2(W56R) follows a rate-limiting process of import, maturation or assembly that yields lower steady-state levels of CcO. Still, the allotopically-expressed Cox2(W56R) restores CcO activity and allows mitochondrial Cox1 synthesis to advance at WT levels. PMID:22985601

  9. 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

  10. 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.

  11. Association between COX-2 gene polymorphisms and risk of hepatocellular carcinoma development: a meta-analysis

    PubMed Central

    Lu, Si-Cong; Zhong, Jian-Hong; Tan, Jun-Tao; Tang, Hua-Lin; Liu, Xiao-Guang; Xiang, Bang-De; Li, Le-Qun; Peng, Tao

    2015-01-01

    Objective To investigate the association between cyclo-oxygenase-2 (COX-2) polymorphism and the risk of hepatocellular carcinoma (HCC) development. Design Systematic review and meta-analysis of COX-2 polymorphism and risk of HCC development among people with or without HCC. Data sources EMBASE, PubMed, Public Library of Science, SCOPUS, Web of Knowledge and Chinese National Knowledge Infrastructure were searched for all clinical and experimental case–control studies of COX-2 polymorphism and HCC risk. Studies published up to March 2015 were included. Review method Ten studies were included for data extraction, which were mainly from Asian countries. Results 2538 people with HCC and 3714 without HCC were found to satisfy the inclusion criteria and included in the review. The associations of specific genotypes in the eight polymorphic variants of COX-2 and the risk of HCC development were analysed. GG genotype at the A-1195G polymorphism may be associated with a reduced risk of HCC development: the OR across all studies was 0.87 (95% CI 0.75 to 1.02) for the G allele versus the A allele, 0.72 (0.53 to 0.97) for GG versus AA, 0.72 (0.57 to 0.92) for GG versus GA+AA and 1.05 (0.77 to 1.44) for AA versus GA+GG. Similar results were found when the meta-analysis was repeated separately for the Chinese subgroup. However, more reliable data are needed to demonstrate associations between variants in G-765C, T+8473C, A-1290G, G-899C and introns 1, 5 and 6 polymorphisms and the risk of HCC development. Conclusions Only the COX-2 A-1195G gene polymorphism may be associated with a decreased risk of HCC development. These conclusions should be verified in further studies. PMID:26438136

  12. Antiproliferative effect of two novel COX-2 inhibitors on human keratinocytes.

    PubMed

    Sticozzi, Claudia; Belmonte, Giuseppe; Cervellati, Franco; Di Capua, Angela; Maioli, Emanuela; Cappelli, Andrea; Giordani, Antonio; Biava, Mariangela; Anzini, Maurizio; Valacchi, Giuseppe

    2013-05-13

    Selective COX-2 inhibitors (COXib) belonging to the class of diaryl heterocycles (e.g., celecoxib, rofecoxib, etc.), are devoid of the undesirable effects due to their capacity to inhibit selectively inducible (COX-2), responsible for inflammatory effects but not constitutive cyclooxygenase-1 (COX-1)(COX); responsible for cytoprotective effects on gastric mucosa. In addition, several reports have identified an increased risk of cardiovascular events associated with the use of COXib. We have developed a new series of anti-inflammatory agents (1,5-diarylpyrrole-3-alkoxyethyl esters and ethers). To evaluate the effect of two 1,5-diarylpyrrole-3-alkoxyethyl ethers, VA441 and VA428 (up to 100 ?M), respectively, in comparison with two well known COXib, celecoxib and rofecoxib, on HaCaT cell (keratinocytes) proliferation and toxicity. Crucial molecules in cell cycle progression, i.e. NF?B and ERK as targets/mediators and cyclin D1 and p21 Cip1/Kip as final effectors were evaluated by Western blot, immunohystochemistry and q-PCR analysis. Both compounds, VA441 and VA428, showed a strong inhibition of cell proliferation, and did not exhibit cytotoxicity. The anti-proliferative effect was accompanied by a strong activation of ERK and induction of the cell cycle inhibitor p21. In addition, there was a clear inhibition of the transcription factor NF-?B and downregulation of cyclin D1, with enforced inhibition of the HaCaT cell cycle progression. These data suggest that compounds VA441 and VA428, along with their role in inhibiting COX-2 and inflammation, could have a possible therapeutic (topical and systemic) use against skin proliferative disorders, such as psoriasis. PMID:23454135

  13. Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors.

    PubMed

    Abdellatif, Khaled R A; Abdelgawad, Mohamed A; Labib, Madlen B; Zidan, Taha H

    2015-12-15

    A new series of triarylpyrazoline derivatives 8a-p containing the most important COX-2 pharmacophore (SO2CH3 or/and SO2NH2) were synthesized by reaction of propen-1-one derivatives 6a-h with different phenyl hydrazine hydrochloride derivatives 7a-b in aqueous ethanol. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and showed good in vivo anti-inflammatory activity. Compounds 8g, 8j and 8o showed the highest anti-inflammatory activity and were less ulcerogenic (Ulcer Index=6.85, 7.7, 5.92, respectively) than indomethacin (Ulcer Index=12.3) and comparable to celecoxib (Ulcer Index=4.85). PMID:26546221

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

    SciTech Connect

    Zhu, Yingting; Tissue Tech Inc, Miami, FL 33173 ; Zhu, Min; Lance, Peter

    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.

  15. 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

  16. Insulin Resistance: Regression and Clustering

    PubMed Central

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

    2014-01-01

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

  17. Self-concordant analysis for logistic regression

    E-print Network

    Bach, Francis

    2009-01-01

    Most of the non-asymptotic theoretical work in regression is carried out for the square loss, where estimators can be obtained through closed-form expressions. In this paper, we use and extend tools from the convex optimization literature, namely self-concordant functions, to provide simple extensions of theoretical results for the square loss to the logistic loss. We apply the extension techniques to logistic regression with regularization by the $\\ell_2$-norm and regularization by the $\\ell_1$-norm, showing that new results for binary classification through logistic regression can be easily derived from corresponding results for least-squares regression.

  18. Geodesic least squares regression on information manifolds

    SciTech Connect

    Verdoolaege, Geert

    2014-12-05

    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. COX-2 Promotes Migration and Invasion by the Side Population of Cancer Stem Cell-Like Hepatocellular Carcinoma Cells.

    PubMed

    Guo, Zhe; Jiang, Jing-Hang; Zhang, Jun; Yang, Hao-Jie; Yang, Fu-Quan; Qi, Ya-Peng; Zhong, Yan-Ping; Su, Jie; Yang, Ri-Rong; Li, Le-Qun; Xiang, Bang-De

    2015-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise to new tumors. Cyclooxygenase-2 (COX-2) is highly expressed in several kinds of CSCs, and it helps promote stem cell renewal, proliferation, and radioresistance. Whether and how COX-2 contributes to CSC migration and invasion is unclear. In this study, COX-2 was overexpressed in the CSC-like side population (SP) of the human hepatocellular carcinoma (HCC) cell line HCCLM3. COX-2 overexpression significantly enhanced migration and invasion of SP cells, while reducing expression of metastasis-related proteins PDCD4 and PTEN. Treating SP cells with the selective COX-2 inhibitor celecoxib down-regulated COX-2 and caused a dose-dependent reduction in cell migration and invasion, which was associated with up-regulation of PDCD4 and PTEN. These results suggest that COX-2 exerts pro-metastatic effects on SP cells, and that these effects are mediated at least partly through regulation of PDCD4 and PTEN expression. These results further suggest that celecoxib may be a promising anti-metastatic agent to reduce migration and invasion by hepatic CSCs. PMID:26554780

  20. Monitoring of Fasciola Species Contamination in Water Dropwort by cox1 Mitochondrial and ITS-2 rDNA Sequencing Analysis.

    PubMed

    Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

    2015-10-01

    Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples. PMID:26537044

  1. Monitoring of Fasciola Species Contamination in Water Dropwort by cox1 Mitochondrial and ITS-2 rDNA Sequencing Analysis

    PubMed Central

    Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

    2015-01-01

    Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples. PMID:26537044

  2. PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

    PubMed Central

    Uddin, Jashim; Vitale, Paola; Panella, Andrea; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; Nickels, Mike; Tantawy, Mohammed N.; Manning, H. Charles; Marnett, Lawrence J.; Scilimati, Antonio

    2015-01-01

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 ?M (purified oCOX-1) and 1.37 ?M (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radio-chemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. PMID:24832612

  3. LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

    SciTech Connect

    Sun Haipeng; Xu Beibei; Sheveleva, Elena; Chen, Qin M.

    2008-10-01

    Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca{sup 2+} concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes.

  4. Relaxing the independent censoring assumption in the Cox proportional hazards model using multiple imputation.

    PubMed

    Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James

    2014-11-30

    The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. PMID:25060703

  5. Optical and electrical studies of vapour phase grown Cd1-xCoxTe crystals.

    PubMed

    Reddy, Y Dwarakanadha; Reddy, B K; Reddy, D Sreekantha; Reddy, D R

    2008-09-01

    The optical properties of vapour phase grown crystals of diluted magnetic semiconductor (DMS) Cd1-xCoxTe were investigated for x=0.001, 0.003, 0.005, 0.007 and 0.009. The reflectivity spectra exhibited a regular shift in the fundamental absorption edge (E0) with composition x. The reflectivity spectra for the present samples of Cd1-xCoxTe of all compositions exhibit broad bands at 5300 and 11,100cm(-1) due to the transitions of 4A2-->4T1 (F) and 4A2-->4T1 (P), respectively. Temperature dependence of resistivity revealed semiconducting behaviour of the samples. Hot probe test revealed that all the samples exhibited p-type conductivity. PMID:18434243

  6. CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models.

    PubMed

    Kim, Sun-Hee; Margalit, Ofer; Katoh, Hiroshi; Wang, Dingzhi; Wu, Hong; Xia, Dianren; Holla, Vijaykumar R; Yang, Peiying; DuBois, Raymond N

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation. These pre-clinical findings suggest a need for further exploration of CG100649 for CRC prevention and treatment. The long-term safety profile of CG100649, particularly regarding its effect on cardiovascular risk, is yet to be determined. PMID:25085205

  7. Barosensitivity in Saccharomyces cerevisiae is Closely Associated with a Deletion of the COX1 Gene.

    PubMed

    Nomura, Kazuki; Iwahashi, Hitoshi; Iguchi, Akinori; Shigematsu, Toru

    2015-05-01

    High hydrostatic pressure causes physical stress to microorganisms; therefore, this technology may be applied to food pasteurization without introducing the unfavorable effects of thermal denaturation. However, its application is limited to high-value foods because the treatment requires a robust steel vessel and expensive pressurization equipment. To reduce these costs, we studied the pasteurization of Saccharomyces cerevisiae using relatively moderate high-pressure levels. A mutant strain isolated by ultraviolet mutagenesis showed significant loss of viability under high-pressure conditions. Gene expression analysis of the mutant strain revealed that it incurred a deletion of the COX1 gene. Our results suggest that the pressure-sensitivity can readily be introduced into industrial/food microorganisms by complementing a COX1 deleted mitochondria. PMID:25881710

  8. 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

  9. c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells

    PubMed Central

    2012-01-01

    Background Endothelin-1 (ET-1) is elevated and participates in the regulation of several brain inflammatory disorders. The deleterious effects of ET-1 on endothelial cells may aggravate brain inflammation mediated through the upregulation of cyclooxygenase-2 (COX-2) gene expression. However, the signaling mechanisms underlying ET-1-induced COX-2 expression in brain microvascular endothelial cells remain unclear. Objective The goal of this study was to examine whether ET-1-induced COX-2 expression and prostaglandin E2 (PGE2) release were mediated through a c-Src-dependent transactivation of epidermal growth factor receptor (EGFR) pathway in brain microvascular endothelial cells (bEnd.3 cells). Methods The expression of COX-2 induced by ET-1 was evaluated by Western blotting and RT-PCR analysis. The COX-2 regulatory signaling pathways were investigated by pretreatment with pharmacological inhibitors, short hairpin RNA (shRNA) or small interfering RNA (siRNA) transfection, chromatin immunoprecipitation (ChIP), and promoter activity reporter assays. Finally, we determined the PGE2 level as a marker of functional activity of COX-2 expression. Results First, the data showed that ET-1-induced COX-2 expression was mediated through a c-Src-dependent transactivation of EGFR/PI3K/Akt cascade. Next, we demonstrated that ET-1 stimulated activation (phosphorylation) of c-Src/EGFR/Akt/MAPKs (ERK1/2, p38 MAPK, and JNK1/2) and then activated the c-Jun/activator protein 1 (AP-1) via Gq/i protein-coupled ETB receptors. The activated c-Jun/AP-1 bound to its corresponding binding sites within COX-2 promoter, thereby turning on COX-2 gene transcription. Ultimately, upregulation of COX-2 by ET-1 promoted PGE2 biosynthesis and release in bEnd.3 cells. Conclusions These results demonstrate that in bEnd.3 cells, c-Src-dependent transactivation of EGFR/PI3K/Akt and MAPKs linking to c-Jun/AP-1 cascade is essential for ET-1-induced COX-2 upregulation. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1/ETB system on brain microvascular endothelial cells may provide rational therapeutic interventions for brain injury and inflammatory diseases. PMID:22747786

  10. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

    PubMed

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P N; Kashfi, Khosrow

    2015-12-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011µM; m-NOSH-ASA, 0.24±0.11µM; p-NOSH-ASA, 0.46±0.17µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006µM, 0.092±0.004µM, and 0.37±0.04µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. PMID:26319435

  11. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling?

    PubMed Central

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P.N.; Kashfi, Khosrow

    2015-01-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5 mM at 24 h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. PMID:26319435

  12. 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

  13. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity

    PubMed Central

    Willenberg, Ina; Meschede, Anna K.; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX–2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA–7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX–2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 ?M, 2.6 ?M, 2.8 ?M and 7.4 ?M. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX–2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested. PMID:26440517

  14. Development of a Cox-Thompson inverse scattering method to charged particles

    E-print Network

    Tamas Palmai; Barnabas Apagyi; Werner Scheid

    2011-11-25

    A Cox-Thompson fixed-energy quantum inverse scattering method is developed further to treat long-range Coulomb interaction. Depending on the reference potentials chosen, two methods have been formulated which produce inverse potentials with singular or finite value at the origin. Based on the quality of reproduction of input experimental phase shifts, it is guessed that the p-alpha interaction possesses an interesting repulsive hard core.

  15. Involvement of PLA2, COX and LOX in Rhinella arenarum oocyte maturation.

    PubMed

    Ortiz, Maria Eugenia; Bühler, Marta Inés; Zelarayán, Liliana Isabel

    2014-11-01

    In Rhinella arenarum, progesterone is the physiological nuclear maturation inducer that interacts with the oocyte surface and starts a cascade of events that leads to germinal vesicle breakdown (GVBD). Polyunsaturated fatty acids and their metabolites produced through cyclooxygenase (COX) and lipoxygenase (LOX) pathways play an important role in reproductive processes. In amphibians, to date, the role of arachidonic acid (AA) metabolites in progesterone (P4)-induced oocyte maturation has not been clarified. In this work we studied the participation of three enzymes involved in AA metabolism - phospholipase A2 (PLA2), COX and LOX in Rhinella arenarum oocyte maturation. PLA2 activation induced maturation in Rhinella arenarum oocytes in a dose-dependent manner. Oocytes when treated with 0.08 ?M melittin showed the highest response (78 ± 6% GVBD). In follicles, PLA2 activation did not significantly induce maturation at the assayed doses (12 ± 3% GVBD). PLA2 inhibition with quinacrine prevented melittin-induced GVBD in a dose-dependent manner, however PLA2 inactivation did not affect P4-induced maturation. This finding suggests that PLA2 is not the only phospholipase involved in P4-induced maturation in this species. P4-induced oocyte maturation was inhibited by the COX inhibitors indomethacin and rofecoxib (65 ± 3% and 63 ± 3% GVBD, respectively), although COX activity was never blocked by their addition. Follicles showed a similar response following the addition of these inhibitors. Participation of LOX metabolites in maturation seems to be correlated with seasonal variation in ovarian response to P4. During the February to June period (low P4 response), LOX inhibition by nordihydroguaiaretic acid or lysine clonixinate increased maturation by up to 70%. In contrast, during the July to January period (high P4 response), LOX inhibition had no effect on hormone-induced maturation. PMID:23443017

  16. 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

  17. Structural, Electronic and Elastic Properties of Ternary Alloy CoxNi1-xSi2

    NASA Astrophysics Data System (ADS)

    Ouchene, S.; Kadri, M. T.; Baaouague, K.; Belkhir, H.

    2013-09-01

    First-principles calculations, by means of the full-potential linearized augmented plane wave (FP-LAPW) method using the generalized gradient approximation (GGA), were carried out for the structural, electronic and elastic properties of transition metals disilicides alloy CoxNi1-xSi2 in the fluorite structure. The composition effect on lattice constants and bulk modulus has been analyzed. The deviations of the lattice constants from Vegard's law and the bulk modulus from linear concentration dependence (LCD) were observed for CoxNi1-xSi2. We also calculated the densities of states for the distorted CoxNi1-xSi2 alloys as well as for the ordered phases CoSi2 and NiSi2. Theoretical values of Young's modulus, shear modulus, Poisson's ratio and Debye temperature are estimated from the computed elastic constants. The analysis of the ratio of shear modulus to bulk modulus shows that the alloy is more brittle than the binary compounds. The calculated results are compared with other reported values.

  18. Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core.

    PubMed

    Sarnpitak, Pakornwit; Mujumdar, Prashant; Morisseau, Christophe; Hwang, Sung Hee; Hammock, Bruce; Iurchenko, Vladimir; Zozulya, Sergey; Gavalas, Antonis; Geronikaki, Athina; Ivanenkov, Yan; Krasavin, Mikhail

    2014-09-12

    A novel series of compounds containing a polar, non-flat 2-imidazoline core was designed based on the SAR information available for aromatic azole cyclooxygenase-2 inhibitors. While the majority of the compounds prepared using an earlier developed imidazoline N-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300 nM) comparable to clinically used Celecoxib and was shown to be more selective. The series represents the first example of selective COX-2 inhibitors built around a distinctly polar core, contradicting an earlier accepted view that a lipophilic scaffold is required for high inhibitor potency. The lead compound demonstrated very good oral bioavailability in mice, slow metabolic degradation, modest distribution into the brain and a remarkable anti-inflammatory efficacy in carrageenan-induced mouse paw edema model. A foundation has therefore been laid for a chemically novel series of COX-2 inhibitors that has a potential for diverse therapeutic applications in inflammatory disease area. PMID:25016374

  19. COX-2 inhibition prevents the appearance of cutaneous squamous cell carcinomas accelerated by BRAF inhibitors

    PubMed Central

    Escuin-Ordinas, Helena; Atefi, Mohammad; Fu, Yong; Cass, Ashley; Ng, Charles; Huang, Rong Rong; Yashar, Sharona; Comin-Anduix, Begonya; Avramis, Earl; Cochran, Alistair J.; Marais, Richard; Lo, Roger S.; Graeber, Thomas G.; Herschman, Harvey R.; Ribas, Antoni

    2014-01-01

    Keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs) develop in 15-30% of patients with BRAFV600E metastatic melanoma treated with BRAF inhibitors (BRAFi). These lesions resemble mouse skin tumors induced by the two-stage DMBA/TPA skin carcinogenesis protocol; in this protocol BRAFi accelerates tumor induction. Since prior studies demonstrated cyclooxygenase 2 (COX-2) is necessary for DMBA/TPA tumor induction, we hypothesized that COX-2 inhibition might prevent BRAFi-accelerated skin tumors. Celecoxib, a COX-2 inhibitor, significantly delayed tumor acceleration by the BRAFi inhibitor PLX7420 and decreased tumor number by 90%. Tumor gene expression profiling demonstrated that celecoxib partially reversed the PLX4720-induced gene signature. In PDV cuSCC cells, vemurafenib (a clinically approved BRAFi) increased ERK phosphorylation and soft agar colony formation; both responses were greatly decreased by celecoxib. In clinical trials trametinib, a MEK inhibitor (MEKi) increases BRAFi therapy efficacy in BRAFV600E melanomas and reduces BRAFi-induced KA and cuSCC frequency. Trametinib also reduced vemurafenib-induced PDV soft agar colonies, but less efficiently than celecoxib. The trametinb/celecoxib combination was more effective than either inhibitor alone. In conclusion, celecoxib suppressed both BRAFi-accelerated skin tumors and soft-agar colonies, warranting its testing as a chemopreventive agent for non-melanoma skin lesions in patients treated with BRAFi alone or in combination with MEKi. PMID:24345644

  20. Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

    PubMed Central

    Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

    2011-01-01

    Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

  1. Cox Proportional Hazards Models for Modeling the Time to Onset of Decompression Sickness in Hypobaric Environments

    NASA Technical Reports Server (NTRS)

    Thompson, Laura A.; Chhikara, Raj S.; Conkin, Johnny

    2003-01-01

    In this paper we fit Cox proportional hazards models to a subset of data from the Hypobaric Decompression Sickness Databank. The data bank contains records on the time to decompression sickness (DCS) and venous gas emboli (VGE) for over 130,000 person-exposures to high altitude in chamber tests. The subset we use contains 1,321 records, with 87% censoring, and has the most recent experimental tests on DCS made available from Johnson Space Center. We build on previous analyses of this data set by considering more expanded models and more detailed model assessments specific to the Cox model. Our model - which is stratified on the quartiles of the final ambient pressure at altitude - includes the final ambient pressure at altitude as a nonlinear continuous predictor, the computed tissue partial pressure of nitrogen at altitude, and whether exercise was done at altitude. We conduct various assessments of our model, many of which are recently developed in the statistical literature, and conclude where the model needs improvement. We consider the addition of frailties to the stratified Cox model, but found that no significant gain was attained above a model that does not include frailties. Finally, we validate some of the models that we fit.

  2. Genomic selection for slaughter age in pigs using the Cox frailty model.

    PubMed

    Santos, V S; Martins Filho, S; Resende, M D V; Azevedo, C F; Lopes, P S; Guimarães, S E F; Glória, L S; Silva, F F

    2015-01-01

    The aim of this study was to compare genomic selection methodologies using a linear mixed model and the Cox survival model. We used data from an F2 population of pigs, in which the response variable was the time in days from birth to the culling of the animal and the covariates were 238 markers [237 single nucleotide polymorphism (SNP) plus the halothane gene]. The data were corrected for fixed effects, and the accuracy of the method was determined based on the correlation of the ranks of predicted genomic breeding values (GBVs) in both models with the corrected phenotypic values. The analysis was repeated with a subset of SNP markers with largest absolute effects. The results were in agreement with the GBV prediction and the estimation of marker effects for both models for uncensored data and for normality. However, when considering censored data, the Cox model with a normal random effect (S1) was more appropriate. Since there was no agreement between the linear mixed model and the imputed data (L2) for the prediction of genomic values and the estimation of marker effects, the model S1 was considered superior as it took into account the latent variable and the censored data. Marker selection increased correlations between the ranks of predicted GBVs by the linear and Cox frailty models and the corrected phenotypic values, and 120 markers were required to increase the predictive ability for the characteristic analyzed. PMID:26505412

  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. Regression Analysis: Legal Applications in Institutional Research

    ERIC Educational Resources Information Center

    Frizell, Julie A.; Shippen, Benjamin S., Jr.; Luna, Andrew L.

    2008-01-01

    This article reviews multiple regression analysis, describes how its results should be interpreted, and instructs institutional researchers on how to conduct such analyses using an example focused on faculty pay equity between men and women. The use of multiple regression analysis will be presented as a method with which to compare salaries of…

  5. 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…

  6. Dealing with Outliers: Robust, Resistant Regression

    ERIC Educational Resources Information Center

    Glasser, Leslie

    2007-01-01

    Least-squares linear regression is the best of statistics and it is the worst of statistics. The reasons for this paradoxical claim, arising from possible inapplicability of the method and the excessive influence of "outliers", are discussed and substitute regression methods based on median selection, which is both robust and resistant, are…

  7. HPV Vaccine Triggers Regression of Precancers.

    PubMed

    2015-12-01

    According to a phase IIb clinical trial, an investigational DNA vaccine that targets the human papillomavirus caused precancerous cervical lesions to regress or disappear. The vaccine stimulated production of CD8+ T cells that make perforin, a protein that helps kill infected cervical cells, and eliminated the virus in 81% of women whose lesions regressed. PMID:26487304

  8. 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…

  9. Incremental Net Effects in Multiple Regression

    ERIC Educational Resources Information Center

    Lipovetsky, Stan; Conklin, Michael

    2005-01-01

    A regular problem in regression analysis is estimating the comparative importance of the predictors in the model. This work considers the 'net effects', or shares of the predictors in the coefficient of the multiple determination, which is a widely used characteristic of the quality of a regression model. Estimation of the net effects can be a…

  10. 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.

  11. 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

  12. Robust Design Strategies for Nonlinear Regression Models

    E-print Network

    O'Brien, Timothy E.

    -lee,(10)1 are called locally D-optimal, those which minimize the maximum (over all X E X) of d1 Robust Design Strategies for Nonlinear Regression Models T. E. O'Brien University of Georgia Abstract In the context of nonlinear regression models, this paper outlines recent de velopments in design

  13. Three-Dimensional Modeling in Linear Regression.

    ERIC Educational Resources Information Center

    Herman, James D.

    Linear regression examines the relationship between one or more independent (predictor) variables and a dependent variable. By using a particular formula, regression determines the weights needed to minimize the error term for a given set of predictors. With one predictor variable, the relationship between the predictor and the dependent variable…

  14. A Simulation Investigation of Principal Component Regression.

    ERIC Educational Resources Information Center

    Allen, David E.

    Regression analysis is one of the more common analytic tools used by researchers. However, multicollinearity between the predictor variables can cause problems in using the results of regression analyses. Problems associated with multicollinearity include entanglement of relative influences of variables due to reduced precision of estimation,…

  15. Local polynomial regression on unknown manifolds

    E-print Network

    Bickel, Peter J

    2007-01-01

    We reveal the phenomenon that ``naive'' multivariate local polynomial regression can adapt to local smooth lower dimensional structure in the sense that it achieves the optimal convergence rate for nonparametric estimation of regression functions belonging to a Sobolev space when the predictor variables live on or close to a lower dimensional manifold.

  16. On convex regression estimators Nstor Aguilera*

    E-print Network

    Morin, Pedro

    using any constrained nonparametric estimate (kernel type, local polynomial, series or spline estimatorOn convex regression estimators Néstor Aguilera* Liliana Forzani* Pedro Morin* June 10, 2010 Abstract A new nonparametric estimator of a convex regression function in any dimension is proposed and its

  17. Bayesian Selection of Geostatistical Regression Models

    E-print Network

    (s)}), where E[Y (s)|Z(s)] = g-1{Z(s)} Parameter model Z = (Z(s1), . . . , Z(sn)) Nn(Xkk; ) where is definedBayesian Selection of Geostatistical Regression Models Devin S. Johnson, Ph.D. Department or commercial services mentioned in this presentation. Bayesian Selection of Geostatistical Regression Models

  18. Regression of Environmental Noise in LIGO Data

    E-print Network

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

    2015-01-01

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

  19. 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.

  20. Regression of environmental noise in LIGO data

    NASA Astrophysics Data System (ADS)

    Tiwari, V.; Drago, M.; Frolov, V.; Klimenko, S.; Mitselmakher, G.; Necula, V.; Prodi, G.; Re, V.; Salemi, F.; Vedovato, G.; Yakushin, I.

    2015-08-01

    We address the problem of noise regression in the output of gravitational-wave (GW) interferometers, using data from the physical environmental monitors (PEM). The objective of the regression analysis is to predict environmental noise in the GW channel from the PEM measurements. One of the most promising regression methods is based on the construction of Wiener-Kolmogorov (WK) filters. Using this method, the seismic noise cancellation from the LIGO GW channel has already been performed. In the presented approach the WK 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 present the first results on regression of the bi-coherent noise in the LIGO data.

  1. 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.

  2. Translational approach utilizing COX-2, p53, and MDM2 expressions in malignant transformation of oral submucous fibrosis.

    PubMed

    Patel, Pratik N; Thennavan, Aatish; Sen, Subhalakshmi; Chandrashekar, Chetana; Radhakrishnan, Raghu

    2015-09-01

    About 20% of the world's population uses some form of betel nut, which suggests that the incidence of oral submucous fibrosis (OSF) is higher than current estimates. OSF has the potential to undergo malignant transformation; thus, there is a need to identify relevant markers to assess its aggressiveness. We evaluated changes in COX-2, p53, and MDM2 expressions in progressive OSF. Expressions of COX-2, p53, and MDM2 increased with OSF progression. There was a strong association between COX-2 overexpression and recurrence of oral squamous cell carcinoma (P < 0.001) and a positive relation between increased MDM2 expression and failure of radiotherapy (P = 0.007). These findings suggest that COX-2 is an important marker of disease progression and that MDM2 expression is useful for treatment planning. PMID:26369479

  3. 2-Carbaborane-3-phenyl-1H-indoles – Synthesis via McMurry Reaction and COX Inhibition Activity

    PubMed Central

    Neumann, Wilma; Scholz, Matthias; Lönnecke, Peter; Crews, Brenda; Marnett, Lawrence J.; Pietzsch, Jens; Kniess, Torsten

    2013-01-01

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

  4. Neuroprotection mediated by the EP? receptor avoids the detrimental side effects of COX-2 inhibitors following ischaemic injury.

    PubMed

    Akram, Asha; Gibson, Claire L; Grubb, Blair D

    2013-02-01

    Although COX-2 inhibition in animal models of ischaemia has shown neuroprotection, clinical trials revealed long term side effects with COX-2 inhibitors. A more focussed approach is necessary to retain the therapeutic effects of prostaglandins. This study investigated the role of the PGE(2) EP(4) receptor using both in vitro and in vivo models of ischaemia. To demonstrate whether targeting the EP(4) receptor is as neuroprotective as COX-2 inhibition, simultaneous experiments were carried out using a selective COX-2 inhibitor. Organotypic hippocampal sliced cultures, exposed to 2 h of oxygen glucose deprivation, were treated with; DMSO only, COX-2 inhibitor (NS-398), EP(4) agonist (L-902688) or EP(4) antagonist (GW627368X) and cell death was assessed. The EP(4) agonist and the COX-2 inhibitor significantly reduced cell death following in vitro ischaemia, whereas treatment with the EP(4) antagonist significantly increased cell death in hippocampal cultures. Following a 1 h occlusion of middle cerebral artery, mice were treated with the COX-2 inhibitor (10 mg kg, I.P), EP(4) agonist (0.75 ?g/kg, I.P) or vehicle (I.P), at the onset of reperfusion and again at 24 h post stroke. The COX-2 inhibitor and EP(4) agonist treated animals showed a significant reduction in infarct volume (P < .05) at 48 h post stroke compared to the vehicle treated group. These results show that selective activation of the EP(4) receptor following acute ischaemic damage is neuroprotective, and support the concept of targeting protective prostaglandin receptor signalling as a potential therapeutic target for cerebral stroke. PMID:23041537

  5. Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: Inefficacy of genetic or pharmacological disruption of COX-2

    PubMed Central

    Fong, Louise Y.Y.; Jiang, Yubao; Riley, Maurisa; Liu, Xianglan; Smalley, Karl J.; Guttridge, Denis C.; Farber, John L.

    2009-01-01

    Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced for-estomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive bio-markers COX-2, nuclear factor (NF)-? B p65 and leukotriene A4 hydrolase (LTA4H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-2?/? forestomachs displayed strong LTA4H immunostaining, indicating activation of an alter-native pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. PMID:17985342

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

    PubMed Central

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

    2012-01-01

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

  7. Early Regression of Severe Left Ventricular Hypertrophy after Transcatheter Aortic Valve Replacement is Associated with Decreased Hospitalizations

    PubMed Central

    Lindman, Brian R.; Stewart, William J.; Pibarot, Philippe; Hahn, Rebecca T.; Otto, Catherine M.; Xu, Ke; Devereux, Richard B.; Weissman, Neil J.; Enriquez-Sarano, Maurice; Szeto, Wilson Y.; Makkar, Raj; Miller, D. Craig; Lerakis, Stamatios; Kapadia, Samir; Bowers, Bruce; Greason, Kevin L.; McAndrew, Thomas C.; Lei, Yang; Leon, Martin B.; Douglas, Pamela S.

    2014-01-01

    Objective Examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). Background LVM regression after valve replacement for aortic stenosis (AS) is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Methods Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 690 had both severe LVH (LVM index [LVMi] ³149 g/m2 men, ³122 g/m2 women) at baseline and an LVMi measurement 30 days post-TAVR. Clinical outcomes were compared for patients with greater than vs. lesser than median percent change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Results Compared to patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p=0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, HR 0.50; 95% CI, 0.32–0.78; p=0.002) and a lower rate of rehospitalizations specifically for heart failure (7.3% vs. 13.6%, p=0.01). The association with a lower rate of hospitalizations was consistent across sub-groups and remained significant after multivariable adjustment (HR 0.53; 95% CI, 0.34–0.84; p=0.007). Patients with greater LVMi regression had lower BNP (p=0.002) and a trend toward better quality of life (p=0.06) at 1 year compared to those with lesser regression. Conclusions In high-risk patients with severe AS and severe LVH undergoing TAVR, those with greater early LV mass regression had half the rate of rehospitalization over the subsequent year. PMID:24947722

  8. Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice.

    PubMed

    Shang, J L; Cheng, Q; Yang, W F; Zhang, M; Cui, Y; Wang, Y F

    2014-12-01

    People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI. PMID:25387671

  9. Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer: potential role for nexrutine.

    PubMed

    Ghosh, Rita; Garcia, Gretchen E; Crosby, Katherine; Inoue, Hiroyasu; Thompson, Ian M; Troyer, Dean A; Kumar, Addanki P

    2007-11-01

    We recently showed that Nexrutine, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Our data also indicate that the anti-proliferative effects of Nexrutine are emediated in part by Akt and Cyclic AMP response element binding protein (CREB). Cyclooxygenase (Cox-2), a pro-inflammatory mediator, is a CREB target that induces prostaglandin E(2) (PGE(2)) and suppresses apoptosis. Treatment of LNCaP cells with Nexrutine reduced tumor necrosis factor alpha-induced enzymatic as well as promoter activities of Cox-2. Nexrutine also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating Nexrutine response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01). We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like Nexrutine, demonstrating a prospective for development of Nexrutine for prostate cancer management. PMID:18030357

  10. Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway.

    PubMed

    Qin, Ge; Xu, Fei; Qin, Tao; Zheng, Qiufan; Shi, Dingbo; Xia, Wen; Tian, Yun; Tang, Yanlai; Wang, Jingshu; Xiao, Xiangshen; Deng, Wuguo; Wang, Shusen

    2015-12-01

    Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells. PMID:26540629

  11. Global Gene Expression Analysis of Canine Osteosarcoma Stem Cells Reveals a Novel Role for COX-2 in Tumour Initiation

    PubMed Central

    Pang, Lisa Y.; Gatenby, Emma L.; Kamida, Ayako; Whitelaw, Bruce A.; Hupp, Ted R.; Argyle, David J.

    2014-01-01

    Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p?=?0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation. PMID:24416158

  12. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    PubMed

    Pang, Lisa Y; Gatenby, Emma L; Kamida, Ayako; Whitelaw, Bruce A; Hupp, Ted R; Argyle, David J

    2014-01-01

    Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p?=?0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation. PMID:24416158

  13. Multiple-Regression Hidden Markov Model 

    E-print Network

    Fujinaga, Katsuhisa; Nakai, Mitsuru; Shimodaira, Hiroshi; Sagayama, Shigeki

    2001-01-01

    This paper proposes a new class of hidden Markov model (HMM) called multiple-regression HMM (MRHMM) that utilizes auxiliary features such as fundamental frequency (F0) and speaking styles that affect spectral parameters to ...

  14. Least quantile regression via modern optimization

    E-print Network

    Mazumder, Rahul

    We address the Least Quantile of Squares (LQS) (and in particular the Least Median of Squares) regression problem using modern optimization methods. We propose a Mixed Integer Optimization (MIO) formulation of the LQS ...

  15. A Library for Locally Weighted Projection Regression 

    E-print Network

    Klanke, Stefan; Vijayakumar, Sethu; Schaal, Stefan

    2008-01-01

    In this paper we introduce an improved implementation of locally weighted projection regression (LWPR), a supervised learning algorithm that is capable of handling high-dimensional input data. As the key features, our ...

  16. Reservoir characterization using nonparametric regression techniques 

    E-print Network

    Mathisen, Trond

    2000-01-01

    to improved permeability prediction uses electrofacies characterization determined from nonparametric regression and multivariate statistical analysis. Step 1 of this method is to classify the well log data into electrofacies types. For the purpose...

  17. Functional data analysis: classification and regression 

    E-print Network

    Lee, Ho-Jin

    2005-11-01

    Functional data refer to data which consist of observed functions or curves evaluated at a finite subset of some interval. In this dissertation, we discuss statistical analysis, especially classification and regression ...

  18. TWSVR: Regression via Twin Support Vector Machine.

    PubMed

    Khemchandani, Reshma; Goyal, Keshav; Chandra, Suresh

    2016-02-01

    Taking motivation from Twin Support Vector Machine (TWSVM) formulation, Peng (2010) attempted to propose Twin Support Vector Regression (TSVR) where the regressor is obtained via solving a pair of quadratic programming problems (QPPs). In this paper we argue that TSVR formulation is not in the true spirit of TWSVM. Further, taking motivation from Bi and Bennett (2003), we propose an alternative approach to find a formulation for Twin Support Vector Regression (TWSVR) which is in the true spirit of TWSVM. We show that our proposed TWSVR can be derived from TWSVM for an appropriately constructed classification problem. To check the efficacy of our proposed TWSVR we compare its performance with TSVR and classical Support Vector Regression(SVR) on various regression datasets. PMID:26624223

  19. Some Simple Computational Formulas for Multiple Regression

    ERIC Educational Resources Information Center

    Aiken, Lewis R., Jr.

    1974-01-01

    Short-cut formulas are presented for direct computation of the beta weights, the standard errors of the beta weights, and the multiple correlation coefficient for multiple regression problems involving three independent variables and one dependent variable. (Author)

  20. 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.

  1. PAR1-dependent COX-2/PGE2 production contributes to cell proliferation via EP2 receptors in primary human cardiomyocytes

    PubMed Central

    Chien, Peter Tzu-Yu; Hsieh, Hsi-Lung; Chi, Pei-Ling; Yang, Chuen-Mao

    2014-01-01

    Background and Purpose Different protease-activated receptors (PARs) activated by thrombin are involved in cardiovascular disease, via up-regulation of inflammatory proteins including COX-2. However, the mechanisms underlying thrombin-regulated COX-2 expression in human cardiomyocytes remain unclear. Experimental Approach Human cardiomyocytes were used in the study. Thrombin-induced COX-2 protein and mRNA expression, and signalling pathways were determined by Western blot, real-time PCR and COX-2 promoter luciferase reporter assays, and pharmacological inhibitors or siRNAs. PGE2 generation and cell proliferation were also determined. Key Results Thrombin-induced COX-2 protein and mRNA expression, promoter activity and PGE2 release was attenuated by the PAR1 antagonist (SCH79797) or the inhibitors of proteinase activity (PPACK), MEK1/2 (U0126), p38 MAPK (SB202190) or JNK1/2 (SP600125), and transfection with small interfering RNA (siRNA) of PAR1, p38, p42 or JNK2. These results suggested that PAR1-dependent MAPKs participate in thrombin-induced COX-2 expression in human cardiomyocytes. Moreover, thrombin stimulated phosphorylation of MAPKs, which was attenuated by PPACK and SCH79797. Furthermore, thrombin-induced COX-2 expression was blocked by the inhibitors of AP-1 (tanshinone IIA) and NF-?B (helenalin). Moreover, thrombin-stimulated phosphorylation of c-Jun/AP-1 and p65/NF-?B was attenuated by tanshinone IIA and helenalin, respectively, suggesting that thrombin induces COX-2 expression via PAR1/MAPKs/AP-1 or the NF-?B pathway. Functionally, thrombin increased human cardiomyocyte proliferation through the COX-2/PGE2 system linking to EP2 receptors, as determined by proliferating cell nuclear antigen and cyclin D1 expression. Conclusions and Implications These findings demonstrate that MAPKs-mediated activation of AP-1/NF-?B pathways is, at least in part, required for COX-2/PGE2/EP2-triggered cell proliferation in human cardiomyocytes. PMID:24902855

  2. Expression of integrin ?3?1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    PubMed Central

    2014-01-01

    Background Expression of integrin ?3?1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin ?3?1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin ?3?1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Methods Immunohistochemistry was performed to assess co-expression of ?3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n?=?59 samples) or obtained from Albany Medical Center archives (n?=?68 samples). Immunostaining intensity for the integrin ?3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Results Although expression of integrin ?3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between ?3 and COX2 in both tissue microarrays (rs?=?0.49, p?COX2 and ?3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin ?3?1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of ?3?1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target ?3?1, and that ?3 expression might serve as an independent prognostic biomarker. PMID:24950714

  3. 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

  4. 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

  5. Streamlining DNA Barcoding Protocols: Automated DNA Extraction and a New cox1 Primer in Arachnid Systematics

    PubMed Central

    Vidergar, Nina; Toplak, Nataša; Kuntner, Matjaž

    2014-01-01

    Background DNA barcoding is a popular tool in taxonomic and phylogenetic studies, but for most animal lineages protocols for obtaining the barcoding sequences—mitochondrial cytochrome C oxidase subunit I (cox1 AKA CO1)—are not standardized. Our aim was to explore an optimal strategy for arachnids, focusing on the species-richest lineage, spiders by (1) improving an automated DNA extraction protocol, (2) testing the performance of commonly used primer combinations, and (3) developing a new cox1 primer suitable for more efficient alignment and phylogenetic analyses. Methodology We used exemplars of 15 species from all major spider clades, processed a range of spider tissues of varying size and quality, optimized genomic DNA extraction using the MagMAX Express magnetic particle processor—an automated high throughput DNA extraction system—and tested cox1 amplification protocols emphasizing the standard barcoding region using ten routinely employed primer pairs. Results The best results were obtained with the commonly used Folmer primers (LCO1490/HCO2198) that capture the standard barcode region, and with the C1-J-2183/C1-N-2776 primer pair that amplifies its extension. However, C1-J-2183 is designed too close to HCO2198 for well-interpreted, continuous sequence data, and in practice the resulting sequences from the two primer pairs rarely overlap. We therefore designed a new forward primer C1-J-2123 60 base pairs upstream of the C1-J-2183 binding site. The success rate of this new primer (93%) matched that of C1-J-2183. Conclusions The use of C1-J-2123 allows full, indel-free overlap of sequences obtained with the standard Folmer primers and with C1-J-2123 primer pair. Our preliminary tests suggest that in addition to spiders, C1-J-2123 will also perform in other arachnids and several other invertebrates. We provide optimal PCR protocols for these primer sets, and recommend using them for systematic efforts beyond DNA barcoding. PMID:25415202

  6. The Geometry of Enhancement in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2011-01-01

    In linear multiple regression, "enhancement" is said to occur when R[superscript 2] = b[prime]r greater than r[prime]r, where b is a p x 1 vector of standardized regression coefficients and r is a p x 1 vector of correlations between a criterion y and a set of standardized regressors, x. When p = 1 then b [is congruent to] r and enhancement cannot…

  7. Fuzzy multiple linear regression: A computational approach

    NASA Technical Reports Server (NTRS)

    Juang, C. H.; Huang, X. H.; Fleming, J. W.

    1992-01-01

    This paper presents a new computational approach for performing fuzzy regression. In contrast to Bardossy's approach, the new approach, while dealing with fuzzy variables, closely follows the conventional regression technique. In this approach, treatment of fuzzy input is more 'computational' than 'symbolic.' The following sections first outline the formulation of the new approach, then deal with the implementation and computational scheme, and this is followed by examples to illustrate the new procedure.

  8. Hemodynamic sequelae of regression of experimental atherosclerosis.

    PubMed Central

    Armstrong, M L; Heistad, D D; Marcus, M L; Piegors, D J; Abboud, F M

    1983-01-01

    Regression of experimental atherosclerosis is characterized by decreased intimal thickness and luminal enlargement, but intimal fibrosis becomes more dense. We tested the hypothesis that fibrosis of arteries during regression might limit vasodilator capacity and restrict hemodynamic improvement despite luminal improvement. We studied limb, coronary, and cerebral hemodynamics in 11 normal cynomolgus monkeys, 10 monkeys given an atherogenic diet for 20 mo and 8 monkeys given a regression diet for an additional 18 mo. The atherogenic diet induced lesions of moderate severity (50-60% stenosis); owing to characteristic vessel growth during the atherogenic period, luminal size did not decrease correspondingly. Regression monkeys showed typical changes of regression with luminal enlargement but increased fibrosis. The iliac artery was perfused at constant blood flow and maximal vasodilatation was produced with papaverine. Blood flow was measured with microspheres during maximal vasodilatation in the coronary bed (adenosine) and cerebral bed (hypercapnia). In normal monkeys, minimal vascular resistances were 1.95 +/- 0.19 mm Hg/ml/min X 100 g (mean +/- SE) (limb), 0.13 +/- 0.01 (coronary), and 0.44 +/- 0.02 (cerebral). In atherosclerotic monkeys minimal resistance increased (P less than 0.05) 108, 62, and 166% in the limb, coronary, and cerebral beds, respectively. In regression monkeys, minimal resistance increased from values found in atherosclerotic animals in the limb (+22%), decreased inconsistently in the coronary bed (-19%), and decreased significantly in the cerebral bed (-44%, P less than 0.05). Thus morphologic regression was accompanied by significant hemodynamic improvement during maximal dilatation only in cerebral vessels. We conclude that increases in luminal size during regression of atherosclerotic lesions may not be associated with increases in vasodilator capacity, as intimal fibrosis may limit physiologically important hemodynamic improvement. PMID:6848553

  9. 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).

  10. COX-2 inhibitors from stem bark of Bauhinia rufescens Lam. (Fabaceae)

    PubMed Central

    Muhammad, Aminu; Sirat, Hasnah Mohd

    2013-01-01

    Chemical investigation of the stem bark of Bauhinia rufescens resulted in the isolation of a new cyanoglucoside and menisdaurin from methanol extract and oxepin from petroleum ether extract. The isolated compounds were tested for their anti-inflammatory potentials based on the cyclooxygenase-2 enzyme (COX-2) model. Cyanoglucoside exhibited the highest activity among the compounds with an inhibition activity of 49.34 % at 100 µM (IC50 0.46 µM) compared to the positive control, indomethacin (79.20 %, IC50 0.24 µM).

  11. [Sexual dimorphism in human medial raphe nuclei. Preliminary study with the Golgi cox method].

    PubMed

    Cordero, M E; Valenzuela, C Y; Torres, R

    1999-05-01

    Brains from a female and a male newborn who died from an asphictic syndrome were examined to study the cytoarchitecture of the median raphe nucleus using the Golgi-Cox and morphometric methods. This nucleus is part of the serotonergic system. The morphometric analysis showed in the female newborn a significant increase of neurons. Also she had a higher proportion of ovoid and multipolar cells and a lower proportion of fusiform cells than the newborn male. Our findings suggest that this neuronal distribution may be the anatomical substrate for a serotonergic specific system in each sex. PMID:10451622

  12. CoxC nanorod magnets: Highly magnetocrystalline anisotropy with lower Curie temperature for potential applications

    SciTech Connect

    El-Gendy, AA; Almugaiteeb, T; Carpenter, EE

    2013-12-01

    Magnetic CoxC nanorods with larger magnetocrystalline anisotropy of 5 x 10(5) J/m(3) as well as larger coercivity and lower Curie temperature are introduced. The particles have an average diameter of 8 nm and shows three different magnetic behaviors. The sample shows ferromagnetism up to 400 K, superparamagnetism at temperature > 400 K and

  13. 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.

  14. Label-noise Robust Logistic Regression and Its Applications

    E-print Network

    Kaban, Ata

    Label-noise Robust Logistic Regression and Its Applications Jakramate Bootkrajang and Ata Kab version of the logistic regression and multinomial logistic regression classifiers and develop based approach and consider a label-noise robust logistic regression and multinomial logistic regression

  15. Species differential regulation of COX2 can be described by an NF?B-dependent logic AND gate.

    PubMed

    Nguyen, Lan K; Cavadas, Miguel A S; Kholodenko, Boris N; Frank, Till D; Cheong, Alex

    2015-06-01

    Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NF?B)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNF?). Here, we report the presence of a molecular logic AND gate composed of two NF?B response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NF?B displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNF?, such that a threshold level of NF?B activation is required before the promoter becomes active and initiates transcription. This NF?B-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNF?. Our data suggest that the NF?B-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNF?, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation. PMID:25697863

  16. Rottlerin enhances IL-1?-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells

    PubMed Central

    Park, Eun Jung

    2011-01-01

    Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1? (IL-1?)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1?-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1? significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1? treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1?-induced COX-2 upregulation. However, suppression of protein kinase C ? (PKC ?) expression by siRNA or overexpression of dominant-negative PKC ? (DN-PKC-?) did not abrogate the rottlerin plus IL-1?-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-? (TNF-?), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1?-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. PMID:21971413

  17. A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition

    PubMed Central

    Chagas-Paula, Daniela A.; Zhang, Tong; Da Costa, Fernando B.; Edrada-Ebel, RuAngelie

    2015-01-01

    The application of metabolomics in phytochemical analysis is an innovative strategy for targeting active compounds from a complex plant extract. Species of the Asteraceae family are well-known to exhibit potent anti-inflammatory (AI) activity. Dual inhibition of the enzymes COX-1 and 5-LOX is essential for the treatment of several inflammatory diseases, but there is not much investigation reported in the literature for natural products. In this study, 57 leaf extracts (EtOH-H2O 7:3, v/v) from different genera and species of the Asteraceae family were tested against COX-1 and 5-LOX while HPLC-ESI-HRMS analysis of the extracts indicated high diversity in their chemical compositions. Using O2PLS-DA (R2 > 0.92; VIP > 1 and positive Y-correlation values), dual inhibition potential of low-abundance metabolites was determined. The O2PLS-DA results exhibited good validation values (cross-validation = Q2 > 0.7 and external validation = P2 > 0.6) with 0% of false positive predictions. The metabolomic approach determined biomarkers for the required biological activity and detected active compounds in the extracts displaying unique mechanisms of action. In addition, the PCA data also gave insights on the chemotaxonomy of the family Asteraceae across its diverse range of genera and tribes. PMID:26184333

  18. Tuning the Kondo effect in YbFe1-xCoxZn20

    NASA Astrophysics Data System (ADS)

    Kong, Tai; Taufour, Valentin; Bud'Ko, Sergey; Canfield, Paul

    2015-03-01

    YbCo2Zn20 is a heavy fermion compound with a Sommerfeld coefficient, ? value, of about 8000 mJ/mol-K2 with an estimated single ion Kondo temperature, TK, of about 1.5 K. One the other hand, YbFe2Zn20 is less heavy with ? ~ 500 mJ/mol-K2 and TK ~ 30 K. From a generalized Kadowaki-Woods picture, degeneracies that relate to their Kondo phenomena are large while different: 8 for YbFe2Zn20 and 4 for YbCo2Zn20. In order to understand the effects of Fe-Co substitution on the Kondo effect, a family of YbFe1-xCoxZn20 were studied. We performed zero-field resistivity and specific heat measurements on single crystals of YbFe1-xCoxZn20 that were synthesized using a high-temperature solution growth technique. The Kondo characteristic temperatures do not change monotonically in between pure YbFe2Zn20andYbCo2Zn20. Data and a summarize phase diagram of characteristic temperatures as a function of Co doping will be presented and discussed. This work is supported by the US DOE, Basic Energy Sciences under Contract No. DE-AC02-07CH11358.

  19. Ferromagnetism in inhomogeneous Zn1-xCoxO thin films

    NASA Astrophysics Data System (ADS)

    Tay, Maureen; Wu, Yihong; Han, Gu Chang; Chong, Tow Chong; Zheng, Yuan Kai; Wang, Shi Jie; Chen, Yanbin; Pan, Xiaoqing

    2006-09-01

    We report on a systematic study of structural, optical, electrical, and magnetic properties of Zn1-xCoxO (x=0.05-0.29) thin films codoped with Al (<0.1%). Both codoped (in which Co is cosputtered with other elements) and ?-doped (in which Co is doped digitally in the host matrix) samples have been prepared and studied. Prior to doping of Co, growth conditions were optimized to produce ZnO:Al films with a resistivity of about 1.3m?cm. Although all the films with x in the range of 0.05-0.29 showed clear hysteresis at room temperature in magnetometry measurement and absorption peaks associated with the d-d transitions of Co2+ ions, only the most heavily doped samples have shown clear anomalous Hall effect. The latter also showed strong, but photon energy dependent, magnetic circular dichroism and negative magnetoresistance at room temperature. These results in combination with detailed structural analysis by transmission electron microscope and x-ray diffraction study revealed that the ferromagnetic properties of Zn1-xCoxO were mostly originated from secondary phases and Co precipitates. The influence of inhomogeneity on the interpretation of various measurement results is also discussed.

  20. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression

    PubMed Central

    Liu, Fei; Mih, Justin D.; Shea, Barry S.; Kho, Alvin T.; Sharif, Asma S.; Tager, Andrew M.

    2010-01-01

    Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and matrix synthesis, accompanied by coordinated decreases in matrix proteolytic gene expression. Increasing matrix stiffness strongly suppresses fibroblast expression of COX-2 (cyclooxygenase-2) and synthesis of prostaglandin E2 (PGE2), an autocrine inhibitor of fibrogenesis. Exogenous PGE2 or an agonist of the prostanoid EP2 receptor completely counteracts the proliferative and matrix synthetic effects caused by increased stiffness. Together, these results demonstrate a dominant role for normal tissue compliance, acting in part through autocrine PGE2, in maintaining fibroblast quiescence and reveal a feedback relationship between matrix stiffening, COX-2 suppression, and fibroblast activation that promotes and amplifies progressive fibrosis. PMID:20733059

  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. 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

  3. 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

  4. A Multiple Logistic Regression Model for Predicting the Development of

    E-print Network

    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

  5. Wavelet Estimators in Nonparametric Regression: A Comparative Simulation Study

    E-print Network

    Wavelet Estimators in Nonparametric Regression: A Comparative Simulation Study Anestis Antoniadis: EM ALGORITHM; EMPIRICAL BAYES; MONTE CARLO EXPERIMENTS; NONPARAMETRIC REGRESSION; SMOOTHING METHODS; SHRINKAGE; THRESHOLDING; WAVELETS. #12;1 INTRODUCTION 3 1 INTRODUCTION Nonparametric regression has been

  6. Linear Models with Nonparametric Regression Unit code: MATH48011

    E-print Network

    Sidorov, Nikita

    MATH48011 Linear Models with Nonparametric Regression Unit code: MATH48011 Credit Rating: 15 Unit, etc. To introduce students to advanced statistical methods in Nonparametric Regression Models and Nonparametric Regression. Overview In many areas of science, technology, social science

  7. Nonparametric Cointegrating Regression with Endogeneity and Long Memory

    E-print Network

    Sydney, University of

    Nonparametric Cointegrating Regression with Endogeneity and Long Memory Qiying Wang School valid asymptotic inference in certain nonparametric cointegrating regression models. In particular, the standard normal limit theory for nonparametric regression estimates in stationary systems applies also

  8. MASTER'S PROJECT NONPARAMETRIC SURVEY REGRESSION ESTIMATION IN TWO-STAGE

    E-print Network

    estimator based on local polynomial regression is extended to incorporate spatial auxiliary information polynomial regression estimator for direct element sampling with scalar auxiliary information availableMASTER'S PROJECT NONPARAMETRIC SURVEY REGRESSION ESTIMATION IN TWO-STAGE SPATIAL SAMPLING Submitted

  9. ESTIMATING DISTRIBUTION FUNCTIONS FROM SURVEY DATA USING NONPARAMETRIC REGRESSION

    E-print Network

    based on local polynomial regression is introduced which removes these parametric restrictions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.2 Local Polynomial Regression . . . . . . . . . . . . . . . . . . . 12 2.2.1 General local polynomial regression . . . . . . . . . . . 12 2.2.2 Application to estimators in survey sampling

  10. Temperature and frequency dependence on electrical properties of polyaniline/Ni(1-x)CoxFe2O4 nanocomposites

    NASA Astrophysics Data System (ADS)

    Chitra, Palanisamy; Muthusamy, Athianna; Dineshkumar, Sengottuvelu; Jayaprakash, Rajan; Chandrasekar, J.

    2015-06-01

    Two nanocomposites of polyaniline (PANI) varying in their percentage composition of Ni(1-x)CoxFe2O4 nanoparticle (20%, 10% w/w of fine powders) were prepared by in-situ chemical oxidative polymerization method with and without ultrasonic treatment. The spinel ferrite nanoparticles of chemical composition Ni(1-x)CoxFe2O4 were prepared by auto combustion method. The structure and morphology of PANI and nanocomposites were characterized by X-ray diffraction (XRD) and High resolution transmission electron microscopy (HRTEM). The chemical structure of Ni(1-x)CoxFe2O4 nanoparticles and its composites were characterized by using Fourier transform infrared (FTIR), UV-visible absorption spectrometer and XRD techniques. Dielectric properties of nanocomposites at different temperature have been performed in the frequency range of 50 Hz to 5 MHz. Dielectric constant, dielectric loss and AC conductivity of PANI/Ni(1-x)CoxFe2O4 nanocomposites are significantly increasing with increase in ferrite content due to the polaron/bipolaron formation. The optical absorption experiments of PANI/Ni(1-x)CoxFe2O4 nanocomposite illustrate a direct transition with an energy band gap of Eg around 1.7.

  11. Computational Structure-Based De Novo Design of Hypothetical Inhibitors against the Anti- Inflammatory Target COX-2

    PubMed Central

    Bafna, Khushboo; Katiyar, Shashank Prakash; Goyal, Sukriti; Grover, Abhinav; Sundar, Durai

    2015-01-01

    Cyclooxygenase-2 (COX-2) produces prostaglandins in inflamed tissues and hence has been considered as an important target for the development of anti-inflammatory drugs since long. Administration of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and other COX-2 selective inhibitors (COXIBS) for the treat of inflammation has been found to be associated with side effects, which mainly includes gastro-intestinal (GI) toxicity. The present study involves developing a virtual library of novel molecules with high druglikeliness using structure-based de novo drug designing and 2D fingerprinting approach. A library of 2657 drug like molecules was generated. 2D fingerprinting based screening of the designed library gave a unique set of compounds. Molecular docking approach was then used to identify two compounds highly specific for COX-2 isoform. Molecular dynamics simulations of protein-ligand complexes revealed that the candidate ligands were dynamically stable within the cyclooxygenase binding site of COX-2. The ligands were further analyzed for their druglikeliness, ADMET properties and synthetic accessibility using knowledge based set of rules. The results revealed that the molecules are predicted to selectively bind to COX-2 enzyme thereby potentially overcoming the limitations posed by the drugs in clinical use. PMID:26241744

  12. Symbolic Regression of Conditional Target Expressions

    NASA Astrophysics Data System (ADS)

    Korns, Michael F.

    This chapter examines techniques for improving symbolic regression systems in cases where the target expression contains conditionals. In three previous papers we experimentedwith combining high performance techniques fromthe literature to produce a large scale, industrial strength, symbolic regression-classification system. Performance metrics across multiple problems show deterioration in accuracy for problems where the target expression contains conditionals. The techniques described herein are shown to improve accuracy on such conditional problems. Nine base test cases, from the literature, are used to test the improvement in accuracy. A previously published regression system combining standard genetic programming with abstract expression grammars, particle swarm optimization, differential evolution, context aware crossover and age-layered populations is tested on the nine base test cases. The regression system is enhanced with these additional techniques: pessimal vertical slicing, splicing of uncorrelated champions via abstract conditional expressions, and abstract mutation and crossover. The enhanced symbolic regression system is applied to the nine base test cases and an improvement in accuracy is observed.

  13. Hierarchical regression for analyses of multiple outcomes.

    PubMed

    Richardson, David B; Hamra, Ghassan B; MacLehose, Richard F; Cole, Stephen R; Chu, Haitao

    2015-09-01

    In cohort mortality studies, there often is interest in associations between an exposure of primary interest and mortality due to a range of different causes. A standard approach to such analyses involves fitting a separate regression model for each type of outcome. However, the statistical precision of some estimated associations may be poor because of sparse data. In this paper, we describe a hierarchical regression model for estimation of parameters describing outcome-specific relative rate functions and associated credible intervals. The proposed model uses background stratification to provide flexible control for the outcome-specific associations of potential confounders, and it employs a hierarchical "shrinkage" approach to stabilize estimates of an exposure's associations with mortality due to different causes of death. The approach is illustrated in analyses of cancer mortality in 2 cohorts: a cohort of dioxin-exposed US chemical workers and a cohort of radiation-exposed Japanese atomic bomb survivors. Compared with standard regression estimates of associations, hierarchical regression yielded estimates with improved precision that tended to have less extreme values. The hierarchical regression approach also allowed the fitting of models with effect-measure modification. The proposed hierarchical approach can yield estimates of association that are more precise than conventional estimates when one wishes to estimate associations with multiple outcomes. PMID:26232395

  14. Spontaneous Regression of Metastatic Visceral Malignant Melanoma

    PubMed Central

    Haight, Kenneth R.; Shapira, David V.; Cates, Geoffrey W.

    1984-01-01

    Spontaneous regressions of malignant tumors are rare. This report describes a patient who, after local recurrence of melanoma in his neck, developed pulmonary metastases which subsequently regressed. The patient was a 72-year-old retired farmer. Over the four years and five months from the discovery of the metastases to his death, this patient's pulmonary nodules regressed. Treatment was palliative, and there is no evidence that his immune system was artificially stimulated. He died from complications of a surgical repair of a hiatus hernia. No increase in the size of the pulmonary nodules was noted in chest X-rays taken during the three months before his death. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:21278950

  15. Efficient Regressions via Optimally Combining Quantile Information*

    PubMed Central

    Zhao, Zhibiao; Xiao, Zhijie

    2014-01-01

    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

  16. Uncertainty quantification in DIC with Kriging regression

    NASA Astrophysics Data System (ADS)

    Wang, Dezhi; DiazDelaO, F. A.; Wang, Weizhuo; Lin, Xiaoshan; Patterson, Eann A.; Mottershead, John E.

    2016-03-01

    A Kriging regression model is developed as a post-processing technique for the treatment of measurement uncertainty in classical subset-based Digital Image Correlation (DIC). Regression is achieved by regularising the sample-point correlation matrix using a local, subset-based, assessment of the measurement error with assumed statistical normality and based on the Sum of Squared Differences (SSD) criterion. This leads to a Kriging-regression model in the form of a Gaussian process representing uncertainty on the Kriging estimate of the measured displacement field. The method is demonstrated using numerical and experimental examples. Kriging estimates of displacement fields are shown to be in excellent agreement with 'true' values for the numerical cases and in the experimental example uncertainty quantification is carried out using the Gaussian random process that forms part of the Kriging model. The root mean square error (RMSE) on the estimated displacements is produced and standard deviations on local strain estimates are determined.

  17. Extraskeletal osteosarcoma with partial spontaneous regression.

    PubMed

    Matsuo, Toshihiro; Shimose, Shoji; Kubo, Tadahiko; Mikami, Yukio; Arihiro, Koji; Yasunaga, Yuji; Ochi, Mitsuo

    2009-12-01

    Resection for a mass in the proximal thigh was performed on a 57-year-old woman, the diagnosis of which was extraskeletal osteosarcoma. In pathological findings, tumor cells gradually decreased from the central area of the mass composed of spindle cell sarcoma and were replaced by fibrocollagenous tissue with no sarcoma cells. CD8(+), T-cell-restricted intracellular antigen-1 (TIA-1)(+), granzyme B(+) T lymphocytes appeared to infiltrate the mass lesion, so that we hypothesize that the immunological system was likely to be involved via T lymphocytes in triggering spontaneous regression in this case. One of the most unusual phenomena in cancer biology is the spontaneous regression of a tumor. Here, we report on the first case of extraskeletal osteosarcoma characterized by partial spontaneous regression of the primary lesion. PMID:20044636

  18. A tutorial on Bayesian Normal linear regression

    NASA Astrophysics Data System (ADS)

    Klauenberg, Katy; Wübbeler, Gerd; Mickan, Bodo; Harris, Peter; Elster, Clemens

    2015-12-01

    Regression is a common task in metrology and often applied to calibrate instruments, evaluate inter-laboratory comparisons or determine fundamental constants, for example. Yet, a regression model cannot be uniquely formulated as a measurement function, and consequently the Guide to the Expression of Uncertainty in Measurement (GUM) and its supplements are not applicable directly. Bayesian inference, however, is well suited to regression tasks, and has the advantage of accounting for additional a priori information, which typically robustifies analyses. Furthermore, it is anticipated that future revisions of the GUM shall also embrace the Bayesian view. Guidance on Bayesian inference for regression tasks is largely lacking in metrology. For linear regression models with Gaussian measurement errors this tutorial gives explicit guidance. Divided into three steps, the tutorial first illustrates how a priori knowledge, which is available from previous experiments, can be translated into prior distributions from a specific class. These prior distributions have the advantage of yielding analytical, closed form results, thus avoiding the need to apply numerical methods such as Markov Chain Monte Carlo. Secondly, formulas for the posterior results are given, explained and illustrated, and software implementations are provided. In the third step, Bayesian tools are used to assess the assumptions behind the suggested approach. These three steps (prior elicitation, posterior calculation, and robustness to prior uncertainty and model adequacy) are critical to Bayesian inference. The general guidance given here for Normal linear regression tasks is accompanied by a simple, but real-world, metrological example. The calibration of a flow device serves as a running example and illustrates the three steps. It is shown that prior knowledge from previous calibrations of the same sonic nozzle enables robust predictions even for extrapolations.

  19. REGRESSION AND SPARSE REGRESSION METHODS FOR VISCOSITY ESTIMATION OF ACID MILK FROM IT'S SLS FEATURES

    E-print Network

    REGRESSION AND SPARSE REGRESSION METHODS FOR VISCOSITY ESTIMATION OF ACID MILK FROM IT'S SLS to estimate the rheological char- acteristics of fermented milk from its SLS features. Acidified milk products the quality of the product. 1.1. Measurement of Rheological Properties The viscosity of acid milk increases

  20. A review of "Perceptions of Retailing in Early Modern England. Hampshire, England." by Nancy Cox and Karin Dannehl 

    E-print Network

    Hayworth, Gene

    2008-01-01

    stream_source_info Nancy Cox, et al.pdf.txt stream_content_type text/plain stream_size 9708 Content-Encoding ISO-8859-1 stream_name Nancy Cox, et al.pdf.txt Content-Type text/plain; charset=ISO-8859-1 202 s e v e n t e e.... Nancy Cox and Karin Dannehl. Perceptions of Retailing in Early Modern England. Hampshire, England: Ashgate Publishing Company, 2007. xv+214 pp. $99.95. Review by Ge n e ha y w o r t h , un i v e r s i t y o f co l o r a d o , Bo u l d e r...

  1. Local polynomial regression and variable selection

    E-print Network

    Miller, Hugh

    2010-01-01

    We propose a method for incorporating variable selection into local polynomial regression. This can improve the accuracy of the regression by extending the bandwidth in directions corresponding to those variables judged to be are unimportant. It also increases our understanding of the dataset by highlighting areas where these variables are redundant. The approach has the potential to effect complete variable removal as well as perform partial removal when a variable redundancy applies only to particular regions of the data. We define a nonparametric oracle property and show that this is more than satisfied by our approach under asymptotic analysis. The usefulness of the method is demonstrated through simulated and real data numerical examples.

  2. Quantile regression modeling for Malaysian automobile insurance premium data

    NASA Astrophysics Data System (ADS)

    Fuzi, Mohd Fadzli Mohd; Ismail, Noriszura; Jemain, Abd Aziz

    2015-09-01

    Quantile regression is a robust regression to outliers compared to mean regression models. Traditional mean regression models like Generalized Linear Model (GLM) are not able to capture the entire distribution of premium data. In this paper we demonstrate how a quantile regression approach can be used to model net premium data to study the effects of change in the estimates of regression parameters (rating classes) on the magnitude of response variable (pure premium). We then compare the results of quantile regression model with Gamma regression model. The results from quantile regression show that some rating classes increase as quantile increases and some decrease with decreasing quantile. Further, we found that the confidence interval of median regression (? = O.5) is always smaller than Gamma regression in all risk factors.

  3. Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

    PubMed Central

    Nachat-Kappes, Rachida; Pinel, Alexandre; Combe, Kristell; Lamas, Bruno; Farges, Marie-Chantal; Rossary, Adrien; Goncalves-Mendes, Nicolas; Caldefie-Chezet, Florence; Vasson, Marie-Paule; Basu, Samar

    2012-01-01

    Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F2-isoprostanes, PGF2?, IL-6, TNF-?, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-?, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels. PMID:23272114

  4. Crystal structure and Raman scattering characterization of Cu2Fe1-xCoxSnS4 chalcogenide compounds

    NASA Astrophysics Data System (ADS)

    López-Vergara, F.; Galdámez, A.; Manríquez, V.; González, Guillermo

    2015-11-01

    This work reports the synthesis by solid-state reaction of Cu2Fe1-xCoxSnS4 solid solutions. Crystal structures of Cu2Fe0.8Co0.2SnS4 and Cu2Fe0.6Co0.4SnS4 were investigated by single crystal X-ray diffraction. Both phases crystallize in the tetragonal stannite-type structure. The volume of the tetrahedral [MS4] (M = Fe, Co) presented the highest distortion, with Edge-Length Distortion (ELD) indices ?2% from the ideal tetrahedron. The powder X-ray diffraction (XRD) patterns of Cu2Fe1-xCoxSnS4 (x = 0.2, 0.4, 0.6 and 0.8) has been refined by Rietveld method. No secondary phases were detected in XRD patterns. An analysis of the vibrational properties of Cu2Fe1-xCoxSnS4 was performed using Raman scattering measurements. The Raman peaks were analyzed by fitting of the spectra and subsequently identifying the vibrational modes by comparison with experimental and theoretical data from Cu2FeSnS4 (CFTS) and Cu2CoSnS4 (CCTS) end-members. The spectra from Cu2Fe1-xCoxSnS4 show that there is a variation in the frequency of the main A1 peak at ?320 cm-1 together with a decrease in the secondary mode intensity at ?285 cm-1. Full Width at Half Maximum (FWHM) and the intensity of the Raman peaks reflect the high crystallinity of Cu2Fe1-xCoxSnS4 solid solutions. The oxidation states of the metals were confirmed by temperature-dependent magnetization measurements performed in the antiferromagnetic Cu2Fe1-xCoxSnS4 solid solutions.

  5. Demonstration of a Fiber Optic Regression Probe

    NASA Technical Reports Server (NTRS)

    Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    The capability to provide localized, real-time monitoring of material regression rates in various applications has the potential to provide a new stream of data for development testing of various components and systems, as well as serving as a monitoring tool in flight applications. These applications include, but are not limited to, the regression of a combusting solid fuel surface, the ablation of the throat in a chemical rocket or the heat shield of an aeroshell, and the monitoring of erosion in long-life plasma thrusters. The rate of regression in the first application is very fast, while the second and third are increasingly slower. A recent fundamental sensor development effort has led to a novel regression, erosion, and ablation sensor technology (REAST). The REAST sensor allows for measurement of real-time surface erosion rates at a discrete surface location. The sensor is optical, using two different, co-located fiber-optics to perform the regression measurement. The disparate optical transmission properties of the two fiber-optics makes it possible to measure the regression rate by monitoring the relative light attenuation through the fibers. As the fibers regress along with the parent material in which they are embedded, the relative light intensities through the two fibers changes, providing a measure of the regression rate. The optical nature of the system makes it relatively easy to use in a variety of harsh, high temperature environments, and it is also unaffected by the presence of electric and magnetic fields. In addition, the sensor could be used to perform optical spectroscopy on the light emitted by a process and collected by fibers, giving localized measurements of various properties. The capability to perform an in-situ measurement of material regression rates is useful in addressing a variety of physical issues in various applications. An in-situ measurement allows for real-time data regarding the erosion rates, providing a quick method for empirically anchoring any analysis geared towards lifetime qualification. Erosion rate data over an operating envelope could also be useful in the modeling detailed physical processes. The sensor has been embedded in many regressing media for the purposes of proof-of-concept testing. A gross demonstration of its capabilities was performed using a sanding wheel to remove layers of metal. A longer-term demonstration measurement involved the placement of the sensor in a brake pad, monitoring the removal of pad material associated with the normal wear-and-tear of driving. It was used to measure the regression rates of the combustable media in small model rocket motors and road flares. Finally, a test was performed using a sand blaster to remove small amounts of material at a time. This test was aimed at demonstrating the unit's present resolution, and is compared with laser profilometry data obtained simultaneously. At the lowest resolution levels, this unit should be useful in locally quantifying the erosion rates of the channel walls in plasma thrusters. .

  6. The cox protein of bacteriophage P2 inhibits the formation of the repressor protein and autoregulates the early operon.

    PubMed

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

    1987-10-01

    The cox gene is the first gene of the early operon of bacteriophage P2. The early promoter Pe and the repressor promoter Pc are located close to each other and in such a way that their transcripts have opposite polarity and show an overlap of about 30 nucleotides. The expression of the early operon and of the C gene was studied in vivo by using fusions to a promoterless cat (chloramphenicol acetyl transferase) gene. The results show that the Cox protein negatively autoregulates the early operon and inhibits the formation of the repressor C. By measuring the efficiency of plating of a series of P2 virulent deletion mutants on bacteria carrying a cloned cox gene, the site of action of the Cox protein was mapped within the Pe-Pc region. The stimulatory effect of the C protein on expression of the Pc promoter was found to be due to inhibition of transcription from Pc; this was demonstrated by mutating Pe which showed that loss of transcription from Pe stimulated transcription from Pc. Hence, this is a case of regulation of gene expression by convergent transcription. By cloning the region C-Pe-Pc-cox such that the cat and kan genes are expressed from Pc and Pe, respectively, it was shown that only one of the resistances (Cm and Km) was expressed. This mimics the choice between lysogeny and lytic growth of the phage. The 'lysogenic' state was very stable whereas the 'lytic' state flipped to the 'lysogenic' at a somewhat higher frequency. The presence of a cloned cox gene drastically stimulated the formation of free phage from a P2-lysogen and dramatically reduced the frequency of lysogenization after P2 infection. We conclude that the pleiotropic effects of the cox (control of excision) gene, namely effects on lysogenization, formation of free phage and site-specific P2 recombination, can be explained by the effect of the Cox protein on the activity of the promoters Pc and Pe. PMID:2826134

  7. Structural, vibrational and magnetic properties of Ni1-xCoxFe2O4 ferrites

    NASA Astrophysics Data System (ADS)

    Nandan, Brajesh; Bhatnagar, M. C.

    2015-08-01

    The ferrite with chemical formula Ni1-xCoxFe2O4 (x= 0.00, 0.50, 1.00) were prepared using sol-gel method. X-ray diffraction (XRD), Raman spectroscopy and physical property measurement system (PPMS) were used to characterize the structural, vibrational and magnetic properties. XRD pattern confirmed single crystalline spinel structure of Nickel ferrite with Co substitution. Lattice parameter variation confirms the substitution of Co2+ ions at the place of Ni2+ into the nickel ferrite. Raman scattering at room temperature is used to study the redistribution of Ni and Co cations between tetrahedral (A) and octahedral (B) sites. A shift is observed in Co substitute nickel ferrite in both XRD and Raman studies. M-H hysteresis is carried out at room temperature. Saturation magnetization of the samples is increased with the Co2+ ions substitution.

  8. Study of magnetoelastic and magnetocrystalline anisotropies in CoxNi1-x nanowire arrays

    NASA Astrophysics Data System (ADS)

    Moskaltsova, Anastasiia; Proenca, Mariana P.; Nedukh, Sergey V.; Sousa, Célia T.; Vakula, Arthur; Kakazei, Gleb N.; Tarapov, Sergey I.; Araujo, Joao P.

    2015-01-01

    Highly ordered CoxNi1-x nanowire (NW) arrays were electrodeposited inside nanoporous anodic aluminum oxide membranes. The control of the applied potential during the electrodeposition process allowed us to easily tune the Co% in the alloy. Systematic studies on the morphological and crystallographic properties together with static and dynamic magnetic characterizations were performed. In this work we focus on the study of the dynamic magnetic properties of CoNi NW arrays using the ferromagnetic resonance method at both room (RT) and low (LT) temperatures. The careful comparison analysis performed between the magnetic anisotropy fields obtained at RT and LT, allowed us to extract for the first time the magnetocrystalline anisotropy effect of the Co component and, most importantly, the magnetoelastic anisotropy effect of Ni.

  9. Magnetic properties of a mechanically alloyed metastable Cu1-xCox system

    NASA Astrophysics Data System (ADS)

    Prieto, P.; Reyes, D.; Cortes, A.; Gomez, M. E.; Lopera, W.; Lopez, M.

    2008-03-01

    We report a detailed study of the magnetic properties of Cu1-xCox with Co concentrations between 7 and 10 at% produced by mechanical alloying, through a reactive milling process by using a Retsch PM 400 planetary ball mill under argon atmosphere. We have magnetically characterized our samples by using a Vibrating Sample magnetometer, VSM, from Quantum Design^TM. We conducted magnetization hysteresis loops at different temperatures from 5 to 300 K. We also measured magnetization as a function of temperature for samples with different milling times. We analyzed the dependence of the coercive field on temperature and found that when milling time increases from 80 to 100h, it reflects an increase in the coercive field from 425 to 525 Oe at 30K; that is the maximum coercive field. We can explain these results by using a dipolar interaction model according to the Co precipitate size in the copper matrix.

  10. Expected Power-Utility Maximization Under Incomplete Information and with Cox-Process Observations

    SciTech Connect

    Fujimoto, Kazufumi; Nagai, Hideo; Runggaldier, Wolfgang J.

    2013-02-15

    We consider the problem of maximization of expected terminal power utility (risk sensitive criterion). The underlying market model is a regime-switching diffusion model where the regime is determined by an unobservable factor process forming a finite state Markov process. The main novelty is due to the fact that prices are observed and the portfolio is rebalanced only at random times corresponding to a Cox process where the intensity is driven by the unobserved Markovian factor process as well. This leads to a more realistic modeling for many practical situations, like in markets with liquidity restrictions; on the other hand it considerably complicates the problem to the point that traditional methodologies cannot be directly applied. The approach presented here is specific to the power-utility. For log-utilities a different approach is presented in Fujimoto et al. (Preprint, 2012).

  11. Theranostic nanoemulsions for macrophage COX-2 inhibition in a murine inflammation model.

    PubMed

    Patel, Sravan Kumar; Beaino, Wissam; Anderson, Carolyn J; Janjic, Jelena M

    2015-09-01

    Targeting macrophages for therapeutic and diagnostic purposes is an attractive approach applicable to multiple diseases. Here, we present a theranostic nanoemulsion platform for simultaneous delivery of an anti-inflammatory drug (celecoxib) to macrophages and monitoring of macrophage migration patterns by optical imaging, as measurement of changes in inflammation. The anti-inflammatory effect of the theranostic nanoemulsions was evaluated in a mouse inflammation model induced with complete Freund's adjuvant (CFA). Nanoemulsions showed greater accumulation in the inflamed vs. control paw, with histology confirming their specific localization in CD68 positive macrophages expressing cyclooxygenase-2 (COX-2) compared to neutrophils. With a single dose administration of the celecoxib-loaded theranostic, we observed a reduction in fluorescence in the paw with time, corresponding to a reduction in macrophage infiltration. Our data strongly suggest that delivery of select agents to infiltrating macrophages can potentially lead to new treatments of inflammatory diseases where macrophage behavior changes are monitored in vivo. PMID:25959685

  12. Human Raphe Magnus Nucleus: a morphometric Golgi-Cox study with emphasis on sex differences.

    PubMed

    Cordero, M E; Rodriguez, A; Torres, R; Valenzuela, C Y

    2001-11-26

    The number and proportion of neurons according to their type and size in the Raphe Magnus Nucleus stained by the Golgi-Cox and Nissl methods were compared in male and female infants. Four female/male pairs aged from 2 to 150 days were studied. While females showed more neurons than males, males showed a higher proportion of large multipolar (more than 40 microm) and fusiform neurons (more than 20 microm) but not of ovoid neurons (more than 15 microm). These differences varied according to the type of cells and age of infants. Some of these results are similar to those found in the human Median Raphe Nucleus with the same methods. PMID:11718839

  13. Origin of the spin reorientation transitions in (Fe1–xCox)2B alloys

    DOE PAGESBeta

    Belashchenko, Kirill D.; Ke, Liqin; Däne, Markus; Benedict, Lorin X.; Lamichhane, Tej Nath; Taufour, Valentin; Jesche, Anton; Bud'ko, Sergey L.; Canfield, Paul C.; Antropov, Vladimir P.

    2015-02-13

    Low-temperature measurements of the magnetocrystalline anisotropy energy K in (Fe1–xCox)2B alloys are reported, and the origin of this anisotropy is elucidated using a first-principles electronic structure analysis. The calculated concentration dependence K(x) with a maximum near x = 0.3 and a minimum near x = 0.8 is in excellent agreement with experiment. This dependence is traced down to spin-orbital selection rules and the filling of electronic bands with increasing electronic concentration. At the optimal Co concentration, K depends strongly on the tetragonality and doubles under a modest 3% increase of the c/a ratio, suggesting that the magnetocrystalline anisotropy can bemore »further enhanced using epitaxial or chemical strain.« less

  14. Assessing risk factors for periodontitis using regression

    NASA Astrophysics Data System (ADS)

    Lobo Pereira, J. A.; Ferreira, Maria Cristina; Oliveira, Teresa

    2013-10-01

    Multivariate statistical analysis is indispensable to assess the associations and interactions between different factors and the risk of periodontitis. Among others, regression analysis is a statistical technique widely used in healthcare to investigate and model the relationship between variables. In our work we study the impact of socio-demographic, medical and behavioral factors on periodontal health. Using regression, linear and logistic models, we can assess the relevance, as risk factors for periodontitis disease, of the following independent variables (IVs): Age, Gender, Diabetic Status, Education, Smoking status and Plaque Index. The multiple linear regression analysis model was built to evaluate the influence of IVs on mean Attachment Loss (AL). Thus, the regression coefficients along with respective p-values will be obtained as well as the respective p-values from the significance tests. The classification of a case (individual) adopted in the logistic model was the extent of the destruction of periodontal tissues defined by an Attachment Loss greater than or equal to 4 mm in 25% (AL?4mm/?25%) of sites surveyed. The association measures include the Odds Ratios together with the correspondent 95% confidence intervals.

  15. Revisiting Regression in Autism: Heller's "Dementia Infantilis"

    ERIC Educational Resources Information Center

    Westphal, Alexander; Schelinski, Stefanie; Volkmar, Fred; Pelphrey, Kevin

    2013-01-01

    Theodor Heller first described a severe regression of adaptive function in normally developing children, something he termed dementia infantilis, over one 100 years ago. Dementia infantilis is most closely related to the modern diagnosis, childhood disintegrative disorder. We translate Heller's paper, Uber Dementia Infantilis, and discuss…

  16. Determining School Effectiveness Following a Regression Analysis.

    ERIC Educational Resources Information Center

    Convey, John J.

    Three methods that can be used subsequent to a regression analysis to determine the relative effectiveness of schools are Dyer's Performance Indices, Scheffe's hyperbolic confidence bands, and Gafarian's linear confidence bands. These methods were applied to data from 54 hypothetical schools randomly generated from a multivariate normal…

  17. Determining School Effectiveness Following a Regression Analysis

    ERIC Educational Resources Information Center

    Convey, John J.

    1977-01-01

    Three methods that can be used subsequent to a regression analysis to determine the relative effectiveness of schools are Dyer's performance indicators, Scheffe's hyperbolic confidence bands, and Gafarian's linear confidence bands. The purpose of this paper is to investigate the relative usefulness of the three methods under various conditions.…

  18. Predicting Social Trust with Binary Logistic Regression

    ERIC Educational Resources Information Center

    Adwere-Boamah, Joseph; Hufstedler, Shirley

    2015-01-01

    This study used binary logistic regression to predict social trust with five demographic variables from a national sample of adult individuals who participated in The General Social Survey (GSS) in 2012. The five predictor variables were respondents' highest degree earned, race, sex, general happiness and the importance of personally assisting…

  19. Robust Multivariate Linear Regression David J. Olive

    E-print Network

    Olive, David

    Robust Multivariate Linear Regression David J. Olive Southern Illinois University May 3, 2013. KEY WORDS: outliers; prediction regions. David J. Olive is Associate Professor, Department: dolive@siu.edu. 1 #12;1 INTRODUCTION Olive (2013b), using results from Su and Cook (2012) and Kakizawa

  20. Uncertainty Techniques Statistics, Least Squares, Regression,

    E-print Network

    Rostock, Universität

    Uncertainty Techniques Statistics, Least Squares, Regression, ML-Estimation, Stochastic Processes Objectives 5 The Fourier series is an example for function approximation using the orthogonality principle. The least-squares principle does not require a statistical framework to make sense. Maximum likelihood

  1. Regression Mutation Testing Lingming Zhang1

    E-print Network

    Marinov, Darko

    Regression Mutation Testing Lingming Zhang1 , Darko Marinov2 , Lu Zhang3 , Sarfraz Khurshid1 1@sei.pku.edu.cn ABSTRACT Mutation testing is one of the most powerful approaches for eval- uating quality of test suites. However, mutation testing is also one of the most expensive testing approaches. This paper presents Re

  2. Developmental Regression in Children with Down Syndrome

    E-print Network

    Bernad Ripoll, Susana

    2011-05-18

    This study presents in detail the data on a group of 20 participants, female and male, from 2 to 12 years old with Down syndrome (DS) who experienced developmental regression. This study took place at the Down syndrome clinic at Kennedy Krieger...

  3. A Constrained Linear Estimator for Multiple Regression

    ERIC Educational Resources Information Center

    Davis-Stober, Clintin P.; Dana, Jason; Budescu, David V.

    2010-01-01

    "Improper linear models" (see Dawes, Am. Psychol. 34:571-582, "1979"), such as equal weighting, have garnered interest as alternatives to standard regression models. We analyze the general circumstances under which these models perform well by recasting a class of "improper" linear models as "proper" statistical models with a single predictor. We…

  4. Nonparametric regression with martingale increment errors

    E-print Network

    Delattre, Sylvain

    2010-01-01

    We consider the problem of adaptive estimation of the regression function in a framework where we replace ergodicity assumptions (such as independence or mixing) by another structural assumption on the model. Namely, we propose adaptive upper bounds for kernel estimators with data-driven bandwidth (Lepski's selection rule) in a regression model where the noise is an increment of martingale. It includes, as very particular cases, the usual i.i.d. regression and auto-regressive models. The cornerstone tool for this study is a new result for self-normalized martingales, called ``stability'', which is of independent interest. In a first part, we only use the martingale increment structure of the noise. We give an adaptive upper bound using a random rate, that involves the occupation time near the estimation point. Thanks to this approach, the theoretical study of the statistical procedure is disconnected from usual ergodicity properties like mixing. Then, in a second part, we make a link with the usual minimax th...

  5. Using Regression Analysis: A Guided Tour.

    ERIC Educational Resources Information Center

    Shelton, Fred Ames

    1987-01-01

    Discusses the use and interpretation of multiple regression analysis with computer programs and presents a flow chart of the process. A general explanation of the flow chart is provided, followed by an example showing the development of a linear equation which could be used in estimating manufacturing overhead cost. (Author/LRW)

  6. Spherical Regression Models Using Projective Linear Transformations

    E-print Network

    Srivastava, Anuj

    studied projected linear regression models in situations where only the response variable was directional and one-dimensional. Due to a growing awareness of geometrical and computational tools there has been-norm constraint on the data, i.e. analysis of unit-length vectors, leads to the representation space becoming

  7. Genetics Home Reference: Caudal regression syndrome

    MedlinePLUS

    ... disorder. Some researchers believe that a disruption of fetal development around day 28 of pregnancy causes caudal regression ... away from the lower areas of the developing fetus. Decreased blood flow to these areas is thought to interfere with their development and result in the signs and symptoms of ...

  8. On Spatial Adaptive Estimation of Nonparametric Regression

    E-print Network

    Nemirovski, Arkadi

    On Spatial Adaptive Estimation of Nonparametric Regression A. Goldenshluger and A. Nemirovski square (piecewise polynomial) estimate equipped with adaptively adjusted window pos- sesses in the value of f at a given point x0, then it is natural to measure the quality by local risks of the type Rx0

  9. Conventional univariate versus multivariate spectrophotometric assisted techniques for simultaneous determination of perindopril arginin and amlodipine besylate in presence of their degradation products.

    PubMed

    Hegazy, Maha A; Abbas, Samah S; Zaazaa, Hala E; Essam, Hebatallah M

    2015-11-01

    The resolving power of spectrophotometric assisted mathematical techniques were demonstrated for the simultaneous determination of perindopril arginin (PER) and amlodipine besylate (AML) in presence of their degradation products. The conventional univariate methods include the absorptivity factor method (AFM) and absorption correction method (ACM), which were able to determine the two drugs, simultaneously, but not in the presence of their degradation products. In both methods, amlodipine was determined directly at 360 nm in the concentration range of 8-28 ?g mL(-1), on the other hand perindopril was determined by AFM at 222.2 nm and by ACM at 208 nm in the concentration range of 10-70 ?g mL(-1). Moreover, the applied multivariate calibration methods were able for the determination of perindopril and amlodipine in presence of their degradation products using concentration residuals augmented classical least squares (CRACLS) and partial least squares (PLS). The proposed multivariate methods were applied to 19 synthetic samples in the concentration ranges of 60-100 ?g mL(-1) perindopril and 20-40 ?g mL(-1) amlodipine. Commercially available tablet formulations were successfully analysed using the developed methods without interference from other dosage form additives except PLS model, which failed to determine both drugs in their pharmaceutical dosage form. PMID:26123511

  10. Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures

    NASA Astrophysics Data System (ADS)

    Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

    2013-02-01

    The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH3 asymmetric, CH2 asymmetric, CH3 symmetric and CH2 symmetric groups, (ii) unsaturation (Cdbnd C) group, and (iii) carbonyl ester (Cdbnd O) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P < 0.05) in nutrient profile and lipid related molecular spectral intensity (CH2 asymmetric stretching peak height, CH2 symmetric stretching peak height, ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality.

  11. CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma.

    PubMed

    Rodríguez-Arámbula, Adriana; Torres-Álvarez, Bertha; Cortés-García, Diego; Fuentes-Ahumada, Cornelia; Castanedo-Cázares, Juan Pablo

    2015-10-01

    The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1?, IL-1?, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature. PMID:26381025

  12. Sevoflurane Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury via Cav-3-Dependent COX-2 Inhibition

    PubMed Central

    Zhao, Jianli; Zhang, Yanqing; Wang, Feng; Jiao, Liyuan; Lau, Wayne Bond; Wang, Lili; Liu, Baojiang; Gao, Erhe; Koch, Walter J.; Ma, Xin-Liang; Wang, Yajing

    2013-01-01

    Background The inhaled anesthetic sevoflurane has been demonstrated to protect against myocardial ischemia/reperfusion (MI/R) injury, via mechanisms involving AMP-activated protein kinase (AMPK) and caveolin-3 (Cav-3). However, the relative contributions of AMPK and Cav-3 to sevoflurane preconditioning-mediated cardioprotection, and their precise underlying mechanisms of action, remain incompletely understood. Methods and Results Sevoflurane preconditioning (SF-PreCon, consisting of 3 cycles of 15 minute-exposures to 2% sevoflurane prior to 30 minutes of MI) decreased MI/R injury in WT mice (caspase-3 activity ?29.1%, infarct size ?20.2%, and LVEDP ?33.8%). In cardiac-specific AMPK?2 dominant negative overexpression (AMPK-DN) mice, the cardioprotective effect of SF-PreCon was largely retained (caspase-3 activity ?26.7%, infarct size ?16.7%, and LVEDP ?25.9%, P<0.01). In contrast, SF-PreCon failed to significantly protect Cav3-knockout (Cav3-KO) mice against MI/R injury (P>0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in WT (?43.6%) and AMPK-DN mice (?35.5%, P<0.01), but not in Cav3-KO mice. SF-PreCon did not affect NADPH oxidase expression, but significantly inhibited COX-2 expression in WT (?38.7%) and AMPK-DN mice (?35.8%), but not in Cav-3KO mice. Conclusions We demonstrate for the first time sevoflurane preconditioning mediates cardioprotection against MI/R injury via Cav-3 dependent-COX-2 inhibition and anti-oxidative effects. PMID:24030395

  13. Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2.

    PubMed

    Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2016-01-01

    Inflammation is a local defensive reaction of a host to cellular injury or infection. Prolonged inflammation can contribute to pathogenesis of many disorders. Identification of naturally occurring phytoconstituents that can suppress inflammatory mediators can lead to the discovery of anti-inflammatory therapeutics. Acacia ferruginea is used traditionally to treat numerous ailments including hemorrhage, irritable bowel syndrome and leprosy. The present study evaluated the anti-inflammatory activity of A. ferruginea extract against acute (carrageenan) and chronic (formaldehyde) inflammation in Balb/c mice. Pre-treatment with A. ferruginea extract (10?mg/kg BW) for 5 consecutive days via intraperitonial (IP) administration significantly inhibited subsequent induction of paw edema in both models; the effects were comparable to that of the standard drug indomethacin. The results also showed the A. ferruginea extract significantly inhibited nitric oxide (NO) synthesis and iNOS expression (as measured in serum), diminished inflammation in - and neutrophil infiltration to - the paw tissues and led to a reduction in the number of COX-2(+) immunoreative cells (as evidenced by histologic and immunohistochemical analyses) in the paws relative to those in paws of mice that received the irritants only. Further, in vitro studies showed the extract could significantly scavenge free radicals generated as in DPPH and NO radical generating assays. Taken together, the results showed that A. ferruginea extract imparted potent anti-oxidant and -inflammatory effects, in part by maintaining oxidative homeostasis, inhibiting NO synthesis and suppressing iNOS and COX-2 expression and so could potentially be exploited as a potential plant-based medication against inflammatory disorders. PMID:25738525

  14. DiffGen: Automated Regression Unit-Test Kunal Taneja

    E-print Network

    Xie, Tao

    DiffGen: Automated Regression Unit-Test Generation Kunal Taneja Department of Computer ScienceGen for automated regression unit-test generation and checking for Java programs. Given two versions of a Java class maintenance cost is in fact spent on regression testing. Developers need to have regression tests that can

  15. Kernel Regression with Correlated Errors K. De Brabanter

    E-print Network

    : It is a well-known problem that obtaining a correct bandwidth in nonparametric regression is difficult support vector machines for regression. Keywords: nonparametric regression, correlated errors, short-range dependence, bimodal kernel, cross­validation 1. INTRODUCTION In nonparametric regression problems, one

  16. GOCPS 2010, Leipzig 3 March 2010 Qualitatively Robust Nonparametric Regression

    E-print Network

    Hable, Robert

    GOCPS 2010, Leipzig 3 March 2010 Qualitatively Robust Nonparametric Regression By Support Vector;Qualitatively Robust Nonparametric Regression By Support Vector Machines Nonparametric Regression Y = f0(X University of Bayreuth Page 01 #12;Qualitatively Robust Nonparametric Regression By Support Vector Machines

  17. POSTERIOR CONSISTENCY IN NONPARAMETRIC REGRESSION PROBLEMS UNDER GAUSSIAN PROCESS PRIORS

    E-print Network

    POSTERIOR CONSISTENCY IN NONPARAMETRIC REGRESSION PROBLEMS UNDER GAUSSIAN PROCESS PRIORS By Taeryon regression is to put a nonparametric prior distribution on the unknown regression function using Gaussian processes. In this paper, we study posterior consistency in nonparametric regression problems using Gaussian

  18. Efficient Locally Weighted Polynomial Regression Predictions Andrew W. Moore

    E-print Network

    Schneider, Jeff

    Efficient Locally Weighted Polynomial Regression Predictions Andrew W. Moore Robotics Institute Regression Locally weighted polynomial regression (LWPR) is a form of instance­based (a.k.a memory­based) al polynomial regression (LWPR) is a popular instance­based al­ gorithm for learning continuous non

  19. The comparison of robust partial least squares regression with robust principal component regression on a real

    NASA Astrophysics Data System (ADS)

    Polat, Esra; Gunay, Suleyman

    2013-10-01

    One of the problems encountered in Multiple Linear Regression (MLR) is multicollinearity, which causes the overestimation of the regression parameters and increase of the variance of these parameters. Hence, in case of multicollinearity presents, biased estimation procedures such as classical Principal Component Regression (CPCR) and Partial Least Squares Regression (PLSR) are then performed. SIMPLS algorithm is the leading PLSR algorithm because of its speed, efficiency and results are easier to interpret. However, both of the CPCR and SIMPLS yield very unreliable results when the data set contains outlying observations. Therefore, Hubert and Vanden Branden (2003) have been presented a robust PCR (RPCR) method and a robust PLSR (RPLSR) method called RSIMPLS. In RPCR, firstly, a robust Principal Component Analysis (PCA) method for high-dimensional data on the independent variables is applied, then, the dependent variables are regressed on the scores using a robust regression method. RSIMPLS has been constructed from a robust covariance matrix for high-dimensional data and robust linear regression. The purpose of this study is to show the usage of RPCR and RSIMPLS methods on an econometric data set, hence, making a comparison of two methods on an inflation model of Turkey. The considered methods have been compared in terms of predictive ability and goodness of fit by using a robust Root Mean Squared Error of Cross-validation (R-RMSECV), a robust R2 value and Robust Component Selection (RCS) statistic.

  20. Comparison of Prediction Model for Cardiovascular Autonomic Dysfunction Using Artificial Neural Network and Logistic Regression Analysis

    PubMed Central

    Zeng, Fangfang; Li, Zhongtao; Yu, Xiaoling; Zhou, Linuo

    2013-01-01

    Background This study aimed to develop the artificial neural network (ANN) and multivariable logistic regression (LR) analyses for prediction modeling of cardiovascular autonomic (CA) dysfunction in the general population, and compare the prediction models using the two approaches. Methods and Materials We analyzed a previous dataset based on a Chinese population sample consisting of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN and LR analysis, and were tested in the validation set. Performances of these prediction models were then compared. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with the prevalence of CA dysfunction (P<0.05). The mean area under the receiver-operating curve was 0.758 (95% CI 0.724–0.793) for LR and 0.762 (95% CI 0.732–0.793) for ANN analysis, but noninferiority result was found (P<0.001). The similar results were found in comparisons of sensitivity, specificity, and predictive values in the prediction models between the LR and ANN analyses. Conclusion The prediction models for CA dysfunction were developed using ANN and LR. ANN and LR are two effective tools for developing prediction models based on our dataset. PMID:23940593

  1. Adding local components to global functions for continuous covariates in multivariable regression modeling.

    PubMed

    Binder, H; Sauerbrei, W

    2010-03-30

    When global techniques, based on fractional polynomials (FPs), are employed for modeling potentially nonlinear effects of several continuous covariates on a response, accessible model equations are obtained. However, local features might be missed. Therefore, a procedure is introduced, which systematically checks model fits, obtained by the multivariable fractional polynomial (MFP) approach, for overlooked local features. Statistically significant local polynomials are then parsimoniously added. This approach, called MFP + L, is seen to result in an effective control of the Type I error with respect to the addition of local components in a small simulation study with univariate and multivariable settings. Prediction performance is compared with that of a penalized regression spline technique. In a setting unfavorable for FPs, the latter outperforms the MFP approach, if there is much information in the data. However, the addition of local features reduces this performance difference. There is only a small detrimental effect in settings where the MFP approach performs better. In an application example with children's respiratory health data, fits from the spline-based approach indicate many local features, but MFP + L adds only few significant features, which seem to have good support in the data. The proposed approach may be expected to be superior in settings with local features, but retains the good properties of the MFP approach in a large number of settings where global functions are sufficient. PMID:20213721

  2. Characterization of Engineered Cartilage Constructs Using Multiexponential T2 Relaxation Analysis and Support Vector Regression

    PubMed Central

    Irrechukwu, Onyi N.; Reiter, David A.; Lin, Ping-Chang; Roque, Remigio A.; Fishbein, Kenneth W.

    2012-01-01

    Increased sensitivity in the characterization of cartilage matrix status by magnetic resonance (MR) imaging, through the identification of surrogate markers for tissue quality, would be of great use in the noninvasive evaluation of engineered cartilage. Recent advances in MR evaluation of cartilage include multiexponential and multiparametric analysis, which we now extend to engineered cartilage. We studied constructs which developed from chondrocytes seeded in collagen hydrogels. MR measurements of transverse relaxation times were performed on samples after 1, 2, 3, and 4 weeks of development. Corresponding biochemical measurements of sulfated glycosaminoglycan (sGAG) were also performed. sGAG per wet weight increased from 7.74±1.34??g/mg in week 1 to 21.06±4.14??g/mg in week 4. Using multiexponential T2 analysis, we detected at least three distinct water compartments, with T2 values and weight fractions of (45?ms, 3%), (200?ms, 4%), and (500?ms, 97%), respectively. These values are consistent with known properties of engineered cartilage and previous studies of native cartilage. Correlations between sGAG and MR measurements were examined using conventional univariate analysis with T2 data from monoexponential fits with individual multiexponential compartment fractions and sums of these fractions, through multiple linear regression based on linear combinations of fractions, and, finally, with multivariate analysis using the support vector regression (SVR) formalism. The phenomenological relationship between T2 from monoexponential fitting and sGAG exhibited a correlation coefficient of r2=0.56, comparable to the more physically motivated correlations between individual fractions or sums of fractions and sGAG; the correlation based on the sum of the two proteoglycan-associated fractions was r2=0.58. Correlations between measured sGAG and those calculated using standard linear regression were more modest, with r2 in the range 0.43–0.54. However, correlations using SVR exhibited r2 values in the range 0.68–0.93. These results indicate that the SVR-based multivariate approach was able to determine tissue sGAG with substantially higher accuracy than conventional monoexponential T2 measurements or conventional regression modeling based on water fractions. This combined technique, in which the results of multiexponential analysis are examined with multivariate statistical techniques, holds the potential to greatly improve the accuracy of cartilage matrix characterization in engineered constructs using noninvasive MR data. PMID:22166112

  3. Embedded Sensors for Measuring Surface Regression

    NASA Technical Reports Server (NTRS)

    Gramer, Daniel J.; Taagen, Thomas J.; Vermaak, Anton G.

    2006-01-01

    The development and evaluation of new hybrid and solid rocket motors requires accurate characterization of the propellant surface regression as a function of key operational parameters. These characteristics establish the propellant flow rate and are prime design drivers affecting the propulsion system geometry, size, and overall performance. There is a similar need for the development of advanced ablative materials, and the use of conventional ablatives exposed to new operational environments. The Miniature Surface Regression Sensor (MSRS) was developed to serve these applications. It is designed to be cast or embedded in the material of interest and regresses along with it. During this process, the resistance of the sensor is related to its instantaneous length, allowing the real-time thickness of the host material to be established. The time derivative of this data reveals the instantaneous surface regression rate. The MSRS could also be adapted to perform similar measurements for a variety of other host materials when it is desired to monitor thicknesses and/or regression rate for purposes of safety, operational control, or research. For example, the sensor could be used to monitor the thicknesses of brake linings or racecar tires and indicate when they need to be replaced. At the time of this reporting, over 200 of these sensors have been installed into a variety of host materials. An MSRS can be made in either of two configurations, denoted ladder and continuous (see Figure 1). A ladder MSRS includes two highly electrically conductive legs, across which narrow strips of electrically resistive material are placed at small increments of length. These strips resemble the rungs of a ladder and are electrically equivalent to many tiny resistors connected in parallel. A substrate material provides structural support for the legs and rungs. The instantaneous sensor resistance is read by an external signal conditioner via wires attached to the conductive legs on the non-eroding end of the sensor. The sensor signal can be transmitted from inside a high-pressure chamber to the ambient environment, using commercially available feedthrough connectors. Miniaturized internal recorders or wireless data transmission could also potentially be employed to eliminate the need for producing penetrations in the chamber case. The rungs are designed so that as each successive rung is eroded away, the resistance changes by an amount that yields a readily measurable signal larger than the background noise. (In addition, signal-conditioning techniques are used in processing the resistance readings to mitigate the effect of noise.) Hence, each discrete change of resistance serves to indicate the arrival of the regressing host material front at the known depth of the affected resistor rung. The average rate of regression between two adjacent resistors can be calculated simply as the distance between the resistors divided by the time interval between their resistance jumps. Advanced data reduction techniques have also been developed to establish the instantaneous surface position and regression rate when the regressing front is between rungs.

  4. An Investigation of Sleep Characteristics, EEG Abnormalities and Epilepsy in Developmentally Regressed and Non-Regressed Children with Autism

    ERIC Educational Resources Information Center

    Giannotti, Flavia; Cortesi, Flavia; Cerquiglini, Antonella; Miraglia, Daniela; Vagnoni, Cristina; Sebastiani, Teresa; Bernabei, Paola

    2008-01-01

    This study investigated sleep of children with autism and developmental regression and the possible relationship with epilepsy and epileptiform abnormalities. Participants were 104 children with autism (70 non-regressed, 34 regressed) and 162 typically developing children (TD). Results suggested that the regressed group had higher incidence of…

  5. Antiinflammatory 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones: novel inhibitors of COX-2.

    PubMed

    Lazer, E S; Sorcek, R; Cywin, C L; Thome, D; Possanza, G J; Graham, A G; Churchill, L

    1998-05-19

    A series of 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones was prepared. Members of this series are potent and selective inhibitors of cyclooxygenase-2 (COX-2) in both microsomal and cellular assays. Two representatives demonstrated activity in the carrageenan-induced paw edema model in rats upon oral administration. PMID:9871731

  6. Ann Williamson, Deputy Director, Office of Environmental Assessment Mike Cox, Manager, Risk Assessment Unit, Office of Environmental Assessment

    E-print Network

    Assessment Unit, Office of Environmental Assessment U.S. Environmental Protection Agency ­ Region 10 Greg. Booth: The U.S. Environmental Protection Agency has provided periodic updates to the Northwest PowerAnn Williamson, Deputy Director, Office of Environmental Assessment Mike Cox, Manager, Risk

  7. ON THE OPTIMAL INSULATION OF CONDUCTORS Steven J. Cox 1 , Bernhard Kawohl 2 , and Paul X. Uhlig 3

    E-print Network

    Kawohl, Bernd

    ON THE OPTIMAL INSULATION OF CONDUCTORS Steven J. Cox 1 , Bernhard Kawohl 2 , and Paul X. Uhlig 3 1 with an insulator and equate the effectiveness of this procedure with the rate at which the body dissipates heat when immersed in an ice-- bath. In the limit, as the thickness and conductivity of the insulator

  8. Sedimentation of an elliptical object in a two-dimensional foam I.T. Davies, S.J. Cox1

    E-print Network

    Cox, Simon

    of the ellipse to deviate from a vertical path. Highly-stretched films are formed in the wake of the ellipseSedimentation of an elliptical object in a two-dimensional foam I.T. Davies, S.J. Cox1 Institute of an elliptical object in a dry two-dimensional, monodisperse foam is simulated. The calculations are quasi

  9. Testosterone, growth and the evolution of sexual size dimorphism R. M. COX, D. S. STENQUIST & R. CALSBEEK

    E-print Network

    Cox, Robert

    as an anabolic steroid that stimulates male growth. However, the Correspondence: Robert M. Cox, Department regulated by sex-specific modifiers (Badyaev, 2002). Sex steroids (i.e. androgens, estrogens and progestins they are produced and secreted in sex-specific fashion by the gonads. However, if sex steroids are to account

  10. New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies.

    PubMed

    Dawood, Dina H; Batran, Rasha Z; Farghaly, Thoraya A; Khedr, Mohammed A; Abdulla, Mohamed M

    2015-12-01

    Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78??M. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. PMID:26462142

  11. Intelligence, Sex and the Single Neuron a Position Paper Paul Adams and Kingsley Cox SUNY, Stony Brook, NY 11790

    E-print Network

    Adams, Paul R.

    1 Intelligence, Sex and the Single Neuron ­ a Position Paper Paul Adams and Kingsley Cox SUNY intelligence is rooted in neuroscience, specifically the assumption that to make progress one must first-understood case of biological intelligence, Darwinian evolution, could provide essential clues. By this we do

  12. Magnetic properties of epitaxially grown semiconducting Zn1-xCoxO thin films by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Kim, Jae Hyun; Kim, Hyojin; Kim, Dojin; Ihm, Young Eon; Choo, Woong Kil

    2002-11-01

    We have characterized Zn1-xCoxO (x=0.25) films grown on sapphire (0001) substrates by pulsed laser deposition using various growth conditions to investigate the growth condition dependence of properties of Co-doped ZnO films. The substrate temperature (TS) was varied from 300 to 700 °C and the O2 pressure (PO2) from 10-6 to 10-1 Torr. When TS is relatively low (?600 °C), homogeneous alloy films with a wurtzite ZnO structure are grown and predominantly paramagnetic, whereas inhomogeneous films of wurtzite ZnO phase mixed with rock-salt CoO and hexagonal Co phases form when TS is relatively high and PO2 is fairly low (?10-5Torr). The presence of Co clusters leads to room temperature ferromagnetism in inhomogeneous films. The temperature dependence of the magnetization for the homogeneous Zn1-xCoxO (x=0.25) films shows spin-glass behavior at low temperature and high temperature Curie-Weiss behavior with a large negative value of the Curie-Weiss temperature, indicating strong antiferromagnetic exchange coupling between Co ions in Zn1-xCoxO. We have found that Co can be dissolved in ZnO over 40% under an optimum growth condition of TS=600 °C and PO2=10-5Torr, where epitaxial homogeneous Zn1-xCoxO (x=0.25) films of the best crystalline quality are obtained.

  13. Modeling of Debris Deposition on an Extrusion Filter Medium E.W. Jenkins and C.L. Cox

    E-print Network

    Jenkins, Lea

    Modeling of Debris Deposition on an Extrusion Filter Medium E.W. Jenkins and C.L. Cox Clemson to the finished product. One of the components of the process is the extrusion filter, which separates debris media and size distributions for debris particles [1.]. The mass flow rate through the filter at any

  14. The Use of Eyetracking for Measuring Immersion Anna L. Cox, Paul Cairns, Nadia Berthouze and Charlene Jennett

    E-print Network

    Cairns, Paul

    The Use of Eyetracking for Measuring Immersion Anna L. Cox, Paul Cairns, Nadia Berthouze and reviewers often refer to the immersive experience of the game as being of particular importance. Moreover, the term immersion can be applied across many different genres of games from first person shooters

  15. Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NF?B-independent manner

    PubMed Central

    Wei, Jinlong; Du, Kejun; Cai, Qinzhen; Ma, Lisha; Jiao, Zhenzhen; Tan, Jinrong; Xu, Zhou; Li, Jingxia; Luo, Wenjin; Chen, Jingyuan; Gao, Jimin; Zhang, Dongyun; Huang, Chuanshu

    2014-01-01

    Epidemiologic studies have provided solid evidence for the neurotoxic effect of lead for decades of years. In view of the fact that children are more vulnerable to the neurotoxicity of lead, lead exposure has been an urgent public health concern for decades of years. The modes of action of lead neurotoxic effects include disturbance of neurotransmitter storage and release, damage of mitochondria, as well as induction of apoptosis in cerebrovascular endothelial cells, astroglia and oligodendroglia. Our studies here, from a novel point of view, demonstrates that lead specifically caused induction of COX-2, a well known inflammatory mediator in neurons and glia cells. Furthermore, we revealed that COX-2 was induced by lead in a transcription-dependent manner, which relayed on transcription factor NFAT, rather than AP-1 and NF?B, in glial cells. Considering the important functions of COX-2 in mediation of inflammation reaction and oxidative stress, our studies here provide a mechanistic insight into the understanding of lead-associated inflammatory neurotoxicity effect via activation of pro-inflammatory NFAT3/COX-2 axis. PMID:25193092

  16. 75 FR 14488 - Public Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox Dayton International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ...Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox Dayton...property for future non-aeronautical use. The land consists of portions of 2 original...Register 30 days before modifying the land-use assurance that requires the...

  17. 75 FR 14488 - Public Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox Dayton International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... Federal Aviation Administration Public Notice for Waiver of Aeronautical Land-Use Assurance; James N. Cox... authorize the release of 9.167 acres of airport property for future non-aeronautical use. The land consists.... There are no requirements to retain the land for airport use. There are no impacts to the airport...

  18. Toxicological Effect of Manganese on NF-?B/iNOS-COX-2 Signaling Pathway in Chicken Testes.

    PubMed

    Du, Ye; Zhu, Yihao; Teng, Xiaojie; Zhang, Kun; Teng, Xiaohua; Li, Shu

    2015-11-01

    Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-?B/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-?B (NF-?B), tumor necrosis factor-? (TNF-?), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-?B, COX-2, TNF-?, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-?B and TNF-? mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-?B/iNOS-COX-2 signaling pathway. PMID:25904117

  19. Appeared as: Cox GM, Gibbons JM, Wood ATA, Craigon J, Ramsden SJ, Crout NMJ (2006). Towards the systematic simplification of mechanistic models. Ecological Modelling 198:240-246.

    E-print Network

    Crout, Neil

    2006-01-01

    Appeared as: Cox GM, Gibbons JM, Wood ATA, Craigon J, Ramsden SJ, Crout NMJ (2006). Towards simplification of mechanistic models1 2 1 G. M. Cox, 1 J. M. Gibbons, 2 A. T. A. Wood, 1 J. Craigon, 1 S. J GM, Gibbons JM, Wood ATA, Craigon J, Ramsden SJ, Crout NMJ (2006). Towards the systematic

  20. 75 FR 3217 - J&T Hydro Company; H. Dean Brooks and W. Bruce Cox; Notice of Application for Transfer of License...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... From the Federal Register Online via the Government Printing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission J&T Hydro Company; H. Dean Brooks and W. Bruce Cox; Notice of Application... 30, 2009, J&T Hydro Company (transferor) and W. Dean Brooks, and H. Bruce Cox (transferees) filed...

  1. Divisive Gaussian processes for nonstationary regression.

    PubMed

    Muñoz-González, Luis; Lázaro-Gredilla, Miguel; Figueiras-Vidal, Aníbal R

    2014-11-01

    Standard Gaussian process regression (GPR) assumes constant noise power throughout the input space and stationarity when combined with the squared exponential covariance function. This can be unrealistic and too restrictive for many real-world problems. Nonstationarity can be achieved by specific covariance functions, though prior knowledge about this nonstationarity can be difficult to obtain. On the other hand, the homoscedastic assumption is needed to allow GPR inference to be tractable. In this paper, we present a divisive GPR model which performs nonstationary regression under heteroscedastic noise using the pointwise division of two nonparametric latent functions. As the inference on the model is not analytically tractable, we propose a variational posterior approximation using expectation propagation (EP) which allows for accurate inference at reduced cost. We have also made a Markov chain Monte Carlo implementation with elliptical slice sampling to assess the quality of the EP approximation. Experiments support the usefulness of the proposed approach. PMID:25330423

  2. Adaptive Nonparametric Regression on Spin Fiber Bundles

    E-print Network

    Durastanti, Claudio; Marinucci, Domenico

    2010-01-01

    The construction of adaptive nonparametric procedures by means of wavelet thresholding techniques is now a classical topic in modern mathematical statistics. In this paper, we extend this framework to the analysis of nonparametric regression on sections of spin fiber bundles defined on the sphere. This can be viewed as a regression problem where the function to be estimated takes as its values algebraic curves (for instance, ellipses) rather than scalars, as usual. The problem is motivated by many important astrophysical applications, concerning for instance the analysis of the weak gravitational lensing effect, i.e. the distortion effect of gravity on the images of distant galaxies. We propose a thresholding procedure based upon the (mixed) spin needlets construction recently advocated by Geller and Marinucci (2008,2010) and Geller et al. (2008,2009), and we investigate their rates of convergence and their adaptive properties over spin Besov balls.

  3. Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression.

    PubMed

    Raisch, Jennifer; Rolhion, Nathalie; Dubois, Anaëlle; Darfeuille-Michaud, Arlette; Bringer, Marie-Agnès

    2015-03-01

    Intestinal dysbiosis has been reported in patients with colorectal cancer, and there is a high prevalence of Escherichia coli belonging to B2 phylogroup and producing a genotoxin, termed colibactin. Macrophages are one of the predominant tumor-infiltrating immune cells supporting key processes in tumor progression by producing protumoral factors such as cyclooxygenase-2 (COX-2). Here, we investigated whether B2 E. coli colonizing colon tumors could influence protumoral activities of macrophages. In contrast to commensal or nonpathogenic E. coli strains that were efficiently and rapidly degraded by macrophages at 24?h after infection, colon cancer-associated E. coli were able to resist killing by human THP-1 macrophages, to replicate intracellularly, and to persist inside host cells until at least 72?h after infection. Significant increases in COX-2 expression were observed in macrophages infected with colon cancer E. coli compared with macrophages infected with commensal and nonpathogenic E. coli strains or uninfected cells at 72?h after infection. Induction of COX-2 expression required live bacteria and was not due to colibactin production, as similar COX-2 levels were observed in macrophages infected with the wild-type colon cancer-associated E. coli 11G5 strain or a clbQ mutant unable to produce colibactin. Treatment of macrophages with ofloxacin, an antibiotic with intracellular tropism, efficiently decreased the number of intracellular bacteria and suppressed bacteria-induced COX-2 expression. This study provides new insights into the understanding of how tumor- infiltrating bacteria could influence cancer progression through their interaction with immune cells. Manipulation of microbes associated with tumors could have a deep influence on the secretion of protumoral molecules by infiltrating macrophages. PMID:25545478

  4. Model selection for logistic regression models

    NASA Astrophysics Data System (ADS)

    Duller, Christine

    2012-09-01

    Model selection for logistic regression models decides which of some given potential regressors have an effect and hence should be included in the final model. The second interesting question is whether a certain factor is heterogeneous among some subsets, i.e. whether the model should include a random intercept or not. In this paper these questions will be answered with classical as well as with Bayesian methods. The application show some results of recent research projects in medicine and business administration.

  5. Cross-validation for densities and regressions

    NASA Technical Reports Server (NTRS)

    Geman, S.

    1982-01-01

    Virtually all nonparametric (infinite dimensional) problems require the choice of a smoothing parameter. It is natural to attempt to use the data to guide the choice of this parameter. The most widely applicable data driven technique is cross validation. The method of cross validation is introduced and results are presented which establish consistency for certain cross validated density estimators and consistency as well as asymptotic normality for rigid regression.

  6. Transfer Learning Based on Logistic Regression

    NASA Astrophysics Data System (ADS)

    Paul, A.; Rottensteiner, F.; Heipke, C.

    2015-08-01

    In this paper we address the problem of classification of remote sensing images in the framework of transfer learning with a focus on domain adaptation. The main novel contribution is a method for transductive transfer learning in remote sensing on the basis of logistic regression. Logistic regression is a discriminative probabilistic classifier of low computational complexity, which can deal with multiclass problems. This research area deals with methods that solve problems in which labelled training data sets are assumed to be available only for a source domain, while classification is needed in the target domain with different, yet related characteristics. Classification takes place with a model of weight coefficients for hyperplanes which separate features in the transformed feature space. In term of logistic regression, our domain adaptation method adjusts the model parameters by iterative labelling of the target test data set. These labelled data features are iteratively added to the current training set which, at the beginning, only contains source features and, simultaneously, a number of source features are deleted from the current training set. Experimental results based on a test series with synthetic and real data constitutes a first proof-of-concept of the proposed method.

  7. Satellite rainfall retrieval by logistic regression

    NASA Technical Reports Server (NTRS)

    Chiu, Long S.

    1986-01-01

    The potential use of logistic regression in rainfall estimation from satellite measurements is investigated. Satellite measurements provide covariate information in terms of radiances from different remote sensors.The logistic regression technique can effectively accommodate many covariates and test their significance in the estimation. The outcome from the logistical model is the probability that the rainrate of a satellite pixel is above a certain threshold. By varying the thresholds, a rainrate histogram can be obtained, from which the mean and the variant can be estimated. A logistical model is developed and applied to rainfall data collected during GATE, using as covariates the fractional rain area and a radiance measurement which is deduced from a microwave temperature-rainrate relation. It is demonstrated that the fractional rain area is an important covariate in the model, consistent with the use of the so-called Area Time Integral in estimating total rain volume in other studies. To calibrate the logistical model, simulated rain fields generated by rainfield models with prescribed parameters are needed. A stringent test of the logistical model is its ability to recover the prescribed parameters of simulated rain fields. A rain field simulation model which preserves the fractional rain area and lognormality of rainrates as found in GATE is developed. A stochastic regression model of branching and immigration whose solutions are lognormally distributed in some asymptotic limits has also been developed.

  8. Nanoemulsion-based gel formulations of COX-2 inhibitors for enhanced efficacy in inflammatory conditions

    NASA Astrophysics Data System (ADS)

    Lala, R. R.; Awari, N. G.

    2013-01-01

    In the present study, we have investigated the potential of a nanoemulsion (thermodynamically stable transparent dispersions of oil and water having a droplet size <200 nm) formulation for the topical delivery of COX-2 inhibitors using etoricoxib as a model drug. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudo-ternary phase diagrams. The prepared nanoemulsions were subjected to thermodynamic stability testing. Those that passed these tests were characterized for viscosity, droplet size and differential scanning calorimetry. Topical permeation of etoricoxib through porcine abdominal skin was estimated using the Franz diffusion cell. The ex vivo skin permeation profile of optimized formulations was compared with that of etoricoxib conventional gel. A significant increase in permeability was observed in optimized nanoemulsion formulations consisting of 2 % w/w of etoricoxib, 20 % w/w of Triacetin, 38 % w/w of a surfactant mixture (Cremophor RH 40:Transcutol P), and 42 % w/w of water. The anti-inflammatory effects of this formulation on carrageenan-induced paw edema in rats showed a significant increase in the percent inhibition value (84.61 % with the nanoemulsion gel and 92.30 % with the nanoemulsion) as compared with the conventional gel (69.23 %) after 6 h when compared with etoricoxib conventional gel. These results suggest that nanoemulsions can serve as potential vehicles for improved transdermal delivery of anti-inflammatory agents such as etoricoxib.

  9. Salt marsh and seagrass communities of Bakkhali Estuary, Cox's Bazar, Bangladesh

    NASA Astrophysics Data System (ADS)

    Hena, M. K. Abu; Short, F. T.; Sharifuzzaman, S. M.; Hasan, M.; Rezowan, M.; Ali, M.

    2007-10-01

    The species identification, distribution pattern, density and biomass of salt marsh and seagrass plants with some of the ecological parameters were studied in the Bakkhali river estuary, Cox's Bazar, Bangladesh during the first half of 2006. Two salt marsh species ( Spartina sp. and Imperata cylindrica) and one seagrass species ( Halophila beccarii) were identified during this investigation, providing the first reports of Spartina sp. and H. beccarii in coastal Bangladesh. Seagrass H. beccarii was found in an accreted area and co-existing with salt marsh, and scattered sparsely in the salt marsh habitat and macroalgae Ulva intestinalis. Flowering and fruiting were recorded from the seagrass H. beccarri during January and February. No flowers and fruits were observed for the salt marsh Spartina sp. during the study period. Results showed that the shoot density of Spartina ranged from 400 to 2875 shoots m -2 with the highest total biomass (165.80 g dry weight (DW) m -2) in March. Shoot density of H. beccarii ranged from 2716 to 14320 shoots m -2 in this estuarine coastal environment. The total biomass of seagrass was higher (17.56 g DW m -2) in March compared to the other months. The highest H. beccarii above ground (AG) biomass and below ground (BG) biomass were 9.59 g DW m -2 and 9.42 g DW m -2, respectively. These parameters are comparable with those generally observed for the salt marsh and seagrass species in the other places of the world.

  10. Cooperative nucleation modes in polycrystalline CoxPd1-x nanowires

    NASA Astrophysics Data System (ADS)

    Viqueira, M. S.; Pozo-López, G.; Urreta, S. E.; Condó, A. M.; Cornejo, D. R.; Fabietti, L. M.

    2015-05-01

    Polycrystalline CoxPd1-x (x = 1, 0.60, 0.45, 0.23, and 0.11) cylindrical nanowires (ø = 18-35 nm, about 1 ?m length) are produced by AC electrodeposition into hexagonally ordered alumina pores. Single-phase nanowires of an fcc Co-Pd solid solution, with randomly oriented equiaxed grains (7-12 nm) are obtained; in all the cases, the grain size is smaller than the wire diameter. The coercive field and the reduced remanence of Co-rich nanowire arrays are hardly sensitive to temperature within the range varying from 4 K to 300 K. On the other hand, in Pd-rich nanowires both magnitudes are smaller and they largely increase when cooling below 100 K. This behavior also depends on the mean grain size. These facts are systematized considering two main aspects: the non-trivial temperature and composition dependence of the crystalline anisotropy and the saturation magnetostriction in Co-Pd alloys; and a random anisotropy effect, which defines a nucleation localization length that may involve more than a single grain, and thus promotes more cooperative nucleation modes.

  11. Getting miles away from Terman: Did the CRPS fund Catharine Cox Miles's unsilenced psychology of sex?

    PubMed

    Hegarty, Peter

    2012-08-01

    Psychologist Catharine Cox Miles (1890-1984) is often remembered as the junior author, with Lewis Terman, of Sex and Personality. Written with support from the Committee for Research on the Problems of Sex (CRPS), Sex and Personality introduced the "masculinity-femininity" personality measure to psychology in 1936. Miles has been overlooked by some historians and constructed as a silent, indirect feminist by others. Private letters show that Terman and Miles had different assumptions about the need for library research work to precede the empirical work for Sex and Personality. Miles's 1935 chapter on the "Social Psychology of Sex" shows that her theoretical formulation of sex differed from Terman's in its emphasis on female embodiment, respect for the emerging tradition of the sex survey, and its opinions about the determinants of marital happiness, and the variability of intelligence. Ironically, CRPS monies wired to Terman may have funded Miles to develop this early formulation of the psychology of sex. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID:23397910

  12. Prospective performance evaluation of selected common virtual screening tools. Case study: Cyclooxygenase (COX) 1 and 2

    PubMed Central

    Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela

    2015-01-01

    Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors. PMID:25916906

  13. PCR-based assay for the mitochondrial cox1 specific amplification of Eucoleus böhmi.

    PubMed

    Di Cesare, Angela; Veronesi, Fabrizia; Frangipane di Regalbono, Antonio; De Liberato, Claudio; Perrucci, Stefania; Iorio, Raffaella; Morganti, Giulia; Marangi, Marianna; Simonato, Giulia; Traversa, Donato

    2015-06-30

    Eucoleus böhmi (syn. Capillaria boehmi) is a trichuroid nematode affecting the epithelium of the nasal turbinates, frontal and paranasal sinuses of wild and domestic canids. Knowledge of the geographic distribution of nasal eucoleosis is fragmentary, despite the infection has been described from Europe and North America. Moreover, gaps exist in information available on the importance of the disease in canine clinical practice. The lack of knowledge on E. böhmi is likely due to limitations inherent to diagnostic methodologies. The aim of the present work was to assess a PCR-based assay instrumental to the amplification of a species-specific region of the mitochondrial DNA (mtDNA) gene encoding for the subunit 1 (cox1) gene of E. böhmi. Adult worms of E. böhmi from red foxes and dogs from Norway, Serbia and Italy and individual fecal samples from naturally infected dogs from Italy were included in the study. Stool samples from dogs negative for E. böhmi, but positive for other common parasites in both single and mixed infections, and adult stages of common dog parasites, were used to assess the specificity of this genetic assay. Using the panel of faecal samples, the assay showed a sensitivity of 85.14% and a specificity of 100%. PMID:25941126

  14. Magnetic and structural properties of (Ru1-xCox)2FeSi alloys

    NASA Astrophysics Data System (ADS)

    Deka, Bhargab; Srinivasan, A.

    2015-11-01

    In this work, we report a systemetic study of Co substitution for Ru in Ru2FeSi. Our previous studies showed that Ru2FeSi and Co2FeSi are antiferromagnetic and ferromagnetic, respectively. In order to understand the influence of Co substitution for Ru, (Ru1-xCox)2FeSi alloys were prepared by arc melting, followed by annealing at 1273 K for 3 days. Structural and magnetic studies were carried out on the quaternary alloys by powder X-ray diffraction and vibrating sample magnetometry, respectively. At room temperature, Ru rich compositions i.e., x=0 and x=0.25 exhibited disordered B2 structure, but with increase in Co concentration L21 ordering appeared in the alloys. From magnetization measurements, it is seen that with increasing x, the ferromagnetic state becomes dominant with the appearance of spontaneous magnetization and increase in the value of magnetization of the alloys. Saturation magnetization measured at 15 kOe increased from 1.02 emu/g to 149.96 emu/g as x was increased from 0 to 1.

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

    NASA Astrophysics Data System (ADS)

    Katz, Yuri A.; Shokhirev, Nikolai V.

    2010-07-01

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

  16. miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells

    SciTech Connect

    Pham, Hung; Department of Medicine, Veterans Affair Greater Los Angeles Healthcare System, Los Angeles, CA 90073 ; Ekaterina Rodriguez, C.; Donald, Graham W.; Hertzer, Kathleen M.; Jung, Xiaoman S.; Chang, Hui-Hua; Moro, Aune; Reber, Howard A.; Hines, O. Joe; Eibl, Guido

    2013-09-13

    Highlights: •Pancreatic cancer cells express low miR-143 levels and elevated p-MEK, p-MAPK and RREB1. •MEK inhibitors U0126 and PD98059 increase miR-143 expression. •miR-143 decreases COX-2 mRNA stability and expression and PGE{sub 2}. •miR-143 decreases p-p38MAPK, p-MEK, p-MAPK and RREB1 expression. -- Abstract: Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3?-untranslated region (3?-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E{sub 2} (PGE{sub 2}) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 ?M of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE{sub 2} levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE{sub 2}, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.

  17. Monthly streamflow forecasting using Gaussian Process Regression

    NASA Astrophysics Data System (ADS)

    Sun, Alexander Y.; Wang, Dingbao; Xu, Xianli

    2014-04-01

    Streamflow forecasting plays a critical role in nearly all aspects of water resources planning and management. In this work, Gaussian Process Regression (GPR), an effective kernel-based machine learning algorithm, is applied to probabilistic streamflow forecasting. GPR is built on Gaussian process, which is a stochastic process that generalizes multivariate Gaussian distribution to infinite-dimensional space such that distributions over function values can be defined. The GPR algorithm provides a tractable and flexible hierarchical Bayesian framework for inferring the posterior distribution of streamflows. The prediction skill of the algorithm is tested for one-month-ahead prediction using the MOPEX database, which includes long-term hydrometeorological time series collected from 438 basins across the U.S. from 1948 to 2003. Comparisons with linear regression and artificial neural network models indicate that GPR outperforms both regression methods in most cases. The GPR prediction of MOPEX basins is further examined using the Budyko framework, which helps to reveal the close relationships among water-energy partitions, hydrologic similarity, and predictability. Flow regime modification and the resulting loss of predictability have been a major concern in recent years because of climate change and anthropogenic activities. The persistence of streamflow predictability is thus examined by extending the original MOPEX data records to 2012. Results indicate relatively strong persistence of streamflow predictability in the extended period, although the low-predictability basins tend to show more variations. Because many low-predictability basins are located in regions experiencing fast growth of human activities, the significance of sustainable development and water resources management can be even greater for those regions.

  18. Multiple linear regression for isotopic measurements

    NASA Astrophysics Data System (ADS)

    Garcia Alonso, J. I.

    2012-04-01

    There are two typical applications of isotopic measurements: the detection of natural variations in isotopic systems and the detection man-made variations using enriched isotopes as indicators. For both type of measurements accurate and precise isotope ratio measurements are required. For the so-called non-traditional stable isotopes, multicollector ICP-MS instruments are usually applied. In many cases, chemical separation procedures are required before accurate isotope measurements can be performed. The off-line separation of Rb and Sr or Nd and Sm is the classical procedure employed to eliminate isobaric interferences before multicollector ICP-MS measurement of Sr and Nd isotope ratios. Also, this procedure allows matrix separation for precise and accurate Sr and Nd isotope ratios to be obtained. In our laboratory we have evaluated the separation of Rb-Sr and Nd-Sm isobars by liquid chromatography and on-line multicollector ICP-MS detection. The combination of this chromatographic procedure with multiple linear regression of the raw chromatographic data resulted in Sr and Nd isotope ratios with precisions and accuracies typical of off-line sample preparation procedures. On the other hand, methods for the labelling of individual organisms (such as a given plant, fish or animal) are required for population studies. We have developed a dual isotope labelling procedure which can be unique for a given individual, can be inherited in living organisms and it is stable. The detection of the isotopic signature is based also on multiple linear regression. The labelling of fish and its detection in otoliths by Laser Ablation ICP-MS will be discussed using trout and salmon as examples. As a conclusion, isotope measurement procedures based on multiple linear regression can be a viable alternative in multicollector ICP-MS measurements.

  19. Triton,... electron,... cosmon,...: An infinite regression?

    PubMed

    Dehmelt, H

    1989-11-01

    I propose an elementary particle model in which the simplest near-Dirac particles triton, proton, and electron are members of the three top layers of a bottomless stack. Each particle is a composite of three particles from the next layer below in an infinite regression approaching Dirac point particles. The cosmon, an immensely heavy lower layer subquark, is the elementary particle. The world-atom, a tightly bound cosmon/anticosmon pair of zero relativistic total mass, arose from the nothing state in a quantum jump. Rapid decay of the pair launched the big bang and created the universe. PMID:16594084

  20. Sparse Multinomial Logistic Regression via Approximate Message Passing

    E-print Network

    Schniter, Philip

    Sparse Multinomial Logistic Regression via Approximate Message Passing A Thesis Presented Generalized Ap- proximate Message Passing (Hybrid-GAMP) to train a multinomial logistic regression model. We classifier . . . . . . . . . . . . . . . . . . . . 6 1.3.3 Justification for the multinomial logistic