Cox's regression model for dynamics of grouped unemployment data

Czech Academy of Sciences Publication Activity Database

Volf, Petr

2003-01-01

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

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

African Journals Online (AJOL)

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

Hierarchical Neural Regression Models for Customer Churn Prediction

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Golshan Mohammadi

2013-01-01

Full Text Available As customers are the main assets of each industry, customer churn prediction is becoming a major task for companies to remain in competition with competitors. In the literature, the better applicability and efficiency of hierarchical data mining techniques has been reported. This paper considers three hierarchical models by combining four different data mining techniques for churn prediction, which are backpropagation artificial neural networks (ANN, self-organizing maps (SOM, alpha-cut fuzzy c-means (α-FCM, and Cox proportional hazards regression model. The hierarchical models are ANN + ANN + Cox, SOM + ANN + Cox, and α-FCM + ANN + Cox. In particular, the first component of the models aims to cluster data in two churner and nonchurner groups and also filter out unrepresentative data or outliers. Then, the clustered data as the outputs are used to assign customers to churner and nonchurner groups by the second technique. Finally, the correctly classified data are used to create Cox proportional hazards model. To evaluate the performance of the hierarchical models, an Iranian mobile dataset is considered. The experimental results show that the hierarchical models outperform the single Cox regression baseline model in terms of prediction accuracy, Types I and II errors, RMSE, and MAD metrics. In addition, the α-FCM + ANN + Cox model significantly performs better than the two other hierarchical models.

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

Science.gov (United States)

Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

2004-09-20

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

Analysis of the Risk of Company's Bankruptcy in Polish Food and Beverage Production Sector Using the Cox Regression

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Przemysław Dominiak

2011-01-01

Full Text Available Analysis of the risk of a company’s bankruptcy in Polish food and beverages production sector (NACE, No. 15 has been carried out using econometric modelling in the form of the Cox regression. The purpose of this paper was to find factors (models describing the risk of a company’s bankruptcy. The described approach to modelling of the risk of bankruptcy is – in the case of quantitative variables – the use of “raw” positions from financial accounts. (original abstract

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

Science.gov (United States)

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

2017-01-01

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

PERBANDINGAN TRANSFORMASI BOX-COX DAN REGRESI KUANTIL MEDIAN DALAM MENGATASI HETEROSKEDASTISITAS

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NI WAYAN YUNI CAHYANI

2015-01-01

Full Text Available Ordinary least square (OLS is a method that can be used to estimate the parameter in linear regression analysis. There are some assumption which should be satisfied on OLS, one of this assumption is homoscedasticity, that is the variance of error is constant. If variance of the error is unequal that so-called heteroscedasticity. The presence heteroscedasticity can cause estimation with OLS becomes inefficient. Therefore, heteroscedasticity shall be overcome. There are some method that can used to overcome heteroscedasticity, two among those are Box-Cox power transformation and median quantile regression. This research compared Box-Cox power transformation and median quantile regression to overcome heteroscedasticity. Applied Box-Cox power transformation on OLS result ????2point are greater, smaller RMSE point and confidencen interval more narrow, therefore can be concluded that applied of Box-Cox power transformation on OLS better of median quantile regression to overcome heteroscedasticity.

PERBANDINGAN TRANSFORMASI BOX-COX DAN REGRESI KUANTIL MEDIAN DALAM MENGATASI HETEROSKEDASTISITAS

Directory of Open Access Journals (Sweden)

NI WAYAN YUNI CAHYANI

2015-03-01

Full Text Available Ordinary least square (OLS is a method that can be used to estimate the parameter in linear regression analysis. There are some assumption which should be satisfied on OLS, one of this assumption is homoscedasticity, that is the variance of error is constant. If variance of the error is unequal that so-called heteroscedasticity. The presence heteroscedasticity can cause estimation with OLS becomes inefficient. Therefore, heteroscedasticity shall be overcome. There are some method that can used to overcome heteroscedasticity, two among those are Box-Cox power transformation and median quantile regression. This research compared Box-Cox power transformation and median quantile regression to overcome heteroscedasticity. Applied Box-Cox power transformation on OLS result ????2point are greater, smaller RMSE point and confidencen interval more narrow, therefore can be concluded that applied of Box-Cox power transformation on OLS better of median quantile regression to overcome heteroscedasticity.

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

DEFF Research Database (Denmark)

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

1993-01-01

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

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

NARCIS (Netherlands)

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

2016-01-01

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

Predictors of unsuccessful outcome in cemented femoral revisions using bone impaction grafting; Cox regression analysis of 208 cases.

Science.gov (United States)

Te Stroet, Martijn A J; Rijnen, Wim H C; Gardeniers, Jean W M; Schreurs, B Willem; Hannink, Gerjon

2016-09-29

Despite improvements in the technique of femoral impaction bone grafting, reconstruction failures still can occur. Therefore, the aim of our study was to determine risk factors for the endpoint re-revision for any reason. We used prospectively collected demographic, clinical and surgical data of all 202 patients who underwent 208 femoral revisions using the X-change Femoral Revision System (Stryker-Howmedica), fresh-frozen morcellised allograft and a cemented polished Exeter stem in our department from 1991 to 2007. Univariable and multivariable Cox regression analyses were performed to identify potential factors associated with re-revision. The mean follow-up was 10.6 (5-21) years. The cumulative re-revision rate was 6.3% (13/208). After univariable selection, sex, age, body mass index (BMI), American Association of Anesthesiologists (ASA) classification, type of removed femoral component, and mesh used for reconstruction were included in multivariable regression analysis.In the multivariable analysis, BMI was the only factor that was significantly associated with the risk of re-revision after bone impaction grafting (BMI ≥30 vs. BMI <30, HR = 6.54 [95% CI 1.89-22.65]; p = 0.003). BMI was the only factor associated with the risk of re-revision for any reason. Besides BMI also other factors, such as Endoklinik score and the type of removed femoral component, can provide guidance in the process of preclinical decision making. With the knowledge obtained from this study, preoperative patient selection, informed consent, and treatment protocols can be better adjusted to the individual patient who needs to undergo a femoral revision with impaction bone grafting.

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

DEFF Research Database (Denmark)

Scheike, Thomas; Juul, Anders

2004-01-01

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

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

Science.gov (United States)

Austin, Peter C

2018-01-01

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

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

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Edwin Roger Parra

2013-12-01

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

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

Science.gov (United States)

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

2016-03-01

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

A SAS-macro for estimation of the cumulative incidence using Poisson regression

DEFF Research Database (Denmark)

Waltoft, Berit Lindum

2009-01-01

the hazard rates, and the hazard rates are often estimated by the Cox regression. This procedure may not be suitable for large studies due to limited computer resources. Instead one uses Poisson regression, which approximates the Cox regression. Rosthøj et al. presented a SAS-macro for the estimation...... of the cumulative incidences based on the Cox regression. I present the functional form of the probabilities and variances when using piecewise constant hazard rates and a SAS-macro for the estimation using Poisson regression. The use of the macro is demonstrated through examples and compared to the macro presented...

COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

Science.gov (United States)

Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

2013-01-01

The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.

Science.gov (United States)

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

2013-06-01

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

Box-Cox transformation of firm size data in statistical analysis

Science.gov (United States)

Chen, Ting Ting; Takaishi, Tetsuya

2014-03-01

Firm size data usually do not show the normality that is often assumed in statistical analysis such as regression analysis. In this study we focus on two firm size data: the number of employees and sale. Those data deviate considerably from a normal distribution. To improve the normality of those data we transform them by the Box-Cox transformation with appropriate parameters. The Box-Cox transformation parameters are determined so that the transformed data best show the kurtosis of a normal distribution. It is found that the two firm size data transformed by the Box-Cox transformation show strong linearity. This indicates that the number of employees and sale have the similar property as a firm size indicator. The Box-Cox parameters obtained for the firm size data are found to be very close to zero. In this case the Box-Cox transformations are approximately a log-transformation. This suggests that the firm size data we used are approximately log-normal distributions.

Box-Cox transformation of firm size data in statistical analysis

International Nuclear Information System (INIS)

Chen, Ting Ting; Takaishi, Tetsuya

2014-01-01

Firm size data usually do not show the normality that is often assumed in statistical analysis such as regression analysis. In this study we focus on two firm size data: the number of employees and sale. Those data deviate considerably from a normal distribution. To improve the normality of those data we transform them by the Box-Cox transformation with appropriate parameters. The Box-Cox transformation parameters are determined so that the transformed data best show the kurtosis of a normal distribution. It is found that the two firm size data transformed by the Box-Cox transformation show strong linearity. This indicates that the number of employees and sale have the similar property as a firm size indicator. The Box-Cox parameters obtained for the firm size data are found to be very close to zero. In this case the Box-Cox transformations are approximately a log-transformation. This suggests that the firm size data we used are approximately log-normal distributions

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

NARCIS (Netherlands)

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

2008-01-01

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

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

Science.gov (United States)

Hong, Xia

2006-07-01

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

Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

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Richard Dela Cruz

2016-06-01

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

Improving Your Data Transformations: Applying the Box-Cox Transformation

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Jason W. Osborne

2010-10-01

Full Text Available Many of us in the social sciences deal with data that do not conform to assumptions of normality and/or homoscedasticity/homogeneity of variance. Some research has shown that parametric tests (e.g., multiple regression, ANOVA can be robust to modest violations of these assumptions. Yet the reality is that almost all analyses (even nonparametric tests benefit from improved the normality of variables, particularly where substantial non-normality is present. While many are familiar with select traditional transformations (e.g., square root, log, inverse for improving normality, the Box-Cox transformation (Box & Cox, 1964 represents a family of power transformations that incorporates and extends the traditional options to help researchers easily find the optimal normalizing transformation for each variable. As such, Box-Cox represents a potential best practice where normalizing data or equalizing variance is desired. This paper briefly presents an overview of traditional normalizing transformations and how Box-Cox incorporates, extends, and improves on these traditional approaches to normalizing data. Examples of applications are presented, and details of how to automate and use this technique in SPSS and SAS are included.

riskRegression

DEFF Research Database (Denmark)

Ozenne, Brice; Sørensen, Anne Lyngholm; Scheike, Thomas

2017-01-01

In the presence of competing risks a prediction of the time-dynamic absolute risk of an event can be based on cause-specific Cox regression models for the event and the competing risks (Benichou and Gail, 1990). We present computationally fast and memory optimized C++ functions with an R interface...... for predicting the covariate specific absolute risks, their confidence intervals, and their confidence bands based on right censored time to event data. We provide explicit formulas for our implementation of the estimator of the (stratified) baseline hazard function in the presence of tied event times. As a by...... functionals. The software presented here is implemented in the riskRegression package....

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data.

Science.gov (United States)

Ching, Travers; Zhu, Xun; Garmire, Lana X

2018-04-01

Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, at both the pathway and gene levels. The outputs from the hidden layer node provide an alternative approach for survival-sensitive dimension reduction. In summary, we have developed a new method for accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at https://github.com/lanagarmire/cox-nnet.

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

Science.gov (United States)

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

2009-02-01

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

COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

International Nuclear Information System (INIS)

Glynn, Sharon A; Ambs, Stefan; Prueitt, Robyn L; Ridnour, Lisa A; Boersma, Brenda J; Dorsey, Tiffany M; Wink, David A; Goodman, Julie E; Yfantis, Harris G; Lee, Dong H

2010-01-01

Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype

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

DEFF Research Database (Denmark)

Scheike, Thomas Harder; Juul, Anders

2004-01-01

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

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

International Nuclear Information System (INIS)

Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.; Crotty, Paul; Murphy, James O.; Hollywood, Donal; Gaffney, Eoin F.; Stephens, Richard B.; Kennedy, M. John

2006-01-01

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

On the use of Cox regression to examine the temporal clustering of flooding and heavy precipitation across the central United States

Science.gov (United States)

Mallakpour, Iman; Villarini, Gabriele; Jones, Michael P.; Smith, James A.

2017-08-01

The central United States is plagued by frequent catastrophic flooding, such as the flood events of 1993, 2008, 2011, 2013, 2014 and 2016. The goal of this study is to examine whether it is possible to describe the occurrence of flood and heavy precipitation events at the sub-seasonal scale in terms of variations in the climate system. Daily streamflow and precipitation time series over the central United States (defined here to include North Dakota, South Dakota, Nebraska, Kansas, Missouri, Iowa, Minnesota, Wisconsin, Illinois, West Virginia, Kentucky, Ohio, Indiana, and Michigan) are used in this study. We model the occurrence/non-occurrence of a flood and heavy precipitation event over time using regression models based on Cox processes, which can be viewed as a generalization of Poisson processes. Rather than assuming that an event (i.e., flooding or precipitation) occurs independently of the occurrence of the previous one (as in Poisson processes), Cox processes allow us to account for the potential presence of temporal clustering, which manifests itself in an alternation of quiet and active periods. Here we model the occurrence/non-occurrence of flood and heavy precipitation events using two climate indices as time-varying covariates: the Arctic Oscillation (AO) and the Pacific-North American pattern (PNA). We find that AO and/or PNA are important predictors in explaining the temporal clustering in flood occurrences in over 78% of the stream gages we considered. Similar results are obtained when working with heavy precipitation events. Analyses of the sensitivity of the results to different thresholds used to identify events lead to the same conclusions. The findings of this work highlight that variations in the climate system play a critical role in explaining the occurrence of flood and heavy precipitation events at the sub-seasonal scale over the central United States.

Properties of spatial Cox process models

DEFF Research Database (Denmark)

Møller, Jesper

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

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

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

2004-01-01

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

In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2

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Nunung Yuniarti

2012-03-01

Full Text Available Curcumin has been widely reported as an anti-inflammatory agent isolated from the plant Curcuma longa L. (turmeric. This anti-inflammatory activity was associated with the ability of this compound to inhibit the activity of both cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2 in arachidonic acid metabolism. Dual COX-1 and COX-2 inhibitors are preferred to be employed in the therapy of chronic inflammatory diseases compared to selective inhibitors, since it was reported that the use of selective inhibitors led to severe adverse side effect. In the present study, in vitro and in silico assays on curcumin and its analogues as dual inhibitors for both COX-1 and COX-2 were performed. The results provide theoretical contribution in understanding the ligand-protein interactions at the molecular level to develop new curcumin analogues which possess better anti-inflammatory activity as well as to avoid unsolicited side effects.

Exploring selectivity requirements for COX-2 versus COX-1 binding of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines using topological and physico-chemical parameters.

Science.gov (United States)

Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

2005-04-01

Considering the current need for development of selective cyclooxygenase-2 (COX-2) inhibitors, an attempt has been made to explore physico-chemical requirements of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines for binding with COX-1 and COX-2 enzyme subtypes and also to explore the selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier & Hall), first order valence connectivity and physicochemical parameters (hydrophobicity pi, Hammett sigma and molar refractivity MR of different ring substituents) were used as independent variables along with suitable dummy parameters in the stepwise regression method. The best equation describing COX-1 binding affinity [n = 25, Q2 = 0.606, R(a)2 = 0.702, R2 = 0.752, R = 0.867, s = 0.447, F = 15.2 (df 4, 20)] suggests that the COX-1 binding affinity increases in the presence of a halogen substituent at R1 position and a p-alkoxy or p-methylthio substituent at R2 position. Furthermore, a difluoromethyl group is preferred over a trifluoromethyl group at R position for the COX-1 binding. The best equation describing COX-2 binding affinity [n = 32, Q2 = 0.622, R(a)2= 0.692, R2 = 0.732, R = 0.856, s = 0.265, F = 18.4 (df 4, 27)] shows that the COX-2 binding affinity increases with the presence of a halogen substituent at R1 position and increase of size of R2 substituents. However, it decreases in case of simultaneous presence of 3-chloro and 4-methoxy groups on the phenyl nucleus and in the presence of highly lipophilic R2 substituents. The best selectivity relation [n = 25, Q2 = 0.455, R(a)2 = 0.605, R2 = 0.670, R = 0.819, s = 0.423, F = 10.2 (df 4, 20)] suggests that the COX-2 selectivity decreases in the presence of p-alkoxy group and electron-withdrawing para substituents at R2 position. Again, a trifluoro group is conductive for the selectivity instead of a difluoromethyl group at R position. Furthermore, branching may also play significant role in

Limitations of Cox Proportional Hazards Analysis in Mortality Prediction of Patients with Acute Coronary Syndrome

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Babińska Magdalena

2015-12-01

Full Text Available The aim of this study was to evaluate the possibility of incorrect assessment of mortality risk factors in a group of patients affected by acute coronary syndrome, due to the lack of hazard proportionality in the Cox regression model. One hundred and fifty consecutive patients with acute coronary syndrome (ACS and no age limit were enrolled. Univariable and multivariable Cox proportional hazard analyses were performed. The proportional hazard assumptions were verified using Schoenfeld residuals, χ2 test and rank correlation coefficient t between residuals and time. In the total group of 150 patients, 33 (22.0% deaths from any cause were registered in the follow-up time period of 64 months. The non-survivors were significantly older and had increased prevalence of diabetes and erythrocyturia, longer history of coronary artery disease, higher concentrations of serum creatinine, cystatin C, uric acid, glucose, C-reactive protein (CRP, homocysteine and B-type natriuretic peptide (NT-proBNP, and lower concentrations of serum sodium. No significant differences in echocardiography parameters were observed between groups. The following factors were risk of death factors and fulfilled the proportional hazard assumption in the univariable model: smoking, occurrence of diabetes and anaemia, duration of coronary artery disease, and abnormal serum concentrations of uric acid, sodium, homocysteine, cystatin C and NT-proBNP, while in the multivariable model, the risk of death factors were: smoking and elevated concentrations of homocysteine and NT-proBNP. The study has demonstrated that violation of the proportional hazard assumption in the Cox regression model may lead to creating a false model that does not include only time-independent predictive factors.

Properties of spatial Cox process models

DEFF Research Database (Denmark)

Møller, Jesper

2005-01-01

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

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

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Herni Utami

2014-03-01

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

Testing among functional forms: an extension of the Generalized Box-Cox formulation.

NARCIS (Netherlands)

Oude Lansink, A.G.J.M.; Thijssen, G.

1998-01-01

This paper uses the Generalized Box - Cox framework and Double Length artificial Regression to test whether different specifications of the profit function are able to mimic the technology underlying panel data of Dutch arable farms for the period 1970 - 1988. To this end, a linear GBC is developed

Lévy based Cox point processes

DEFF Research Database (Denmark)

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

2008-01-01

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

riskRegression

DEFF Research Database (Denmark)

Ozenne, Brice; Sørensen, Anne Lyngholm; Scheike, Thomas

2017-01-01

In the presence of competing risks a prediction of the time-dynamic absolute risk of an event can be based on cause-specific Cox regression models for the event and the competing risks (Benichou and Gail, 1990). We present computationally fast and memory optimized C++ functions with an R interface......-product we obtain fast access to the baseline hazards (compared to survival::basehaz()) and predictions of survival probabilities, their confidence intervals and confidence bands. Confidence intervals and confidence bands are based on point-wise asymptotic expansions of the corresponding statistical...

[Use of multiple regression models in observational studies (1970-2013) and requirements of the STROBE guidelines in Spanish scientific journals].

Science.gov (United States)

Real, J; Cleries, R; Forné, C; Roso-Llorach, A; Martínez-Sánchez, J M

In medicine and biomedical research, statistical techniques like logistic, linear, Cox and Poisson regression are widely known. The main objective is to describe the evolution of multivariate techniques used in observational studies indexed in PubMed (1970-2013), and to check the requirements of the STROBE guidelines in the author guidelines in Spanish journals indexed in PubMed. A targeted PubMed search was performed to identify papers that used logistic linear Cox and Poisson models. Furthermore, a review was also made of the author guidelines of journals published in Spain and indexed in PubMed and Web of Science. Only 6.1% of the indexed manuscripts included a term related to multivariate analysis, increasing from 0.14% in 1980 to 12.3% in 2013. In 2013, 6.7, 2.5, 3.5, and 0.31% of the manuscripts contained terms related to logistic, linear, Cox and Poisson regression, respectively. On the other hand, 12.8% of journals author guidelines explicitly recommend to follow the STROBE guidelines, and 35.9% recommend the CONSORT guideline. A low percentage of Spanish scientific journals indexed in PubMed include the STROBE statement requirement in the author guidelines. Multivariate regression models in published observational studies such as logistic regression, linear, Cox and Poisson are increasingly used both at international level, as well as in journals published in Spanish. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Synthesis, characterization and performance of CoxNi1−xS compounds for application in lithium batteries

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Atef Y. Shenouda

2017-06-01

Full Text Available This study reports a process to prepare CoxNi1−xS (x = 0, 0.25, 0.5, 0.75 and 1 samples by hydrothermal process at 250 °C using stoichiometric weight ratios of raw materials. The prepared powder samples were annealed in Ar atmosphere at 450 °C for 3 h. The crystal structure of prepared annealed CoxNi1−xS samples was characterized by XRD. SEM investigations were carried out explaining the morphology of these samples. Electrochemical impedance spectra (EIS measurements, Cyclic voltammetric (CV and galvanostatic measurements were carried out. The life cycle performance was carried out for the cells and Li/Co0.25Ni0.75S cell gave specific discharge capacities of about 330 mA h g−1.

Predicting a future lifetime through Box-Cox transformation.

Science.gov (United States)

Yang, Z

1999-09-01

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

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

Science.gov (United States)

Joachimi, B.; Taylor, A. N.

2011-09-01

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

Generalised shot noise Cox processes

DEFF Research Database (Denmark)

Møller, Jesper; Torrisi, Giovanni Luca

2005-01-01

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

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

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Michelle A Carey

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

Adverse Effects of COX-2 Inhibitors

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Jagdish N. Sharma

2005-01-01

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

Catalytic Ammonia Decomposition over High-Performance Ru/Graphene Nanocomposites for Efficient COx-Free Hydrogen Production

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Gang Li

2017-01-01

Full Text Available Highly-dispersed Ru nanoparticles were grown on graphene nanosheets by simultaneously reducing graphene oxide and Ru ions using ethylene glycol (EG, and the resultant Ru/graphene nanocomposites were applied as a catalyst to ammonia decomposition for COx-free hydrogen production. Tuning the microstructures of Ru/graphene nanocomposites was easily accomplished in terms of Ru particle size, morphology, and loading by adjusting the preparation conditions. This was the key to excellent catalytic activity, because ammonia decomposition over Ru catalysts is structure-sensitive. Our results demonstrated that Ru/graphene prepared using water as a co-solvent greatly enhanced the catalytic performance for ammonia decomposition, due to the significantly improved nano architectures of the composites. The long-term stability of Ru/graphene catalysts was evaluated for COx-free hydrogen production from ammonia at high temperatures, and the structural evolution of the catalysts was investigated during the catalytic reactions. Although there were no obvious changes in the catalytic activities at 450 °C over a duration of 80 h, an aggregation of the Ru nanoparticles was still observed in the nanocomposites, which was ascribed mainly to a sintering effect. However, the performance of the Ru/graphene catalyst was decreased gradually at 500 °C within 20 h, which was ascribed mainly to both the effect of the methanation of the graphene nanosheet under a H2 atmosphere and to enhanced sintering under high temperatures.

Comparing spatial regression to random forests for large ...

Science.gov (United States)

Environmental data may be “large” due to number of records, number of covariates, or both. Random forests has a reputation for good predictive performance when using many covariates, whereas spatial regression, when using reduced rank methods, has a reputation for good predictive performance when using many records. In this study, we compare these two techniques using a data set containing the macroinvertebrate multimetric index (MMI) at 1859 stream sites with over 200 landscape covariates. Our primary goal is predicting MMI at over 1.1 million perennial stream reaches across the USA. For spatial regression modeling, we develop two new methods to accommodate large data: (1) a procedure that estimates optimal Box-Cox transformations to linearize covariate relationships; and (2) a computationally efficient covariate selection routine that takes into account spatial autocorrelation. We show that our new methods lead to cross-validated performance similar to random forests, but that there is an advantage for spatial regression when quantifying the uncertainty of the predictions. Simulations are used to clarify advantages for each method. This research investigates different approaches for modeling and mapping national stream condition. We use MMI data from the EPA's National Rivers and Streams Assessment and predictors from StreamCat (Hill et al., 2015). Previous studies have focused on modeling the MMI condition classes (i.e., good, fair, and po

Detecting and Analyzing I/O Performance Regressions

NARCIS (Netherlands)

Bezemer, C.P.; Milon, E.; Zaidman, A.; Pouwelse, J.

2014-01-01

Regression testing can be done by re-executing a test suite on different software versions and comparing the outcome. For functional testing, the outcome of such tests is either pass (correct behaviour) or fail (incorrect behaviour). For non-functional testing, such as performance testing, this is

Palm distributions for log Gaussian Cox processes

DEFF Research Database (Denmark)

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

2017-01-01

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

SEKULARISASI DALAM PANDANGAN HARVEY COX

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Fauzan Fauzan

2017-02-01

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

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

Science.gov (United States)

2014-01-01

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

Regulation of COX and LOX by curcumin.

Science.gov (United States)

Rao, Chinthalapally V

2007-01-01

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

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

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Puddu Paolo

2012-07-01

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

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

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Yunbei Ma

2014-01-01

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

Radioprotection of intestinal crypt cells by cox-inhibitors

International Nuclear Information System (INIS)

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

2006-01-01

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

Box-Cox transformation for QTL mapping.

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Yang, Runqing; Yi, Nengjun; Xu, Shizhong

2006-01-01

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

Marginal regression analysis of recurrent events with coarsened censoring times.

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Hu, X Joan; Rosychuk, Rhonda J

2016-12-01

Motivated by an ongoing pediatric mental health care (PMHC) study, this article presents weakly structured methods for analyzing doubly censored recurrent event data where only coarsened information on censoring is available. The study extracted administrative records of emergency department visits from provincial health administrative databases. The available information of each individual subject is limited to a subject-specific time window determined up to concealed data. To evaluate time-dependent effect of exposures, we adapt the local linear estimation with right censored survival times under the Cox regression model with time-varying coefficients (cf. Cai and Sun, Scandinavian Journal of Statistics 2003, 30, 93-111). We establish the pointwise consistency and asymptotic normality of the regression parameter estimator, and examine its performance by simulation. The PMHC study illustrates the proposed approach throughout the article. © 2016, The International Biometric Society.

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

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

2014-12-30

For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns. Copyright © 2014 John Wiley & Sons

Matérn thinned Cox processes

DEFF Research Database (Denmark)

Andersen, Ina Trolle; Hahn, Ute

2016-01-01

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

Matérn thinned Cox processes

DEFF Research Database (Denmark)

Andersen, Ina Trolle; Hahn, Ute

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

A simple linear regression method for quantitative trait loci linkage analysis with censored observations.

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Anderson, Carl A; McRae, Allan F; Visscher, Peter M

2006-07-01

Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however, they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using simulation we compare this method to both the Cox and Weibull proportional hazards models and a standard linear regression method that ignores censoring. The grouped linear regression method is of equivalent power to both the Cox and Weibull proportional hazards methods and is significantly better than the standard linear regression method when censored observations are present. The method is also robust to the proportion of censored individuals and the underlying distribution of the trait. On the basis of linear regression methodology, the grouped linear regression model is computationally simple and fast and can be implemented readily in freely available statistical software.

Multivariate Linear Regression and CART Regression Analysis of TBM Performance at Abu Hamour Phase-I Tunnel

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Jakubowski, J.; Stypulkowski, J. B.; Bernardeau, F. G.

2017-12-01

The first phase of the Abu Hamour drainage and storm tunnel was completed in early 2017. The 9.5 km long, 3.7 m diameter tunnel was excavated with two Earth Pressure Balance (EPB) Tunnel Boring Machines from Herrenknecht. TBM operation processes were monitored and recorded by Data Acquisition and Evaluation System. The authors coupled collected TBM drive data with available information on rock mass properties, cleansed, completed with secondary variables and aggregated by weeks and shifts. Correlations and descriptive statistics charts were examined. Multivariate Linear Regression and CART regression tree models linking TBM penetration rate (PR), penetration per revolution (PPR) and field penetration index (FPI) with TBM operational and geotechnical characteristics were performed for the conditions of the weak/soft rock of Doha. Both regression methods are interpretable and the data were screened with different computational approaches allowing enriched insight. The primary goal of the analysis was to investigate empirical relations between multiple explanatory and responding variables, to search for best subsets of explanatory variables and to evaluate the strength of linear and non-linear relations. For each of the penetration indices, a predictive model coupling both regression methods was built and validated. The resultant models appeared to be stronger than constituent ones and indicated an opportunity for more accurate and robust TBM performance predictions.

Decomposition of variance for spatial Cox processes

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Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

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

Decomposition of variance for spatial Cox processes

DEFF Research Database (Denmark)

Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

2013-01-01

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

Decomposition of variance for spatial Cox processes

DEFF Research Database (Denmark)

Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

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

Introduction to the use of regression models in epidemiology.

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Bender, Ralf

2009-01-01

Regression modeling is one of the most important statistical techniques used in analytical epidemiology. By means of regression models the effect of one or several explanatory variables (e.g., exposures, subject characteristics, risk factors) on a response variable such as mortality or cancer can be investigated. From multiple regression models, adjusted effect estimates can be obtained that take the effect of potential confounders into account. Regression methods can be applied in all epidemiologic study designs so that they represent a universal tool for data analysis in epidemiology. Different kinds of regression models have been developed in dependence on the measurement scale of the response variable and the study design. The most important methods are linear regression for continuous outcomes, logistic regression for binary outcomes, Cox regression for time-to-event data, and Poisson regression for frequencies and rates. This chapter provides a nontechnical introduction to these regression models with illustrating examples from cancer research.

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

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Torsten Kniess

2013-05-01

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

Survival Prediction and Feature Selection in Patients with Breast Cancer Using Support Vector Regression

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Shahrbanoo Goli

2016-01-01

Full Text Available The Support Vector Regression (SVR model has been broadly used for response prediction. However, few researchers have used SVR for survival analysis. In this study, a new SVR model is proposed and SVR with different kernels and the traditional Cox model are trained. The models are compared based on different performance measures. We also select the best subset of features using three feature selection methods: combination of SVR and statistical tests, univariate feature selection based on concordance index, and recursive feature elimination. The evaluations are performed using available medical datasets and also a Breast Cancer (BC dataset consisting of 573 patients who visited the Oncology Clinic of Hamadan province in Iran. Results show that, for the BC dataset, survival time can be predicted more accurately by linear SVR than nonlinear SVR. Based on the three feature selection methods, metastasis status, progesterone receptor status, and human epidermal growth factor receptor 2 status are the best features associated to survival. Also, according to the obtained results, performance of linear and nonlinear kernels is comparable. The proposed SVR model performs similar to or slightly better than other models. Also, SVR performs similar to or better than Cox when all features are included in model.

The Moxie of Kathy Cox

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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.…

Ensembling Variable Selectors by Stability Selection for the Cox Model

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Qing-Yan Yin

2017-01-01

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

Box-Cox transformation on dataset from compositional studies of archaeological potteries

International Nuclear Information System (INIS)

Santos, J.O.; Santana Reis, Michael; Silva, J.E.

2017-01-01

In archaeometric data set it was verified by statistical tests that some variables almost never follow a multivariate normal distribution using logarithmic transformation or other. This work presents a multivariate Box-Cox transformation for Mardia's and Royton's tests for a data set of fifty ceramic fragments from archaeological site Justino, Xingo, Brazil, and one clay sample collected near of the site. The samples were analyzed by instrumental neutron activation analysis, INAA. The study was made using companion to applied regression package from R software and was tested by Hotelling's T"2 statistics. (author)

Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data.

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Han, Cong; Kronmal, Richard

2004-12-15

Box-Cox transformation is investigated for regression models for left-censored data. Examples are provided using coronary calcification data from the Multi-Ethnic Study of Atherosclerosis and pharmacokinetic data of a nicotine nasal spray. Copyright 2004 John Wiley & Sons, Ltd.

LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression.

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Nicholas S Kirkby

Full Text Available There are two schools of thought regarding the cyclooxygenase (COX isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.

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

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

2001-01-01

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

Determinants of Non-Performing Assets in India - Panel Regression

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Saikat Ghosh Roy

2014-12-01

Full Text Available It is well known that level of banks‟ credit plays an important role in economic developments. Indian banking sector has played a seminal role in supporting economic growth in India. Recently, Indian banks are experiencing consistent increase in non-performing assets (NPA. In this perspective, this paper investigates the trends in NPA in Indian banks and its determinants. The panel regressions, fixed effect allows evaluating the impact of selected macroeconomic variables on the NPA. The Panel regression result indicates that the GDP growth, change in exchange rate and global volatility have major effects on the NPA level of Indian banking sector.

Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

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

2010-01-01

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

COX-2 and p53 in human sinonasal cancer

DEFF Research Database (Denmark)

Holmila, Reetta; Cyr, Diane; Luce, Danièle

2008-01-01

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

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

International Nuclear Information System (INIS)

Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

2011-01-01

Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

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Lagerstedt Kristina

2011-06-01

Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

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Joseph Menczer

2016-03-01

Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

Effects of electroacupuncture on luteal regression and steroidogenesis in ovarian hyperstimulation syndrome model rat.

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Huang, Xuan; Chen, Li; Xia, You-Bing; Xie, Min; Sun, Qin; Yao, Bing

2018-03-15

Electroacupuncture (EA) is an effective and safe therapeutic method widely used for treating clinical diseases. Previously, we found that EA could decrease serum hormones and reduce ovarian size in ovarian hyperstimulation syndrome (OHSS) rat model. Nevertheless, the mechanisms that contribute to these improvements remain unclear. HE staining was used to count the number of corpora lutea (CL) and follicles. Immunohistochemical and ELISA were applied to examine luteal functional and structural regression. Immunoprecipitation was used for analyzing the interaction between NPY (neuropeptide Y) and COX-2; western blotting and qRT-PCR were used to evaluate the expressions of steroidogenic enzymes and PKA/CREB pathway. EA treatment significantly reduced the ovarian weight and the number of CL, also decreased ovarian and serum levels of PGE2 and COX-2 expression; increased ovarian PGF2α levels and PGF2α/PGE2 ratio; decreased PCNA expression and distribution; and increased cyclin regulatory inhibitor p27 expression to have further effect on the luteal formation, and promote luteal functional and structural regression. Moreover, expression of COX-2 in ovaries was possessed interactivity increased expression of NPY. Furthermore, EA treatment lowered the serum hormone levels, inhibited PKA/CREB pathway and decreased the expressions of steroidogenic enzymes. Hence, interaction with COX-2, NPY may affect the levels of PGF2α and PGE2 as well as impact the proliferation of granulosa cells in ovaries, thus further reducing the luteal formation, and promoting luteal structural and functional regression, as well as the ovarian steroidogenesis following EA treatment. EA treatment could be an option for preventing OHSS in ART. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimating functions for inhomogeneous Cox processes

DEFF Research Database (Denmark)

Waagepetersen, Rasmus

2006-01-01

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

Model performance analysis and model validation in logistic regression

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Rosa Arboretti Giancristofaro

2007-10-01

Full Text Available In this paper a new model validation procedure for a logistic regression model is presented. At first, we illustrate a brief review of different techniques of model validation. Next, we define a number of properties required for a model to be considered "good", and a number of quantitative performance measures. Lastly, we describe a methodology for the assessment of the performance of a given model by using an example taken from a management study.

Functional form diagnostics for Cox's proportional hazards model.

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León, Larry F; Tsai, Chih-Ling

2004-03-01

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

Accounting for estimated IQ in neuropsychological test performance with regression-based techniques.

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Testa, S Marc; Winicki, Jessica M; Pearlson, Godfrey D; Gordon, Barry; Schretlen, David J

2009-11-01

Regression-based normative techniques account for variability in test performance associated with multiple predictor variables and generate expected scores based on algebraic equations. Using this approach, we show that estimated IQ, based on oral word reading, accounts for 1-9% of the variability beyond that explained by individual differences in age, sex, race, and years of education for most cognitive measures. These results confirm that adding estimated "premorbid" IQ to demographic predictors in multiple regression models can incrementally improve the accuracy with which regression-based norms (RBNs) benchmark expected neuropsychological test performance in healthy adults. It remains to be seen whether the incremental variance in test performance explained by estimated "premorbid" IQ translates to improved diagnostic accuracy in patient samples. We describe these methods, and illustrate the step-by-step application of RBNs with two cases. We also discuss the rationale, assumptions, and caveats of this approach. More broadly, we note that adjusting test scores for age and other characteristics might actually decrease the accuracy with which test performance predicts absolute criteria, such as the ability to drive or live independently.

A Box-Cox normal model for response times.

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

2009-11-01

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

A new approach to the Box-Cox transformation

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Jorge Iván eVélez

2015-10-01

Full Text Available We propose a new methodology to estimate λ, the parameter of the Box-Cox transformation, as well as an alternative method to determine plausible values for it. The former is accomplished by defining a grid of values for λ and further perform a normality test on the λ -transformed data. The optimum value of λ, say λ * , is such that the p-value from the normality test is the highest. The set of plausible values is determined using the inverse probability method after plotting the p-values against the values of λ on the grid. Our methodology is illustrated with two real-world data sets. Furthermore, a simulation study suggests that our method improves the symmetry, kurtosis and, hence, the normality of data, making it a feasible alternative to the traditional Box-Cox transformation.

The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox 1 and Cox4 are down-regulated, by copper deficiency.

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Getz, Jean; Lin, Dingbo; Medeiros, Denis M

2011-10-01

Copper is ferried in a cell complexed to chaperone proteins, and in the heart much copper is required for cytochrome c oxidase (Cox). It is not completely understood how copper status affects the levels of these proteins. Here we determined if dietary copper deficiency could up- or down-regulate select copper chaperone proteins and Cox subunits 1 and 4 in cardiac tissue of rats. Sixteen weanling male Long-Evans rats were randomized into treatment groups, one group receiving a copper-deficient diet (CCS, Sco1, Ctr1, Cox17, Cox1, and Cox4 by SDS-PAGE and Western blotting. No changes were observed in the concentrations of CTR1 and Cox17 between copper-adequate and copper-deficient rats. CCS and Sco1 were up-regulated and Cox1 and Cox4 were both down-regulated as a result of copper deficiency. These data suggest that select chaperone proteins and may be up-regulated, and Cox1 and 4 down-regulated, by a dietary copper deficiency, whereas others appear not to be affected by copper status.

Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

Science.gov (United States)

Yang, Lixue; Chen, Kean

2015-11-01

To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy.

The CoxD protein, a novel AAA+ ATPase involved in metal cluster assembly: hydrolysis of nucleotide-triphosphates and oligomerization.

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Tobias Maisel

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

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

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Bazer Fuller W

2003-08-01

Full Text Available Abstract In sheep, the uterus produces luteolytic pulses of prostaglandin F2α (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 (IFNτ, 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 α (ERα (directly and OTR (indirectly genes. Conflicting studies indicate that IFNτ 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 IFNτ 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 IFNτ has no effect on expression of the COX-2 gene in the ovine endometrium. Therefore, antiluteolytic effects of IFNτ are to inhibit ERα 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.

Decomposition of Variance for Spatial Cox Processes.

Science.gov (United States)

Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

2013-03-01

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

Comparing performances of clements, box-cox, Johnson methods with weibull distributions for assessing process capability

Energy Technology Data Exchange (ETDEWEB)

Senvar, O.; Sennaroglu, B.

2016-07-01

This study examines Clements’ Approach (CA), Box-Cox transformation (BCT), and Johnson transformation (JT) methods for process capability assessments through Weibull-distributed data with different parameters to figure out the effects of the tail behaviours on process capability and compares their estimation performances in terms of accuracy and precision. Design/methodology/approach: Usage of process performance index (PPI) Ppu is handled for process capability analysis (PCA) because the comparison issues are performed through generating Weibull data without subgroups. Box plots, descriptive statistics, the root-mean-square deviation (RMSD), which is used as a measure of error, and a radar chart are utilized all together for evaluating the performances of the methods. In addition, the bias of the estimated values is important as the efficiency measured by the mean square error. In this regard, Relative Bias (RB) and the Relative Root Mean Square Error (RRMSE) are also considered. Findings: The results reveal that the performance of a method is dependent on its capability to fit the tail behavior of the Weibull distribution and on targeted values of the PPIs. It is observed that the effect of tail behavior is more significant when the process is more capable. Research limitations/implications: Some other methods such as Weighted Variance method, which also give good results, were also conducted. However, we later realized that it would be confusing in terms of comparison issues between the methods for consistent interpretations... (Author)

COX-2, VEGF and tumour angiogenesis.

LENUS (Irish Health Repository)

Toomey, D P

2009-06-01

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

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

Science.gov (United States)

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

2013-10-15

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

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

Science.gov (United States)

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

2013-01-01

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

Acute upregulation of COX-2 by renal artery stenosis

DEFF Research Database (Denmark)

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

2001-01-01

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

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

LENUS (Irish Health Repository)

Khan, M

2012-04-01

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

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

NARCIS (Netherlands)

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

2008-01-01

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

The Regression Analysis of Individual Financial Performance: Evidence from Croatia

OpenAIRE

Bahovec, Vlasta; Barbić, Dajana; Palić, Irena

2017-01-01

Background: A large body of empirical literature indicates that gender and financial literacy are significant determinants of individual financial performance. Objectives: The purpose of this paper is to recognize the impact of the variable financial literacy and the variable gender on the variation of the financial performance using the regression analysis. Methods/Approach: The survey was conducted using the systematically chosen random sample of Croatian financial consumers. The cross sect...

Geometric anisotropic spatial point pattern analysis and Cox processes

DEFF Research Database (Denmark)

Møller, Jesper; Toftaker, Håkon

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

Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data.

Science.gov (United States)

Yelland, Lisa N; Salter, Amy B; Ryan, Philip

2011-10-15

Modified Poisson regression, which combines a log Poisson regression model with robust variance estimation, is a useful alternative to log binomial regression for estimating relative risks. Previous studies have shown both analytically and by simulation that modified Poisson regression is appropriate for independent prospective data. This method is often applied to clustered prospective data, despite a lack of evidence to support its use in this setting. The purpose of this article is to evaluate the performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data, by using generalized estimating equations to account for clustering. A simulation study is conducted to compare log binomial regression and modified Poisson regression for analyzing clustered data from intervention and observational studies. Both methods generally perform well in terms of bias, type I error, and coverage. Unlike log binomial regression, modified Poisson regression is not prone to convergence problems. The methods are contrasted by using example data sets from 2 large studies. The results presented in this article support the use of modified Poisson regression as an alternative to log binomial regression for analyzing clustered prospective data when clustering is taken into account by using generalized estimating equations.

Palm distributions for log Gaussian Cox processes

DEFF Research Database (Denmark)

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

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

Efek ekstrak daun singkong (Manihot utilissima terhadap ekspresi COX-2 pada monosit yang dipapar LPS E.coli (The effect of Manihot utilissima extracts on COX-2 expression of monocytes induced by LPS E. coli

Directory of Open Access Journals (Sweden)

Zahara Meilawaty

2013-12-01

Full Text Available Background: Periodontal disease is a common and widespread disease in the community. Gram negative bacteria have a role inperiodontitis. These bacteria secrete a variety of products such as endotoxin lipopolysaccharide (LPS, which causes the occurrenceof inflammation or infection. The body defense responses are neutrophils and mononuclear cells (monocytes and macrophages. Inresponse to defense mechanism, the body will be expressed enzyme cyclooxygenase (COX which functions convert arachidonic acidto prostaglandins. Cassava leaf cells known to play a role in reducing inflammation, but the mechanism for inhibiting COX-2, is notknown. Purpose: The study was aimed to determine the effect of cassava leaf extract (Manihot utilissima on expression of enzyme COX-2 in monocytes which were exposed by LPS E. coli. Methods: This study was in vitro experimental studies with the design of posttestonly control group design. The sample was the cassava leaves extract (Manihot utilissima at concentration of 12.5 % and 25 %. Theexpression of COX-2 was determined by immunocytochemistry method. Isolated monocytes were incubated in cassava leaf extract, andthen exposed to LPS, after washing imunostaning procedure was performed using a monoclonal antibody (MAb anti-human COX-2.The research data was the number of monocytes that express COX-2. Results: Expression of COX-2 in the group cassava leaf extractwas higher than the group that induced by LPS E. coli only. Conclusion: Cassava leaf extract did not inhibit the expression of COX-2in monocytes which were exposed by LPS E. coli.Latar belakang: Penyakit periodontal merupakan penyakit umum dan tersebar luas di masyarakat. Bakteri yang banyak berperanpada periodontitis adalah Gram negatif. Bakteri ini mengeluarkan berbagai produk antara lain endotoksin lipopolisakarida (LPS yangmenyebabkan inflamasi atau infeksi. Respon pertahanan tubuh pertama adalah netrofil dan sel mononuklear (monosit dan makrofag.Pada respon

Modeling and prediction of flotation performance using support vector regression

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Despotović Vladimir

2017-01-01

Full Text Available Continuous efforts have been made in recent year to improve the process of paper recycling, as it is of critical importance for saving the wood, water and energy resources. Flotation deinking is considered to be one of the key methods for separation of ink particles from the cellulose fibres. Attempts to model the flotation deinking process have often resulted in complex models that are difficult to implement and use. In this paper a model for prediction of flotation performance based on Support Vector Regression (SVR, is presented. Representative data samples were created in laboratory, under a variety of practical control variables for the flotation deinking process, including different reagents, pH values and flotation residence time. Predictive model was created that was trained on these data samples, and the flotation performance was assessed showing that Support Vector Regression is a promising method even when dataset used for training the model is limited.

Prognostic factorsin inoperable adenocarcinoma of the lung: A multivariate regression analysis of 259 patiens

DEFF Research Database (Denmark)

Sørensen, Jens Benn; Badsberg, Jens Henrik; Olsen, Jens

1989-01-01

The prognostic factors for survival in advanced adenocarcinoma of the lung were investigated in a consecutive series of 259 patients treated with chemotherapy. Twenty-eight pretreatment variables were investigated by use of Cox's multivariate regression model, including histological subtypes and ...

The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity: a meta-analysis.

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Zhiyuan Weng

Full Text Available OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643 from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595, 6 (344/698, 10 (588/878 and 7 (209/676 articles (patients/controls qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2. The risk estimate was expressed as odds ratio (OR and 95% confidence interval (95% CI. Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005 and rs1126643 (2.37; 1.44-3.89; 0.001 with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03. Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034 and averaged platelet numbers (P = 0.012 between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. CONCLUSION: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

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

Science.gov (United States)

Herschman, Harvey

2014-01-01

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

COX-2 Inhibitors for Cancer Treatment in Dogs

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Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

2011-10-01

Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

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

Science.gov (United States)

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

2004-01-01

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

Predictors of course in obsessive-compulsive disorder: logistic regression versus Cox regression for recurrent events

NARCIS (Netherlands)

Kempe, P. T.; van Oppen, P.; de Haan, E.; Twisk, J. W. R.; Sluis, A.; Smit, J. H.; van Dyck, R.; van Balkom, A. J. L. M.

2007-01-01

Two methods for predicting remissions in obsessive-compulsive disorder (OCD) treatment are evaluated. Y-BOCS measurements of 88 patients with a primary OCD (DSM-III-R) diagnosis were performed over a 16-week treatment period, and during three follow-ups. Remission at any measurement was defined as a

Management of Industrial Performance Indicators: Regression Analysis and Simulation

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Walter Roberto Hernandez Vergara

2017-11-01

Full Text Available Stochastic methods can be used in problem solving and explanation of natural phenomena through the application of statistical procedures. The article aims to associate the regression analysis and systems simulation, in order to facilitate the practical understanding of data analysis. The algorithms were developed in Microsoft Office Excel software, using statistical techniques such as regression theory, ANOVA and Cholesky Factorization, which made it possible to create models of single and multiple systems with up to five independent variables. For the analysis of these models, the Monte Carlo simulation and analysis of industrial performance indicators were used, resulting in numerical indices that aim to improve the goals’ management for compliance indicators, by identifying systems’ instability, correlation and anomalies. The analytical models presented in the survey indicated satisfactory results with numerous possibilities for industrial and academic applications, as well as the potential for deployment in new analytical techniques.

A generalized multivariate regression model for modelling ocean wave heights

Science.gov (United States)

Wang, X. L.; Feng, Y.; Swail, V. R.

2012-04-01

In this study, a generalized multivariate linear regression model is developed to represent the relationship between 6-hourly ocean significant wave heights (Hs) and the corresponding 6-hourly mean sea level pressure (MSLP) fields. The model is calibrated using the ERA-Interim reanalysis of Hs and MSLP fields for 1981-2000, and is validated using the ERA-Interim reanalysis for 2001-2010 and ERA40 reanalysis of Hs and MSLP for 1958-2001. The performance of the fitted model is evaluated in terms of Pierce skill score, frequency bias index, and correlation skill score. Being not normally distributed, wave heights are subjected to a data adaptive Box-Cox transformation before being used in the model fitting. Also, since 6-hourly data are being modelled, lag-1 autocorrelation must be and is accounted for. The models with and without Box-Cox transformation, and with and without accounting for autocorrelation, are inter-compared in terms of their prediction skills. The fitted MSLP-Hs relationship is then used to reconstruct historical wave height climate from the 6-hourly MSLP fields taken from the Twentieth Century Reanalysis (20CR, Compo et al. 2011), and to project possible future wave height climates using CMIP5 model simulations of MSLP fields. The reconstructed and projected wave heights, both seasonal means and maxima, are subject to a trend analysis that allows for non-linear (polynomial) trends.

A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs.

Science.gov (United States)

Marjan, Mojtabavi Naeini; Hamzeh, Mesrian Tanha; Rahman, Emamzadeh; Sadeq, Vallian

2014-08-01

Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of the influence of quantile regression model on mainland tourists' service satisfaction performance.

Science.gov (United States)

Wang, Wen-Cheng; Cho, Wen-Chien; Chen, Yin-Jen

2014-01-01

It is estimated that mainland Chinese tourists travelling to Taiwan can bring annual revenues of 400 billion NTD to the Taiwan economy. Thus, how the Taiwanese Government formulates relevant measures to satisfy both sides is the focus of most concern. Taiwan must improve the facilities and service quality of its tourism industry so as to attract more mainland tourists. This paper conducted a questionnaire survey of mainland tourists and used grey relational analysis in grey mathematics to analyze the satisfaction performance of all satisfaction question items. The first eight satisfaction items were used as independent variables, and the overall satisfaction performance was used as a dependent variable for quantile regression model analysis to discuss the relationship between the dependent variable under different quantiles and independent variables. Finally, this study further discussed the predictive accuracy of the least mean regression model and each quantile regression model, as a reference for research personnel. The analysis results showed that other variables could also affect the overall satisfaction performance of mainland tourists, in addition to occupation and age. The overall predictive accuracy of quantile regression model Q0.25 was higher than that of the other three models.

Analysis of the Influence of Quantile Regression Model on Mainland Tourists' Service Satisfaction Performance

Science.gov (United States)

Wang, Wen-Cheng; Cho, Wen-Chien; Chen, Yin-Jen

2014-01-01

It is estimated that mainland Chinese tourists travelling to Taiwan can bring annual revenues of 400 billion NTD to the Taiwan economy. Thus, how the Taiwanese Government formulates relevant measures to satisfy both sides is the focus of most concern. Taiwan must improve the facilities and service quality of its tourism industry so as to attract more mainland tourists. This paper conducted a questionnaire survey of mainland tourists and used grey relational analysis in grey mathematics to analyze the satisfaction performance of all satisfaction question items. The first eight satisfaction items were used as independent variables, and the overall satisfaction performance was used as a dependent variable for quantile regression model analysis to discuss the relationship between the dependent variable under different quantiles and independent variables. Finally, this study further discussed the predictive accuracy of the least mean regression model and each quantile regression model, as a reference for research personnel. The analysis results showed that other variables could also affect the overall satisfaction performance of mainland tourists, in addition to occupation and age. The overall predictive accuracy of quantile regression model Q0.25 was higher than that of the other three models. PMID:24574916

Analysis of the Influence of Quantile Regression Model on Mainland Tourists’ Service Satisfaction Performance

Directory of Open Access Journals (Sweden)

Wen-Cheng Wang

2014-01-01

Full Text Available It is estimated that mainland Chinese tourists travelling to Taiwan can bring annual revenues of 400 billion NTD to the Taiwan economy. Thus, how the Taiwanese Government formulates relevant measures to satisfy both sides is the focus of most concern. Taiwan must improve the facilities and service quality of its tourism industry so as to attract more mainland tourists. This paper conducted a questionnaire survey of mainland tourists and used grey relational analysis in grey mathematics to analyze the satisfaction performance of all satisfaction question items. The first eight satisfaction items were used as independent variables, and the overall satisfaction performance was used as a dependent variable for quantile regression model analysis to discuss the relationship between the dependent variable under different quantiles and independent variables. Finally, this study further discussed the predictive accuracy of the least mean regression model and each quantile regression model, as a reference for research personnel. The analysis results showed that other variables could also affect the overall satisfaction performance of mainland tourists, in addition to occupation and age. The overall predictive accuracy of quantile regression model Q0.25 was higher than that of the other three models.

Control of Co content and SOFC cathode performance in Y1-ySr2+yCu3-xCoxO7+δ

Science.gov (United States)

Šimo, F.; Payne, J. L.; Demont, A.; Sayers, R.; Li, Ming; Collins, C. M.; Pitcher, M. J.; Claridge, J. B.; Rosseinsky, M. J.

2014-11-01

The electrochemical performance of the layered perovskite YSr2Cu3-xCoxO7+δ, a potential solid oxide fuel cell (SOFC) cathode, is improved by increasing the Co content from x = 1.00 to a maximum of x = 1.30. Single phase samples with x > 1.00 are obtained by tuning the Y/Sr ratio, yielding the composition Y1-ySr2+yCu3-xCoxO7+δ (where y ≤ 0.05). The high temperature structure of Y0.95Sr2.05Cu1.7Co1.3O7+δ at 740 °C is characterised by powder neutron diffraction and the potential of this Co-enriched material as a SOFC cathode is investigated by combining AC impedance spectroscopy, four-probe DC conductivity and powder XRD measurements to determine its electrochemical properties along with its thermal stability and compatibility with a range of commercially available electrolytes. The material is shown to be compatible with doped ceria electrolytes at 900 °C.

An appreciation of Richard Threlkeld Cox

Science.gov (United States)

Tribus, Myron

2002-05-01

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

COX-2 is associated with periodontitis in Europeans

NARCIS (Netherlands)

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

2010-01-01

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

Prospective performance evaluation of selected common virtual screening tools. Case study: Cyclooxygenase (COX) 1 and 2.

Science.gov (United States)

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. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Bootstrapping Cox’s Regression Model.

Science.gov (United States)

1985-11-01

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

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

Science.gov (United States)

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.

Regression models for the restricted residual mean life for right-censored and left-truncated data

DEFF Research Database (Denmark)

Cortese, Giuliana; Holmboe, Stine A.; Scheike, Thomas H.

2017-01-01

The hazard ratios resulting from a Cox's regression hazards model are hard to interpret and to be converted into prolonged survival time. As the main goal is often to study survival functions, there is increasing interest in summary measures based on the survival function that are easier to inter......The hazard ratios resulting from a Cox's regression hazards model are hard to interpret and to be converted into prolonged survival time. As the main goal is often to study survival functions, there is increasing interest in summary measures based on the survival function that are easier...... to interpret than the hazard ratio; the residual mean time is an important example of those measures. However, because of the presence of right censoring, the tail of the survival distribution is often difficult to estimate correctly. Therefore, we consider the restricted residual mean time, which represents...... a partial area under the survival function, given any time horizon τ, and is interpreted as the residual life expectancy up to τ of a subject surviving up to time t. We present a class of regression models for this measure, based on weighted estimating equations and inverse probability of censoring weighted...

On spatio-temporal Lévy based Cox processes

DEFF Research Database (Denmark)

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

2006-01-01

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

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

Science.gov (United States)

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

2016-10-07

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

Corporate Social Responsibility and Financial Performance: A Two Least Regression Approach

Directory of Open Access Journals (Sweden)

Alexander Olawumi Dabor

2017-12-01

Full Text Available The objective of this study is to investigate the casuality between corporate social responsibility and firm financial performance. The study employed two least square regression approaches. Fifty-two firms were selected using the scientific method. The findings revealed that corporate social responsibility and firm performance in manufacturing sector are mutually related at 5%. The study recommended that management of manufacturing companies in Nigeria should expend on CSR to boost profitability and corporate image.

Predicting Performance on MOOC Assessments using Multi-Regression Models

OpenAIRE

Ren, Zhiyun; Rangwala, Huzefa; Johri, Aditya

2016-01-01

The past few years has seen the rapid growth of data min- ing approaches for the analysis of data obtained from Mas- sive Open Online Courses (MOOCs). The objectives of this study are to develop approaches to predict the scores a stu- dent may achieve on a given grade-related assessment based on information, considered as prior performance or prior ac- tivity in the course. We develop a personalized linear mul- tiple regression (PLMR) model to predict the grade for a student, prior to attempt...

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

International Nuclear Information System (INIS)

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

2014-01-01

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

The performance of random coefficient regression in accounting for residual confounding.

Science.gov (United States)

Gustafson, Paul; Greenland, Sander

2006-09-01

Greenland (2000, Biometrics 56, 915-921) describes the use of random coefficient regression to adjust for residual confounding in a particular setting. We examine this setting further, giving theoretical and empirical results concerning the frequentist and Bayesian performance of random coefficient regression. Particularly, we compare estimators based on this adjustment for residual confounding to estimators based on the assumption of no residual confounding. This devolves to comparing an estimator from a nonidentified but more realistic model to an estimator from a less realistic but identified model. The approach described by Gustafson (2005, Statistical Science 20, 111-140) is used to quantify the performance of a Bayesian estimator arising from a nonidentified model. From both theoretical calculations and simulations we find support for the idea that superior performance can be obtained by replacing unrealistic identifying constraints with priors that allow modest departures from those constraints. In terms of point-estimator bias this superiority arises when the extent of residual confounding is substantial, but the advantage is much broader in terms of interval estimation. The benefit from modeling residual confounding is maintained when the prior distributions employed only roughly correspond to reality, for the standard identifying constraints are equivalent to priors that typically correspond much worse.

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

Directory of Open Access Journals (Sweden)

Evrim eGurpinar

2013-07-01

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

CoX zeolites and their exchange with deuterium

Energy Technology Data Exchange (ETDEWEB)

Novakova, J; Kubelkova, L; Jiru, P [Ceskoslovenska Akademie Ved, Prague. Ustav Fyzikalni Chemie

1976-04-01

An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D/sub 2/+OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D/sub 2/+H/sub 2/ exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm/sup -1/ band are exchanged more slowly than are the other hydrogens.

CoX zeolites and their exchange with deuterium

International Nuclear Information System (INIS)

Novakova, J.; Kubelkova, L.; Jiru, P.

1976-01-01

An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D 2 +OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D 2 +H 2 exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm -1 band are exchanged more slowly than are the other hydrogens. (author)

Extensions and Applications of the Cox-Aalen Survival Model

DEFF Research Database (Denmark)

Scheike, Thomas H.; Zhang, Mei-Jie

2003-01-01

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

DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB

International Nuclear Information System (INIS)

Morris, R.H.K.; Tonks, A.J.; Jones, K.P.; Ahluwalia, M.K.; Thomas, A.W.; Tonks, A.; Jackson, S.K.

2008-01-01

The major phospholipid in pulmonary surfactant dipalmitoyl phosphatidylcholine (DPPC) has been shown to modulate inflammatory responses. Using human monocytes, this study demonstrates that DPPC significantly increased PGE 2 (P < 0.05) production by 2.5-fold when compared to untreated monocyte controls. Mechanistically, this effect was concomitant with an increase in COX-2 expression which was abrogated in the presence of a COX-2 inhibitor. The regulation of COX-2 expression was independent of NF-κB activity. Further, DPPC increased the phosphorylation of the cyclic AMP response element binding protein (CREB; an important nuclear transcription factor important in regulating COX-2 expression). In addition, we also show that changing the fatty acid groups of PC (e.g. using L-α-phosphatidylcholine β-arachidonoyl-γ-palmitoyl (PAPC)) has a profound effect on the regulation of COX-2 expression and CREB activation. This study provides new evidence for the anti-inflammatory activity of DPPC and that this activity is at least in part mediated via CREB activation of COX-2

Late Results of Cox Maze III Procedure in Patients with Atrial Fibrillation Associated with Structural Heart Disease.

Science.gov (United States)

Gomes, Gustavo Gir; Gali, Wagner Luis; Sarabanda, Alvaro Valentim Lima; Cunha, Claudio Ribeiro da; Kessler, Iruena Moraes; Atik, Fernando Antibas

2017-07-01

Cox-Maze III procedure is one of the surgical techniques used in the surgical treatment of atrial fibrillation (AF). To determine late results of Cox-Maze III in terms of maintenance of sinus rhythm, and mortality and stroke rates. Between January 2006 and January 2013, 93 patients were submitted to the cut-and-sew Cox-Maze III procedure in combination with structural heart disease repair. Heart rhythm was determined by 24-hour Holter monitoring. Procedural success rates were determined by longitudinal methods and recurrence predictors by multivariate Cox regression models. Thirteen patients that obtained hospital discharge alive were excluded due to lost follow-up. The remaining 80 patients were aged 49.9 ± 12 years and 47 (58.7%) of them were female. Involvement of mitral valve and rheumatic heart disease were found in 67 (83.7%) and 63 (78.7%) patients, respectively. Seventy patients (87.5%) had persistent or long-standing persistent AF. Mean follow-up with Holter monitoring was 27.5 months. There were no hospital deaths. Sinus rhythm maintenance rates were 88%, 85.1% and 80.6% at 6 months, 24 months and 36 months, respectively. Predictors of late recurrence of AF were female gender (HR 3.52; 95% CI 1.21-10.25; p = 0.02), coronary artery disease (HR 4.73 95% CI 1.37-16.36; p = 0.01) and greater left atrium diameter (HR 1.05; 95% CI 1.01-1.09; p = 0.02). Actuarial survival was 98.5% at 12, 24 and 48 months and actuarial freedom from stroke was 100%, 100% and 97.5% in the same time frames. The Cox-Maze III procedure, in our experience, is efficacious for sinus rhythm maintenance, with very low late mortality and stroke rates. A operação de Cox-Maze III é uma das variantes técnicas no tratamento cirúrgico da fibrilação atrial (FA). Estudar os resultados tardios da operação de Cox-Maze III, quanto à eficácia na manutenção de ritmo sinusal e taxas de mortalidade e acidente vascular cerebral (AVC). Entre janeiro de 2006 a janeiro de 2013, 93 pacientes

Generalised shot noise Cox processes

DEFF Research Database (Denmark)

Møller, Jesper; Torrisi, Giovanni Luca

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

Nucleobindin co-localizes and associates with cyclooxygenase (COX-2 in human neutrophils.

Directory of Open Access Journals (Sweden)

Patrick Leclerc

2008-05-01

Full Text Available The inducible cyclooxygenase isoform (COX-2 is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc, a ubiquitous Ca(2+-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2 biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2 biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2. Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2 biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis.

Identifying individual changes in performance with composite quality indicators while accounting for regression to the mean.

Science.gov (United States)

Gajewski, Byron J; Dunton, Nancy

2013-04-01

Almost a decade ago Morton and Torgerson indicated that perceived medical benefits could be due to "regression to the mean." Despite this caution, the regression to the mean "effects on the identification of changes in institutional performance do not seem to have been considered previously in any depth" (Jones and Spiegelhalter). As a response, Jones and Spiegelhalter provide a methodology to adjust for regression to the mean when modeling recent changes in institutional performance for one-variable quality indicators. Therefore, in our view, Jones and Spiegelhalter provide a breakthrough methodology for performance measures. At the same time, in the interests of parsimony, it is useful to aggregate individual quality indicators into a composite score. Our question is, can we develop and demonstrate a methodology that extends the "regression to the mean" literature to allow for composite quality indicators? Using a latent variable modeling approach, we extend the methodology to the composite indicator case. We demonstrate the approach on 4 indicators collected by the National Database of Nursing Quality Indicators. A simulation study further demonstrates its "proof of concept."

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

Science.gov (United States)

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

2017-10-12

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

Regression Benchmarking: An Approach to Quality Assurance in Performance

OpenAIRE

Bulej, Lubomír

2005-01-01

The paper presents a short summary of our work in the area of regression benchmarking and its application to software development. Specially, we explain the concept of regression benchmarking, the requirements for employing regression testing in a software project, and methods used for analyzing the vast amounts of data resulting from repeated benchmarking. We present the application of regression benchmarking on a real software project and conclude with a glimpse at the challenges for the fu...

COxSwAIN: Compressive Sensing for Advanced Imaging and Navigation

Science.gov (United States)

Kurwitz, Richard; Pulley, Marina; LaFerney, Nathan; Munoz, Carlos

2015-01-01

The COxSwAIN project focuses on building an image and video compression scheme that can be implemented in a small or low-power satellite. To do this, we used Compressive Sensing, where the compression is performed by matrix multiplications on the satellite and reconstructed on the ground. Our paper explains our methodology and demonstrates the results of the scheme, being able to achieve high quality image compression that is robust to noise and corruption.

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

Science.gov (United States)

2013-01-01

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

Performance of a New Restricted Biased Estimator in Logistic Regression

Directory of Open Access Journals (Sweden)

Yasin ASAR

2017-12-01

Full Text Available It is known that the variance of the maximum likelihood estimator (MLE inflates when the explanatory variables are correlated. This situation is called the multicollinearity problem. As a result, the estimations of the model may not be trustful. Therefore, this paper introduces a new restricted estimator (RLTE that may be applied to get rid of the multicollinearity when the parameters lie in some linear subspace  in logistic regression. The mean squared errors (MSE and the matrix mean squared errors (MMSE of the estimators considered in this paper are given. A Monte Carlo experiment is designed to evaluate the performances of the proposed estimator, the restricted MLE (RMLE, MLE and Liu-type estimator (LTE. The criterion of performance is chosen to be MSE. Moreover, a real data example is presented. According to the results, proposed estimator has better performance than MLE, RMLE and LTE.

MCEM algorithm for the log-Gaussian Cox process

OpenAIRE

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

2014-01-01

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

Hepatic ischemia and reperfusion injury in the absence of myeloid cell-derived COX-2 in mice.

Directory of Open Access Journals (Sweden)

Sergio Duarte

Full Text Available Cyclooxygenase-2 (COX-2 is a mediator of hepatic ischemia and reperfusion injury (IRI. While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2-M/-M to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2-M/-M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2-M/-M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2-M/-M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2-M/-M and WT mice. COX-2-M/-M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9 expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2-M/-M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype.

Time-adaptive quantile regression

DEFF Research Database (Denmark)

Møller, Jan Kloppenborg; Nielsen, Henrik Aalborg; Madsen, Henrik

2008-01-01

and an updating procedure are combined into a new algorithm for time-adaptive quantile regression, which generates new solutions on the basis of the old solution, leading to savings in computation time. The suggested algorithm is tested against a static quantile regression model on a data set with wind power......An algorithm for time-adaptive quantile regression is presented. The algorithm is based on the simplex algorithm, and the linear optimization formulation of the quantile regression problem is given. The observations have been split to allow a direct use of the simplex algorithm. The simplex method...... production, where the models combine splines and quantile regression. The comparison indicates superior performance for the time-adaptive quantile regression in all the performance parameters considered....

Prognostic implications of tumor volume response and COX-2 expression change during radiotherapy in cervical cancer patients

International Nuclear Information System (INIS)

Noh, Jae Myoung; Park, Won; Huh, Seung Jae; Cho, Eun Yoon; Choi, Yoon La; Bae, Duk Soo; Kim, Byoung Gie

2012-01-01

The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed. Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months. The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response (V2R ≥ 0.4). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with V2R ≥ 0.4 (p 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively). Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer.

COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ

International Nuclear Information System (INIS)

Kulkarni, Swati; Patil, Deepa B; Diaz, Leslie K; Wiley, Elizabeth L; Morrow, Monica; Khan, Seema A

2008-01-01

In women with duct carcinoma in-situ (DCIS) receiving breast conservation therapy (BCT), in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS. Women treated for DCIS with BCT, who later developed in-breast recurrence (cases) were matched by age and year of treatment to women who remained free of recurrence (controls). A total of 69 women were included in the study, 31 cases and 38 controls. Immunohistochemical evaluation of DCIS tissue arrays was performed for estrogen receptor, progesterone receptor, HER-2/neu, cyclin D1, p53, p21, cycloxygenase-2 (COX-2) and peroxisome proliferator activated receptor γ (PPARγ). Two markers were significantly different between cases and controls on univariate analysis: strong COX-2 expression was associated with increased risk of recurrence, with 67% vs. 24% positivity in cases and controls p = 0.006; and nuclear expression of PPARγ was associated with protection from recurrence with 4% vs. 27% positivity in cases and controls, p = 0.024. In a multivariate model which included size, grade, COX-2 and PPARγ positivity, we found COX-2 positivity to be a strong independent risk factor for recurrence (OR 7.90, 95% CI 1.72–36.23)., whereas size and grade were of borderline significance. PPARγ expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06–1.84). Our findings suggest that COX-2 and PPARγ should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

Science.gov (United States)

Oak, Nikhil R; Gumucio, Jonathan P; Flood, Michael D; Saripalli, Anjali L; Davis, Max E; Harning, Julie A; Lynch, Evan B; Roche, Stuart M; Bedi, Asheesh; Mendias, Christopher L

2014-12-01

The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. Controlled laboratory study. Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development

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

International Nuclear Information System (INIS)

Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar; Jarlsfelt, Ingvar; Sun Xiaofeng

2005-01-01

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

Distance Based Root Cause Analysis and Change Impact Analysis of Performance Regressions

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Junzan Zhou

2015-01-01

Full Text Available Performance regression testing is applied to uncover both performance and functional problems of software releases. A performance problem revealed by performance testing can be high response time, low throughput, or even being out of service. Mature performance testing process helps systematically detect software performance problems. However, it is difficult to identify the root cause and evaluate the potential change impact. In this paper, we present an approach leveraging server side logs for identifying root causes of performance problems. Firstly, server side logs are used to recover call tree of each business transaction. We define a novel distance based metric computed from call trees for root cause analysis and apply inverted index from methods to business transactions for change impact analysis. Empirical studies show that our approach can effectively and efficiently help developers diagnose root cause of performance problems.

Population death sequences and Cox processes driven by interacting Feller diffusions

CERN Document Server

Wei Gang; Feng Jian Feng

2002-01-01

We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

Population death sequences and Cox processes driven by interacting Feller diffusions

International Nuclear Information System (INIS)

Wei Gang; Clifford, Peter; Feng Jianfeng

2002-01-01

We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations

Population death sequences and Cox processes driven by interacting Feller diffusions

Energy Technology Data Exchange (ETDEWEB)

Wei Gang [Department of Mathematics, Baptist University, Hong Kong (China); Clifford, Peter [Department of Statistics, 1 South Parks Road, Oxford (United Kingdom); Feng Jianfeng [COGS, Sussex University, Brighton (United Kingdom)

2002-11-08

We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

2D and 3D CT Radiomics Features Prognostic Performance Comparison in Non-Small Cell Lung Cancer

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Chen Shen

2017-12-01

Full Text Available OBJECTIVE: To compare 2D and 3D radiomics features prognostic performance differences in CT images of non-small cell lung cancer (NSCLC. METHOD: We enrolled 588 NSCLC patients from three independent cohorts. Two sets of 463 patients from two different institutes were used as the training cohort. The remaining cohort with 125 patients was set as the validation cohort. A total of 1014 radiomics features (507 2D features and 507 3D features correspondingly were assessed. Based on the dichotomized survival data, 2D and 3D radiomics indicators were calculated for each patient by trained classifiers. We used the area under the receiver operating characteristic curve (AUC to assess the prediction performance of trained classifiers (the support vector machine and logistic regression. Kaplan–Meier and Cox hazard survival analyses were also employed. Harrell's concordance index (C-Index and Akaike's information criteria (AIC were applied to assess the trained models. RESULTS: Radiomics indicators were built and compared by AUCs. In the training cohort, 2D_AUC = 0.653, 3D_AUC = 0.671. In the validation cohort, 2D_AUC = 0.755, 3D_AUC = 0.663. Both 2D and 3D trained indicators achieved significant results (P < .05 in the Kaplan-Meier analysis and Cox regression. In the validation cohort, 2D Cox model had a C-Index = 0.683 and AIC = 789.047; 3D Cox model obtained a C-Index = 0.632 and AIC = 799.409. CONCLUSION: Both 2D and 3D CT radiomics features have a certain prognostic ability in NSCLC, but 2D features showed better performance in our tests. Considering the cost of the radiomics features calculation, 2D features are more recommended for use in the current study.

Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

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Wang Min

2010-11-01

Full Text Available Abstract Background DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2 in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis. Methods Total DNA was extracted from the blood samples of 108 systemically healthy non-periodontitis subjects, and the gingival tissues and blood samples of 110 chronic periodontitis patient as well as neoplastic tissues of 106 breast cancer patients. Methylation-specific PCR for E-Cadherin and COX-2 was performed on these samples and the PCR products were analyzed on 2% agarose gel. Results Hypermethylation of E-Cadherin and COX-2 was observed in 38% and 35% of the breast cancer samples, respectively. In chronic periodontitis patients the detection rate was 25% and 19% respectively, and none was found in the systemically healthy non-periodontitis control subjects. The hypermethylation status was shown to be correlated among the three groups with statistical significance (p Conclusions This set of data shows that the epigenetic change in E-Cadherin and Cyclooxygenase-2 is associated with chronic periodontitis. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic periodontitis to some extent might be associated with DNA hypermethylation which is related to cancer risk factors.

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

African Journals Online (AJOL)

Objectives: This study was performed to explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi (GST-Pi) in the pathogenesis of HCC risk. Methods: 120 Wistar rats were divided into three groups at random: normal control group (control group), HCC risk group without ...

COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ

Directory of Open Access Journals (Sweden)

Wiley Elizabeth L

2008-01-01

Full Text Available Abstract Background In women with duct carcinoma in-situ (DCIS receiving breast conservation therapy (BCT, in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS. Methods Women treated for DCIS with BCT, who later developed in-breast recurrence (cases were matched by age and year of treatment to women who remained free of recurrence (controls. Results A total of 69 women were included in the study, 31 cases and 38 controls. Immunohistochemical evaluation of DCIS tissue arrays was performed for estrogen receptor, progesterone receptor, HER-2/neu, cyclin D1, p53, p21, cycloxygenase-2 (COX-2 and peroxisome proliferator activated receptor γ (PPARγ. Two markers were significantly different between cases and controls on univariate analysis: strong COX-2 expression was associated with increased risk of recurrence, with 67% vs. 24% positivity in cases and controls p = 0.006; and nuclear expression of PPARγ was associated with protection from recurrence with 4% vs. 27% positivity in cases and controls, p = 0.024. In a multivariate model which included size, grade, COX-2 and PPARγ positivity, we found COX-2 positivity to be a strong independent risk factor for recurrence (OR 7.90, 95% CI 1.72–36.23., whereas size and grade were of borderline significance. PPARγ expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06–1.84. Conclusion Our findings suggest that COX-2 and PPARγ should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets.

State ownership and corporate performance: A quantile regression analysis of Chinese listed companies

NARCIS (Netherlands)

Li, T.; Sun, L.; Zou, L.

2009-01-01

This study assesses the impact of government shareholding on corporate performance using a sample of 643 non-financial companies listed on the Chinese stock exchanges. In view of the controversial empirical findings in the literature and the limitations of the least squares regressions, we adopt the

The synthesis of isotopic fluorine and iodine-labeled COX-II inhibitor and in vitro validation

Energy Technology Data Exchange (ETDEWEB)

An, Gwang Gil; Lee, Tae Sub; Lee, Kyo Chul; Moon, Byung Seok; Choi, Chang Woon; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2005-07-01

In these day, NASIDs (non-steroidal antiinflammatory drugs) such as aspirin, diclofenac and ibuprofen are the most common medications used to reduce pain and inflammation. However, they act by inhibiting both COX-I and COX-II which can cause serious gastrointestinal side effects such as ulcers, stomach perforations and bleeds. COX-I produces prostaglandins believed to be responsible for the protection of the stomach lining. However, COX-II produces prostaglandins believed to be responsible for pain and inflammation. Recently, the most widely studied selective COX-II inhibitor such as celecoxib and rofecoxib' one work by inhibiting the effect of COX-II on pain and inflammation without inhibiting COX-I which protects gastrointestinal lining.

Synthesis and evaluation of ortho-[18F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Directory of Open Access Journals (Sweden)

Chang CW

2018-05-01

Full Text Available Chi-Wei Chang,1,* Chun-Nan Yeh,2,* Yi-Hsiu Chung,3,* Yong-Ren Chen,4 Shi-Wei Tien,4 Tsung-Wen Chen,2 Shiou-Shiow Farn,4,5 Ying-Cheng Huang,6 Chung-Shan Yu4,7 1Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Surgery, Liver Research Center, Chang-Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; 3Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu, Taiwan; 5Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 6Department of Neurosurgery, Chang-Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; 7Institute of Nuclear Engineering and Science, National Tsinghua University, Hsinchu, Taiwan *These authors contributed equally to this work Background: An 18F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development. Methods: The in vivo uptake of celecoxib was monitored with ortho-[18F]fluorocelecoxib using positron emission tomography (PET. The binding affinity of ortho-[18F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib. Results: The IC50 values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1. COX-2 overexpressed cholangiocarcinoma (CCA murine cells took up more ortho-[18F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking of the tracer uptake of ortho-[18F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC50 values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min, PET scanning was performed 30–60 min after the

Gaussian Process Regression for WDM System Performance Prediction

DEFF Research Database (Denmark)

Wass, Jesper; Thrane, Jakob; Piels, Molly

2017-01-01

Gaussian process regression is numerically and experimentally investigated to predict the bit error rate of a 24 x 28 CiBd QPSK WDM system. The proposed method produces accurate predictions from multi-dimensional and sparse measurement data.......Gaussian process regression is numerically and experimentally investigated to predict the bit error rate of a 24 x 28 CiBd QPSK WDM system. The proposed method produces accurate predictions from multi-dimensional and sparse measurement data....

COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

DEFF Research Database (Denmark)

Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

2011-01-01

It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP m...... osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2......(-/-) mice, but after WD plasma AVP was unchanged between COX-2(-/-) and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice. Medullary interstitial osmolality increased and did not differ between COX-2(-/-) and WT after WD. Aquaporin-2 (AQP2; cortex...

Expression of Beta-catenin, COX-2 and iNOS in Colorectal Cancer: Relevance of COX-2 and iNOS Inhibitors for Treatment in Malaysia

Directory of Open Access Journals (Sweden)

Seok Kwan Hong

2004-01-01

Conclusions: The accumulation of β-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

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

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Albert Cohen

2017-04-01

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

Characterization and Sequencing of MT-Cox1 Gene in Khorasan ...

African Journals Online (AJOL)

The aim of this study was to investigate the nucleotide sequence of COX1 gene in mitochondrial genome of Khorasan native chicken and detect the possible mutations in the genome. For this purpose, after sampling and extracting DNA from the whole blood samples, the COX1 gene was amplified using specific primers and ...

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

Science.gov (United States)

Sneeringer, Stacy

2010-04-01

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

Use of the Box-Cox Transformation in Detecting Changepoints in Daily Precipitation Data Series

Science.gov (United States)

Wang, X. L.; Chen, H.; Wu, Y.; Pu, Q.

2009-04-01

This study integrates a Box-Cox power transformation procedure into two statistical tests for detecting changepoints in Gaussian data series, to make the changepoint detection methods applicable to non-Gaussian data series, such as daily precipitation amounts. The detection power aspects of transformed methods in a common trend two-phase regression setting are assessed by Monte Carlo simulations for data of a log-normal or Gamma distribution. The results show that the transformed methods have increased the power of detection, in comparison with the corresponding original (untransformed) methods. The transformed data much better approximate to a Gaussian distribution. As an example of application, the new methods are applied to a series of daily precipitation amounts recorded at a station in Canada, showing satisfactory detection power.

Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

DEFF Research Database (Denmark)

Kolko, Miriam; Nielsen, Marianne; Bazan, Nicolas G

2002-01-01

and immunohistochemistry. An up-regulation of COX-2, c-fos, and c-jun, but not COX-1, was observed around the lesion as well as in the neocortex 4 hr after the injection. Hippocampal up-regulation of COX-2 was seen in dentate gyrus 8 hr after injection. When glutamate was injected, up-regulation of the early...

Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

International Nuclear Information System (INIS)

Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I.; Barik, Tapan Kumar

2012-01-01

COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

Energy Technology Data Exchange (ETDEWEB)

Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I., E-mail: prem_indra@yahoo.co.in [Radiation Biosciences Division, Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Barik, Tapan Kumar [P.G. Department of Zoology, Berhampur University, Berhampur (India)

2012-07-01

COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

Science.gov (United States)

Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

2014-03-01

This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study.

Science.gov (United States)

Hu, Huang-Ming; Kuo, Chao-Hung; Lee, Chien-Hung; Wu, I-Chen; Lee, Ka-Wo; Lee, Jang-Ming; Goan, Yih-Gang; Chou, Shah-Hwa; Kao, Ein-Long; Wu, Ming-Tsang; Wu, Deng-Chyang

2009-05-23

Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 - 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 - 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 - 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 - 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 - 0.47, p for

Prognostic significance of COX-2 and β-catenin in colorectal ...

African Journals Online (AJOL)

Amani Kazem

2013-07-17

Jul 17, 2013 ... (wingless type) signaling pathway, increased protein concentrations promote transcription of genes .... under a light microscope and the histological type of colorectal .... of signet ring cell carcinoma showed weak COX-2 positivity. 3.2. Analysis .... COX-2 expression was detected in other tumors, and was be-.

HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway

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Chi F

2016-05-01

Full Text Available Feng Chi, Rong Wu, Xueying Jin, Min Jiang, Xike Zhu Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: HER2 positivity has been well studied in various cancers, but its importance in non-small-cell lung cancer (NSCLC is still being explored. In this study, quantitative reverse transcription polymerase chain reaction (qRT-PCR was performed to detect HER2 and COX-2 expression in NSCLC tissues. Then, pcDNA3.1-HER2 was used to overexpress HER2, while HER2 siRNA and COX-2 siRNA were used to silence HER2 and COX-2 expression. MTT assay and invasion assay were used to detect the effects of HER2 on cell proliferation and invasion. Our study revealed that HER2 and COX-2 expression were upregulated in NSCLC tissues and HER2 exhibited a significant positive correlation with the levels of COX-2 expression. Overexpression of HER2 evidently elevated COX-2 expression, while silencing of HER2 evidently decreased COX-2 expression. Furthermore, overexpressed HER2 induced the ERK phosphorylation, and this was abolished by the treatment with U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. HER2-induced expression and promoter activity of COX-2 were also suppressed by U0126, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, HER2 induced activation of AKT signaling pathway, which was reversed by pretreatment with U0126 and COX-2 siRNA. MTT and invasion assays revealed that HER2 induced cell proliferation and invasion that were reversed by pretreatment with U0126 and COX-2 siRNA. In this study, our results demonstrated for the first time that HER2 elevated COX-2 expression through the activation of MEK/ERK pathway, which subsequently induced cell proliferation and invasion via AKT pathway in NSCLC tissues. Keywords: HER2, MEK/ERK, COX-2, AKT signaling pathway, non-small-cell lung cancer

Using a Regression Method for Estimating Performance in a Rapid Serial Visual Presentation Target-Detection Task

Science.gov (United States)

2017-12-01

Fig. 2 Simulation method; the process for one iteration of the simulation . It was repeated 250 times per combination of HR and FAR. Analysis was...distribution is unlimited. 8 Fig. 2 Simulation method; the process for one iteration of the simulation . It was repeated 250 times per combination of HR...stimuli. Simulations show that this regression method results in an unbiased and accurate estimate of target detection performance. The regression

Comparing performances of clements, box-cox, Johnson methods with weibull distributions for assessing process capability

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Ozlem Senvar

2016-08-01

Full Text Available Purpose: This study examines Clements’ Approach (CA, Box-Cox transformation (BCT, and Johnson transformation (JT methods for process capability assessments through Weibull-distributed data with different parameters to figure out the effects of the tail behaviours on process capability and compares their estimation performances in terms of accuracy and precision. Design/methodology/approach: Usage of process performance index (PPI Ppu is handled for process capability analysis (PCA because the comparison issues are performed through generating Weibull data without subgroups. Box plots, descriptive statistics, the root-mean-square deviation (RMSD, which is used as a measure of error, and a radar chart are utilized all together for evaluating the performances of the methods. In addition, the bias of the estimated values is important as the efficiency measured by the mean square error. In this regard, Relative Bias (RB and the Relative Root Mean Square Error (RRMSE are also considered. Findings: The results reveal that the performance of a method is dependent on its capability to fit the tail behavior of the Weibull distribution and on targeted values of the PPIs. It is observed that the effect of tail behavior is more significant when the process is more capable. Research limitations/implications: Some other methods such as Weighted Variance method, which also give good results, were also conducted. However, we later realized that it would be confusing in terms of comparison issues between the methods for consistent interpretations. Practical implications: Weibull distribution covers a wide class of non-normal processes due to its capability to yield a variety of distinct curves based on its parameters. Weibull distributions are known to have significantly different tail behaviors, which greatly affects the process capability. In quality and reliability applications, they are widely used for the analyses of failure data in order to understand how

Ab-initio calculations of Co-based diluted magnetic semiconductors Cd 1-xCoxX (X=S, Se, Te)

KAUST Repository

Saeed, Yasir

2010-10-01

Ab-initio calculations are performed to investigate the structural, electronic and magnetic properties of spin-polarized diluted magnetic semiconductors composed of IIVI compounds Cd1-xCoxX (X=S, Se, Te) at x=0.25. From the calculated results of band structure and density of states, the half-metallic character and stability of ferromagnetic state for Cd1-xCoxS, Cd1-xCoxSe and Cd 1-xCoxTe alloys are determined. It is found that the tetrahedral crystal field gives rise to triple degeneracy t2g and double degeneracy eg. Furthermore, we predict the values of spin-exchange splitting energies Δx(d) and Δ x(p-d) and exchange constants N0α and N 0β produced by the Co 3d states. Calculated total magnetic moments and the robustness of half-metallicity of Cd1-xCo xX (X=S, Se, Te) with respect to the variation in lattice parameters are also discussed. We also extend our calculations to x=0.50, 0.75 for S compounds in order to observe the change due to increase in Co. © 2010 Elsevier B.V.

Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.

Science.gov (United States)

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

2012-04-01

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.

Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis

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Dai P

2018-02-01

Full Text Available Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2 inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48. Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib and treatment line (first or second chemotherapy. The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin, GP (double fluorine cytidine + cisplatin or carboplatin, or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin. The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25 and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50. However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1

Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

DEFF Research Database (Denmark)

Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

2010-01-01

the enzyme levels of COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use of NSAID would modify the associations. We also wanted to investigate associations with blood lipid levels. Methods: A case–cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested......), such that variant allele carriers with low alcohol intake had the lowest lipid levels. No statistically significant associations were observed in females. Conclusion: This study suggests that genetically determined COX-2 levels are associated with risk of ACS and blood lipid levels among males. No consistent......Background: The use of specific COX-2 inhibitors in cancer prevention has been associated with higher risk of acute coronary syndrome (ACS) and myocardial infarction. The aim of this study was to investigate if the polymorphisms COX2 T8473C (rs5275), and COX2 A-1195G (rs689466), which modify...

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

African Journals Online (AJOL)

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

[Identification of Clonorchis sinensis metacercariae based on PCR targeting ribosomal DNA ITS regions and COX1 gene].

Science.gov (United States)

Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Yang, Yi-Chao; Li, Hong-Mei; Chen, Ying-Dan; Zhou, Xiao-Nong

2014-06-01

To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.

Seizure following the Use of the COX-2 Inhibitor Etoricoxib

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Valentina Arnao

2017-01-01

Full Text Available We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

Science.gov (United States)

Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

2013-01-01

SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-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

Regression analysis with categorized regression calibrated exposure: some interesting findings

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Hjartåker Anette

2006-07-01

Full Text Available Abstract Background Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis. Methods We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC. Results In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis. Conclusion Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a

Logistic regression function for detection of suspicious performance during baseline evaluations using concussion vital signs.

Science.gov (United States)

Hill, Benjamin David; Womble, Melissa N; Rohling, Martin L

2015-01-01

This study utilized logistic regression to determine whether performance patterns on Concussion Vital Signs (CVS) could differentiate known groups with either genuine or feigned performance. For the embedded measure development group (n = 174), clinical patients and undergraduate students categorized as feigning obtained significantly lower scores on the overall test battery mean for the CVS, Shipley-2 composite score, and California Verbal Learning Test-Second Edition subtests than did genuinely performing individuals. The final full model of 3 predictor variables (Verbal Memory immediate hits, Verbal Memory immediate correct passes, and Stroop Test complex reaction time correct) was significant and correctly classified individuals in their known group 83% of the time (sensitivity = .65; specificity = .97) in a mixed sample of young-adult clinical cases and simulators. The CVS logistic regression function was applied to a separate undergraduate college group (n = 378) that was asked to perform genuinely and identified 5% as having possibly feigned performance indicating a low false-positive rate. The failure rate was 11% and 16% at baseline cognitive testing in samples of high school and college athletes, respectively. These findings have particular relevance given the increasing use of computerized test batteries for baseline cognitive testing and return-to-play decisions after concussion.

Statistical methods for elimination of guarantee-time bias in cohort studies: a simulation study

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In Sung Cho

2017-08-01

Full Text Available Abstract Background Aspirin has been considered to be beneficial in preventing cardiovascular diseases and cancer. Several pharmaco-epidemiology cohort studies have shown protective effects of aspirin on diseases using various statistical methods, with the Cox regression model being the most commonly used approach. However, there are some inherent limitations to the conventional Cox regression approach such as guarantee-time bias, resulting in an overestimation of the drug effect. To overcome such limitations, alternative approaches, such as the time-dependent Cox model and landmark methods have been proposed. This study aimed to compare the performance of three methods: Cox regression, time-dependent Cox model and landmark method with different landmark times in order to address the problem of guarantee-time bias. Methods Through statistical modeling and simulation studies, the performance of the above three methods were assessed in terms of type I error, bias, power, and mean squared error (MSE. In addition, the three statistical approaches were applied to a real data example from the Korean National Health Insurance Database. Effect of cumulative rosiglitazone dose on the risk of hepatocellular carcinoma was used as an example for illustration. Results In the simulated data, time-dependent Cox regression outperformed the landmark method in terms of bias and mean squared error but the type I error rates were similar. The results from real-data example showed the same patterns as the simulation findings. Conclusions While both time-dependent Cox regression model and landmark analysis are useful in resolving the problem of guarantee-time bias, time-dependent Cox regression is the most appropriate method for analyzing cumulative dose effects in pharmaco-epidemiological studies.

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

OpenAIRE

Showalter, Mark H

1994-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

2015-05-01

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

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

Directory of Open Access Journals (Sweden)

Maria Mulet

2017-06-01

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

Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

LENUS (Irish Health Repository)

2012-02-01

BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

Allan Cox 1926”1987

Science.gov (United States)

Coe, Rob; Dalrymple, Brent

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

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

Directory of Open Access Journals (Sweden)

Lee Jang-Ming

2009-05-01

Full Text Available Abstract Background Overexpression of Cyclooxygenase-2 (COX-2 was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC. One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP, H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9. COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3. The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5. Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9, and the effect was observed to be enhanced for the lower third ESCC

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

Directory of Open Access Journals (Sweden)

Tania Dehesh

2015-01-01

Full Text Available 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.

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

Science.gov (United States)

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

2015-01-01

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. 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. 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. 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.

Using the Ridge Regression Procedures to Estimate the Multiple Linear Regression Coefficients

Science.gov (United States)

Gorgees, HazimMansoor; Mahdi, FatimahAssim

2018-05-01

This article concerns with comparing the performance of different types of ordinary ridge regression estimators that have been already proposed to estimate the regression parameters when the near exact linear relationships among the explanatory variables is presented. For this situations we employ the data obtained from tagi gas filling company during the period (2008-2010). The main result we reached is that the method based on the condition number performs better than other methods since it has smaller mean square error (MSE) than the other stated methods.

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

Science.gov (United States)

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 Δ(9)-tetrahydrocannabinol (Δ(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 Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ 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 Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(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. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells.

Science.gov (United States)

Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın

2017-10-01

Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

Optical, magnetic and structural characterization of Zn1−xCoxO ...

Indian Academy of Sciences (India)

attracted considerable attention, both theoretically and experi- mentally, due to their ... C and finally ground to powder. Zn1−x Cox O ... Figure 1. Flowchart for solvothermal synthesis of Zn1−x Cox O (x = 0·038, 0·072 and 0·115) nanoparticles.

Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore

Science.gov (United States)

Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

2016-01-01

INTRODUCTION Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. METHODS Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. RESULTS Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. CONCLUSION The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. PMID:26805667

Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore.

Science.gov (United States)

Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

2016-12-01

Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. Copyright: © Singapore Medical Association

Insights into chirality distributions of single-walled carbon nanotubes grown on different CoxMg1-xO solid solutions

DEFF Research Database (Denmark)

He, Maoshuai; Jiang, Hua; Kauppi, Inkeri

2014-01-01

Low-temperature chemical vapor deposition (CVD) growth of single-walled carbon nanotubes (SWNTs) was achieved on two different types of Co xMg1-xO catalysts prepared by different techniques: atomic layer deposition (ALD) and impregnation. The chirality distribution of SWNTs grown on the ALD......-prepared CoxMg1-xO catalyst is wider than that of SWNTs grown on the impregnation-prepared CoxMg 1-xO catalyst. The different chirality distributions of SWNTs are related to their different growth modes. The ALD-prepared CoxMg 1-xO catalyzes the growth of SWNTs by "tip growth" mode, as revealed by in situ...... for the synthesis of SWNTs with high chiral-selectivity. In addition, impregnation-prepared Co xMg1-xO catalysts calcinated at different temperatures were systematically studied and their catalytic performances in synthesizing carbon nanotubes were elucidated. This work illustrates the influence of metal...

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

Science.gov (United States)

McCarty, Mark F

2012-01-01

A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

Ab-initio calculations of Co-based diluted magnetic semiconductors Cd 1-xCoxX (X=S, Se, Te)

KAUST Repository

Saeed, Yasir; Nazir, Safdar; Shaukat, Ali; Reshak, A. H.

2010-01-01

Ab-initio calculations are performed to investigate the structural, electronic and magnetic properties of spin-polarized diluted magnetic semiconductors composed of IIVI compounds Cd1-xCoxX (X=S, Se, Te) at x=0.25. From the calculated results

PREDICTION OF MALIGNANT BREAST LESIONS FROM MRI FEATURES: A COMPARISON OF ARTIFICIAL NEURAL NETWORK AND LOGISTIC REGRESSION TECHNIQUES

Science.gov (United States)

McLaren, Christine E.; Chen, Wen-Pin; Nie, Ke; Su, Min-Ying

2009-01-01

Rationale and Objectives Dynamic contrast enhanced MRI (DCE-MRI) is a clinical imaging modality for detection and diagnosis of breast lesions. Analytical methods were compared for diagnostic feature selection and performance of lesion classification to differentiate between malignant and benign lesions in patients. Materials and Methods The study included 43 malignant and 28 benign histologically-proven lesions. Eight morphological parameters, ten gray level co-occurrence matrices (GLCM) texture features, and fourteen Laws’ texture features were obtained using automated lesion segmentation and quantitative feature extraction. Artificial neural network (ANN) and logistic regression analysis were compared for selection of the best predictors of malignant lesions among the normalized features. Results Using ANN, the final four selected features were compactness, energy, homogeneity, and Law_LS, with area under the receiver operating characteristic curve (AUC) = 0.82, and accuracy = 0.76. The diagnostic performance of these 4-features computed on the basis of logistic regression yielded AUC = 0.80 (95% CI, 0.688 to 0.905), similar to that of ANN. The analysis also shows that the odds of a malignant lesion decreased by 48% (95% CI, 25% to 92%) for every increase of 1 SD in the Law_LS feature, adjusted for differences in compactness, energy, and homogeneity. Using logistic regression with z-score transformation, a model comprised of compactness, NRL entropy, and gray level sum average was selected, and it had the highest overall accuracy of 0.75 among all models, with AUC = 0.77 (95% CI, 0.660 to 0.880). When logistic modeling of transformations using the Box-Cox method was performed, the most parsimonious model with predictors, compactness and Law_LS, had an AUC of 0.79 (95% CI, 0.672 to 0.898). Conclusion The diagnostic performance of models selected by ANN and logistic regression was similar. The analytic methods were found to be roughly equivalent in terms of

MENENTUKAN PROBABILITAS QUALITAS LULUSAN PROGRAM STUDI MENGGUNAKAN LOGISTIC REGRESSION

Directory of Open Access Journals (Sweden)

Maxsi Ary

2016-03-01

Full Text Available Abstract – Human resources (HR is one of the success factors in the economic field, namely how to create a human resources (HR qualified and have the skills and highly competitive in the global competition. Educational level of the labor force that is still relatively low. The structure of education of the workforce is still dominated Indonesian basic education which is about 63.2%. The issue raised is to determine the probability of a program of study (whether or not to see some of the ratio of the number of graduates by the number of students per class, the amount of quota size class (large or small using logistic regression models. Data were obtained from a search result based on the amount of data the study program students and graduates in 2010 Data processing using SPSS. The results of the analysis by assessing model fit and the results will be given for each model fit. Starting with the hypothesis for assessing model fit, statistical -2LogL, Cox and Snell's R Square, Hosmer and Lemeshow's Goodness of Fit Test, and the classification table. The results of the analysis using SPSS as a tool aimed at measuring quality of graduate courses at a university, college, or academy, whether or not based on the ratio of the number of graduates and class quotas. Keywords: Quota Class, Probability, Logistic Regression Abstrak – Sumberdaya manusia (SDM adalah salah satu faktor kesuksesan dalam bidang ekonomi, yaitu bagaimana menciptakan sumber daya manusia (SDM yang berkualitas dan memiliki keterampilan serta berdaya saing tinggi dalam persaingan global. Tingkat pendidikan angkatan kerja yang ada masih relatif rendah. Struktur pendidikan angkatan kerja Indonesia masih didominasi pendidikan dasar yaitu sekitar 63,2%. Persoalan yang dikemukakan adalah menentukan probabilitas sebuah program studi (baik atau tidak dengan melihat beberapa rasio jumlah lulusan dengan jumlah mahasiswa per angkatan, ukuran besarnya kuota kelas (besar atau kecil menggunakan

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

DEFF Research Database (Denmark)

Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela

2012-01-01

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...

Regression Trees Identify Relevant Interactions: Can This Improve the Predictive Performance of Risk Adjustment?

Science.gov (United States)

Buchner, Florian; Wasem, Jürgen; Schillo, Sonja

2017-01-01

Risk equalization formulas have been refined since their introduction about two decades ago. Because of the complexity and the abundance of possible interactions between the variables used, hardly any interactions are considered. A regression tree is used to systematically search for interactions, a methodologically new approach in risk equalization. Analyses are based on a data set of nearly 2.9 million individuals from a major German social health insurer. A two-step approach is applied: In the first step a regression tree is built on the basis of the learning data set. Terminal nodes characterized by more than one morbidity-group-split represent interaction effects of different morbidity groups. In the second step the 'traditional' weighted least squares regression equation is expanded by adding interaction terms for all interactions detected by the tree, and regression coefficients are recalculated. The resulting risk adjustment formula shows an improvement in the adjusted R 2 from 25.43% to 25.81% on the evaluation data set. Predictive ratios are calculated for subgroups affected by the interactions. The R 2 improvement detected is only marginal. According to the sample level performance measures used, not involving a considerable number of morbidity interactions forms no relevant loss in accuracy. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

International Nuclear Information System (INIS)

Zhu, Yingting; Zhu, Min; Lance, Peter

2012-01-01

Highlights: ► Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE 2 . ► The fibroblasts interact with human colonic epithelial cancer cells. ► Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. ► 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.

Optimization of Acid Orange 7 Degradation in Heterogeneous Fenton-like Reaction Using Fe3-xCoxO4 Catalyst

Science.gov (United States)

Ibrahim, M. Z.; Alrozi, R.; Zubir, N. A.; Bashah, N. A.; Ali, S. A. Md; Ibrahim, N.

2018-05-01

The oxidation process such as heterogeneous Fenton and/or Fenton-like reactions is considered as an effective and efficient method for treatment of dye degradation. In this study, the degradation of Acid Orange 7 (AO7) was investigated by using Fe3-xCoxO4 as a heterogeneous Fenton-like catalyst. Response surface methodology (RSM) was used to optimize the operational parameters condition and the interaction of two or more parameters. The parameter studies were catalyst dosage (X1 ), pH (X2 ) and H2O2 concentration (X3 ) towards AO7 degradation. Based on analysis of variance (ANOVA), the derived quadratic polynomial model was significant whereby the predicted values matched the experimental values with regression coefficient of R2 = 0.9399. The optimum condition for AO7 degradation was obtained at catalyst dosage of 0.84 g/L, pH of 3 and H2O2 concentration of 46.70 mM which resulted in 86.30% removal of AO7 dye. These findings present new insights into the influence of operational parameters in the heterogeneous Fenton-like oxidation of AO7 using Fe3-xCoxO4 catalyst.

Predictions of biochar production and torrefaction performance from sugarcane bagasse using interpolation and regression analysis.

Science.gov (United States)

Chen, Wei-Hsin; Hsu, Hung-Jen; Kumar, Gopalakrishnan; Budzianowski, Wojciech M; Ong, Hwai Chyuan

2017-12-01

This study focuses on the biochar formation and torrefaction performance of sugarcane bagasse, and they are predicted using the bilinear interpolation (BLI), inverse distance weighting (IDW) interpolation, and regression analysis. It is found that the biomass torrefied at 275°C for 60min or at 300°C for 30min or longer is appropriate to produce biochar as alternative fuel to coal with low carbon footprint, but the energy yield from the torrefaction at 300°C is too low. From the biochar yield, enhancement factor of HHV, and energy yield, the results suggest that the three methods are all feasible for predicting the performance, especially for the enhancement factor. The power parameter of unity in the IDW method provides the best predictions and the error is below 5%. The second order in regression analysis gives a more reasonable approach than the first order, and is recommended for the predictions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Approximate median regression for complex survey data with skewed response.

Science.gov (United States)

Fraser, Raphael André; Lipsitz, Stuart R; Sinha, Debajyoti; Fitzmaurice, Garrett M; Pan, Yi

2016-12-01

The ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and weighting. In this article, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS)'based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box-Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey. © 2016, The International Biometric Society.

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

Science.gov (United States)

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

[Specific inhibitors of cyclooxygenase-2 (COX-2): current knowledge and perspectives].

Science.gov (United States)

Rioda, W T; Nervetti, A

2001-01-01

The Authors summarize the current knowledge on a new class of nonsteroidal anti-inflammatory drugs (NSAIDs), the coxib (celecoxib and rofecoxib), in the treatment of rheumatic diseases. Celecoxib and rofecoxib are selective cyclooxygenase-2 (COX-2) inhibitors which possess the same anti-inflammatory and analgesic activities, but a better gastric tolerability compared to the non-selective COX-1 and COX-2 inhibitors. The Authors also report other possible therapeutic effects of these NSADIs as evidenced by the more recent data of the literature. Celecoxib seems to reduce the incidence of new polyps in patients with familial adenomatous polyposis. It has been suggested the use of celecoxib as a protective drug against the development of colorectal cancer. Other (neoplastic) or pre-neoplastic conditions, such as bladder dysplasia, Barret esophagus, attinic keratosis and Alzheimer's disease seem to have benefit from this class of drugs.

Replica analysis of overfitting in regression models for time-to-event data

Science.gov (United States)

Coolen, A. C. C.; Barrett, J. E.; Paga, P.; Perez-Vicente, C. J.

2017-09-01

Overfitting, which happens when the number of parameters in a model is too large compared to the number of data points available for determining these parameters, is a serious and growing problem in survival analysis. While modern medicine presents us with data of unprecedented dimensionality, these data cannot yet be used effectively for clinical outcome prediction. Standard error measures in maximum likelihood regression, such as p-values and z-scores, are blind to overfitting, and even for Cox’s proportional hazards model (the main tool of medical statisticians), one finds in literature only rules of thumb on the number of samples required to avoid overfitting. In this paper we present a mathematical theory of overfitting in regression models for time-to-event data, which aims to increase our quantitative understanding of the problem and provide practical tools with which to correct regression outcomes for the impact of overfitting. It is based on the replica method, a statistical mechanical technique for the analysis of heterogeneous many-variable systems that has been used successfully for several decades in physics, biology, and computer science, but not yet in medical statistics. We develop the theory initially for arbitrary regression models for time-to-event data, and verify its predictions in detail for the popular Cox model.

Optimal pricing in retail: a Cox regression approach

NARCIS (Netherlands)

Meijer, R.; Bhulai, S.

2013-01-01

Purpose: The purpose of this paper is to study the optimal pricing problem that retailers are challenged with when dealing with seasonal products. The friction between expected demand and realized demand creates a risk that supply during the season is not cleared, thus forcing the retailer to

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

Energy Technology Data Exchange (ETDEWEB)

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

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.

Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

Science.gov (United States)

Lu, Chieh-Hua; Chung, Chi-Hsiang; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Hung, Yi-Jen; Lin, Fu-Huang; Tsao, Chang-Huei; Hsieh, Po-Shiuan; Chien, Wu-Chien

2018-01-01

Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601-0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination

Multiple Imputation of a Randomly Censored Covariate Improves Logistic Regression Analysis.

Science.gov (United States)

Atem, Folefac D; Qian, Jing; Maye, Jacqueline E; Johnson, Keith A; Betensky, Rebecca A

2016-01-01

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semiparametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.

Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability

Directory of Open Access Journals (Sweden)

Ahmed M. Gouda

2016-02-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile.

Intravenous glutamine enhances COX-2 activity giving cardioprotection.

LENUS (Irish Health Repository)

McGuinness, Jonathan

2009-03-01

Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

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Mandar Dave

2017-12-01

Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

Directory of Open Access Journals (Sweden)

Panagiotis A. Konstantinopoulos

2007-01-01

Full Text Available Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN, p-Iκ:B-α (phosphorylated Iκ:B-α, EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.

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

Science.gov (United States)

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

2005-10-01

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

Bayesian analysis of log Gaussian Cox processes for disease mapping

DEFF Research Database (Denmark)

Benes, Viktor; Bodlák, Karel; Møller, Jesper

We consider a data set of locations where people in Central Bohemia have been infected by tick-borne encephalitis, and where population census data and covariates concerning vegetation and altitude are available. The aims are to estimate the risk map of the disease and to study the dependence...... of the risk on the covariates. Instead of using the common area level approaches we consider a Bayesian analysis for a log Gaussian Cox point process with covariates. Posterior characteristics for a discretized version of the log Gaussian Cox process are computed using markov chain Monte Carlo methods...

Una estimación no paramétrica y robusta de la transformación Box-Cox para el modelo de regresión

Directory of Open Access Journals (Sweden)

Elkin Castaño Vélez

2011-12-01

Full Text Available In regression analysis, it is frequently required to transform the dependent variable in order to obtain additivity and normal errors with constant variance. Box and Cox (1964 proposed a parametric power transformation based on the assumption of normality with the aim to achieve these goals. However, some authors such as Carroll (1980, 1982b, Bickel and Doksum (1981, Powell (1991, Chamberlain (1994, Buchinsky (1995, Marazzi and Yohai (2004 and Fitzenberger et al. (2005 have pointed out that this transformation is not robust to the presence of outliers, and propose robust estimators for the transformation parameter by replacing the normal likelihood with an objective function that is less sensitive to them. This paper presents a non-parametric alternative procedure for obtaining a power transformation within the Box-Cox family which is robust to the presence of outliers in the dependent variable. The procedure is an extension of the one proposed by Castaño (1994, 1995 for a symmetry transformation of a dataset.

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

Energy Technology Data Exchange (ETDEWEB)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R. [University Hospital Zurich, Cardiac Imaging, Department of Nuclear Medicine, Zurich (Switzerland)

2017-11-15

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

International Nuclear Information System (INIS)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R.

2017-01-01

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

IL1β-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

International Nuclear Information System (INIS)

Zhu, Yingting; Zhu, Min; Lance, Peter

2012-01-01

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 IL1β 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-1β, 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 IL1β. Further analysis indicated that the major COX-2 product, prostaglandin E 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-1β. 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-1β in the fibroblasts.

Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.

Science.gov (United States)

Montaño, Luis M; Carbajal, Verónica; Vargas, Mario H; García-Hernández, Luz M; Díaz-Hernández, Verónica; Checa, Marco; Barajas-López, Carlos

2013-08-01

Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.

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

OpenAIRE

Shang, Han Lin

2015-01-01

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

Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

International Nuclear Information System (INIS)

Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.; Raju, Uma; Andratschke, Nickolaus H.; Milas, Luka; Rodemann, H. Peter

2008-01-01

Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by γH 2 AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observed radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual γH2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2

Geographically weighted negative binomial regression applied to zonal level safety performance models.

Science.gov (United States)

Gomes, Marcos José Timbó Lima; Cunto, Flávio; da Silva, Alan Ricardo

2017-09-01

Generalized Linear Models (GLM) with negative binomial distribution for errors, have been widely used to estimate safety at the level of transportation planning. The limited ability of this technique to take spatial effects into account can be overcome through the use of local models from spatial regression techniques, such as Geographically Weighted Poisson Regression (GWPR). Although GWPR is a system that deals with spatial dependency and heterogeneity and has already been used in some road safety studies at the planning level, it fails to account for the possible overdispersion that can be found in the observations on road-traffic crashes. Two approaches were adopted for the Geographically Weighted Negative Binomial Regression (GWNBR) model to allow discrete data to be modeled in a non-stationary form and to take note of the overdispersion of the data: the first examines the constant overdispersion for all the traffic zones and the second includes the variable for each spatial unit. This research conducts a comparative analysis between non-spatial global crash prediction models and spatial local GWPR and GWNBR at the level of traffic zones in Fortaleza/Brazil. A geographic database of 126 traffic zones was compiled from the available data on exposure, network characteristics, socioeconomic factors and land use. The models were calibrated by using the frequency of injury crashes as a dependent variable and the results showed that GWPR and GWNBR achieved a better performance than GLM for the average residuals and likelihood as well as reducing the spatial autocorrelation of the residuals, and the GWNBR model was more able to capture the spatial heterogeneity of the crash frequency. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Monte Carlo simulation study comparing linear regression, beta regression, variable-dispersion beta regression and fractional logit regression at recovering average difference measures in a two sample design.

Science.gov (United States)

Meaney, Christopher; Moineddin, Rahim

2014-01-24

response data are generated from a discrete multinomial distribution with support on (0,1). The linear regression model, the variable-dispersion beta regression model and the fractional logit regression model all perform well across the simulation experiments under consideration. When employing beta regression to estimate covariate effects on (0,1) response data, researchers should ensure their dispersion sub-model is properly specified, else inferential errors could arise.

Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

Science.gov (United States)

Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

2011-07-01

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

A Box-Cox normal model for response times

NARCIS (Netherlands)

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

2009-01-01

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

Antiinflamatórios não esteróides inibidores da ciclooxigenase-2 (COX-2: aspectos atuais Antiinflamatorios no esteróides inhibidores de la ciclooxigenasa-2 (COX-2: aspectos actuales Cycloxygenase-2 inhibitors nonsteroid anti-inflammatory drugs: current issues

Directory of Open Access Journals (Sweden)

Carmen Luize Kummer

2002-07-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Devido à alta incidência de efeitos colaterais relacionados aos antiinflamatórios não hormonais (AINES, a descoberta de duas isoformas da enzima ciclooxigenase, classificadas como: COX-1 ou constitutiva e COX-2 ou indutiva, formulou o paradigma que as propriedades antiinflamatórias dos AINES seriam mediadas através da inibição da enzima COX-2; já os efeitos colaterais, do bloqueio da COX-1. Entretanto, a isoforma COX-2 tem sido detectada constitutivamente em tecidos normais, levantando a dúvida sobre o quão realmente são seguros os inibidores específicos desta enzima. O objetivo desta revisão é relatar as mais recentes evidências clínicas e experimentais envolvendo a COX-2 e os compostos inibidores desta isoforma. CONTEÚDO: São exibidos os novos conceitos sobre as diferenças estruturais entre COX-1 e COX-2, a existência destas isoformas nos diversos tecidos, os resultados de experimentos em animais e humanos, além da observação clínica dos compostos inibidores específicos COX-2 (coxibs. Algumas prováveis novas indicações de antiinflamatórios não esteróides, principalmente coxibs, na demência de Alzheimer e em neoplasias são exemplificadas. CONCLUSÕES: Os coxibs representam importante avanço farmacológico no tratamento antiinflamatório, reduzindo a incidência de lesões gastrointestinais e apresentando possível indicação na prevenção de neoplasias e doenças neurológicas. No entanto, tais compostos apresentam efeitos colaterais indistinguíveis dos AINES convencionais e são drogas de alto custo. Como toda medicação de recente lançamento no arsenal médico, maiores avaliações são necessárias para o estabelecimento da real segurança destes compostos.JUSTIFICATIVA Y OBJETIVOS: Debido a la alta incidencia de efectos colaterales relacionados a los antiinflamatorios no hormonales (AINES, la descubierta de dos isoformas de la enzima ciclooxigenasa, clasificadas como: COX-1

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

International Nuclear Information System (INIS)

Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

2013-01-01

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-κB dependent. Inhibition of NF-κB 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-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-04-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Teraoka, Hiroki, E-mail: hteraoka@rakuno.ac.jp [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Peterson, Richard E. [School of Pharmacy, University of Wisconsin, Madison, WI (United States); Stegeman, John J. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Kitazawa, Takio; Hiraga, Takeo [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Kubota, Akira [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States)

2014-09-15

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

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

Science.gov (United States)

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

2016-03-01

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

Academic performance of children born preterm: a meta-analysis and meta-regression.

Science.gov (United States)

Twilhaar, E Sabrina; de Kieviet, Jorrit F; Aarnoudse-Moens, Cornelieke Sh; van Elburg, Ruurd M; Oosterlaan, Jaap

2017-08-28

Advances in neonatal healthcare have resulted in decreased mortality after preterm birth but have not led to parallel decreases in morbidity. Academic performance provides insight in the outcomes and specific difficulties and needs of preterm children. To study academic performance in preterm children born in the antenatal steroids and surfactant era and possible moderating effects of perinatal and demographic factors. PubMed, Web of Science and PsycINFO were searched for peer-reviewed articles. Cohort studies with a full-term control group reporting standardised academic performance scores of preterm children (Academic test scores and special educational needs of preterm and full-term children were analysed using random effects meta-analysis. Random effects meta-regressions were performed to explore the predictive role of perinatal and demographic factors for between-study variance in effect sizes. The 17 eligible studies included 2390 preterm children and 1549 controls. Preterm children scored 0.71 SD below full-term peers on arithmetic (pacademic performance (p=0.006). Preterm children born in the antenatal steroids and surfactant era show considerable academic difficulties. Preterm children with bronchopulmonarydysplasia are at particular risk for poor academic outcome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

COX-2 inhibition in osteoarthritis:effects on cartilage

NARCIS (Netherlands)

Mastbergen, Simon Carl

2005-01-01

The topic of this thesis was to provide more insight in the direct effects of one of the selective COX-2 inhibitors, celecoxib on articular cartilage. Issues of major relevance to clinical practice since it is essential that compounds used to treat osteoarthritis do not impair the ability of

Induced mutants of Cox's Orange Pippin apple with apparent increased self-compatibility. Pt. 2

International Nuclear Information System (INIS)

Church, R.M.; Lacey, C.N.D.; Richardson, P.

1982-01-01

Fruit set on clones of Cox's Orange Pippin apple which had been produced by gamma-irradiation, and found in a previous trial to crop when isolated from the pollen of other cultivars, was compared after open or hand-pollination. Some clones set more fruit than the unirradiated control trees when open pollinated or when hand-pollinated with pollen from the same tree or control Cox trees. Pollen from some mutant clones also improved set on standard Cox (EMLA). Estimates of the numbers of pollen tubes reaching the base of the style indicated that the increased set was due to enhanced tube growth. (orig.)

Performance of an Axisymmetric Rocket Based Combined Cycle Engine During Rocket Only Operation Using Linear Regression Analysis

Science.gov (United States)

Smith, Timothy D.; Steffen, Christopher J., Jr.; Yungster, Shaye; Keller, Dennis J.

1998-01-01

The all rocket mode of operation is shown to be a critical factor in the overall performance of a rocket based combined cycle (RBCC) vehicle. An axisymmetric RBCC engine was used to determine specific impulse efficiency values based upon both full flow and gas generator configurations. Design of experiments methodology was used to construct a test matrix and multiple linear regression analysis was used to build parametric models. The main parameters investigated in this study were: rocket chamber pressure, rocket exit area ratio, injected secondary flow, mixer-ejector inlet area, mixer-ejector area ratio, and mixer-ejector length-to-inlet diameter ratio. A perfect gas computational fluid dynamics analysis, using both the Spalart-Allmaras and k-omega turbulence models, was performed with the NPARC code to obtain values of vacuum specific impulse. Results from the multiple linear regression analysis showed that for both the full flow and gas generator configurations increasing mixer-ejector area ratio and rocket area ratio increase performance, while increasing mixer-ejector inlet area ratio and mixer-ejector length-to-diameter ratio decrease performance. Increasing injected secondary flow increased performance for the gas generator analysis, but was not statistically significant for the full flow analysis. Chamber pressure was found to be not statistically significant.

Sparse reduced-rank regression with covariance estimation

KAUST Repository

Chen, Lisha

2014-12-08

Improving the predicting performance of the multiple response regression compared with separate linear regressions is a challenging question. On the one hand, it is desirable to seek model parsimony when facing a large number of parameters. On the other hand, for certain applications it is necessary to take into account the general covariance structure for the errors of the regression model. We assume a reduced-rank regression model and work with the likelihood function with general error covariance to achieve both objectives. In addition we propose to select relevant variables for reduced-rank regression by using a sparsity-inducing penalty, and to estimate the error covariance matrix simultaneously by using a similar penalty on the precision matrix. We develop a numerical algorithm to solve the penalized regression problem. In a simulation study and real data analysis, the new method is compared with two recent methods for multivariate regression and exhibits competitive performance in prediction and variable selection.

Sparse reduced-rank regression with covariance estimation

KAUST Repository

Chen, Lisha; Huang, Jianhua Z.

2014-01-01

Improving the predicting performance of the multiple response regression compared with separate linear regressions is a challenging question. On the one hand, it is desirable to seek model parsimony when facing a large number of parameters. On the other hand, for certain applications it is necessary to take into account the general covariance structure for the errors of the regression model. We assume a reduced-rank regression model and work with the likelihood function with general error covariance to achieve both objectives. In addition we propose to select relevant variables for reduced-rank regression by using a sparsity-inducing penalty, and to estimate the error covariance matrix simultaneously by using a similar penalty on the precision matrix. We develop a numerical algorithm to solve the penalized regression problem. In a simulation study and real data analysis, the new method is compared with two recent methods for multivariate regression and exhibits competitive performance in prediction and variable selection.

Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I.

Science.gov (United States)

Singh, Mohan; Chaudhry, Parvesh; Parent, Sophie; Asselin, Eric

2012-01-01

Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.

Pengaruh kualitas Udara ( Debu,COx, NOx, SOx Terminal Terhadap Gangguan Fungsi Paru Pada Pedagang Tetap Terminal Bus Induk Jawa Tengah, 2002

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Soedjono Soedjono

2015-12-01

Full Text Available ABSTRACT Background : The high growth of motor vehicle in Central Java in 2000 reached 11,8% a year and from these number the city bus, 4,5%. This condition has seriously brought negative effect to environment. Many researchers found that the equipment of transportation and the industry are sources of air pollution, which very large and very dominant. The bus terminal is one location that is the highest air pollution than other locations because the bus terminal is a central of activities that need a transportation service. Beside that the bus terminal is a influence of sir quality dust, COx, NOx, SOx, in the bus terminal to the lung dysfunction of the permanent seller in the 15 prime bus terminals in Central Java, 2002 and to find the exposed duration, the work duration, the habit of smoking and age which can influence  the lung disfunction. Method : This was an analytic research using cross sectional approach. The samples of this research were 309 respondents (total population. The concentration of dust, COx, NOx, SOx, was directly  measured in the 15 prime bus terminals. The other data was measured by  interviewing with the sellers in the bus terminal who had been limited their ages (40 years old to down. The logistic regression analysis was used to test the influence of dust, COx, NOx, SOx, the exposed duration, the work duration, the habit of smoking and age. Result : The result of descriptive analysis shows that all variables have influence to the instance of the lung disfunction. It can be seen from the number of percentage of respondent who experienced the lung disfunction in  each variable. From analitical statistic, only the variable of anamnesis / the other diseases has influence which very significant to the instance of the lung disfunction. Other variables are risk factors to the instance of the lung disfunction. Key word : Dust, COx, NOx, SOx, concentration, interference lung – function, Seller, Bus Terminal.

Screening of Missense SNPs in Coding Regions of COX-2 as a Key Enzyme Involved in Cancer

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Sodabeh Jahanbakhsh-Godehkahriz

2013-09-01

Full Text Available Background & Objectives: Non-synonymous single nucleotide polymorphism (nsSNPs which results in disruption of protein function are used as markers in linkage and association of human proteins that might be involved in diseases and cancers .   Methods: To study the functional effect of nsSNP in cyclooxygenase-2 (COX2 amino acids, the nucleotide sequences encoding COX-2 gene in cancers were extracted from the NCBI (gi|223941909 data bank (283 cases and analyzed by SIFT, I-Mutant 2.0, SNP and GO, PANTHER and FASTSNP servers. These servers involve programs that predict the effects of amino acid substitution on protein function, stability and missense .   Results: COX-2 is an essential enzyme for the production of pro-inflammatory prostaglandins which are relevant to cancer development and progression. The substitutions in some positions such as R228H and S428A of COX-2 in most of cancers linked to reformed protein function through disruption in enzyme active site.   Conclusion: Amino acid substitutions as a consequence of COX-2 nsSNPs have important role in human disease. Substitutions which are located in catalytic domain are important for the enzymatic function of COX-2 and associated with higher expression of COX-2.

Linear regression in astronomy. I

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Isobe, Takashi; Feigelson, Eric D.; Akritas, Michael G.; Babu, Gutti Jogesh

1990-01-01

Five methods for obtaining linear regression fits to bivariate data with unknown or insignificant measurement errors are discussed: ordinary least-squares (OLS) regression of Y on X, OLS regression of X on Y, the bisector of the two OLS lines, orthogonal regression, and 'reduced major-axis' regression. These methods have been used by various researchers in observational astronomy, most importantly in cosmic distance scale applications. Formulas for calculating the slope and intercept coefficients and their uncertainties are given for all the methods, including a new general form of the OLS variance estimates. The accuracy of the formulas was confirmed using numerical simulations. The applicability of the procedures is discussed with respect to their mathematical properties, the nature of the astronomical data under consideration, and the scientific purpose of the regression. It is found that, for problems needing symmetrical treatment of the variables, the OLS bisector performs significantly better than orthogonal or reduced major-axis regression.

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

Science.gov (United States)

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

2013-12-01

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

Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

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Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

2006-07-01

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

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

Science.gov (United States)

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

2004-01-01

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

Identifying nonproportional covariates in the Cox model

Czech Academy of Sciences Publication Activity Database

Kraus, David

2008-01-01

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

Differentiating regressed melanoma from regressed lichenoid keratosis.

Science.gov (United States)

Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

2017-04-01

Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

Science.gov (United States)

Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2013-01-01

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

Kaempferol attenuates COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema by targeting STAT3 and NF-kB

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Anandita Basu

2017-10-01

Full Text Available Dietary polyphenols are reported to possess varied pharmacological activities, viz. antioxidant, anti-inflammatory, anti-cancer, anti-allergic actions. Here, we report the efficacy of Kaempferol (kae to attenuate expression of IL-6 induced cycloxygenase-2 (COX-2, an inducible isoform of cycloxygenase enzyme family that catalyzes synthesis of inflammatory mediators, prostanoids and prostaglandins. IL-6 is a pleiotropic cytokine involved in both acute and chronic inflammation. Our results showed that kae attenuated COX-2 expression at both mRNA and protein level in IL-6-induced THP1 macrophages. This attenuation of COX-2 expression by kae involved dose-dependent inhibition of phosphorylation of STAT3 (Tyr 705 and NF-kB p65 (Ser 536 leading to their deactivation and reduced nuclear localization in THP-1 macrophages. Moreover, kae modulates COX-2 expression as well as STAT3 and NF-kB activation in carrageenan-induced mouse paw edema model. RT-PCR and western blot analysis from paw tissues were harvested after kae injection (i.p followed by carrageenan-treatment in sub-plantar region of right hind paw. Results showed that kae attenuated COX-2 expression and STAT3 and NF-kB activation in carrageenan-induced mouse paw edema, suggesting that inhibition of both IL-6-STAT3-COX-2 and IL-6-NFkB-COX-2 axes by kae might be stimulus-independent. To understand binding affinity of kae with NF-kB and STAT3, docking analysis was performed using Patchdock server. From our findings, we observed strong binding affinity and transient interaction in both NF-kB/kae and STAT3/kae complexes. We noticed negative atomic contact energy and greater interface area for both the complexes. Selected complexes obtained from Patchdock were refined using Firedock online server which also suggested similar negative binding energy profile. It is plausible that kae attenuates COX-2 expression by directly binding to both STAT3 and NF-kB proteins and inhibiting their activation and

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

International Nuclear Information System (INIS)

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

2008-01-01

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 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

Testing the Box-Cox Parameter for an Integrated Process

NARCIS (Netherlands)

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

2011-01-01

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

The Distribution of the Interval between Events of a Cox Process with Shot Noise Intensity

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Angelos Dassios

2008-01-01

Full Text Available Applying piecewise deterministic Markov processes theory, the probability generating function of a Cox process, incorporating with shot noise process as the claim intensity, is obtained. We also derive the Laplace transform of the distribution of the shot noise process at claim jump times, using stationary assumption of the shot noise process at any times. Based on this Laplace transform and from the probability generating function of a Cox process with shot noise intensity, we obtain the distribution of the interval of a Cox process with shot noise intensity for insurance claims and its moments, that is, mean and variance.

Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

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Marcos A.S. Leal

2017-12-01

Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

A Proportional Hazards Regression Model for the Subdistribution with Covariates-adjusted Censoring Weight for Competing Risks Data

DEFF Research Database (Denmark)

He, Peng; Eriksson, Frank; Scheike, Thomas H.

2016-01-01

function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate-adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate-adjusted weight......With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution...... and the covariates are independent. Covariate-dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate-dependent censoring. We consider a covariate-adjusted weight...

The comparison of landslide ratio-based and general logistic regression landslide susceptibility models in the Chishan watershed after 2009 Typhoon Morakot

Science.gov (United States)

WU, Chunhung

2015-04-01

The research built the original logistic regression landslide susceptibility model (abbreviated as or-LRLSM) and landslide ratio-based ogistic regression landslide susceptibility model (abbreviated as lr-LRLSM), compared the performance and explained the error source of two models. The research assumes that the performance of the logistic regression model can be better if the distribution of landslide ratio and weighted value of each variable is similar. Landslide ratio is the ratio of landslide area to total area in the specific area and an useful index to evaluate the seriousness of landslide disaster in Taiwan. The research adopted the landside inventory induced by 2009 Typhoon Morakot in the Chishan watershed, which was the most serious disaster event in the last decade, in Taiwan. The research adopted the 20 m grid as the basic unit in building the LRLSM, and six variables, including elevation, slope, aspect, geological formation, accumulated rainfall, and bank erosion, were included in the two models. The six variables were divided as continuous variables, including elevation, slope, and accumulated rainfall, and categorical variables, including aspect, geological formation and bank erosion in building the or-LRLSM, while all variables, which were classified based on landslide ratio, were categorical variables in building the lr-LRLSM. Because the count of whole basic unit in the Chishan watershed was too much to calculate by using commercial software, the research took random sampling instead of the whole basic units. The research adopted equal proportions of landslide unit and not landslide unit in logistic regression analysis. The research took 10 times random sampling and selected the group with the best Cox & Snell R2 value and Nagelkerker R2 value as the database for the following analysis. Based on the best result from 10 random sampling groups, the or-LRLSM (lr-LRLSM) is significant at the 1% level with Cox & Snell R2 = 0.190 (0.196) and Nagelkerke R2

Prediction of unwanted pregnancies using logistic regression, probit regression and discriminant analysis.

Science.gov (United States)

Ebrahimzadeh, Farzad; Hajizadeh, Ebrahim; Vahabi, Nasim; Almasian, Mohammad; Bakhteyar, Katayoon

2015-01-01

Unwanted pregnancy not intended by at least one of the parents has undesirable consequences for the family and the society. In the present study, three classification models were used and compared to predict unwanted pregnancies in an urban population. In this cross-sectional study, 887 pregnant mothers referring to health centers in Khorramabad, Iran, in 2012 were selected by the stratified and cluster sampling; relevant variables were measured and for prediction of unwanted pregnancy, logistic regression, discriminant analysis, and probit regression models and SPSS software version 21 were used. To compare these models, indicators such as sensitivity, specificity, the area under the ROC curve, and the percentage of correct predictions were used. The prevalence of unwanted pregnancies was 25.3%. The logistic and probit regression models indicated that parity and pregnancy spacing, contraceptive methods, household income and number of living male children were related to unwanted pregnancy. The performance of the models based on the area under the ROC curve was 0.735, 0.733, and 0.680 for logistic regression, probit regression, and linear discriminant analysis, respectively. Given the relatively high prevalence of unwanted pregnancies in Khorramabad, it seems necessary to revise family planning programs. Despite the similar accuracy of the models, if the researcher is interested in the interpretability of the results, the use of the logistic regression model is recommended.

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

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Donald D. Nolting

2013-01-01

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

Log Gaussian Cox processes on the sphere

DEFF Research Database (Denmark)

Pacheco, Francisco Andrés Cuevas; Møller, Jesper

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

Evaluating the Performance of Polynomial Regression Method with Different Parameters during Color Characterization

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Bangyong Sun

2014-01-01

Full Text Available The polynomial regression method is employed to calculate the relationship of device color space and CIE color space for color characterization, and the performance of different expressions with specific parameters is evaluated. Firstly, the polynomial equation for color conversion is established and the computation of polynomial coefficients is analysed. And then different forms of polynomial equations are used to calculate the RGB and CMYK’s CIE color values, while the corresponding color errors are compared. At last, an optimal polynomial expression is obtained by analysing several related parameters during color conversion, including polynomial numbers, the degree of polynomial terms, the selection of CIE visual spaces, and the linearization.

Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway

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Lee, Jaetae; Lee, Young Sup

2015-01-01

The COX-2/PGE2 pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, PGE2, in cancer survival remain unknown. Herein, we investigated PGE2-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with PGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. PGE2 not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of PGE2, and restored the menadione-induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the PGE2-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that PGE2 signaling acts in an autocrine manner, and specific inhibition of PGE2 will provide a novel approach for the treatment of leukemia. [BMB Reports 2015; 48(2): 109-114] PMID:24965577

Analysis of the cytochrome c oxidase subunit II (COX2) gene in giant panda, Ailuropoda melanoleuca.

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Ling, S S; Zhu, Y; Lan, D; Li, D S; Pang, H Z; Wang, Y; Li, D Y; Wei, R P; Zhang, H M; Wang, C D; Hu, Y D

2017-01-23

The giant panda, Ailuropoda melanoleuca (Ursidae), has a unique bamboo-based diet; however, this low-energy intake has been sufficient to maintain the metabolic processes of this species since the fourth ice age. As mitochondria are the main sites for energy metabolism in animals, the protein-coding genes involved in mitochondrial respiratory chains, particularly cytochrome c oxidase subunit II (COX2), which is the rate-limiting enzyme in electron transfer, could play an important role in giant panda metabolism. Therefore, the present study aimed to isolate, sequence, and analyze the COX2 DNA from individuals kept at the Giant Panda Protection and Research Center, China, and compare these sequences with those of the other Ursidae family members. Multiple sequence alignment showed that the COX2 gene had three point mutations that defined three haplotypes, with 60% of the sequences corresponding to haplotype I. The neutrality tests revealed that the COX2 gene was conserved throughout evolution, and the maximum likelihood phylogenetic analysis, using homologous sequences from other Ursidae species, showed clustering of the COX2 sequences of giant pandas, suggesting that this gene evolved differently in them.

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Protective effect of NSAIDs on cancer and influence of COX-2 C-765G genotype

NARCIS (Netherlands)

C. Siemes (Claire); L.E. Visser (Loes); J.W.W. Coebergh (Jan Willem); A. Hofman (Albert); A.G. Uitterlinden (André); B.H.Ch. Stricker (Bruno)

2008-01-01

textabstractPurpose: Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common non-skin related cancers and modification by COX-2 G-765C genotype.

Pronounced radiosensitization of cultured human cancer cells by COX inhibitor under acidic microenvironment

International Nuclear Information System (INIS)

Shah, Tushar; Ryu, Samuel; Lee, Ho Jun; Brown, Stephen; Kim, Jae Ho

2002-01-01

Purpose: To demonstrate the influence of pH on the cytotoxicity and radiosensitization by COX (cyclooxygenase) -1 and -2 inhibitors using established human cancer cells in culture. Methods and Materials: Nonselective COX inhibitor, ibuprofen (IB), and selective COX-2 inhibitor, SC-236, were used to determine the cytotoxicity and radiosensitization at varying pH of culture media. Human colon carcinoma cell line (HT-29) was exposed to the drug alone and in combination with radiation at different pH of the cell culture media. The end point was clonogenic ability of the single-plated cells after the treatment. Results: Cytotoxicity and radiosensitization of IB increased with higher drug concentration and longer exposure time. The most significant radiosensitization was seen with IB (1.5 mM) for 2-h treatment at pH 6.7 before irradiation. The dose-modifying factor as defined by the ratio of radiation doses required to achieve the same effect on cell survival was 1.8 at 10% survival level. In contrast, SC-236 (50 μM for 2-8 h) showed no pH-dependent cytotoxicity. There was modest increase in the cell killing at lower doses of radiation. Conclusion: An acidic pH was an important factor affecting the increased cytotoxicity and radiosensitization by ibuprofen. Radiation response was enhanced at shoulder portion of the cell survival curve by selective COX-2 inhibitor

Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

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Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt

2017-06-01

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts. © 2017 Wiley Periodicals, Inc.

Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice.

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Sato, Taiki; Kishimoto, Yu; Asakawa, Sanki; Mizuno, Natsumi; Hiratsuka, Masahiro; Hirasawa, Noriyasu

2016-07-01

Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24h. NiCl2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl2 and further potentiated by PGE2. Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be

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

DEFF Research Database (Denmark)

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

2004-01-01

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

COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

Science.gov (United States)

Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

2014-01-01

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

Science.gov (United States)

Liu, Shuo; Zhang, Cun; Zhang, Kuo; Gao, Yuan; Wang, Zhaowei; Li, Xiaoju; Cheng, Guang; Wang, Shuning; Xue, Xiaochang; Li, Weina; Zhang, Wei; Zhang, Yingqi; Xing, Xianghui; Li, Meng; Hao, Qiang

2017-07-04

Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

10 km running performance predicted by a multiple linear regression model with allometrically adjusted variables.

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Abad, Cesar C C; Barros, Ronaldo V; Bertuzzi, Romulo; Gagliardi, João F L; Lima-Silva, Adriano E; Lambert, Mike I; Pires, Flavio O

2016-06-01

The aim of this study was to verify the power of VO 2max , peak treadmill running velocity (PTV), and running economy (RE), unadjusted or allometrically adjusted, in predicting 10 km running performance. Eighteen male endurance runners performed: 1) an incremental test to exhaustion to determine VO 2max and PTV; 2) a constant submaximal run at 12 km·h -1 on an outdoor track for RE determination; and 3) a 10 km running race. Unadjusted (VO 2max , PTV and RE) and adjusted variables (VO 2max 0.72 , PTV 0.72 and RE 0.60 ) were investigated through independent multiple regression models to predict 10 km running race time. There were no significant correlations between 10 km running time and either the adjusted or unadjusted VO 2max . Significant correlations (p 0.84 and power > 0.88. The allometrically adjusted predictive model was composed of PTV 0.72 and RE 0.60 and explained 83% of the variance in 10 km running time with a standard error of the estimate (SEE) of 1.5 min. The unadjusted model composed of a single PVT accounted for 72% of the variance in 10 km running time (SEE of 1.9 min). Both regression models provided powerful estimates of 10 km running time; however, the unadjusted PTV may provide an uncomplicated estimation.

Comparative Analysis of A, B Type and Exchange Traded Funds Performances with Mutual Fund Performance Measures, Regression Analysis and Manova Technique.

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Mehmet Arslan

2010-06-01

Full Text Available The objective of the study is to evaluate risk- reward relationship and relative performances of the 4 different groups of mutual funds. To this end, daily return data of these 12 mutual funds (3 type variable fund; 3 B type variable fund; 3 A type stock fund and 3 A type Exchange traded fund together with daily market index (imkb100 return and daily return of riskless rate for the period from January 2006 to Feb 2010. The 180-day maturity T-Bill has been selected to represent riskless rate. To determine performances of mutual funds; Sharpe ratio, M2 measure, Treynor index, Jensen index, Sortino ratio, T2 ratio, Valuation ratio has been applied and these indicators produced conflicting results in ranking mutual funds. Then timingand selection capability of the fund manager has been determined by applying simple regression and Quadratic regression. Interestingly all funds found to have positive coefficient, indicating positive election capability of managers; but in terms of timing capability only one fund managers showed success. Finally, to determine extent to which mean returns are differs between mutual funds, market index (imkb100 and riskless rate (180 day TBill results of the analysis revealed that mean returns of individual security returns differs at P≤0,01 level. That shows instability in returns and poor ex-ante forecast modeling capability.

MiR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression.

Science.gov (United States)

Chen, Zheng-Gang; Zheng, Chuan-Yi; Cai, Wang-Qing; Li, Da-Wei; Ye, Fu-Yue; Zhou, Jian; Wu, Ran; Yang, Kun

2017-08-11

Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA (miR)-26b/cyclooxygenase (COX)-2 axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased level of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting miR-26b mimic into U-373 cells. The invasive cell number and wounld closing rate were reduced in U-373 cells transfected with miR-26b mimic. Besides, COX2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume and the expression of matrix metalloproteinase (MMP)-2, MMP-9). Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for treatment of glioma.

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

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Mingzhu Zhuang

Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/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-κB 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.

A Conversation with Sally Coxe: A Primate Partnership Culture

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Riane Eisler

2017-10-01

Full Text Available IJPS Editor-in-Chief Riane Eisler talks with Sally Coxe, founding director of the Bonobo Conservation Initiative (BCI, dedicated to protecting these uniquely peaceful primates who share more than 98 percent of our human species’ genes and are on the brink of extinction, as well as protecting their rainforest home.

Two-step estimation procedures for inhomogeneous shot-noise Cox processes

DEFF Research Database (Denmark)

Prokesová, Michaela; Dvorák, Jirí; Jensen, Eva B. Vedel

In the present paper we develop several two-step estimation procedures for inhomogeneous shot-noise Cox processes. The intensity function is parametrized by the inhomogeneity parameters while the pair-correlation function is parametrized by the interaction parameters. The suggested procedures...

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

Science.gov (United States)

Sun, Liuquan; Tong, Xingwei; Zhou, Xian

2011-04-01

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

Tumor regression patterns in retinoblastoma

International Nuclear Information System (INIS)

Zafar, S.N.; Siddique, S.N.; Zaheer, N.

2016-01-01

To observe the types of tumor regression after treatment, and identify the common pattern of regression in our patients. Study Design: Descriptive study. Place and Duration of Study: Department of Pediatric Ophthalmology and Strabismus, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from October 2011 to October 2014. Methodology: Children with unilateral and bilateral retinoblastoma were included in the study. Patients were referred to Pakistan Institute of Medical Sciences, Islamabad, for chemotherapy. After every cycle of chemotherapy, dilated funds examination under anesthesia was performed to record response of the treatment. Regression patterns were recorded on RetCam II. Results: Seventy-four tumors were included in the study. Out of 74 tumors, 3 were ICRB group A tumors, 43 were ICRB group B tumors, 14 tumors belonged to ICRB group C, and remaining 14 were ICRB group D tumors. Type IV regression was seen in 39.1% (n=29) tumors, type II in 29.7% (n=22), type III in 25.6% (n=19), and type I in 5.4% (n=4). All group A tumors (100%) showed type IV regression. Seventeen (39.5%) group B tumors showed type IV regression. In group C, 5 tumors (35.7%) showed type II regression and 5 tumors (35.7%) showed type IV regression. In group D, 6 tumors (42.9%) regressed to type II non-calcified remnants. Conclusion: The response and success of the focal and systemic treatment, as judged by the appearance of different patterns of tumor regression, varies with the ICRB grouping of the tumor. (author)

Retro-regression--another important multivariate regression improvement.

Science.gov (United States)

Randić, M

2001-01-01

We review the serious problem associated with instabilities of the coefficients of regression equations, referred to as the MRA (multivariate regression analysis) "nightmare of the first kind". This is manifested when in a stepwise regression a descriptor is included or excluded from a regression. The consequence is an unpredictable change of the coefficients of the descriptors that remain in the regression equation. We follow with consideration of an even more serious problem, referred to as the MRA "nightmare of the second kind", arising when optimal descriptors are selected from a large pool of descriptors. This process typically causes at different steps of the stepwise regression a replacement of several previously used descriptors by new ones. We describe a procedure that resolves these difficulties. The approach is illustrated on boiling points of nonanes which are considered (1) by using an ordered connectivity basis; (2) by using an ordering resulting from application of greedy algorithm; and (3) by using an ordering derived from an exhaustive search for optimal descriptors. A novel variant of multiple regression analysis, called retro-regression (RR), is outlined showing how it resolves the ambiguities associated with both "nightmares" of the first and the second kind of MRA.

Modified Regression Correlation Coefficient for Poisson Regression Model

Science.gov (United States)

Kaengthong, Nattacha; Domthong, Uthumporn

2017-09-01

This study gives attention to indicators in predictive power of the Generalized Linear Model (GLM) which are widely used; however, often having some restrictions. We are interested in regression correlation coefficient for a Poisson regression model. This is a measure of predictive power, and defined by the relationship between the dependent variable (Y) and the expected value of the dependent variable given the independent variables [E(Y|X)] for the Poisson regression model. The dependent variable is distributed as Poisson. The purpose of this research was modifying regression correlation coefficient for Poisson regression model. We also compare the proposed modified regression correlation coefficient with the traditional regression correlation coefficient in the case of two or more independent variables, and having multicollinearity in independent variables. The result shows that the proposed regression correlation coefficient is better than the traditional regression correlation coefficient based on Bias and the Root Mean Square Error (RMSE).

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

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Alireza Mousavi Nia

2017-03-01

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

Some functional limit theorems for compound Cox processes

Energy Technology Data Exchange (ETDEWEB)

Korolev, Victor Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Institute of Informatics Problems FRC CSC RAS (Russian Federation); Chertok, A. V. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Euphoria Group LLC (Russian Federation); Korchagin, A. Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Kossova, E. V. [Higher School of Economics National Research University, Moscow (Russian Federation); Zeifman, Alexander I. [Vologda State University, S.Orlova, 6, Vologda (Russian Federation); Institute of Informatics Problems FRC CSC RAS, ISEDT RAS (Russian Federation)

2016-06-08

An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

Some functional limit theorems for compound Cox processes

International Nuclear Information System (INIS)

Korolev, Victor Yu.; Chertok, A. V.; Korchagin, A. Yu.; Kossova, E. V.; Zeifman, Alexander I.

2016-01-01

An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

Convergent synthesis and evaluation of {sup 18}F-labeled azulenic COX2 probes for cancer imaging

Energy Technology Data Exchange (ETDEWEB)

Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Peterson, Todd E. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Crews, Brenda C. [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Marnett, Larry [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Gore, John C. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN (United States); Pham, Wellington, E-mail: wellington.pham@vanderbilt.edu [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Neuroscience, Vanderbilt University, Nashville, TN (United States)

2013-01-03

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

Demonstration of a Fiber Optic Regression Probe

Science.gov (United States)

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

Spontaneous regression of a congenital melanocytic nevus

Directory of Open Access Journals (Sweden)

Amiya Kumar Nath

2011-01-01

Full Text Available Congenital melanocytic nevus (CMN may rarely regress which may also be associated with a halo or vitiligo. We describe a 10-year-old girl who presented with CMN on the left leg since birth, which recently started to regress spontaneously with associated depigmentation in the lesion and at a distant site. Dermoscopy performed at different sites of the regressing lesion demonstrated loss of epidermal pigments first followed by loss of dermal pigments. Histopathology and Masson-Fontana stain demonstrated lymphocytic infiltration and loss of pigment production in the regressing area. Immunohistochemistry staining (S100 and HMB-45, however, showed that nevus cells were present in the regressing areas.

Variable importance in latent variable regression models

NARCIS (Netherlands)

Kvalheim, O.M.; Arneberg, R.; Bleie, O.; Rajalahti, T.; Smilde, A.K.; Westerhuis, J.A.

2014-01-01

The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable

Ekspresi COX-2 dan Jumlah Neutrofil Fase Inflamasi pada Proses Penyembuhan Luka Setelah Pemberian Sistemik Ekstrak Etanolik Rosela (Hibiscus sabdariffa (studi in vivo pada Tikus Wistar

Directory of Open Access Journals (Sweden)

Endah Kusumastuti

2014-06-01

sebagai bahan anti-inflamasi.  Expression of COX-2 and The Number of Neutrophil in Inflammation stage of Wound Healing Process after Systemic Administration of Ethanolic Extract Rosela. Inflammation is an initial stage of body’s natural response to tissue damage.The use  empirically plants often used for traditional medicine because it is easily found in the community and fewer side effects. Flavanoid presence of roselle (Hibiscus sabdariffa is thought to have anti inflammatory effects. This study aimed to know the effect of systemic administration of Roselle ethanolic extract toward COX-2 expression and neutrophils number in the inflammatory phase of wound healing processes. Roselle was obtained from plantations in Bulusari hamlet, Tarokan, Kediri, EastJava. Making roselle extract was performed in LPPT unit 1 UGM Yogyakarta by percolation ways. Wistar rats were given a total of 36 injuries with ɵ 3 mm punch biopsy of the buccal mucosa. Subjects were divided into three groups, each group of 12 rats. The division consists of the negative control group (saline, positive control (ibuprofen 20 mg/kg and treatment (roselle extract 500 mg/kg. Giving drink suitable group once daily for four days. On day 1, the 2nd, 3rd and fourth rats were sacrificed, and mucosal tissue injury was made histological preparat. Hematoxylin eosin staining (HE was performed to observe the number of neutrophils. COX-2 expression was found in preparations for immunohistochemical staining using rabbit polyclonal COX-2 antibody (Lab Vision, USA. The number of neutrophils and expression of COX-2 is calculated under a light microscope data were analyzed using Two-way ANOVA and LSD. The results showed that the expression of COX-2 and neutrophil number were least in the treatment group compared to the control. Clinical observation on day four also appears around the wound has completely closed the subject after administration of roselle drink. It was concluded that the ethanolic extract of roselle can

Bcr-Abl-independent mechanism of resistance to imatinib in K562 cells: Induction of cyclooxygenase-2 (COX-2) by histone deacetylases (HDACs).

Science.gov (United States)

Kalle, Arunasree M; Sachchidanand, Sachchidanand; Pallu, Reddanna

2010-09-01

Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE(2) to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE(2)-cAMP-PKC-mediated pathway. Copyright 2010 Elsevier Ltd. All rights reserved.

NSAIDs and serious cardiovascular disorders: especially cox-2 inhibitors and diclofenac.

Science.gov (United States)

2016-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) used as analgesics expose patients to cardiovascular risks that can be predicted from their pharmacological properties. As of mid-2015, what is known about the cardiovascular harms of the NSAIDs of choice, ibuprofen and naproxen? Most of the data from comparative trials of NSAIDs concern cox-2 inhibitors, diclofenac, ibuprofen and naproxen. Few studies have addressed the serious cardiovascular effects of other NSAIDs. In 2013, a U.K. team published a large meta-analysis of hundreds of randomised trials comparing NSAIDs with placebo or one NSAID with another NSAID. Compared with placebo, a statistically significant increase in the risk of serious cardiovascular adverse effects was demonstrated with cox-2 inhibitors and with diclofenac (about +40%). This risk is mainly due to an increase in myocardial infarctions and vascular deaths. Another meta-analysis found similar results in terms of cardiovascular deaths. The results of epidemiological studies are consistent with those of randomised clinical trials. According to meta-analyses of randomised trials, high-dose ibuprofen increases cardiovascular risks to the same degree as diclofenac or cox-2 inhibitors. The risk seems to mainly apply to daily doses of 2400 mg, a finding borne out by epidemiological studies that showed no increased risk with ibuprofen 1200 mg. Two meta-analyses of clinical trials showed that all NSAIDs roughly double the risk of heart failure. One meta-analysis showed a small, statistically significant increase in the risk of atrial fibrillation. In practice, from a cardiovascular perspective, the NSAIDs of choice are ibuprofen, on condition that the dose does not exceed 1200 mg per day, and naproxen. In contrast, it would appear from the study data that cox-2 inhibitors, diclofenac and high-dose ibuprofen (2400 mg per day) are best avoided. As for other NSAIDs, the clinical data are too sparse to allow a meaningful comparison with the better studied

Ridge Regression Signal Processing

Science.gov (United States)

Kuhl, Mark R.

1990-01-01

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

CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

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Marianne Houssier

2008-02-01

Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

Extracellular histones disarrange vasoactive mediators release through a COX-NOS interaction in human endothelial cells.

Science.gov (United States)

Pérez-Cremades, Daniel; Bueno-Betí, Carlos; García-Giménez, José Luis; Ibañez-Cabellos, José Santiago; Hermenegildo, Carlos; Pallardó, Federico V; Novella, Susana

2017-08-01

Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

Science.gov (United States)

Lo, Kenneth; Gottardo, Raphael

2012-01-01

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

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

Science.gov (United States)

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 μM 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.

and Multinomial Logistic Regression

African Journals Online (AJOL)

This work presented the results of an experimental comparison of two models: Multinomial Logistic Regression (MLR) and Artificial Neural Network (ANN) for classifying students based on their academic performance. The predictive accuracy for each model was measured by their average Classification Correct Rate (CCR).

Expressão de p53, p16 E COX-2 em carcinoma escamoso de esôfago e associação histopatológica p53, p16 E COX-2 expression in esophageal squamous cell carcinoma and histopathological association

Directory of Open Access Journals (Sweden)

Izabella Paz Danezi Felin

2008-12-01

Full Text Available RACIONAL: O câncer de esôfago representa cerca de 2% dos tumores malignos e a terceira causa mais comum de câncer do trato gastrointestinal. A associação do prognóstico do câncer de esôfago com alguns marcadores imunoistoquímicos, como as proteínas p53, p16 e a ciclooxigenase 2 (COX-2 tem sido relatada. A detecção de marcadores moleculares através de imunoistoquímica pode ser utilizada para avaliação prognóstica. OBJETIVOS: Investigar a associação entre a expressão das proteínas p53, p16 e a COX-2 com o estádio do carcinoma escamoso de esôfago. MÉTODOS: Foram analisadas 31 amostras de ressecção cirúrgica por esofagectomia diagnosticadas como carcinoma de células escamosas de esôfago e 31 amostras não-tumorais referentes a cada caso. Realizou-se a revisão histopatológica e o estádio pTNM. Amostras tumorais e não-tumorais adjacentes foram submetidas a análise imunoistoquímica para avaliar o conteúdo das proteínas p53, p16 e COX-2. Foi considerada positiva a expressão nuclear para p53 em quantidade igual ou superior a 10,00% das células e presença da expressão citoplasmática de acordo com três escores (1, 2, 3 de intensidade (leve, moderada, acentuada de imunocoloração para COX-2. RESULTADOS: Em área tumoral, as análises revelaram 48,38% de positividade para p53, 16,12% de positividade para p16, e 100,00% de positividade escores 1+, 2+ ou 3+ para COX-2. No entanto, quando se avaliou possível relação da expressão destes marcadores com o estádio, apenas a COX-2, escore 3+ intensidade acentuada mostraram associação significativa. CONCLUSÃO: O presente estudo demonstrou que existe relação positiva entre a expressão de COX-2, escore 3+ e estádio mais avançado no carcinoma de esôfago.BACKGROUND: The esophageal carcinoma represents about 2% of malignant tumors and is the third most common cause of gastrointestinal cancer. The correlation between immunohistochemistry markers, such as p53, p16

COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data

International Nuclear Information System (INIS)

Leng, Wei-Dong; Wen, Xiu-Jie; Kwong, Joey S. W.; Huang, Wei; Chen, Jian-Gang; Zeng, Xian-Tao

2016-01-01

Numerous case–control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. Finally 8 case–control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association

Hierarchical regression analysis in structural Equation Modeling

NARCIS (Netherlands)

de Jong, P.F.

1999-01-01

In a hierarchical or fixed-order regression analysis, the independent variables are entered into the regression equation in a prespecified order. Such an analysis is often performed when the extra amount of variance accounted for in a dependent variable by a specific independent variable is the main

Convergence of posteriors for discretized log Gaussian Cox processes

DEFF Research Database (Denmark)

Waagepetersen, Rasmus Plenge

2004-01-01

In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...... when the cell sizes of the discretization tends to zero. The effect of discretization is studied in a data example....

Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

Directory of Open Access Journals (Sweden)

Rita Ghosh

2007-11-01

Full Text Available We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB. Cyclooxygenase (Cox-2, a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2 and suppresses apoptosis. Treatment of LNCaP cells with NexrutineR reduced tumor necrosis factor α-induced enzymatic as well as promoter activities of Cox-2. NexrutineR also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating NexrutineR response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01. We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like NexrutineR, demonstrating a prospective for development of NexrutineR for prostate cancer management.

DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network.

Science.gov (United States)

Katzman, Jared L; Shaham, Uri; Cloninger, Alexander; Bates, Jonathan; Jiang, Tingting; Kluger, Yuval

2018-02-26

Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

OpenAIRE

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

2013-01-01

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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmaco...

Cox2 and β-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

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Jianping Kong

2011-09-01

Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis.

Science.gov (United States)

Kirkby, Nicholas S; Tesfai, Abel; Ahmetaj-Shala, Blerina; Gashaw, Hime H; Sampaio, Walkyria; Etelvino, Gisele; Leão, Nádia Miricéia; Santos, Robson A; Mitchell, Jane A

2016-12-01

Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their antiinflammatory effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused by blocking COX-2 in the vasculature and/or kidney, with our recent work implicating the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose effects can be prevented by l-arginine. The ibuprofen salt ibuprofen arginate (Spididol) was created to increase solubility but we suggest that it could also augment the NO pathway through codelivery of arginine. Here we investigated the idea that ibuprofen arginate can act to simultaneously inhibit COX-2 and preserve the NO pathway. Ibuprofen arginate functioned similarly to ibuprofen sodium for inhibition of mouse/human COX-2, but only ibuprofen arginate served as a substrate for NOS. Ibuprofen arginate but not ibuprofen sodium also reversed the inhibitory effects of ADMA and N G -nitro-l-arginine methyl ester on inducible NOS (macrophages) and endothelial NOS in vitro (aorta) and in vivo (blood pressure). These observations show that ibuprofen arginate provides, in one preparation, a COX-2 inhibitor and NOS substrate that could act to negate the harmful cardiovascular consequences mediated by blocking renal COX-2 and increased ADMA. While remarkably simple, our findings are potentially game-changing in the nonsteroidal antiinflammatory drug arena.-Kirkby, N. S., Tesfai, A., Ahmetaj-Shala, B., Gashaw, H. H., Sampaio, W., Etelvino, G., Leão, N. M., Santos, R. A., Mitchell, J. A. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis. © The Author(s).

Post-processing through linear regression

Science.gov (United States)

van Schaeybroeck, B.; Vannitsem, S.

2011-03-01

Various post-processing techniques are compared for both deterministic and ensemble forecasts, all based on linear regression between forecast data and observations. In order to evaluate the quality of the regression methods, three criteria are proposed, related to the effective correction of forecast error, the optimal variability of the corrected forecast and multicollinearity. The regression schemes under consideration include the ordinary least-square (OLS) method, a new time-dependent Tikhonov regularization (TDTR) method, the total least-square method, a new geometric-mean regression (GM), a recently introduced error-in-variables (EVMOS) method and, finally, a "best member" OLS method. The advantages and drawbacks of each method are clarified. These techniques are applied in the context of the 63 Lorenz system, whose model version is affected by both initial condition and model errors. For short forecast lead times, the number and choice of predictors plays an important role. Contrarily to the other techniques, GM degrades when the number of predictors increases. At intermediate lead times, linear regression is unable to provide corrections to the forecast and can sometimes degrade the performance (GM and the best member OLS with noise). At long lead times the regression schemes (EVMOS, TDTR) which yield the correct variability and the largest correlation between ensemble error and spread, should be preferred.

Cytotoxic of Ganoderma lucidum in Colon Cancer through Cyclooxygenase 2 (COX-2 as Its Molecular Target

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Agustina Setiawati

2017-05-01

Full Text Available Many studies were designed explore chemopreventive activity of natural products on colon cancer especially addressing COX-2 as molecular target. Another promising source of natural product that potentially exhibit anticancer activity on colon cancer is Ganoderma lucidum. This study assessed selectivity of cytotoxic effect of G. lucidum extract on WiDr to Vero cells and investigated molecular mechanism on COX-2. G. lucidum ex-tract was prepared by reflux extraction method; in vitro anticancer was assayed by MTT method on WiDr and Vero cell line. This study applied apoptosis induction assay to observe cell death mechanism using double staining method; further COX-2 expression was stained by immunocytochemistry method. G. lucidum extract has cytotoxic effect on WiDr cells with IC50 135 µg/mL. However, the cytotoxic effect had low selectivity to-wards Vero cells with Selectivity Index (SI 3.66. The extract induced apoptosis and suppressed COX-2 ex-pression in WiDr cells. G. lucidum extract was potential to be developed as anticancer agent towards colon cancer.

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

Science.gov (United States)

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.

Multivariate Product-Shot-noise Cox Point Process Models

DEFF Research Database (Denmark)

Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

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

Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

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Qiliu Peng

Full Text Available OBJECTIVE: Cyclooxygenase-2 (COX-2 is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs. RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004 and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004. In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for

Abstract Expression Grammar Symbolic Regression

Science.gov (United States)

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.

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

Science.gov (United States)

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)-κ 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

A novel, modernized Golgi-Cox stain optimized for CLARITY cleared tissue.

Science.gov (United States)

Kassem, Mustafa S; Fok, Sandra Y Y; Smith, Kristie L; Kuligowski, Michael; Balleine, Bernard W

2018-01-15

High resolution neuronal information is extraordinarily useful in understanding the brain's functionality. The development of the Golgi-Cox stain allowed observation of the neuron in its entirety with unrivalled detail. Tissue clearing techniques, e.g., CLARITY and CUBIC, provide the potential to observe entire neuronal circuits intact within tissue and without previous restrictions with regard to section thickness. Here we describe an improved Golgi-Cox stain method, optimised for use with CLARITY and CUBIC that can be used in both fresh and fixed tissue. Using this method, we were able to observe neurons in their entirety within a fraction of the time traditionally taken to clear tissue (48h). We were also able to show for the first-time that Golgi stained tissue is fluorescent when visualized using a multi-photon microscope, allowing us to image synaptic spines with a detail previously unachievable. These novel methods provide cheap and easy to use techniques to investigate the morphology of cellular processes in the brain at a new-found depth, speed, utility and detail, without previous restrictions of time, tissue type and section thickness. This is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain. Copyright © 2017 Elsevier B.V. All rights reserved.

Flurbiprofen : A non-selective cyclooxygenase (COX) inhibitor for treatment of non-infectious, non-necrotising anterior scleritis

Science.gov (United States)

Agrawal, Rupesh; Lee, Cecilia; Gonzalez-Lopez, Julio J.; Khan, Sharmina; Rodrigues, Valeria; Pavesio, Carlos

2016-01-01

Objective To analyse the safety and efficacy of a non-selective cyclo-oxygenase (COX) inhibitor in the management of non-infectious, non-necrotising anterior scleritis. Methods Retrospective chart review of 126 patients with non-necrotising anterior scleritis treated with oral flurbiprofen (Froben®(Abbott Healthcare)) with ( group B, n=61) or without topical steroids (group A, n=65) was performed and time to remission was plotted. Results The observed incidence rate was 1.07 (95% CI: 0.57–1.99) per 1000 person-years with failure rate of 0.68 (95% CI: 0.22–2.12) per 1000 person-years in group A and 1.41 (95% CI: 0.67–2.96) per 1000 person-years in group B. The failure rate was 3.97(1.89–9.34) per 1000 person-years with hazard ratio of 10.01 ( 95% CI: 2.52–39.65; p<0.001) for patients with associated systemic disease. Conclusion To our best knowledge, this is the first and largest case series on the safety and efficacy of a non-selective COX inhibitor in the management of anterior scleritis. PMID:26308394

Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

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Xinyun WANG

2010-02-01

Full Text Available Background and objective Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2, which can regulate growth, invasion and metastasis of tumor through relevant signaling pathway, have been detected in a variety of solid tumors. The aim of this study is to investigate the biological significance of EGFR and COX-2 expression in lung cancer and the relationship between them. Methods The expression of EGFR and COX-2 was detected in 89 primary lung cancer tissues, 12 premaliganant lesions, 12 lymph node metastases, and 10 normal lung tissues as the control by immunohistochemical method on a tissue microarray section. Results EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively, which were significantly higher than those of the control (P 0.05. COX-2 expression was related to gross type (P < 0.05. A highly positive correlation was observed between EGFR and COX-2 expression (P < 0.01. Conclusion Overexpression of EGFR and COX-2 may play an important role in the tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

Dual Regression

OpenAIRE

Spady, Richard; Stouli, Sami

2012-01-01

We propose dual regression as an alternative to the quantile regression process for the global estimation of conditional distribution functions under minimal assumptions. Dual regression provides all the interpretational power of the quantile regression process while avoiding the need for repairing the intersecting conditional quantile surfaces that quantile regression often produces in practice. Our approach introduces a mathematical programming characterization of conditional distribution f...

Analysis of the cytochrome c oxidase subunit 1 (COX1) gene reveals the unique evolution of the giant panda.

Science.gov (United States)

Hu, Yao-Dong; Pang, Hui-Zhong; Li, De-Sheng; Ling, Shan-Shan; Lan, Dan; Wang, Ye; Zhu, Yun; Li, Di-Yan; Wei, Rong-Ping; Zhang, He-Min; Wang, Cheng-Dong

2016-11-05

As the rate-limiting enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (COX) plays a crucial role in biological metabolism. "Living fossil" giant panda (Ailuropoda melanoleuca) is well-known for its special bamboo diet. In an effort to explore functional variation of COX1 in the energy metabolism behind giant panda's low-energy bamboo diet, we looked at genetic variation of COX1 gene in giant panda, and tested for its selection effect. In 1545 base pairs of the gene from 15 samples, 9 positions were variable and 1 mutation leaded to an amino acid sequence change. COX1 gene produces six haplotypes, nucleotide (pi), haplotype diversity (Hd). In addition, the average number of nucleotide differences (k) is 0.001629±0.001036, 0.8083±0.0694 and 2.517, respectively. Also, dN/dS ratio is significantly below 1. These results indicated that giant panda had a low population genetic diversity, and an obvious purifying selection of the COX1 gene which reduces synthesis of ATP determines giant panda's low-energy bamboo diet. Phylogenetic trees based on the COX1 gene were constructed to demonstrate that giant panda is the sister group of other Ursidae. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparison of back propagation and Generalized Regression Neural Networks performance in neutron spectrometry

International Nuclear Information System (INIS)

Martínez-Blanco, Ma. del Rosario

2016-01-01

The process of unfolding the neutron energy spectrum has been subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the research of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in neutron spectrometry and dosimetry domains, however, the structure and learning parameters are factors that highly impact in the networks performance. In ANN domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, requiring no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training on the development data. In the network development phase, the only hurdle is to optimize the hyper-parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained it can be observed that despite the very similar results, GRNN performs better than BPNN.

GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS.

Science.gov (United States)

Salgado, Flávio L L; Artigiani-Neto, Ricardo; Lopes-Filho, Gaspar de Jesus

2016-01-01

Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and

Refractive regression after laser in situ keratomileusis.

Science.gov (United States)

Yan, Mabel K; Chang, John Sm; Chan, Tommy Cy

2018-04-26

Uncorrected refractive errors are a leading cause of visual impairment across the world. In today's society, laser in situ keratomileusis (LASIK) has become the most commonly performed surgical procedure to correct refractive errors. However, regression of the initially achieved refractive correction has been a widely observed phenomenon following LASIK since its inception more than two decades ago. Despite technological advances in laser refractive surgery and various proposed management strategies, post-LASIK regression is still frequently observed and has significant implications for the long-term visual performance and quality of life of patients. This review explores the mechanism of refractive regression after both myopic and hyperopic LASIK, predisposing risk factors and its clinical course. In addition, current preventative strategies and therapies are also reviewed. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

[Analysis of COX1 sequences of Taenia isolates from four areas of Guangxi].

Science.gov (United States)

Yang, Yi-Chao; Ou-Yang, Yi; Su, Ai-Rong; Wan, Xiao-Ling; Li, Shu-Lin

2012-06-01

To analyze the COX1 sequences of Taenia isolates from four areas of Guangxi Zhuang Autonomous Region, and to understand the distribution of Taenia asiatica in Guangxi. Patients with taeniasis in Luzhai, Rongshui, Tiandong and Sanjiang in Guangxi were treated by deworming, and the Taenia isolates were collected. Cyclooxygenase-1 (COX1) sequences of these isolates were amplified by PCR, and the PCR products were sequenced by T-A clone sequencing. The homogeneities and genetic distances were calculated and analyzed, and the phylogenic trees were constructed by some softwares. Meanwhile, the COX1 sequences of the isolates from the 4 areas were compared separately with the sequences of Taenia species in GenBank. The COX1 sequence of the 5 Taenia isolates collected had the same length of 444 bp. There were 5 variable positions between the Luzhai isolate and Taenia asiatica, the homogeneity was 98.87% and their genetic distance was 0.011. The phylogenetic tree analysis revealed that the Luzhai isolate and Taenia asiatica locating at the same node had a close relationship. The homogeneity between Rongshui isolate A and Taenia solium was 100%, while the homogeneity of Rongshui isolate B with Taeniasis saginata and Taenia asiatica were 98.20% and 96.17%, respectively. The homogeneities of the Tiandong and Sanjiang isolates with Taenia solium were 99.55% and 96.40%, respectively, and the genetic distances were 0.005 and 0.037, respectively. The homogeneity between the Luzhai isolate and Taeniasis saginate was 96.40%. Taenia asiatica exists in Luzhai and Taenia solium and Taenia saginata coexist in Rongshui, Guangxi Zhuang Autonomous Region.

Dual Regulating Effect of Shaoyao-Gangcao-Tang on COX- 2 ...

African Journals Online (AJOL)

through the differential regulation of cell adhesion molecules and chemokines expression [9]. These data indicate that 15d-PGJ2 can tightly regulate the resolution of acute inflammation. As the key enzyme of regulating PGE2 generation, COX-2 has been thought to be a pro- inflammatory mediator. However, Gilroy et al [10].

Gaussian Process Regression Model in Spatial Logistic Regression

Science.gov (United States)

Sofro, A.; Oktaviarina, A.

2018-01-01

Spatial analysis has developed very quickly in the last decade. One of the favorite approaches is based on the neighbourhood of the region. Unfortunately, there are some limitations such as difficulty in prediction. Therefore, we offer Gaussian process regression (GPR) to accommodate the issue. In this paper, we will focus on spatial modeling with GPR for binomial data with logit link function. The performance of the model will be investigated. We will discuss the inference of how to estimate the parameters and hyper-parameters and to predict as well. Furthermore, simulation studies will be explained in the last section.

Transforming RNA-Seq data to improve the performance of prognostic gene signatures.

Science.gov (United States)

Zwiener, Isabella; Frisch, Barbara; Binder, Harald

2014-01-01

Gene expression measurements have successfully been used for building prognostic signatures, i.e for identifying a short list of important genes that can predict patient outcome. Mostly microarray measurements have been considered, and there is little advice available for building multivariable risk prediction models from RNA-Seq data. We specifically consider penalized regression techniques, such as the lasso and componentwise boosting, which can simultaneously consider all measurements and provide both, multivariable regression models for prediction and automated variable selection. However, they might be affected by the typical skewness, mean-variance-dependency or extreme values of RNA-Seq covariates and therefore could benefit from transformations of the latter. In an analytical part, we highlight preferential selection of covariates with large variances, which is problematic due to the mean-variance dependency of RNA-Seq data. In a simulation study, we compare different transformations of RNA-Seq data for potentially improving detection of important genes. Specifically, we consider standardization, the log transformation, a variance-stabilizing transformation, the Box-Cox transformation, and rank-based transformations. In addition, the prediction performance for real data from patients with kidney cancer and acute myeloid leukemia is considered. We show that signature size, identification performance, and prediction performance critically depend on the choice of a suitable transformation. Rank-based transformations perform well in all scenarios and can even outperform complex variance-stabilizing approaches. Generally, the results illustrate that the distribution and potential transformations of RNA-Seq data need to be considered as a critical step when building risk prediction models by penalized regression techniques.

Transforming RNA-Seq data to improve the performance of prognostic gene signatures.

Directory of Open Access Journals (Sweden)

Isabella Zwiener

Full Text Available Gene expression measurements have successfully been used for building prognostic signatures, i.e for identifying a short list of important genes that can predict patient outcome. Mostly microarray measurements have been considered, and there is little advice available for building multivariable risk prediction models from RNA-Seq data. We specifically consider penalized regression techniques, such as the lasso and componentwise boosting, which can simultaneously consider all measurements and provide both, multivariable regression models for prediction and automated variable selection. However, they might be affected by the typical skewness, mean-variance-dependency or extreme values of RNA-Seq covariates and therefore could benefit from transformations of the latter. In an analytical part, we highlight preferential selection of covariates with large variances, which is problematic due to the mean-variance dependency of RNA-Seq data. In a simulation study, we compare different transformations of RNA-Seq data for potentially improving detection of important genes. Specifically, we consider standardization, the log transformation, a variance-stabilizing transformation, the Box-Cox transformation, and rank-based transformations. In addition, the prediction performance for real data from patients with kidney cancer and acute myeloid leukemia is considered. We show that signature size, identification performance, and prediction performance critically depend on the choice of a suitable transformation. Rank-based transformations perform well in all scenarios and can even outperform complex variance-stabilizing approaches. Generally, the results illustrate that the distribution and potential transformations of RNA-Seq data need to be considered as a critical step when building risk prediction models by penalized regression techniques.

FREQFIT: Computer program which performs numerical regression and statistical chi-squared goodness of fit analysis

International Nuclear Information System (INIS)

Hofland, G.S.; Barton, C.C.

1990-01-01

The computer program FREQFIT is designed to perform regression and statistical chi-squared goodness of fit analysis on one-dimensional or two-dimensional data. The program features an interactive user dialogue, numerous help messages, an option for screen or line printer output, and the flexibility to use practically any commercially available graphics package to create plots of the program's results. FREQFIT is written in Microsoft QuickBASIC, for IBM-PC compatible computers. A listing of the QuickBASIC source code for the FREQFIT program, a user manual, and sample input data, output, and plots are included. 6 refs., 1 fig

Evaluation of Linear Regression Simultaneous Myoelectric Control Using Intramuscular EMG.

Science.gov (United States)

Smith, Lauren H; Kuiken, Todd A; Hargrove, Levi J

2016-04-01

The objective of this study was to evaluate the ability of linear regression models to decode patterns of muscle coactivation from intramuscular electromyogram (EMG) and provide simultaneous myoelectric control of a virtual 3-DOF wrist/hand system. Performance was compared to the simultaneous control of conventional myoelectric prosthesis methods using intramuscular EMG (parallel dual-site control)-an approach that requires users to independently modulate individual muscles in the residual limb, which can be challenging for amputees. Linear regression control was evaluated in eight able-bodied subjects during a virtual Fitts' law task and was compared to performance of eight subjects using parallel dual-site control. An offline analysis also evaluated how different types of training data affected prediction accuracy of linear regression control. The two control systems demonstrated similar overall performance; however, the linear regression method demonstrated improved performance for targets requiring use of all three DOFs, whereas parallel dual-site control demonstrated improved performance for targets that required use of only one DOF. Subjects using linear regression control could more easily activate multiple DOFs simultaneously, but often experienced unintended movements when trying to isolate individual DOFs. Offline analyses also suggested that the method used to train linear regression systems may influence controllability. Linear regression myoelectric control using intramuscular EMG provided an alternative to parallel dual-site control for 3-DOF simultaneous control at the wrist and hand. The two methods demonstrated different strengths in controllability, highlighting the tradeoff between providing simultaneous control and the ability to isolate individual DOFs when desired.

Correlation analysis between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer.

Science.gov (United States)

Qiu, Xiaoming; Mei, Jixin; Yin, Jianjun; Wang, Hong; Wang, Jinqi; Xie, Ming

2017-09-01

This study investigated expression of proliferating cell nuclear antigen (PCNA), proliferation-associated nuclear antigen (Ki-67) and cyclooxygenase-2 (COX-2) in tissues of breast invasive ductal carcinoma, and analyzed the correlations between these indexes and X-ray features in mammography. A total of 90 patients who were admitted to Huangshi Central Hospital and diagnosed as breast invasive ductal carcinoma from January 2014 to January 2016 were selected. The expression of PCNA, Ki-67 and COX-2 in cancer tissues and cancer-adjacent normal tissues of patients were detected by immunohistochemical staining, and X-ray features in mammography of patients were observed. By using Spearman correlation analysis, the correlations between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer were investigated. As a result, the positive expression rates of PCNA, Ki-67 and COX-2 in cancer tissues of the patient groups were respectively 42.2, 45.6 and 51.1%, which were significantly higher than those in cancer-adjacent normal tissues of the control group (pcorrelation with age and tumor size (p>0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group had no correlation with the existence of lumps and localized density-increased shadows (p>0.05), but were associated with manifestations of architectural distortion, calcification as well as skin and nipple depression (pcorrelation analysis revealed that there was a significantly positive correlation between the expression of PCNA and COX-2 in cancer tissues of the patient group (r=0.676, pcorrelation between the expression of Ki-67 and COX-2 (r=0.724, pcorrelation with the expression of Ki-67 (p>0.05). In conclusion, PCNA, Ki-67 and COX-2 expression is of great significance in the occurrence, invasion and metastasis of breast invasive ductal carcinoma. There is a strong correlation between PCNA, Ki-67 and COX-2 expression levels and X-ray features in mammography in breast

Post-processing through linear regression

Directory of Open Access Journals (Sweden)

B. Van Schaeybroeck

2011-03-01

Full Text Available Various post-processing techniques are compared for both deterministic and ensemble forecasts, all based on linear regression between forecast data and observations. In order to evaluate the quality of the regression methods, three criteria are proposed, related to the effective correction of forecast error, the optimal variability of the corrected forecast and multicollinearity. The regression schemes under consideration include the ordinary least-square (OLS method, a new time-dependent Tikhonov regularization (TDTR method, the total least-square method, a new geometric-mean regression (GM, a recently introduced error-in-variables (EVMOS method and, finally, a "best member" OLS method. The advantages and drawbacks of each method are clarified.

These techniques are applied in the context of the 63 Lorenz system, whose model version is affected by both initial condition and model errors. For short forecast lead times, the number and choice of predictors plays an important role. Contrarily to the other techniques, GM degrades when the number of predictors increases. At intermediate lead times, linear regression is unable to provide corrections to the forecast and can sometimes degrade the performance (GM and the best member OLS with noise. At long lead times the regression schemes (EVMOS, TDTR which yield the correct variability and the largest correlation between ensemble error and spread, should be preferred.

Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System.

Science.gov (United States)

Chojnacka, Magdalena; Gornicka, Agnieszka; Oeljeklaus, Silke; Warscheid, Bettina; Chacinska, Agnieszka

2015-06-12

The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity. This interaction does not involve Sco1, a partner of Cox17 in transferring copper ions to cytochrome c oxidase. However, the Cox17-MICOS interaction is regulated by copper ions. We propose that Cox17 is a newly identified factor involved in maintaining the architecture of the MICOS complex. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Bayesian ARTMAP for regression.

Science.gov (United States)

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regression of environmental noise in LIGO data

International Nuclear Information System (INIS)

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

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 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. (paper)

COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

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Petasis Nicos A

2008-05-01

Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

Significance testing in ridge regression for genetic data

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De Iorio Maria

2011-09-01

Full Text Available Abstract Background Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. Results We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. Conclusions The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible.

-765 G>C POLYMORPHISM OF THE COX-2 GENE AND GASTRIC CANCER RISK IN BRAZILIAN POPULATION

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Vanessa Maria de Lima Pazine CAMPANHOLO

2014-04-01

Full Text Available Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033. A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90. Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

Performance and separation occurrence of binary probit regression estimator using maximum likelihood method and Firths approach under different sample size

Science.gov (United States)

Lusiana, Evellin Dewi

2017-12-01

The parameters of binary probit regression model are commonly estimated by using Maximum Likelihood Estimation (MLE) method. However, MLE method has limitation if the binary data contains separation. Separation is the condition where there are one or several independent variables that exactly grouped the categories in binary response. It will result the estimators of MLE method become non-convergent, so that they cannot be used in modeling. One of the effort to resolve the separation is using Firths approach instead. This research has two aims. First, to identify the chance of separation occurrence in binary probit regression model between MLE method and Firths approach. Second, to compare the performance of binary probit regression model estimator that obtained by MLE method and Firths approach using RMSE criteria. Those are performed using simulation method and under different sample size. The results showed that the chance of separation occurrence in MLE method for small sample size is higher than Firths approach. On the other hand, for larger sample size, the probability decreased and relatively identic between MLE method and Firths approach. Meanwhile, Firths estimators have smaller RMSE than MLEs especially for smaller sample sizes. But for larger sample sizes, the RMSEs are not much different. It means that Firths estimators outperformed MLE estimator.

Quantile Regression With Measurement Error

KAUST Repository

Wei, Ying; Carroll, Raymond J.

2009-01-01

. The finite sample performance of the proposed method is investigated in a simulation study, and compared to the standard regression calibration approach. Finally, we apply our methodology to part of the National Collaborative Perinatal Project growth data, a

Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.

Science.gov (United States)

Yang, Cheng-Chieh; Tu, Hsi-Feng; Wu, Cheng-Hsien; Chang, Hsiu-Chuan; Chiang, Wei-Fan; Shih, Nai-Chia; Lee, Yong-Syu; Kao, Shou-Yen; Chang, Kuo-Wei

2016-05-01

When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages

International Nuclear Information System (INIS)

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

2013-01-01

Highlights: •Downregulation of RXRα in senescent macrophage. •RXRα suppresses NF-κB activity and COX2 expression. •Increased PGE2 production due to downregulation of RXRα. -- 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 RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, TNF-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases

Performance regression manager for large scale systems

Science.gov (United States)

Faraj, Daniel A.

2017-08-01

System and computer program product to perform an operation comprising generating, based on a first output generated by a first execution instance of a command, a first output file specifying a value of at least one performance metric, wherein the first output file is formatted according to a predefined format, comparing the value of the at least one performance metric in the first output file to a value of the performance metric in a second output file, the second output file having been generated based on a second output generated by a second execution instance of the command, and outputting for display an indication of a result of the comparison of the value of the at least one performance metric of the first output file to the value of the at least one performance metric of the second output file.

Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells.

Directory of Open Access Journals (Sweden)

Tiziana Angrisano

Full Text Available Bacterial lipopolysaccharide (LPS induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3, methylation (H3K4, H3K9, H3K27 and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.

Modeling Personalized Email Prioritization: Classification-based and Regression-based Approaches

Energy Technology Data Exchange (ETDEWEB)

Yoo S.; Yang, Y.; Carbonell, J.

2011-10-24

Email overload, even after spam filtering, presents a serious productivity challenge for busy professionals and executives. One solution is automated prioritization of incoming emails to ensure the most important are read and processed quickly, while others are processed later as/if time permits in declining priority levels. This paper presents a study of machine learning approaches to email prioritization into discrete levels, comparing ordinal regression versus classier cascades. Given the ordinal nature of discrete email priority levels, SVM ordinal regression would be expected to perform well, but surprisingly a cascade of SVM classifiers significantly outperforms ordinal regression for email prioritization. In contrast, SVM regression performs well -- better than classifiers -- on selected UCI data sets. This unexpected performance inversion is analyzed and results are presented, providing core functionality for email prioritization systems.

Forecasting Uncertainty in Electricity Smart Meter Data by Boosting Additive Quantile Regression

KAUST Repository

Taieb, Souhaib Ben

2016-03-02

Smart electricity meters are currently deployed in millions of households to collect detailed individual electricity consumption data. Compared with traditional electricity data based on aggregated consumption, smart meter data are much more volatile and less predictable. There is a need within the energy industry for probabilistic forecasts of household electricity consumption to quantify the uncertainty of future electricity demand in order to undertake appropriate planning of generation and distribution. We propose to estimate an additive quantile regression model for a set of quantiles of the future distribution using a boosting procedure. By doing so, we can benefit from flexible and interpretable models, which include an automatic variable selection. We compare our approach with three benchmark methods on both aggregated and disaggregated scales using a smart meter data set collected from 3639 households in Ireland at 30-min intervals over a period of 1.5 years. The empirical results demonstrate that our approach based on quantile regression provides better forecast accuracy for disaggregated demand, while the traditional approach based on a normality assumption (possibly after an appropriate Box-Cox transformation) is a better approximation for aggregated demand. These results are particularly useful since more energy data will become available at the disaggregated level in the future.

Semisupervised Clustering by Iterative Partition and Regression with Neuroscience Applications

Directory of Open Access Journals (Sweden)

Guoqi Qian

2016-01-01

Full Text Available Regression clustering is a mixture of unsupervised and supervised statistical learning and data mining method which is found in a wide range of applications including artificial intelligence and neuroscience. It performs unsupervised learning when it clusters the data according to their respective unobserved regression hyperplanes. The method also performs supervised learning when it fits regression hyperplanes to the corresponding data clusters. Applying regression clustering in practice requires means of determining the underlying number of clusters in the data, finding the cluster label of each data point, and estimating the regression coefficients of the model. In this paper, we review the estimation and selection issues in regression clustering with regard to the least squares and robust statistical methods. We also provide a model selection based technique to determine the number of regression clusters underlying the data. We further develop a computing procedure for regression clustering estimation and selection. Finally, simulation studies are presented for assessing the procedure, together with analyzing a real data set on RGB cell marking in neuroscience to illustrate and interpret the method.

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

Science.gov (United States)

Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

Wavelet regression model in forecasting crude oil price

Science.gov (United States)

Hamid, Mohd Helmie; Shabri, Ani

2017-05-01

This study presents the performance of wavelet multiple linear regression (WMLR) technique in daily crude oil forecasting. WMLR model was developed by integrating the discrete wavelet transform (DWT) and multiple linear regression (MLR) model. The original time series was decomposed to sub-time series with different scales by wavelet theory. Correlation analysis was conducted to assist in the selection of optimal decomposed components as inputs for the WMLR model. The daily WTI crude oil price series has been used in this study to test the prediction capability of the proposed model. The forecasting performance of WMLR model were also compared with regular multiple linear regression (MLR), Autoregressive Moving Average (ARIMA) and Generalized Autoregressive Conditional Heteroscedasticity (GARCH) using root mean square errors (RMSE) and mean absolute errors (MAE). Based on the experimental results, it appears that the WMLR model performs better than the other forecasting technique tested in this study.

Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study.

Science.gov (United States)

Chlapek, Petr; Redova, Martina; Zitterbart, Karel; Hermanova, Marketa; Sterba, Jaroslav; Veselska, Renata

2010-05-11

We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA) and inhibitors of lipoxygenases (LOX) and cyclooxygenases (COX). This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2) or SH-SY5Y) after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX) in combination with ATRA in both cell lines. Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

A comparison of back propagation and Generalized Regression Neural Networks performance in neutron spectrometry.

Science.gov (United States)

Martínez-Blanco, Ma Del Rosario; Ornelas-Vargas, Gerardo; Solís-Sánchez, Luis Octavio; Castañeda-Miranada, Rodrigo; Vega-Carrillo, Héctor René; Celaya-Padilla, José M; Garza-Veloz, Idalia; Martínez-Fierro, Margarita; Ortiz-Rodríguez, José Manuel

2016-11-01

The process of unfolding the neutron energy spectrum has been subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the research of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in neutron spectrometry and dosimetry domains, however, the structure and learning parameters are factors that highly impact in the networks performance. In ANN domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, requiring no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training on the development data. In the network development phase, the only hurdle is to optimize the hyper-parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained it can be observed that despite the very similar results, GRNN performs better than BPNN. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comparison of back propagation and generalized regression neural networks performance in neutron spectrometry

International Nuclear Information System (INIS)

Ortiz R, J. M.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R.; Vega C, H. R.

2015-10-01

The process of unfolding the neutron energy spectrum has been the subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in the neutron spectrometry and dosimetry domains, however, the structure and the learning parameters are factors that contribute in a significant way in the networks performance. In artificial neural network domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, which mean require no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training with the development data. In the network development phase, the only hurdle is to tune the hyper parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained can be observed that despite the very similar results, GRNN performs better than BPNN. (Author)

A comparison of back propagation and generalized regression neural networks performance in neutron spectrometry

Energy Technology Data Exchange (ETDEWEB)

Ortiz R, J. M.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R. [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Av. Ramon Lopez Velarde 801, Col. Centro, 98000 Zacatecas, Zac. (Mexico); Vega C, H. R., E-mail: morvymm@yahoo.com.mx [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)

2015-10-15

The process of unfolding the neutron energy spectrum has been the subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in the neutron spectrometry and dosimetry domains, however, the structure and the learning parameters are factors that contribute in a significant way in the networks performance. In artificial neural network domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, which mean require no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training with the development data. In the network development phase, the only hurdle is to tune the hyper parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained can be observed that despite the very similar results, GRNN performs better than BPNN. (Author)

Estimation in the positive stable shared frailty Cox proportional hazards model

DEFF Research Database (Denmark)

Martinussen, Torben; Pipper, Christian Bressen

2005-01-01

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

Increased evidence for the prognostic value of primary tumor asphericity in pretherapeutic FDG PET for risk stratification in patients with head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Hofheinz, Frank; Lougovski, Alexandr [Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Dresden (Germany); Zoephel, Klaus; Hentschel, Maria [University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Nuclear Medicine, Dresden (Germany); Steffen, Ingo G.; Wedel, Florian; Buchert, Ralph; Brenner, Winfried [Charite - Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Apostolova, Ivayla [Universitaetsklinikum Magdeburg A.oe.R., Klinik fuer Radiologie und Nuklearmedizin, Magdeburg (Germany); Baumann, Michael [University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); OncoRay - National Center for Radiation Research in Oncology, Dresden (Germany); Institute of Radiooncology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Kotzerke, Joerg; Hoff, Joerg van den [Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Dresden (Germany); University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Nuclear Medicine, Dresden (Germany)

2014-11-22

In a previous study, we demonstrated the first evidence that the asphericity (ASP) of pretherapeutic FDG uptake in the primary tumor provides independent prognostic information in patients with head and neck cancer. The aim of this work was to confirm these results in an independent patient group examined at a different site. FDG-PET/CT was performed in 37 patients. The primary tumor was delineated by an automatic algorithm based on adaptive thresholding. For the resulting ROIs, the metabolically active part of the tumor (MTV), SUV{sub max}, SUV{sub mean}, total lesion glycolysis (TLG) and ASP were computed. Univariate Cox regression with respect to progression free survival (PFS) and overall survival (OS) was performed. For survival analysis, patients were divided in groups of high and low risk according to the parameter cut-offs defined in our previous work. In a second step, the cut-offs were adjusted to the present data. Univariate and multivariate Cox regression was performed for the pooled data consisting of the current and the previously described patient group (N = 68). In multivariate Cox regression, clinically relevant parameters were included. Univariate Cox regression using the previously published cut-off values revealed TLG (hazard ratio (HR) = 3) and ASP (HR = 3) as significant predictors for PFS. For OS MTV (HR = 2.7) and ASP (HR = 5.9) were significant predictors. Using the adjusted cutoffs MTV (HR = 2.9/3.3), TLG (HR = 3.1/3.3) and ASP (HR = 3.1/5.9) were prognostic for PFS/OS. In the pooled data, multivariate Cox regression revealed a significant prognostic value with respect to PFS/OS for MTV (HR = 2.3/2.1), SUV{sub max} (HR = 2.1/2.5), TLG (HR = 3.5/3.6), and ASP (HR = 3.4/4.4). Our results confirm the independent prognostic value of ASP of the pretherapeutic FDG uptake in the primary tumor in patients with head and neck cancer. Moreover, these results demonstrate that ASP can be determined unambiguously across different sites. (orig.)

COX-2 Gene Promoter Polymorphism and Coronary Artery Disease in Middle-Aged Men: The Helsinki Sudden Death Study

Directory of Open Access Journals (Sweden)

Kati H. Huuskonen

2008-01-01

Full Text Available Cyclooxygenase (COX catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the −765G→C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300 comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024 and a higher number of coronary arteries that had over 50% stenosis (P = .036 compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.

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

Science.gov (United States)

Pal, Suvra; Balakrishnan, Narayanaswamy

2018-05-01

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

Linear regression and sensitivity analysis in nuclear reactor design

International Nuclear Information System (INIS)

Kumar, Akansha; Tsvetkov, Pavel V.; McClarren, Ryan G.

2015-01-01

Highlights: • Presented a benchmark for the applicability of linear regression to complex systems. • Applied linear regression to a nuclear reactor power system. • Performed neutronics, thermal–hydraulics, and energy conversion using Brayton’s cycle for the design of a GCFBR. • Performed detailed sensitivity analysis to a set of parameters in a nuclear reactor power system. • Modeled and developed reactor design using MCNP, regression using R, and thermal–hydraulics in Java. - Abstract: The paper presents a general strategy applicable for sensitivity analysis (SA), and uncertainity quantification analysis (UA) of parameters related to a nuclear reactor design. This work also validates the use of linear regression (LR) for predictive analysis in a nuclear reactor design. The analysis helps to determine the parameters on which a LR model can be fit for predictive analysis. For those parameters, a regression surface is created based on trial data and predictions are made using this surface. A general strategy of SA to determine and identify the influential parameters those affect the operation of the reactor is mentioned. Identification of design parameters and validation of linearity assumption for the application of LR of reactor design based on a set of tests is performed. The testing methods used to determine the behavior of the parameters can be used as a general strategy for UA, and SA of nuclear reactor models, and thermal hydraulics calculations. A design of a gas cooled fast breeder reactor (GCFBR), with thermal–hydraulics, and energy transfer has been used for the demonstration of this method. MCNP6 is used to simulate the GCFBR design, and perform the necessary criticality calculations. Java is used to build and run input samples, and to extract data from the output files of MCNP6, and R is used to perform regression analysis and other multivariate variance, and analysis of the collinearity of data

Higher aluminum concentration in Alzheimer's disease after Box-Cox data transformation.

Science.gov (United States)

Rusina, Robert; Matěj, Radoslav; Kašparová, Lucie; Kukal, Jaromír; Urban, Pavel

2011-11-01

Evidence regarding the role of mercury and aluminum in the pathogenesis of Alzheimer's disease (AD) remains controversial. The aims of our project were to investigate the content of the selected metals in brain tissue samples and the use of a specific mathematical transform to eliminate the disadvantage of a strong positive skew in the original data distribution. In this study, we used atomic absorption spectrophotometry to determine mercury and aluminum concentrations in the hippocampus and associative visual cortex of 29 neuropathologically confirmed AD and 27 age-matched controls. The Box-Cox data transformation was used for statistical evaluation. AD brains had higher mean aluminum concentrations in the hippocampus than controls (0.357 vs. 0.090 μg/g; P = 0.039) after data transformation. Results for mercury were not significant. Original data regarding microelement concentrations are heavily skewed and do not pass the normality test in general. A Box-Cox transformation can eliminate this disadvantage and allow parametric testing.

Regression: A Bibliography.

Science.gov (United States)

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.…

The Application of CPA to Calculations of the Mean Magnetic Moment in the Gd1-xNi, Gd1-xFe, Gd1xCox, and Y1-xCox Intermetallic Compounds

DEFF Research Database (Denmark)

Szpunar, B.; Kozarzewski, B.

1977-01-01

with a narrow d-band is considered. The magnetic moment of the alloy at zero temperature is calculated within the molecular field and Hartree-Fock approximations. Disorder is treated in the coherent potential approximation. Results are in good agreement with the experimental data obtained for the crystalline......Calculations are made of the mean magnetic moment per atom of the transition metal and the rare-earth metal in the intermetallic compounds, Gd1-x,Nix, Gd1-x Fex, Gd1-x Cox, and Y1-x Cox. A simple model of the disordered alloy consisting of spins localized on the rare-earth atoms and interacting...

Impact of multicollinearity on small sample hydrologic regression models

Science.gov (United States)

Kroll, Charles N.; Song, Peter

2013-06-01

Often hydrologic regression models are developed with ordinary least squares (OLS) procedures. The use of OLS with highly correlated explanatory variables produces multicollinearity, which creates highly sensitive parameter estimators with inflated variances and improper model selection. It is not clear how to best address multicollinearity in hydrologic regression models. Here a Monte Carlo simulation is developed to compare four techniques to address multicollinearity: OLS, OLS with variance inflation factor screening (VIF), principal component regression (PCR), and partial least squares regression (PLS). The performance of these four techniques was observed for varying sample sizes, correlation coefficients between the explanatory variables, and model error variances consistent with hydrologic regional regression models. The negative effects of multicollinearity are magnified at smaller sample sizes, higher correlations between the variables, and larger model error variances (smaller R2). The Monte Carlo simulation indicates that if the true model is known, multicollinearity is present, and the estimation and statistical testing of regression parameters are of interest, then PCR or PLS should be employed. If the model is unknown, or if the interest is solely on model predictions, is it recommended that OLS be employed since using more complicated techniques did not produce any improvement in model performance. A leave-one-out cross-validation case study was also performed using low-streamflow data sets from the eastern United States. Results indicate that OLS with stepwise selection generally produces models across study regions with varying levels of multicollinearity that are as good as biased regression techniques such as PCR and PLS.

Photovoltaic Array Condition Monitoring Based on Online Regression of Performance Model

DEFF Research Database (Denmark)

Spataru, Sergiu; Sera, Dezso; Kerekes, Tamas

2013-01-01

regression modeling, from PV array production, plane-of-array irradiance, and module temperature measurements, acquired during an initial learning phase of the system. After the model has been parameterized automatically, the condition monitoring system enters the normal operation phase, where...

Advanced statistics: linear regression, part I: simple linear regression.

Science.gov (United States)

Marill, Keith A

2004-01-01

Simple linear regression is a mathematical technique used to model the relationship between a single independent predictor variable and a single dependent outcome variable. In this, the first of a two-part series exploring concepts in linear regression analysis, the four fundamental assumptions and the mechanics of simple linear regression are reviewed. The most common technique used to derive the regression line, the method of least squares, is described. The reader will be acquainted with other important concepts in simple linear regression, including: variable transformations, dummy variables, relationship to inference testing, and leverage. Simplified clinical examples with small datasets and graphic models are used to illustrate the points. This will provide a foundation for the second article in this series: a discussion of multiple linear regression, in which there are multiple predictor variables.

ST6Gal1, Cox-2 and HB-EGF mRNA Expression in Breast Cancer

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Aliakbar Taherian

2015-01-01

Full Text Available Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student's t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040, Cox- 2 (P= 0.001 and HB-EGF (P= 0.009 in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001. There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis.

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

Science.gov (United States)

Gong, Xiajing; Hu, Meng; Zhao, Liang

2018-05-01

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

International Nuclear Information System (INIS)

Kang, Ju-Hee; Song, Ki-Hoon; Jeong, Kyung-Chae; Kim, Sunshin; Choi, Changsun; Lee, Chang Hoon; Oh, Seung Hyun

2011-01-01

A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

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Xiangshu Xian

2016-11-01

Full Text Available Background: Cannabinoids (the active components of Cannabis sativa and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN was associated with gastric cancer (GC metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2 expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

A duplicated coxI gene is associated with cytoplasmic male sterility ...

Indian Academy of Sciences (India)

In plants where male sterility broke down under high temperature during the later part of the growing season, the 2.4 kb coxI transcript was absent, which ... Institute, New Delhi 110012, India; Directorate of Oilseeds Research, Hyderabad, 500030, India; Department of Plant Sciences, University of Hyderabad, 500046, India ...

A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression

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María de la Luz García-Hernández

2017-05-01

Full Text Available ObjectiveMultiple solid cancers contain tertiary lymphoid organs (TLO. However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function.MethodsWe used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17, tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg, T bet+ Th1 cells, granzyme B+ cytotoxic cells, and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV, stromal cells, which promote prostate tumor growth or are critical components of tumor-associated TLO.ResultsGenerally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2. Finally, consistent with tumor regression, prostate stem cell antigen was

Research and analyze of physical health using multiple regression analysis

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T. S. Kyi

2014-01-01

Full Text Available This paper represents the research which is trying to create a mathematical model of the "healthy people" using the method of regression analysis. The factors are the physical parameters of the person (such as heart rate, lung capacity, blood pressure, breath holding, weight height coefficient, flexibility of the spine, muscles of the shoulder belt, abdominal muscles, squatting, etc.., and the response variable is an indicator of physical working capacity. After performing multiple regression analysis, obtained useful multiple regression models that can predict the physical performance of boys the aged of fourteen to seventeen years. This paper represents the development of regression model for the sixteen year old boys and analyzed results.

Learning a Nonnegative Sparse Graph for Linear Regression.

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Fang, Xiaozhao; Xu, Yong; Li, Xuelong; Lai, Zhihui; Wong, Wai Keung

2015-09-01

Previous graph-based semisupervised learning (G-SSL) methods have the following drawbacks: 1) they usually predefine the graph structure and then use it to perform label prediction, which cannot guarantee an overall optimum and 2) they only focus on the label prediction or the graph structure construction but are not competent in handling new samples. To this end, a novel nonnegative sparse graph (NNSG) learning method was first proposed. Then, both the label prediction and projection learning were integrated into linear regression. Finally, the linear regression and graph structure learning were unified within the same framework to overcome these two drawbacks. Therefore, a novel method, named learning a NNSG for linear regression was presented, in which the linear regression and graph learning were simultaneously performed to guarantee an overall optimum. In the learning process, the label information can be accurately propagated via the graph structure so that the linear regression can learn a discriminative projection to better fit sample labels and accurately classify new samples. An effective algorithm was designed to solve the corresponding optimization problem with fast convergence. Furthermore, NNSG provides a unified perceptiveness for a number of graph-based learning methods and linear regression methods. The experimental results showed that NNSG can obtain very high classification accuracy and greatly outperforms conventional G-SSL methods, especially some conventional graph construction methods.

AN APPLICATION OF FUNCTIONAL MULTIVARIATE REGRESSION MODEL TO MULTICLASS CLASSIFICATION

OpenAIRE

Krzyśko, Mirosław; Smaga, Łukasz

2017-01-01

In this paper, the scale response functional multivariate regression model is considered. By using the basis functions representation of functional predictors and regression coefficients, this model is rewritten as a multivariate regression model. This representation of the functional multivariate regression model is used for multiclass classification for multivariate functional data. Computational experiments performed on real labelled data sets demonstrate the effectiveness of the proposed ...

Using Dominance Analysis to Determine Predictor Importance in Logistic Regression

Science.gov (United States)

Azen, Razia; Traxel, Nicole

2009-01-01

This article proposes an extension of dominance analysis that allows researchers to determine the relative importance of predictors in logistic regression models. Criteria for choosing logistic regression R[superscript 2] analogues were determined and measures were selected that can be used to perform dominance analysis in logistic regression. A…

2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells

OpenAIRE

Messner, Maria C.; Albert, Carolyn J.; Ford, David A.

2008-01-01

2-Chlorohexadecanal (2-ClHDA), a 16-carbon chain chlorinated fatty aldehyde that is produced by reactive chlorinating species attack of plasmalogens, is elevated in atherosclerotic plaques, infarcted myocardium, and activated leukocytes. We tested the hypothesis that 2-ClHDA and its metabolites, 2-chlorohexadecanoic acid (2-ClHA) and 2-chlorohexadecanol (2-ClHOH), induce COX-2 expression in human coronary artery endothelial cells (HCAEC). COX-2 protein expression increased in response to 2-Cl...

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

DEFF Research Database (Denmark)

Møller, Jesper; Diaz-Avalos, Carlos

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

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

DEFF Research Database (Denmark)

Møller, Jesper; Diaz-Avalos, Carlos

2010-01-01

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

A land use regression model for ambient ultrafine particles in Montreal, Canada: A comparison of linear regression and a machine learning approach.

Science.gov (United States)

Weichenthal, Scott; Ryswyk, Keith Van; Goldstein, Alon; Bagg, Scott; Shekkarizfard, Maryam; Hatzopoulou, Marianne

2016-04-01

Existing evidence suggests that ambient ultrafine particles (UFPs) (regression model for UFPs in Montreal, Canada using mobile monitoring data collected from 414 road segments during the summer and winter months between 2011 and 2012. Two different approaches were examined for model development including standard multivariable linear regression and a machine learning approach (kernel-based regularized least squares (KRLS)) that learns the functional form of covariate impacts on ambient UFP concentrations from the data. The final models included parameters for population density, ambient temperature and wind speed, land use parameters (park space and open space), length of local roads and rail, and estimated annual average NOx emissions from traffic. The final multivariable linear regression model explained 62% of the spatial variation in ambient UFP concentrations whereas the KRLS model explained 79% of the variance. The KRLS model performed slightly better than the linear regression model when evaluated using an external dataset (R(2)=0.58 vs. 0.55) or a cross-validation procedure (R(2)=0.67 vs. 0.60). In general, our findings suggest that the KRLS approach may offer modest improvements in predictive performance compared to standard multivariable linear regression models used to estimate spatial variations in ambient UFPs. However, differences in predictive performance were not statistically significant when evaluated using the cross-validation procedure. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Lisa Y Pang

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

A recombination point is conserved in the mitochondrial genome of higher plant species and located downstream from the cox2 pseudogene in Solanum tuberosum L.

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Susely F.S. Tada

2006-01-01

Full Text Available The potato (Solanum tuberosum L. mitochondrial cox3/sdh4/pseudo-cox2 gene cluster has previously been identified by heterologous hybridization using a Marchantia polymorpha sdh4 probe. In our present study we used Southern blotting using sdh4 and cox2 probes to show that the sdh4 and cox2 genes are clustered in the mitochondria of potato, soybean and pea. Northern blotting revealed cotranscription of sdh4 and cox2 in potato but not in cauliflower, indicating that these genes are not clustered in cauliflower. A putative recombination point was detected downstream of the cox2 pseudogene (pseudo-cox2 in potato mitochondrial DNA (mtDNA. This sequence corresponds to a 32 bp sequence which appears to be well-conserved and is adjacent to the terminals of some mitochondrial genes in Citrullus lanatus, Beta vulgaris and Arabidopsis thaliana and is probably involved in the genic rearrangements. It is possible the potato mtDNA pseudo-cox2 gene was generated by recombination during evolution in the same way as that of several other mitochondrial genes and remains as an inactive partial copy of the functional cox2 which was also detected in potato mtDNA.

A comparison of the performances of an artificial neural network and a regression model for GFR estimation.

Science.gov (United States)

Liu, Xun; Li, Ning-shan; Lv, Lin-sheng; Huang, Jian-hua; Tang, Hua; Chen, Jin-xia; Ma, Hui-juan; Wu, Xiao-ming; Lou, Tan-qi

2013-12-01

Accurate estimation of glomerular filtration rate (GFR) is important in clinical practice. Current models derived from regression are limited by the imprecision of GFR estimates. We hypothesized that an artificial neural network (ANN) might improve the precision of GFR estimates. A study of diagnostic test accuracy. 1,230 patients with chronic kidney disease were enrolled, including the development cohort (n=581), internal validation cohort (n=278), and external validation cohort (n=371). Estimated GFR (eGFR) using a new ANN model and a new regression model using age, sex, and standardized serum creatinine level derived in the development and internal validation cohort, and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2009 creatinine equation. Measured GFR (mGFR). GFR was measured using a diethylenetriaminepentaacetic acid renal dynamic imaging method. Serum creatinine was measured with an enzymatic method traceable to isotope-dilution mass spectrometry. In the external validation cohort, mean mGFR was 49±27 (SD) mL/min/1.73 m2 and biases (median difference between mGFR and eGFR) for the CKD-EPI, new regression, and new ANN models were 0.4, 1.5, and -0.5 mL/min/1.73 m2, respectively (P30% from mGFR) were 50.9%, 77.4%, and 78.7%, respectively (Psource of systematic bias in comparisons of new models to CKD-EPI, and both the derivation and validation cohorts consisted of a group of patients who were referred to the same institution. An ANN model using 3 variables did not perform better than a new regression model. Whether ANN can improve GFR estimation using more variables requires further investigation. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

Science.gov (United States)

Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

2015-11-01

Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2017-07-19

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

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

Directory of Open Access Journals (Sweden)

Yusuke Yamaguchi

2017-07-01

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

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

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

2015-08-01

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

The Chaotic Prediction for Aero-Engine Performance Parameters Based on Nonlinear PLS Regression

Directory of Open Access Journals (Sweden)

Chunxiao Zhang

2012-01-01

Full Text Available The prediction of the aero-engine performance parameters is very important for aero-engine condition monitoring and fault diagnosis. In this paper, the chaotic phase space of engine exhaust temperature (EGT time series which come from actual air-borne ACARS data is reconstructed through selecting some suitable nearby points. The partial least square (PLS based on the cubic spline function or the kernel function transformation is adopted to obtain chaotic predictive function of EGT series. The experiment results indicate that the proposed PLS chaotic prediction algorithm based on biweight kernel function transformation has significant advantage in overcoming multicollinearity of the independent variables and solve the stability of regression model. Our predictive NMSE is 16.5 percent less than that of the traditional linear least squares (OLS method and 10.38 percent less than that of the linear PLS approach. At the same time, the forecast error is less than that of nonlinear PLS algorithm through bootstrap test screening.

Combined Analysis of COX-2 and p53 Expressions Reveals Synergistic Inverse Correlations with Microsatellite Instability and CpG Island Methylator Phenotype in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Shuji Ogino

2006-06-01

Full Text Available Cyclooxygenase-2 (COX-2 overexpression and mutations of p53 (a known COX-2 regulator are inversely associated with microsatellite instability—high (MSI-H and CpG island methylator phenotype (CIMP, characterized by extensive promoter methylation, is associated with MSI-H. However, no studies have comprehensively examined interrelations between COX-2, p53, MSI, and CIMP. Using MethyLight, we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A, CRABP1, MLH1, and NEUROG1] in relatively unbiased samples of 751 colorectal cancer cases obtained from two large prospective cohorts; 115 (15% tumors were CIMP-high (≥ 4 of 5 methylated promoters, 251 (33% were CIMP-low (1 to 3 methylated promoters, and the remaining 385 (51% were CIMP-0 (no methylated promoters. CIMP-high tumors were much less frequent in COX-2+/p53+ tumors (4.6% than in COX-2+/p53- tumors (19%; P < .0001, COX-2-/p53+ tumors (17%; P = .04, and COX-2-/p53- tumors (28%; P < .0001. In addition, COX-2+/p53+ tumors were significantly less common in MSI-H CIMP-high tumors (9.7% than in non-MSI-H CIMP-low/CIMP-0 tumors (44–47%; P < .0001. In conclusion, COX-2 and p53 alterations were synergistically inversely correlated with both MSI-H and CIMP-high. Our data suggest that a combined analysis of COX-2 and p53 may be more useful for the molecular classification of colorectal cancer than either COX-2 or p53 analysis alone.

Identifying Domain-General and Domain-Specific Predictors of Low Mathematics Performance: A Classification and Regression Tree Analysis

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David J. Purpura

2017-12-01

Full Text Available Many children struggle to successfully acquire early mathematics skills. Theoretical and empirical evidence has pointed to deficits in domain-specific skills (e.g., non-symbolic mathematics skills or domain-general skills (e.g., executive functioning and language as underlying low mathematical performance. In the current study, we assessed a sample of 113 three- to five-year old preschool children on a battery of domain-specific and domain-general factors in the fall and spring of their preschool year to identify Time 1 (fall factors associated with low performance in mathematics knowledge at Time 2 (spring. We used the exploratory approach of classification and regression tree analyses, a strategy that uses step-wise partitioning to create subgroups from a larger sample using multiple predictors, to identify the factors that were the strongest classifiers of low performance for younger and older preschool children. Results indicated that the most consistent classifier of low mathematics performance at Time 2 was children’s Time 1 mathematical language skills. Further, other distinct classifiers of low performance emerged for younger and older children. These findings suggest that risk classification for low mathematics performance may differ depending on children’s age.

Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug

Science.gov (United States)

Ranjbar, Mohammad Mehdi; Assadolahi, Vahideh; Yazdani, Mohsen; Nikaein, Donya; Rashidieh, Behnam

2016-01-01

Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs

Box-Cox transformation for resolving the Peelle's Pertinent Puzzle in a curve fitting

International Nuclear Information System (INIS)

Oh, S. Y.; Seo, C. G.

2004-01-01

Incorporating the Box-Cox transformation into a curve fitting is presented as one of methods for resolving an anomaly known as the Peelle's Pertinent Puzzle in the nuclear data community. The Box-Cox transformation is a strategy to make non-normal distribution data resemble normal distribution data. The proposed method consists of the following steps: transform the raw data to be fitted with the optimized Box-Cox transformation parameter, fit the transformed data using a conventional curve fitting tool, the least-squares method in this study, then inverse-transform the fitted results to the final estimates. Covariance matrices are correspondingly transformed and inverse-transformed with the aid of the law of error propagation. In addition to a sensible answer to the Puzzle, the proposed method resulted in reasonable estimates for a test evaluation with pseudo-experimental 6 Li(n, t) cross sections in several to 800 keV energy region, while the GMA code resulted in systematic underestimates that characterize the Puzzle. Meanwhile, it is observed that the present method and the Chiba-Smith method yield almost the same estimates for the test evaluation on 6 Li(n, t). Conceptually, however, two methods are very different from each other and further discussions are needed for a consensus on the issue of how to resolve the Puzzle. (authors)

Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive

NARCIS (Netherlands)

Baertling, F.; Al-Murshedi, F.; Sanchez Caballero, L.M.; Al-Senaidi, K.; Joshi, N.P.; Venselaar, H.; Brand, M.A.M. van den; Nijtmans, L.G.J.; Rodenburg, R.J.T.

2017-01-01

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia,

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

LENUS (Irish Health Repository)

Barry, M

2009-06-01

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

Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study

Directory of Open Access Journals (Sweden)

Hermanova Marketa

2010-05-01

Full Text Available Abstract Background We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2 and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA and inhibitors of lipoxygenases (LOX and cyclooxygenases (COX. This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Methods Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Results Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2 or SH-SY5Y after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX in combination with ATRA in both cell lines. Conclusions Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

Stellar atmospheric parameter estimation using Gaussian process regression

Science.gov (United States)

Bu, Yude; Pan, Jingchang

2015-02-01

As is well known, it is necessary to derive stellar parameters from massive amounts of spectral data automatically and efficiently. However, in traditional automatic methods such as artificial neural networks (ANNs) and kernel regression (KR), it is often difficult to optimize the algorithm structure and determine the optimal algorithm parameters. Gaussian process regression (GPR) is a recently developed method that has been proven to be capable of overcoming these difficulties. Here we apply GPR to derive stellar atmospheric parameters from spectra. Through evaluating the performance of GPR on Sloan Digital Sky Survey (SDSS) spectra, Medium resolution Isaac Newton Telescope Library of Empirical Spectra (MILES) spectra, ELODIE spectra and the spectra of member stars of galactic globular clusters, we conclude that GPR can derive stellar parameters accurately and precisely, especially when we use data preprocessed with principal component analysis (PCA). We then compare the performance of GPR with that of several widely used regression methods (ANNs, support-vector regression and KR) and find that with GPR it is easier to optimize structures and parameters and more efficient and accurate to extract atmospheric parameters.

Variable Selection for Regression Models of Percentile Flows

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Fouad, G.

2017-12-01

Percentile flows describe the flow magnitude equaled or exceeded for a given percent of time, and are widely used in water resource management. However, these statistics are normally unavailable since most basins are ungauged. Percentile flows of ungauged basins are often predicted using regression models based on readily observable basin characteristics, such as mean elevation. The number of these independent variables is too large to evaluate all possible models. A subset of models is typically evaluated using automatic procedures, like stepwise regression. This ignores a large variety of methods from the field of feature (variable) selection and physical understanding of percentile flows. A study of 918 basins in the United States was conducted to compare an automatic regression procedure to the following variable selection methods: (1) principal component analysis, (2) correlation analysis, (3) random forests, (4) genetic programming, (5) Bayesian networks, and (6) physical understanding. The automatic regression procedure only performed better than principal component analysis. Poor performance of the regression procedure was due to a commonly used filter for multicollinearity, which rejected the strongest models because they had cross-correlated independent variables. Multicollinearity did not decrease model performance in validation because of a representative set of calibration basins. Variable selection methods based strictly on predictive power (numbers 2-5 from above) performed similarly, likely indicating a limit to the predictive power of the variables. Similar performance was also reached using variables selected based on physical understanding, a finding that substantiates recent calls to emphasize physical understanding in modeling for predictions in ungauged basins. The strongest variables highlighted the importance of geology and land cover, whereas widely used topographic variables were the weakest predictors. Variables suffered from a high

Ordinary least square regression, orthogonal regression, geometric mean regression and their applications in aerosol science

International Nuclear Information System (INIS)

Leng Ling; Zhang Tianyi; Kleinman, Lawrence; Zhu Wei

2007-01-01

Regression analysis, especially the ordinary least squares method which assumes that errors are confined to the dependent variable, has seen a fair share of its applications in aerosol science. The ordinary least squares approach, however, could be problematic due to the fact that atmospheric data often does not lend itself to calling one variable independent and the other dependent. Errors often exist for both measurements. In this work, we examine two regression approaches available to accommodate this situation. They are orthogonal regression and geometric mean regression. Comparisons are made theoretically as well as numerically through an aerosol study examining whether the ratio of organic aerosol to CO would change with age

Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy.

Science.gov (United States)

Hallmann, Kerstin; Kudin, Alexei P; Zsurka, Gábor; Kornblum, Cornelia; Reimann, Jens; Stüve, Burkhard; Waltz, Stephan; Hattingen, Elke; Thiele, Holger; Nürnberg, Peter; Rüb, Cornelia; Voos, Wolfgang; Kopatz, Jens; Neumann, Harald; Kunz, Wolfram S

2016-02-01

Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Science.gov (United States)

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

Effect of Box-Cox transformation on power of Haseman-Elston and maximum-likelihood variance components tests to detect quantitative trait Loci.

Science.gov (United States)

Etzel, C J; Shete, S; Beasley, T M; Fernandez, J R; Allison, D B; Amos, C I

2003-01-01

Non-normality of the phenotypic distribution can affect power to detect quantitative trait loci in sib pair studies. Previously, we observed that Winsorizing the sib pair phenotypes increased the power of quantitative trait locus (QTL) detection for both Haseman-Elston (HE) least-squares tests [Hum Hered 2002;53:59-67] and maximum likelihood-based variance components (MLVC) analysis [Behav Genet (in press)]. Winsorizing the phenotypes led to a slight increase in type 1 error in H-E tests and a slight decrease in type I error for MLVC analysis. Herein, we considered transforming the sib pair phenotypes using the Box-Cox family of transformations. Data were simulated for normal and non-normal (skewed and kurtic) distributions. Phenotypic values were replaced by Box-Cox transformed values. Twenty thousand replications were performed for three H-E tests of linkage and the likelihood ratio test (LRT), the Wald test and other robust versions based on the MLVC method. We calculated the relative nominal inflation rate as the ratio of observed empirical type 1 error divided by the set alpha level (5, 1 and 0.1% alpha levels). MLVC tests applied to non-normal data had inflated type I errors (rate ratio greater than 1.0), which were controlled best by Box-Cox transformation and to a lesser degree by Winsorizing. For example, for non-transformed, skewed phenotypes (derived from a chi2 distribution with 2 degrees of freedom), the rates of empirical type 1 error with respect to set alpha level=0.01 were 0.80, 4.35 and 7.33 for the original H-E test, LRT and Wald test, respectively. For the same alpha level=0.01, these rates were 1.12, 3.095 and 4.088 after Winsorizing and 0.723, 1.195 and 1.905 after Box-Cox transformation. Winsorizing reduced inflated error rates for the leptokurtic distribution (derived from a Laplace distribution with mean 0 and variance 8). Further, power (adjusted for empirical type 1 error) at the 0.01 alpha level ranged from 4.7 to 17.3% across all tests

Polynomial regression analysis and significance test of the regression function

International Nuclear Information System (INIS)

Gao Zhengming; Zhao Juan; He Shengping

2012-01-01

In order to analyze the decay heating power of a certain radioactive isotope per kilogram with polynomial regression method, the paper firstly demonstrated the broad usage of polynomial function and deduced its parameters with ordinary least squares estimate. Then significance test method of polynomial regression function is derived considering the similarity between the polynomial regression model and the multivariable linear regression model. Finally, polynomial regression analysis and significance test of the polynomial function are done to the decay heating power of the iso tope per kilogram in accord with the authors' real work. (authors)

Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

Directory of Open Access Journals (Sweden)

Borhane Annabi

2012-01-01

Full Text Available The occurrence of a functional relationship between the release of metalloproteinases (MMPs and the expression of cyclooxygenase (COX-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB, increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA, a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1.

Fuzzy multiple linear regression: A computational approach

Science.gov (United States)

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.

Aggravation of Alzheimer's disease due to the COX-2-mediated reciprocal regulation of IL-1β and Aβ between glial and neuron cells.

Science.gov (United States)

Wang, Pu; Guan, Pei-Pei; Wang, Tao; Yu, Xin; Guo, Jian-Jun; Wang, Zhan-You

2014-08-01

Alzheimer's disease (AD) is the most common form of dementia and displays the characteristics of chronic neurodegenerative disorders; amyloid plaques (AP) that contain amyloid β-protein (Aβ) accumulate in AD, which is also characterized by tau phosphorylation. Epidemiological evidence has demonstrated that long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) markedly reduces the risk of AD by inhibiting the expression of cyclooxygenase 2 (COX-2). Although the levels of COX-2 and its metabolic product prostaglandin (PG)E2 are elevated in the brain of AD patients, the mechanisms for the development of AD remain unknown. Using human- or mouse-derived glioblastoma and neuroblastoma cell lines as model systems, we delineated the signaling pathways by which COX-2 mediates the reciprocal regulation of interleukin-1β (IL-1β) and Aβ between glial and neuron cells. In glioblastoma cells, COX-2 regulates the synthesis of IL-1β in a PGE2 -dependent manner. Moreover, COX-2-derived PGE2 signals the activation of the PI3-K/AKT and PKA/CREB pathways via cyclic AMP; these pathways transactivate the NF-κB p65 subunit via phosphorylation at Ser 536 and Ser 276, leading to IL-1β synthesis. The secretion of IL-1β from glioblastoma cells in turn stimulates the expression of COX-2 in human or mouse neuroblastoma cells. Similar regulatory mechanisms were found for the COX-2 regulation of BACE-1 expression in neuroblastoma cells. More importantly, Aβ deposition mediated the inflammatory response of glial cells via inducing the expression of COX-2 in glioblastoma cells. These findings not only provide new insights into the mechanisms of COX-2-induced AD but also initially define the therapeutic targets of AD. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Reduced Rank Regression

DEFF Research Database (Denmark)

Johansen, Søren

2008-01-01

The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study

Science.gov (United States)

2013-01-01

Background Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. Methods Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. Results Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P < 0.04). Conclusions We conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP. PMID:23642086

Nonparametric Mixture of Regression Models.

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Huang, Mian; Li, Runze; Wang, Shaoli

2013-07-01

Motivated by an analysis of US house price index data, we propose nonparametric finite mixture of regression models. We study the identifiability issue of the proposed models, and develop an estimation procedure by employing kernel regression. We further systematically study the sampling properties of the proposed estimators, and establish their asymptotic normality. A modified EM algorithm is proposed to carry out the estimation procedure. We show that our algorithm preserves the ascent property of the EM algorithm in an asymptotic sense. Monte Carlo simulations are conducted to examine the finite sample performance of the proposed estimation procedure. An empirical analysis of the US house price index data is illustrated for the proposed methodology.

ANALYSIS OF THE FINANCIAL PERFORMANCES OF THE FIRM, BY USING THE MULTIPLE REGRESSION MODEL

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Constantin Anghelache

2011-11-01

Full Text Available The information achieved through the use of simple linear regression are not always enough to characterize the evolution of an economic phenomenon and, furthermore, to identify its possible future evolution. To remedy these drawbacks, the special literature includes multiple regression models, in which the evolution of the dependant variable is defined depending on two or more factorial variables.

Estimating the Performance of Random Forest versus Multiple Regression for Predicting Prices of the Apartments

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Marjan Čeh

2018-05-01

Full Text Available The goal of this study is to analyse the predictive performance of the random forest machine learning technique in comparison to commonly used hedonic models based on multiple regression for the prediction of apartment prices. A data set that includes 7407 records of apartment transactions referring to real estate sales from 2008–2013 in the city of Ljubljana, the capital of Slovenia, was used in order to test and compare the predictive performances of both models. Apparent challenges faced during modelling included (1 the non-linear nature of the prediction assignment task; (2 input data being based on transactions occurring over a period of great price changes in Ljubljana whereby a 28% decline was noted in six consecutive testing years; and (3 the complex urban form of the case study area. Available explanatory variables, organised as a Geographic Information Systems (GIS ready dataset, including the structural and age characteristics of the apartments as well as environmental and neighbourhood information were considered in the modelling procedure. All performance measures (R2 values, sales ratios, mean average percentage error (MAPE, coefficient of dispersion (COD revealed significantly better results for predictions obtained by the random forest method, which confirms the prospective of this machine learning technique on apartment price prediction.

Quantile Regression Methods

DEFF Research Database (Denmark)

Fitzenberger, Bernd; Wilke, Ralf Andreas

2015-01-01

if the mean regression model does not. We provide a short informal introduction into the principle of quantile regression which includes an illustrative application from empirical labor market research. This is followed by briefly sketching the underlying statistical model for linear quantile regression based......Quantile regression is emerging as a popular statistical approach, which complements the estimation of conditional mean models. While the latter only focuses on one aspect of the conditional distribution of the dependent variable, the mean, quantile regression provides more detailed insights...... by modeling conditional quantiles. Quantile regression can therefore detect whether the partial effect of a regressor on the conditional quantiles is the same for all quantiles or differs across quantiles. Quantile regression can provide evidence for a statistical relationship between two variables even...

Multitask Quantile Regression under the Transnormal Model.

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Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2016-01-01

We consider estimating multi-task quantile regression under the transnormal model, with focus on high-dimensional setting. We derive a surprisingly simple closed-form solution through rank-based covariance regularization. In particular, we propose the rank-based ℓ 1 penalization with positive definite constraints for estimating sparse covariance matrices, and the rank-based banded Cholesky decomposition regularization for estimating banded precision matrices. By taking advantage of alternating direction method of multipliers, nearest correlation matrix projection is introduced that inherits sampling properties of the unprojected one. Our work combines strengths of quantile regression and rank-based covariance regularization to simultaneously deal with nonlinearity and nonnormality for high-dimensional regression. Furthermore, the proposed method strikes a good balance between robustness and efficiency, achieves the "oracle"-like convergence rate, and provides the provable prediction interval under the high-dimensional setting. The finite-sample performance of the proposed method is also examined. The performance of our proposed rank-based method is demonstrated in a real application to analyze the protein mass spectroscopy data.

Exploring emergency department 4-hour target performance and cancelled elective operations: a regression analysis of routinely collected and openly reported NHS trust data.

Science.gov (United States)

Keogh, Brad; Culliford, David; Guerrero-Ludueña, Richard; Monks, Thomas

2018-05-24

To quantify the effect of intrahospital patient flow on emergency department (ED) performance targets and indicate if the expectations set by the National Health Service (NHS) England 5-year forward review are realistic in returning emergency services to previous performance levels. Linear regression analysis of routinely reported trust activity and performance data using a series of cross-sectional studies. NHS trusts in England submitting routine nationally reported measures to NHS England. 142 acute non-specialist trusts operating in England between 2012 and 2016. The primary outcome measures were proportion of 4-hour waiting time breaches and cancelled elective operations. Univariate and multivariate linear regression models were used to show relationships between the outcome measures and various measures of trust activity including empty day beds, empty night beds, day bed to night bed ratio, ED conversion ratio and delayed transfers of care. Univariate regression results using the outcome of 4-hour breaches showed clear relationships with empty night beds and ED conversion ratio between 2012 and 2016. The day bed to night bed ratio showed an increasing ability to explain variation in performance between 2015 and 2016. Delayed transfers of care showed little evidence of an association. Multivariate model results indicated that the ability of patient flow variables to explain 4-hour target performance had reduced between 2012 and 2016 (19% to 12%), and had increased in explaining cancelled elective operations (7% to 17%). The flow of patients through trusts is shown to influence ED performance; however, performance has become less explainable by intratrust patient flow between 2012 and 2016. Some commonly stated explanatory factors such as delayed transfers of care showed limited evidence of being related. The results indicate some of the measures proposed by NHS England to reduce pressure on EDs may not have the desired impact on returning services to previous

Methods for identifying SNP interactions: a review on variations of Logic Regression, Random Forest and Bayesian logistic regression.

Science.gov (United States)

Chen, Carla Chia-Ming; Schwender, Holger; Keith, Jonathan; Nunkesser, Robin; Mengersen, Kerrie; Macrossan, Paula

2011-01-01

Due to advancements in computational ability, enhanced technology and a reduction in the price of genotyping, more data are being generated for understanding genetic associations with diseases and disorders. However, with the availability of large data sets comes the inherent challenges of new methods of statistical analysis and modeling. Considering a complex phenotype may be the effect of a combination of multiple loci, various statistical methods have been developed for identifying genetic epistasis effects. Among these methods, logic regression (LR) is an intriguing approach incorporating tree-like structures. Various methods have built on the original LR to improve different aspects of the model. In this study, we review four variations of LR, namely Logic Feature Selection, Monte Carlo Logic Regression, Genetic Programming for Association Studies, and Modified Logic Regression-Gene Expression Programming, and investigate the performance of each method using simulated and real genotype data. We contrast these with another tree-like approach, namely Random Forests, and a Bayesian logistic regression with stochastic search variable selection.

The effects of a cyclooxygenase-2 (COX-2 expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production

Directory of Open Access Journals (Sweden)

Marshall Jean-Claude

2007-01-01

Full Text Available Abstract Background Cyclooxygenase-2 (COX-2 expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages. Methods Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac. Results Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition. Conclusion Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.

AVALIAÇÃO DA DISPENSAÇÃO DE FÁRMACOS PARCIALMENTE SELETIVOS PARA COX-2

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Cícero Cardoso VALLE FILHO

2015-12-01

Full Text Available Uma pesquisa foi realizada com o objetivo de avaliar um potencial aumento na venda de fármacos anti-inflamatórios não esteroidais (AINEs parcialmente seletivos para a COX-2 durante o período de julho de 2009 a junho de 2011, em uma drogaria localizada no município de Itaperuna, estado do Rio de Janeiro. Durante o período estudado foi dispensado um total de 802 AINEs parcialmente seletivos para a COX-2, dentre os quais 59,85% foram de nimesulida, 5,74% de etodolaco e 34,41% de meloxicam.   No primeiro semestre avaliado a dispensação total de AINEs parcialmente seletivos foi equivalente a 92, no segundo semestre a dispensação total foi equivalente a 159, no terceiro semestre a dispensação total foi de 219 AINEs parcialmente seletivos para COX-2 e no quarto semestre foram dispensados 332.  Os resultados indicaram maior dispensação dos medicamentos desta classe no mês de abril de 2011 sendo que tanto a nimesulida, quanto o meloxicam e o etodolaco foram mais dispensados no último semestre do estudo. De acordo com a metodologia utilizada pode-se concluir que a dispensação dos AINEs parcialmente seletivos vem crescendo a cada ano e que a nimesulida apresenta o maior índice de crescimento; a maior indicação da nimesulida tem sido para crianças; os meses correspondentes ao período de inverno apresentam maior dispensação de AINEs parcialmente seletivos para a COX-2.

Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations.

Science.gov (United States)

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

2014-06-01

This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). LVM regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index [LVMi] ≥ 149 g/m(2) men, ≥ 122 g/m(2) women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Compared with 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%, hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression. In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression. Copyright © 2014 American College of