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1

Bootstrapping Cox's Regression Model.  

National Technical Information Service (NTIS)

Statistical inference in Cox's regression model is usually carried out using traditional (first order) large sample theory. In the spirit of earlier success stories one might try to bootstrap data in order to better assess the sampling variability of the ...

N. L. Hjort

1985-01-01

2

Proportional hazards (Cox) regression  

Microsoft Academic Search

PROPORTIONAL HAZARDS (Cox) REGRESSION is a powerful analytic tool for testing whether several factors (e.g., cigarette smoking, hypertension) are independently related to the rate (over time) of a specific event (e.g., heart attack yes\\/no). It can also be used to control for baseline differences between groups in nonrandomized studies and randomized clinical trials (RCTs). The availability of desktop computers and

Mitchell H. Katz; Walter W. Hauck

1993-01-01

3

Partial least squares Cox regression for genome-wide data.  

PubMed

Most methods for survival prediction from high-dimensional genomic data combine the Cox proportional hazards model with some technique of dimension reduction, such as partial least squares regression (PLS). Applying PLS to the Cox model is not entirely straightforward, and multiple approaches have been proposed. The method of Park etal. (Bioinformatics 18(Suppl. 1):S120-S127, 2002) uses a reformulation of the Cox likelihood to a Poisson type likelihood, thereby enabling estimation by iteratively reweighted partial least squares for generalized linear models. We propose a modification of the method of Park et al. (2002) such that estimates of the baseline hazard and the gene effects are obtained in separate steps. The resulting method has several advantages over the method of Park et al. (2002) and other existing Cox PLS approaches, as it allows for estimation of survival probabilities for new patients, enables a less memory-demanding estimation procedure, and allows for incorporation of lower-dimensional non-genomic variables like disease grade and tumor thickness. We also propose to combine our Cox PLS method with an initial gene selection step in which genes are ordered by their Cox score and only the highest-ranking k% of the genes are retained, obtaining a so-called supervised partial least squares regression method. In simulations, both the unsupervised and the supervised version outperform other Cox PLS methods. PMID:18188699

Nygård, Ståle; Borgan, Ornulf; Lingjaerde, Ole Christian; Størvold, Hege Leite

2008-06-01

4

Sinusoidal Cox Regression--A Rare Cancer Example  

PubMed Central

Evidence of an association between survival time and date of birth would suggest an etiologic role for a seasonally variable environmental exposure occurring within a narrow perinatal time period. Risk factors that may exhibit seasonal epidemicity include diet, infectious agents, allergens, and antihistamine use. Typically data has been analyzed by simply categorizing births into months or seasons of the year and performing multiple pairwise comparisons. This paper presents a statistically robust alternative, based upon a trigonometric Cox regression model, to analyze the cyclic nature of birth dates related to patient survival. Disease birth-date results are presented using a sinusoidal plot with peak date(s) of relative risk and a single P value that indicates whether an overall statistically significant seasonal association is present. Advantages of this derivative-free method include ease of use, increased power to detect statistically significant associations, and the ability to avoid arbitrary, subjective demarcation of seasons.

Efird, Jimmy Thomas

2010-01-01

5

Misspecification of Cox regression models with composite endpoints.  

PubMed

Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. PMID:22736519

Wu, Longyang; Cook, Richard J

2012-06-27

6

Misspecification of Cox regression models with composite endpoints  

PubMed Central

Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. Copyright © 2012 John Wiley & Sons, Ltd.

Wu, Longyang; Cook, Richard J

2012-01-01

7

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

ERIC Educational Resources Information Center

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

Vidal, Sherry

8

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

PubMed

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

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

2008-10-28

9

Bias due to Aggregation of Individual Covariates in the Cox Regression Model  

Microsoft Academic Search

The impact of covariate aggregation, well studied in relation to linear regression, is less clear in the Cox model. In this paper, the authors use real-life epidemiologic data to illustrate how aggregating individual covariate values may lead to important underestimation of the exposure effect. The issue is then systematically assessed through simulations, with six alternative covariate representations. It is shown

Michal Abrahamowicz; Roxane du Berger; Daniel Krewski; Richard Burnett; Gillian Bartlett; Robyn M. Tamblyn; Karen Leffondré

2004-01-01

10

Cox Regression with Alternative Concepts of Waiting Time: The New Orleans Yellow Fever Epidemic of 1853  

Microsoft Academic Search

Event data can often be analysed using different concepts of waiting time. Our application offers three choices: calendar-time, age, and duration of residence in New Orleans. We exploit the semi-parametric features of Cox regression and estimate parallel specifications in which mortality risk is treated as an arbitrary function of one of the three alternative time measures, while the remaining two

Insan Tunali; JONATHAN B. PRITCHETT

1997-01-01

11

MULCOX: a computer program for the Cox regression analysis of multiple failure time variables.  

PubMed

MULCOX is a user-friendly FORTRAN program for the analysis of regression effects when individual study subjects may experience multiple events or failures. Each marginal distribution of the multivariate failure time variable is formulated by a Cox proportional hazards model. The maximum partial likelihood estimators of the regression parameters in these marginal models are approximately jointly normal. The MULCOX program estimates the marginal models as well as the joint covariance matrix. In addition, it implements several multivariate inference procedures. The program runs on both mainframe computers and microcomputers. The running time is quite acceptable even for large samples. A simple example is provided to illustrate the features of the program. PMID:2397636

Lin, D Y

1990-06-01

12

Box-Cox Transformation and Random Regression Models for Fecal egg Count Data  

PubMed Central

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

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

2012-01-01

13

Dynamics of HPV vaccination initiation in Flanders (Belgium) 2007-2009: a Cox regression model  

PubMed Central

Background We investigated dynamic patterns and predictors of HPV vaccination initiation in Flanders (Belgium) by girls aged 12 to 18, between 2007 and 2009, the period immediately after the introduction of the HPV vaccines on the Belgian market. During this period the initiative for vaccination was taken by the girl, her family or the general practitioner/pediatrician/gynecologist. Methods We used a Cox regression model with time constant and time varying predictors to model hazard rates of HPV vaccination initiation. The sample existed of 117,151 female members of the National Alliance of Christian Mutualities, the largest sickness fund in Flanders. Results The study showed that the hazard of HPV vaccination initiation was higher (1) for older girls, (2) for girls with a more favorable socio-economic background, (3) under more generous reimbursement regimes (with this effect being more pronounced for girls with weak socioeconomic backgrounds), (4) for girls that were informed personally about the reimbursement rules. Conclusions When the initiative for HPV vaccination lies with the girls, their families or the physicians (no organized setting) the uptake of the vaccines is affected by both individual and organizational factors.

2011-01-01

14

Quantile regression, Box-Cox transformation model, and the U.S. wage structure, 1963–1987  

Microsoft Academic Search

This study examines changes in the increments (‘returns’) to education and experience at different points of the wage distribution. It also examines changes in within-group wage inequality. Newly developed quantile regression techniques are applied to the Box-Cox transformation model using the Current Population Survey data. The increments differ, but they changed in similar pattern at different points of the wage

Moshe Buchinsky

1995-01-01

15

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

NASA Astrophysics Data System (ADS)

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

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

2009-04-01

16

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

PubMed

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

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

2004-03-22

17

A semi-parametric generalization of the Cox proportional hazards regression model: Inference and Applications  

PubMed Central

The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike’s Information Criterion is developed. We illustrate the applicability of our approach using real-life data.

Devarajan, Karthik; Ebrahimi, Nader

2010-01-01

18

Focused Information Criteria and Model Averaging for the Cox Hazard Regression Model  

Microsoft Academic Search

This article is concerned with variable selection methods for the pro- portional hazards regression model. Including too many covariates causes extra variability and in?ated confldence intervals for regression parameters, so regimes for discarding the less informative ones are needed. Our framework has p covari- ates designated as 'protected' while variables from a further set of q covariates are examined for

Nils Lid Hjort; Gerda Claeskens

2006-01-01

19

Gene identification and survival prediction with Lp Cox regression and novel similarity measure.  

PubMed

In this paper, Cox's proportional hazards model with Lp penalty method is developed for simultaneous gene selection and survival prediction. Lp penalty shrinks coefficients and produces some coefficients that are exactly zero, and therefore can be used to identify survival related downstream genes. We also define a novel similarity measure to hunt the regulatory genes that their gene expression changes may be low but they are highly correlated with the selected genes. Experimental results with gene expression data demonstrate that the proposed procedures can be used for identifying important gene clusters that are related to time to death due to cancer and for building parsimonious model for predicting the survival of future patients. PMID:20052904

Liu, Zhenqiu; Jiang, Feng

2009-01-01

20

A Comparison of the Polytomous Logistic Regression and Joint Cox Proportional Hazards Models for Evaluating Multiple Disease Subtypes in Prospective Cohort Studies  

PubMed Central

Background Polytomous logistic regression models are commonly used in case-control studies of cancer to directly compare the risks associated with an exposure variable across multiple cancer subtypes. However, the validity, accuracy and efficiency of this approach for prospective cohort studies have not been formally evaluated. Methods We investigated the performance of the polytomous logistic regression model and compared it to an alternative approach based on a joint Cox proportional hazards model using simulation studies. We then applied both methods to a prospective cohort study to assess whether the association of breast cancer with body size differs according to estrogen and progesterone receptor-defined subtypes. Results Our simulations showed that the polytomous logistic regression model but not the joint Cox regression model yielded biased results in comparing exposure and disease subtype associations when the baseline hazards for different disease subtypes are non-proportional. For this reason, an analysis of a real data set was based on the joint Cox proportional hazards model and showed that body size has a significantly greater association with estrogen and progesterone positive breast cancer than with other subtypes. Conclusions Because of the limitations of the polytomous logistic regression model for the comparison of exposure-disease associations across disease subtypes, the joint Cox proportional hazards model is recommended over the polytomous logistic regression model in prospective cohort studies. Impact The paper will promote the use of the joint Cox model in a prospective cohort study. Examples of SAS and S-plus programming codes are provided to facilitate use by non-statisticians.

Xue, Xiaonan; Kim, Mimi Y.; Gaudet, Mia M.; Park, Yikyung; Heo, Moonseong; Hollenbeck, Albert R.; Strickler, Howard D.; Gunter, Marc J.

2012-01-01

21

Inhibition of COX-2 in Colon Cancer Modulates Tumor Growth and MDR-1 Expression to Enhance Tumor Regression in Therapy-Refractory Cancers In Vivo12  

PubMed Central

Higher cyclooxygenase 2 (COX-2) expression is often observed in aggressive colorectal cancers (CRCs). Here, we attempt to examine the association between COX-2 expression in therapy-refractory CRC, how it affects chemosensitivity, and whether, in primary tumors, it is predictive of clinical outcomes. Our results revealed higher COX-2 expression in chemoresistant CRC cells and tumor xenografts. In vitro, the combination of either aspirin or celecoxib with 5-fluorouracil (5-FU) was capable of improving chemosensitivity in chemorefractory CRC cells, but a synergistic effect with 5-FU could only be demonstrated with celecoxib. To examine the potential clinical significance of these observations, in vivo studies were undertaken, which also showed that the greatest tumor regression was achieved in chemoresistant xenografts after chemotherapy in combination with celecoxib, but not aspirin. We also noted that these chemoresistant tumors with higher COX-2 expression had a more aggressive growth rate. Given the dramatic response to a combination of celecoxib + 5-FU, the possibility that celecoxib may modulate chemosensitivity as a result of its ability to inhibit MDR-1 was examined. In addition, assessment of a tissue microarray consisting of 130 cases of CRCs revealed that, in humans, higher COX-2 expression was associated with poorer survival with a 68% increased risk of mortality, indicating that COX-2 expression is a marker of poor clinical outcome. The findings of this study point to a potential benefit of combining COX-2 inhibitors with current regimens to achieve better response in the treatment of therapy-refractory CRC and in using COX-2 expression as a prognostic marker to help identify individuals who would benefit the greatest from closer follow-up and more aggressive therapy.

Rahman, Mahbuba; Selvarajan, Krithika; Hasan, Mohammad R; Chan, Annie P; Jin, Chaoyang; Kim, Jieun; Chan, Simon K; Le, Nhu D; Kim, Young-Bae; Tai, Isabella T

2012-01-01

22

Univariate Probability Distributions  

ERIC Educational Resources Information Center

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

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

2012-01-01

23

Regression  

NSDL National Science Digital Library

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

Anderson-Cook, C.; Robinson, T.; Dorai-Raj, S.

2008-12-18

24

Screening of cerebral infarction-related genetic markers using a Cox regression analysis between onset age and heterozygosity at randomly selected short tandem repeat loci.  

PubMed

The aim of this paper is to explore whether the heterozygosity at the 9 CODIS short tandem repeats (STR) loci including D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 is associated with the risk of atherosclerotic cerebral infarction (CI). The DNA samples were collected from patients with CI (n = 72) and people over the age of 90 years without CI (n = 59). Alleles of the STR loci were determined using the STR Profiler Plus PCR amplification kit. The relationship between the age of onset and heterozygosity was determined with the Cox regression method. A correlation between the age of onset and heterozygosity was observed for the D8S1179 locus (p < 0.05). It implied that regions in the vicinity of locus D8S1179 may harbor susceptibility genes for CI. The analysis of heterozygosity for particular loci as genetic markers using our new study design may be an efficient and reliable approach to estimate genetic predispositions. PMID:22476643

Hui, Liu; Jun, Tian; Jing, Ye; Yu, Weijian

2012-05-01

25

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma  

PubMed Central

Background: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. Methods: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. Results: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. Conclusions: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.

Baldi, A; Santini, D; Vasaturo, F; Santini, M; Vicidomini, G; Di, M; Esposito, V; Groeger, A; Liuzzi, G; Vincenzi, B; Tonini, G; Piccoli, M; Baldi, F; Scarpa, S

2004-01-01

26

Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications  

PubMed Central

Background Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis. Methods Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression. Results The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors. Conclusions Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.

2011-01-01

27

There Is More Than One Univariate Normal Distribution: What Is the Normal Distribution, Really?  

ERIC Educational Resources Information Center

|Many univariate statistical methods, such as the analysis of variance, t-test, and regression, assume that the dependent variable data have a univariate normal distribution (Hinkle, Weirsma, and Jurs, 1998). Various other statistical methods assume that the error scores are normally distributed (Thompson, 1992). Violating this assumption can be…

Team, Rachel M.

28

Functional Trees for Regression  

Microsoft Academic Search

In this paper we present and evaluate a new algorithm for supervised learning regression problems. The algorithm combines\\u000a a univariate regression tree with a linear regression function by means of constructive induction. When growing the tree,\\u000a at each internal node, a linear-regression function creates one new attribute. This new attribute is the instantiation of\\u000a the regression function for each example

Joao Gama

2001-01-01

29

Use of Penalized Splines in Extended Cox-Type Additive Hazard Regression to Flexibly Estimate the Effect of Time-varying Serum Uric Acid on Risk of Cancer Incidence: A Prospective, Population-Based Study in 78,850 Men  

PubMed Central

Purpose We sough to investigate the effect of serum uric acid (SUA) levels on risk of cancer incidence in men and to flexibly determine the shape of this association by using a novel analytical approach. Methods A population-based cohort of 78,850 Austrian men who received 264,347 serial SUA measurements was prospectively followed-up for a median of 12.4 years. Data were collected between 1985 and 2003. Penalized splines (P-splines) in extended Cox-type additive hazard regression were used to flexibly model the association between SUA, as a time-dependent covariate, and risk of overall and site-specific cancer incidence and to calculate adjusted hazard ratios with their 95% confidence intervals. Results During follow-up 5189 incident cancers were observed. Restricted maximum-likelihood optimizing P-spline models revealed a moderately J-shaped effect of SUA on risk of overall cancer incidence, with statistically significantly increased hazard ratios in the upper third of the SUA distribution. Increased SUA (?8.00 mg/dL) further significantly increased risk for several site-specific malignancies, with P-spline analyses providing detailed insight about the shape of the association with these outcomes. Conclusions Our study is the first to demonstrate a dose–response association between SUA and cancer incidence in men, simultaneously reporting on the usefulness of a novel methodological framework in epidemiologic research.

Strasak, Alexander M.; Lang, Stefan; Kneib, Thomas; Brant, Larry J.; Klenk, Jochen; Hilbe, Wolfgang; Oberaigner, Willi; Ruttmann, Elfriede; Kaltenbach, Lalit; Concin, Hans; Diem, Gunter; Pfeiffer, Karl P.; Ulmer, Hanno

2009-01-01

30

Univariate input models for stochastic simulation  

Microsoft Academic Search

Techniques are presented for modeling and randomly sampling many of the multivariate probabilistic input processes that drive discrete-event simulation experiments. Emphasis is given to bivariate and trivariate extensions of the univariate beta, Johnson, and Bézier dist ribution families because of the flexibility of these families to model a wide range of shapes for the marginal distributions while also representing the

Michael E. Kuhl; Julie S. Ivy; Emily K. Lada; Natalie M. Steiger; Mary Ann Flanigan Wagner; James R. Wilson

2010-01-01

31

Manuals for Univariate and Multivariate Statistics  

NSDL National Science Digital Library

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

Wendorf, Craig A.

2009-07-30

32

Multivariate Multiple Regression in Communication Research.  

ERIC Educational Resources Information Center

|This paper examines the multivariate multiple regression model and explores its applicability to communication research. The first section discusses partitioning of a data matrix, as a heuristic device for distinguishing among alternative regression models. Section two examines various aspects of univariate multiple regression, including the form…

Monge, Peter R.

33

A GENERAL PURPOSE UNIVARIATE PROBABILITY MODEL FOR ENVIRONMENTAL DATA ANALYSIS  

EPA Science Inventory

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

34

COX-2 chronology  

PubMed Central

The role of selective cyclooxygenase (COX)-2 inhibitors in medical practice has become controversial since evidence emerged that their use is associated with an increased risk of myocardial infarction. Selective COX-2 inhibitors were seen as successor to non-selective non-steroidal anti-inflammatory drugs, in turn successors to aspirin. The importance of pain relief means that such drugs have always attracted attention. The fact that they work through inhibition of cyclooxygenase, are widespread, and have multiple effects also means that adverse effects that were unanticipated (even though predictable) have always emerged. In this paper I therefore present an historical perspective so that the lessons of the past may be applied to the present.

Hawkey, C J

2005-01-01

35

A univariate model for long-term streamflow forecasting  

Microsoft Academic Search

This paper, the second in the series, verifies the entropy-based univariate model developed in the first paper for long-term streamflow forecasting on five rivers from different regions of the world. The results of the model are compared with the corresponding results of ARIMA and state-space model. The Lagrange multipliers of the univariate model are found similar to autocorrelation coefficients of

P. F. Krstanovic; V. P. Singh

1991-01-01

36

Estimating the effective degrees of freedom in univariate multiple regression analysis  

Microsoft Academic Search

Abstract The general linear model,provides the most widely applied statistical framework,for analyzing functional MRI (fMRI) data. With the increasing temporal resolution of recent scanning protocols, and more elaborate data preprocessing schemes, data independency is no longer a valid assumption. In this paper, we revise the statistical background of the general linear model in the presence of temporal autocorrelations. First, when

Frithjof Kruggel; Mélanie Pélégrini-Issac; Habib Benali

2002-01-01

37

Quantile Regression with Censored Data  

ERIC Educational Resources Information Center

|The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where…

Lin, Guixian

2009-01-01

38

The REBMIX Algorithm and the Univariate Finite Mixture Estimation  

Microsoft Academic Search

The REBMIX algorithm is presented and applied to estimation of finite univariate mixture densities. The algorithm identifies the component parameters, mixing weights, and number of the components successively. Significant improvement is achieved by replacing the rigid restraints with the loose ones, which enables improved modelling of overlapped components. The algorithm is controlled by the extreme relative deviations, total of positive

Marko Nagode; Matija Fajdiga

2011-01-01

39

Univariate Analysis of Multivariate Outcomes in Educational Psychology.  

ERIC Educational Resources Information Center

The author examined the prevalence of multiple operational definitions of outcome constructs and an estimate of the incidence of Type I error rates when univariate procedures were applied to multiple variables in educational psychology. Multiple operational definitions of constructs were advocated and wider use of multivariate analysis was…

Hubble, L. M.

1984-01-01

40

A univariate model for long-term streamflow forecasting  

Microsoft Academic Search

This paper, the first in a series of two, employs the principle of maximum entropy (POME) via maximum entropy spectral analysis (MESA) to develop a univariate model for long-term streamflow forecasting. Three cases of streamflow forecasting are investigated: forward forecasting, backward forecasting (or reconstruction) and intermittent forecasting (or filling in missing records). Application of the model is discussed in the

P. F. Krstanovic; V. P. Singh

1991-01-01

41

Inference of identity of source using univariate and bivariate methods  

Microsoft Academic Search

In this study we explore the inference of identity of source using a two-dimensional feature vector. As an example, we study the use of the Bayesian framework for the estimation of the value of evidence of color measurements for identity of source of blue ballpoint pen inks. Univariate as well as bivariate analyses are carried out for color data that

C. E. H. Berger

2009-01-01

42

Univariate Analysis of Multivariate Outcomes in Educational Psychology.  

ERIC Educational Resources Information Center

|The author examined the prevalence of multiple operational definitions of outcome constructs and an estimate of the incidence of Type I error rates when univariate procedures were applied to multiple variables in educational psychology. Multiple operational definitions of constructs were advocated and wider use of multivariate analysis was…

Hubble, L. M.

1984-01-01

43

Estimating Components of Univariate Gaussian Mixtures Using Prony's Method  

Microsoft Academic Search

A new technique for estimating the component parameters of a mixture of univariate Gaussian distributions using the method of moments is presented. The method of moments basically involves equating the sample moments to the corresponding mixture moments expressed in terms of component parameters and solving these equations for the unknown parameters. These moment equations, however, are nonlinear in the unknown

Haluk Derin

1987-01-01

44

Univariate and Bivariate Loglinear Models for Discrete Test Score Distributions.  

ERIC Educational Resources Information Center

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

Holland, Paul W.; Thayer, Dorothy T.

2000-01-01

45

COX-2: friend or foe?  

PubMed

It wasn't until 1990, when the existence of two different cyclooxygenases was hypothesized, based on the evidence that steroids inhibited the increase in COX activity induced by bacterial lipopolysaccharides in macrophages, without any effects on the basal production of prostaglandins or leukotrienes. The first isoform, COX-1 is responsible for the production of "housekeeping" prostaglandins critical to the maintenance of normal renal function, gastric mucosal integrity, platelet aggregation, and the autocrine response to circulating hormones. COX-2 on the other hand is an inducible enzyme, upregulated 20-fold in macrophages, monocytes, synoviocytes, chondrocytes, fibroblasts, osteoblasts and endothelial cells by various inflammatory stimuli and cytochines. Classical findings shown that the therapeutics effects of NSAIDs are largely dependent on COX-2 inhibition, whereas some undesirable side effects are bound to COX-1 blockade, such as gastrointestinal bleeding and renal failure. Therefore, agents that selectively inhibit COX-2 over COX-1 are desirable for the treatment of inflammation. However, since September 2004 reports of increased risk of thrombotic cardiovascular events had accumulated for coxibs, the COX-2 inhibitors. Our goal is to provide an overview of the relevant biology and pharmacology of this enzyme in atherosclerosis. PMID:17584101

Iezzi, Annalisa; Ferri, Claudio; Mezzetti, Andrea; Cipollone, Francesco

2007-01-01

46

Stacked Regressions  

Microsoft Academic Search

Stacking regressions is a method for forming linear combinations of different predictors to give improved prediction accuracy. The idea is to use cross-validation data and least squares under non-negativity constraints to determine the coefficients in the combination. Its effectiveness is demonstrated in stacking regression trees of different sizes and in a simulation stacking linear subset and ridge regressions. Reasons why

Leo Breiman; Ross Quinlan

1996-01-01

47

Stacked Regressions  

Microsoft Academic Search

Stacking regressions is a method for forming linear combinations of different predictors to give improved prediction accuracy. The idea is to use cross-validation data and least squares under non negativity constraints to determine the coefficients in the combination. Its effectiveness is demonstrated in stacking regression trees of different sizes and in a simulation stacking linear subset and ridge regressions. Reasons

Leo Breiman

1996-01-01

48

Evaluation of droplet size distributions using univariate and multivariate approaches.  

PubMed

Pharmaceutically relevant material characteristics are often analyzed based on univariate descriptors instead of utilizing the whole information available in the full distribution. One example is droplet size distribution, which is often described by the median droplet size and the width of the distribution. The current study was aiming to compare univariate and multivariate approach in evaluating droplet size distributions. As a model system, the atomization of a coating solution from a two-fluid nozzle was investigated. The effect of three process parameters (concentration of ethyl cellulose in ethanol, atomizing air pressure, and flow rate of coating solution) on the droplet size and droplet size distribution using a full mixed factorial design was used. The droplet size produced by a two-fluid nozzle was measured by laser diffraction and reported as volume based size distribution. Investigation of loading and score plots from principal component analysis (PCA) revealed additional information on the droplet size distributions and it was possible to identify univariate statistics (volume median droplet size), which were similar, however, originating from varying droplet size distributions. The multivariate data analysis was proven to be an efficient tool for evaluating the full information contained in a distribution. PMID:23215949

Gaunø, Mette Høg; Larsen, Crilles Casper; Vilhelmsen, Thomas; Møller-Sonnergaard, Jørn; Wittendorff, Jørgen; Rantanen, Jukka

2012-12-05

49

The Robust Inference for the Cox Proportional Hazards Model  

Microsoft Academic Search

We derive the asymptotic distribution of the maximum partial likelihood estimator ? for the vector of regression coefficients ? under a possibly misspecified Cox proportional hazards model. As in the parametric setting, this estimator ? converges to a well-defined constant vector ?*. In addition, the random vector n (? – ?*) is asymptotically normal with mean 0 and with a

D. Y. Lin; L. J. Wei

1989-01-01

50

Regression Activity  

NSDL National Science Digital Library

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

2009-01-28

51

Multiple Regression  

NSDL National Science Digital Library

This resource explains multiple regression and concepts associated with it. These are some of the key concepts addressed: predicted values, residuals, dummy variables, interaction effects, t-test, regression coefficients, correlation, partial correlation, r-squared, adjusted r-squared, multicollinearity, variance-inflation factors, transformation, Cook's distance, validity, Durbin-Watson coefficient. The site features a key concepts section, different assumptions of the models and also frequently asked questions about the contents.

Garson, G. D.

2009-01-23

52

Inference of identity of source using univariate and bivariate methods.  

PubMed

In this study we explore the inference of identity of source using a two-dimensional feature vector. As an example, we study the use of the Bayesian framework for the estimation of the value of evidence of color measurements for identity of source of blue ballpoint pen inks. Univariate as well as bivariate analyses are carried out for color data that was acquired with a flatbed scanner. While this might not be the best method to discriminate inks, we will use it as an example to estimate what the value of the evidence is, however low or high it may be. It is hoped that this exercise is instructional, as a similar approach can readily be applied in other situations. PMID:20120605

Berger, C E H

2009-12-01

53

Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2.  

PubMed

The development of mice deficient in either cyclooxygenase-1 (COX-1) or COX-2, as well as mice deficient in both COX isoforms, has provided models to elucidate the physiological and pathophysiological roles of these enzymes. The findings obtained with the COX-deficient mice suggest that COX-2 may be more important than COX-1 for supplying prostaglandins (PGs) to maintain tissue homeostasis. Furthermore, both isoforms may be involved in the development of diseases, such as inflammation and cancer. Therefore, the contribution of each isoform to the prevention or development of disease is more complex than originally described. Studies with the COX-deficient mice suggest that in addition to COX-2-selective inhibition, therapeutic advances may also be achieved with COX-1-selective inhibitors which lack gastrointestinal side effects. PMID:12432917

Loftin, Charles D; Tiano, Howard F; Langenbach, Robert

2002-08-01

54

Cox-2 gene expression in chemically induced skin papillomas cannot predict subsequent tumor fate  

PubMed Central

Elevated cyclooxygenase-2 (COX-2) expression is observed in a variety of premalignant neoplastic tissues, suggesting COX-2 expression might serve as a potential indicator of subsequent tumor development. However, it has not been possible to compare the relationship between Cox-2 gene expression in premalignant lesions and their subsequent fate, because conventional studies require tissue destruction for analysis of gene expression. To monitor COX-2 expression non-invasively during tumor development, we created a Cox-2 luciferase knock-in mouse, Cox-2luc, in which the firefly luciferase coding region replaces the Cox-2 coding region. Luciferase activity was non-invasively, quantitatively and repeatedly monitored in Cox-2luc/+ mice subjected to DMBA/TPA multistage skin tumor induction. Luciferase activity is significantly higher in all papillomas than in surrounding skin. However, the magnitude of Cox-2 promoter-driven luciferase activity in small papillomas cannot predict subsequent papilloma regression or growth. Elevated Cox-2 promoter-driven luciferase signal can be detected when papillomas first become visible, but not before this time.

Ishikawa, Tomo-o; Jain, Naveen K.; Herschman, Harvey R.

2010-01-01

55

Autistic Regression  

ERIC Educational Resources Information Center

|Autistic regression is one of the many mysteries in the developmental course of autism and pervasive developmental disorders not otherwise specified (PDD-NOS). Various definitions of this phenomenon have been used, further clouding the study of the topic. Despite this problem, some efforts at establishing prevalence have been made. The purpose of…

Matson, Johnny L.; Kozlowski, Alison M.

2010-01-01

56

Dynamic treatment of invariant and univariant reactions in metamorphic systems  

SciTech Connect

A simple model is presented that incorporates the essential dynamics of metamorphic processes leading to reactions along univariant curves and up to and beyond the invariant point. The model includes both heat flow by conduction and convection as well as fluid flow in and out of a representative volume. Overall mineral reactions can then take place within this rock volume in response to internal and external factors. The paper derives a simple back-of-the-envelope expression for the steady state reached by the system. The steady state composition of the fluid and the steady state temperature are then compared with the composition and temperature predicted by the assumption of thermodynamic equilibrium. Expressions for the amount of fluid passing through the system based on the kinetic model are compared with previous calculations of the mass of fluid added to the system using the equilibrium assumptions. The approach to this steady state is also analyzed and an analytical solution is obtained for the time evolution up to the steady state. Both the steady state and the time evolution solution are then applied to an understanding of the dynamics involved in obtaining T-X-t paths in nature. The results of the kinetic approach lead to major revisions in many of the previously held concepts used in petrologic fluid flow models. These include the expected reaction pathway, the role of metastable reactions, the calculation of fluid flux, the role of the invariant point, and the interpretation of mineral textures and modal abundances of minerals.

Lasaga, A.C.; Luettge, A.; Rye, D.M.; Bolton, E.W.

2000-03-01

57

Phenotypes of the COXdeficient mice indicate physiological and pathophysiological roles for COX1 and COX2  

Microsoft Academic Search

The development of mice deficient in either cyclooxygenase-1 (COX-1) or COX-2, as well as mice deficient in both COX isoforms, has provided models to elucidate the physiological and pathophysiological roles of these enzymes. The findings obtained with the COX-deficient mice suggest that COX-2 may be more important than COX-1 for supplying prostaglandins (PGs) to maintain tissue homeostasis. Furthermore, both isoforms

Charles D Loftin; Howard F Tiano; Robert Langenbach

2002-01-01

58

Nonparametric regression using linear combinations of basis functions  

Microsoft Academic Search

This paper discusses a Bayesian approach to nonparametric regression initially proposed by Smith and Kohn (1996. Journal of Econometrics 75: 317–344). In this approach the regression function is represented as a linear combination of basis terms. The basis terms can be univariate or multivariate functions and can include polynomials, natural splines and radial basis functions. A Bayesian hierarchical model is

Robert Kohn; Michael Smith; David Chan

2001-01-01

59

Multivariate linear regression with missing values.  

PubMed

This contribution presents and discusses an efficient algorithm for multivariate linear regression analysis of data sets with missing values. The algorithm is based on the insight that multivariate linear regression can be formulated as a set of individual univariate linear regressions. All available information is used and the calculations are explicit. The only restriction is that the independent variable matrix has to be non-singular. There is no need for imputation of interpolated or otherwise guessed values which require subsequent iterative refinement. PMID:24016580

Beyad, Yaser; Maeder, Marcel

2013-08-20

60

Histomorphologic Tumor Regression and Lymph Node Metastases Determine Prognosis Following Neoadjuvant Radiochemotherapy for Esophageal Cancer  

PubMed Central

Objective: We sought to quantitatively and objectively evaluate histomorphologic tumor regression and establish a relevant prognostic regression classification system for esophageal cancer patients receiving neoadjuvant radiochemotherapy. Patients and Methods: Eighty-five consecutive patients with localized esophageal cancers (cT2-4, Nx, M0) received standardized neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, 36 Gy). Seventy-four (87%) patients were resected by transthoracic en bloc esophagectomy and 2-field lymphadenectomy. The entire tumor beds of the resected specimens were evaluated histomorphologically, and regression was categorized into grades I to IV based on the percentage of vital residual tumor cells (VRTCs). A major response was achieved when specimens contained either less than 10% VRTCs (grade III) or a pathologic complete remission (grade IV). Results: Complete resections (R0) were performed in 66 of 74 (89%) patients with 3-year survival rates of 54% ± 7.05% for R0-resected cases and 0% for patients with incomplete resections ortumor progression during neoadjuvant therapy (P < 0.01). Minor histopathologic response was present in 44 (59.5%) and major histopathologic response in 30 (40.5%) tumors. Significantly different 3-year survival rates (38.8% ± 8.1% for minor versus 70.7 ± 10.1% for major response) were observed. Univariate survival analysis identified histomorphologic tumor regression (P < 0.004) and lymph node category (P < 0.01) as significant prognostic factors. Pathologic T category (P < 0.08), histologic type (P = 0.15), or grading (P = 0.33) had no significant impact on survival. Cox regression analysis identified dichotomized regression grades (minor and major histomorphologic regression, P < 0.028) and lymph node status (ypN0 and ypN1, P < 0.036) as significant independent prognostic parameters. A 2-parameter regression classification system that includes histomorphologic regression (major versus minor) and nodal status (ypN0 versus ypN1) was established (P < 0.001). Conclusions: Histomorphologic tumor regression and lymph node status (ypN) were significant prognostic parameters for patients with complete resections (R0) following neoadjuvant radiochemotherapy for esophageal cancer. A regression classification based on 2 parameters could lead to improved objective evaluation of the effectiveness of treatment protocols, accuracy of staging and restaging modalities, and molecular response prediction.

Schneider, Paul M.; Baldus, Stephan E.; Metzger, Ralf; Kocher, Martin; Bongartz, Rudolf; Bollschweiler, Elfriede; Schaefer, Hartmut; Thiele, Juergen; Dienes, Hans P.; Mueller, Rolf P.; Hoelscher, Arnulf H.

2005-01-01

61

Cyclooxygenase (COX) inhibitors and the intestine.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins. PMID:17552439

Little, Dianne; Jones, Samuel L; Blikslager, Anthony T

62

ELASTIC NET FOR COX'S PROPORTIONAL HAZARDS MODEL WITH A SOLUTION PATH ALGORITHM  

PubMed Central

For least squares regression, Efron et al. (2004) proposed an efficient solution path algorithm, the least angle regression (LAR). They showed that a slight modification of the LAR leads to the whole LASSO solution path. Both the LAR and LASSO solution paths are piecewise linear. Recently Wu (2011) extended the LAR to generalized linear models and the quasi-likelihood method. In this work we extend the LAR further to handle Cox’s proportional hazards model. The goal is to develop a solution path algorithm for the elastic net penalty (Zou and Hastie (2005)) in Cox’s proportional hazards model. This goal is achieved in two steps. First we extend the LAR to optimizing the log partial likelihood plus a fixed small ridge term. Then we define a path modification, which leads to the solution path of the elastic net regularized log partial likelihood. Our solution path is exact and piecewise determined by ordinary differential equation systems.

Wu, Yichao

2012-01-01

63

ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL  

PubMed Central

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.

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

2013-01-01

64

Expression of COX-1 and COX-2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids  

PubMed Central

Background Cyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy and estrous cycle. Methods Uteri were collected from the cyclic rats on each day of estrous cycle, after every two days for pregnant (days 2 to 22) and pseudopregnant rats (days 1 to 9). In vitro primary endometrial stromal cells were cultured in the presence of steroid hormones and their respective inhibitors for the possible modulation of COX-1 and COX-2. Endometrial protein extracts were used for western blot analysis and tissue sections were prepared for protein localization using immunofluorescence. Measurements of PGF2alpha and PGE2 metabolites in serum were performed by enzyme immunoassay (EIA). Results COX-1 expression was found to be elevated during implantation and parturition, however, the levels of COX-1 decreased during decidualization periods. COX-2 was detected during early pregnancy from day 2 to 5, increased during decidual regression, and was also expressed at the time of parturition. COX-2 protein expression was found to be increased at estrus phase in cyclic rats. Both enzymes were found to be modulated in the endometrium of pseudopregnant rats, suggesting that they are regulated by 17beta-estradiol and progesterone. A significant increase in PGE2 metabolite levels was observed on day 10, 12 and 14 of pregnancy. However, an increase in PGF2alpha metabolite levels was observed only on day 14. The concentration of both these metabolites changed during pseudopregnancy and maximum levels were observed at day 7. Significant increase in PGE2 metabolite was observed at proestrus phase, on the other hand, PGF2alpha metabolite was significantly increased at proestrus and metestrus phase. COX-2 protein was regulated by 17beta-estradiol in cultured endometrial stromal cells which was blocked in the presence of ICI-182,780. Conclusions Taken together, these results suggest that COX-1 and COX-2 could be differentially regulated by steroid hormones and might be the key factors involved in embryo implantation, decidualization, decidua basalis regression and parturition in rats.

2010-01-01

65

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

Microsoft Academic Search

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

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

2000-01-01

66

Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors.  

PubMed

In vitro evaluations of the selectivity of COX inhibitors are based on a great variety of experimental protocols. As a result, data available on cyclooxygenase (COX)-1/COX-2/5- lipoxygenase (LOX) selectivity of COX inhibitors lack consistency. We, therefore, performed a systematic analysis of the COX-1/COX-2/5-LOX selectivity of 14 compounds with selective COX inhibitory activity (Coxibs). The compounds belonged to different structural classes and were analyzed employing the well-recognized whole-blood assay. 5-LOX activity was also tested on isolated human polymorphonuclear leukocytes. Among COX inhibitors, celecoxib and ML-3000 (licofelone) inhibited 5-LOX in human neutrophils at micromolar ranges. Surprisingly, ML-3000 had no effect on 5-LOX product synthesis in whole-blood assay. In addition, we could show that inhibition of COX pathways did not increase the transformation of arachidonic acid by the 5-LOX pathway. PMID:18280718

Sud'ina, G F; Pushkareva, M A; Shephard, P; Klein, T

2008-02-15

67

There Are Infinitely Many Univariate Normal Distributions: Distribution "Bells" Come in Many Appearances.  

ERIC Educational Resources Information Center

|Many univariate statistical methods assume that dependent variable data have a univariate distribution. Some statistical methods assume that the error scores are normally distributed. It is clear that the concept of data normality is an important one in statistics. This paper explains that, notwithstanding common misconceptions to the contrary,…

Rollins, Dahl A.

68

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

Microsoft Academic Search

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

Wolfgang Schmid; Dobromir Tzotchev

69

A comparison of univariate methods for forecasting electricity demand up to a day ahead  

Microsoft Academic Search

This empirical paper compares the accuracy of six univariate methods for short-term electricity demand forecasting for lead times up to a day ahead. The very short lead times are of particular interest as univariate methods are often replaced by multivariate methods for prediction beyond about six hours ahead. The methods considered include the recently proposed exponential smoothing method for double

James W. Taylor; Lilian M. de Menezes; Patrick E. McSharry

2006-01-01

70

Cyclooxygenase2 (COX2), aromatase and breast cancer: a possible role for COX2 inhibitors in breast cancer chemoprevention  

Microsoft Academic Search

breast. The main target of NSAID activity is the cyclooxygenase (COX) enzyme. Two isoforms of COX have been identified: COX-1, the constitutive isoform; and COX-2, the inducible form of the enzyme. COX-2 can undergo rapid induction in response to many factors such as bacterial lipopolysaccharides, growth factors, cytokines and phorbol esters. COX-2 is overexpressed in some malignancies including carcinoma of

G. Davies; L.-A. Martin; N. Sacks; M. Dowsett

2002-01-01

71

Gene-gene interaction analysis for the survival phenotype based on the Cox model  

PubMed Central

Motivation: For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP–SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene–gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) method to the survival phenotype by using the log-rank test for defining a binary attribute. However, the Surv-MDR method has some drawbacks in the sense that it needs more intensive computations and does not allow for a covariate adjustment. In this article, we propose a new approach, called Cox-MDR, which is an extension of the generalized multifactor dimensionality reduction (GMDR) to the survival phenotype by using a martingale residual as a score to classify multi-level genotypes as high- and low-risk groups. The advantages of Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative covariates in the frame of Cox regression model and to require less computation than Surv-MDR. Results: Through simulation studies, we compared the power of Cox-MDR with those of Surv-MDR and Cox regression model for various heritability and minor allele frequency combinations without and with adjusting for covariate. We found that Cox-MDR and Cox regression model perform better than Surv-MDR for low minor allele frequency of 0.2, but Surv-MDR has high power for minor allele frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR and Cox regression model perform much better than Surv-MDR. We also compared the performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to detect the gene–gene interactions with the survival time. Contact: leesy@sejong.ac.kr; tspark@snu.ac.kr

Lee, Seungyeoun; Kwon, Min-Seok; Oh, Jung Mi; Park, Taesung

2012-01-01

72

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

SciTech Connect

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.

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

2006-02-01

73

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

PubMed Central

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

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

2008-01-01

74

Regression Calibration with Heteroscedastic Error Variance  

PubMed Central

The problem of covariate measurement error with heteroscedastic measurement error variance is considered. Standard regression calibration assumes that the measurement error has a homoscedastic measurement error variance. An estimator is proposed to correct regression coefficients for covariate measurement error with heteroscedastic variance. Point and interval estimates are derived. Validation data containing the gold standard must be available. This estimator is a closed-form correction of the uncorrected primary regression coefficients, which may be of logistic or Cox proportional hazards model form, and is closely related to the version of regression calibration developed by Rosner et al. (1990). The primary regression model can include multiple covariates measured without error. The use of these estimators is illustrated in two data sets, one taken from occupational epidemiology (the ACE study) and one taken from nutritional epidemiology (the Nurses’ Health Study). In both cases, although there was evidence of moderate heteroscedasticity, there was little difference in estimation or inference using this new procedure compared to standard regression calibration. It is shown theoretically that unless the relative risk is large or measurement error severe, standard regression calibration approximations will typically be adequate, even with moderate heteroscedasticity in the measurement error model variance. In a detailed simulation study, standard regression calibration performed either as well as or better than the new estimator. When the disease is rare and the errors normally distributed, or when measurement error is moderate, standard regression calibration remains the method of choice.

Spiegelman, Donna; Logan, Roger; Grove, Douglas

2011-01-01

75

The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea  

PubMed Central

Background/Aims The potential role of the cyclooxygenase (COX)-2 polymorphism has been reported in relation to the risk of gastrointestinal tract malignancies. Therefore, we investigated whether COX-2 polymorphisms are associated with the risk of gastric cancer (GC) in Korea, one of the areas with a high prevalence of this condition. Methods We evaluated the genotypic frequencies of COX-2-765 and -1195 in 100 peptic ulcer patients, 100 GC patients, and 100 healthy controls. The polymorphisms of the COX-2-765 and -1195 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphisms. Results The frequencies of the COX-2-1195 GG, GA, and AA genotype were 20%, 60%, and 20% in intestinal-type GC and 8%, 48%, and 44% in diffuse-type GC, respectively (p=0.021). There were no significant differences in the frequency of COX-2-765 genotypes between intestinal-type GC and diffuse-type GC (p=0.603). Age- and sex-adjusted logistic regression analysis showed that the COX-2-1195 AA genotype was the independent risk factor of diffuse-type GC compared with the COX-2-1195 GG genotype (p=0.041; odds ratio, 6.22; 95% confidence interval, 1.077 to 35.870). Conclusions The COX-2-1195 AA genotype may render subjects more susceptible to diffuse-type GC.

Shin, Woon Geon; Kim, Ha Jung; Cho, Sung Jin; Kim, Hyoung Su; Kim, Kyung Ho; Jang, Myoung Kuk; Lee, Jin Heon

2012-01-01

76

Logistic regression: a brief primer.  

PubMed

Regression techniques are versatile in their application to medical research because they can measure associations, predict outcomes, and control for confounding variable effects. As one such technique, logistic regression is an efficient and powerful way to analyze the effect of a group of independent variables on a binary outcome by quantifying each independent variable's unique contribution. Using components of linear regression reflected in the logit scale, logistic regression iteratively identifies the strongest linear combination of variables with the greatest probability of detecting the observed outcome. Important considerations when conducting logistic regression include selecting independent variables, ensuring that relevant assumptions are met, and choosing an appropriate model building strategy. For independent variable selection, one should be guided by such factors as accepted theory, previous empirical investigations, clinical considerations, and univariate statistical analyses, with acknowledgement of potential confounding variables that should be accounted for. Basic assumptions that must be met for logistic regression include independence of errors, linearity in the logit for continuous variables, absence of multicollinearity, and lack of strongly influential outliers. Additionally, there should be an adequate number of events per independent variable to avoid an overfit model, with commonly recommended minimum "rules of thumb" ranging from 10 to 20 events per covariate. Regarding model building strategies, the three general types are direct/standard, sequential/hierarchical, and stepwise/statistical, with each having a different emphasis and purpose. Before reaching definitive conclusions from the results of any of these methods, one should formally quantify the model's internal validity (i.e., replicability within the same data set) and external validity (i.e., generalizability beyond the current sample). The resulting logistic regression model's overall fit to the sample data is assessed using various goodness-of-fit measures, with better fit characterized by a smaller difference between observed and model-predicted values. Use of diagnostic statistics is also recommended to further assess the adequacy of the model. Finally, results for independent variables are typically reported as odds ratios (ORs) with 95% confidence intervals (CIs). PMID:21996075

Stoltzfus, Jill C

2011-10-01

77

Imputing missing covariate values for the Cox model  

PubMed Central

Multiple imputation is commonly used to impute missing data, and is typically more efficient than complete cases analysis in regression analysis when covariates have missing values. Imputation may be performed using a regression model for the incomplete covariates on other covariates and, importantly, on the outcome. With a survival outcome, it is a common practice to use the event indicator D and the log of the observed event or censoring time T in the imputation model, but the rationale is not clear. We assume that the survival outcome follows a proportional hazards model given covariates X and Z. We show that a suitable model for imputing binary or Normal X is a logistic or linear regression on the event indicator D, the cumulative baseline hazard H0(T), and the other covariates Z. This result is exact in the case of a single binary covariate; in other cases, it is approximately valid for small covariate effects and/or small cumulative incidence. If we do not know H0(T), we approximate it by the Nelson–Aalen estimator of H(T) or estimate it by Cox regression. We compare the methods using simulation studies. We find that using log T biases covariate-outcome associations towards the null, while the new methods have lower bias. Overall, we recommend including the event indicator and the Nelson–Aalen estimator of H(T) in the imputation model. Copyright © 2009 John Wiley & Sons, Ltd.

White, Ian R; Royston, Patrick

2009-01-01

78

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

PubMed

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

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

2012-01-08

79

Weighted scores method for regression models with dependent data.  

PubMed

There are copula-based statistical models in the literature for regression with dependent data such as clustered and longitudinal overdispersed counts, for which parameter estimation and inference are straightforward. For situations where the main interest is in the regression and other univariate parameters and not the dependence, we propose a "weighted scores method", which is based on weighting score functions of the univariate margins. The weight matrices are obtained initially fitting a discretized multivariate normal distribution, which admits a wide range of dependence. The general methodology is applied to negative binomial regression models. Asymptotic and small-sample efficiency calculations show that our method is robust and nearly as efficient as maximum likelihood for fully specified copula models. An illustrative example is given to show the use of our weighted scores method to analyze utilization of health care based on family characteristics. PMID:21436109

Nikoloulopoulos, Aristidis K; Joe, Harry; Chaganty, N Rao

2011-03-23

80

Dietary habits and risk of death due to hepatocellular carcinoma in a large scale cohort study in Japan. Univariate analysis of JACC study data.  

PubMed

To explore the association between dietary habits and risk of hepatocellular carcinoma (HCC) mortality in Japan, univariate analyses was performed using data from the JACC Study. A cohort of 46,465 males and 64,327 females aged 40 to 79 in 19 prefectures in Japan completed the baseline survey during 1988-1990 and were followed up until the end of 1999. The hazard ratio (HR) of HCC mortality for each food item by gender, age group (40-59 and 60-79 years) and history of liver diseases was obtained by Cox proportional hazards model. Some categories, such as boiled rice, ham and sausage, chicken, fish and pickles among men without history of liver diseases and those of miso-soup, fish, carrots and squash, and potatoes among women without history of liver diseases showed a significant inverse association with HCC mortality. Frequent intake of eggs was significantly associated with increased HCC mortality in men without history of liver diseases. Potatoes and foods boiled down in soy sauce (tsukudani) showed a significant positive association, and pickles had a significant inverse association with HCC mortality in men with history of liver diseases. Frequent intake of coffee showed a significant inverse association with HCC mortality both in men and women with history of liver diseases. It is considered that further analysis using a multivariate Cox proportional hazards model including other confounding factors will be required for a more meaningful interpretation of the data. PMID:15373231

Kurozawa, Youichi; Ogimoto, Itsuro; Shibata, Akira; Nose, Takayuki; Yoshimura, Takesumi; Suzuki, Hiroshi; Sakata, Ritsu; Fujita, Yuki; Ichikawa, Shoko; Iwai, Nobuo; Fukuda, Katsuhiro; Tamakoshi, Akiko

2004-01-01

81

No mitochondrial cytochrome oxidase (COX) gene mutations in 18 cases of COX deficiency.  

PubMed

Cytochrome c oxidase (COX) deficiency causes a variety of neuromuscular and non-neuromuscular disorders in childhood and adulthood and can theoretically undergo either a nuclear or a mitochondrial (mt) mode of inheritance, making genetic counseling in COX deficiency particularly hazardous. In an attempt to determine the respective roles of mtDNA and nuclear DNA mutations in COX deficiency, we sequenced the three mitochondrially encoded COX subunits (COXI-III) in a series of 18 patients with isolated COX deficiency, especially as COXI-III code for the catalytic site of the enzyme. We failed to detect any deleterious mutations in this series. Moreover, no mtDNA deletion was observed and sequencing of the flanking tRNA genes involved in the maturation of the COX transcripts failed to detect deleterious mutations as well. The present study supports the view that the disease-causing mutations do not lie in the mt genome but, rather, in the nuclear genes encoding either the COX subunits or the proteins involved in assembly of the complex and suggests a recurrent risk of 25% rather than other modes of inheritance in COX deficiencies. PMID:9402980

Parfait, B; Percheron, A; Chretien, D; Rustin, P; Munnich, A; Rötig, A

1997-12-01

82

Simple Logistic Regression  

NSDL National Science Digital Library

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

Lowry, Richard, 1940-

2008-09-05

83

Meloxicam: Selective COX2 inhibition in clinical practice  

Microsoft Academic Search

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibitingcyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with

Daniel E. Furst

1997-01-01

84

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

PubMed Central

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

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

2013-01-01

85

Partial residuals for the proportional hazards regression model  

Microsoft Academic Search

SUMMARY Residuals are defined for the proportional hazards regression model introduced by Cox (1972). These residuals can be plotted against time to test the proportional hazards assumption. Histograms of these residuals can be used to examine fit and detect outlying covariate values.

DAVID SCHOENFELD

1982-01-01

86

Analysis of Cross-Sectional Univariate Measurements for Family Dyads Using Linear Mixed Modeling  

Microsoft Academic Search

Outcome measurements from members of the same family are likely correlated. Such intrafamilial correlation (IFC) is an important dimension of the family as a unit but is not always accounted for in analyses of family data. This article demonstrates the use of linear mixed modeling to account for IFC in the important special case of univariate measurements for family dyads

George J. Knafl; Jane K. Dixon; Jean P. OMalley; Margaret Grey; Janet A. Deatrick; Agatha M. Gallo; Kathleen A. Knafl

2009-01-01

87

Forecasting monthly electric energy consumption in eastern Saudi Arabia using univariate time-series analysis  

Microsoft Academic Search

Univariate Box-Jenkins time-series analysis has been used for modeling and forecasting monthly domestic electric energy consumption in the Eastern Province of Saudi Arabia. Autoregressive integrated moving average (ARIMA) models were developed using data for 5 yr and evaluated on forecasting new data for the sixth year. The optimum model derived is a multiplicative combination of seasonal and nonseasonal autoregressive parts,

R. E. Abdel-Aal; A. Z. Al-Garni

1997-01-01

88

A new monitoring design for uni-variate statistical quality control charts  

Microsoft Academic Search

In this research, an iterative approach is employed to analyze and classify the states of uni-variate quality control systems. To do this, a measure (called the belief that process is in-control) is first defined and then an equation is developed to update the belief recursively by taking new observations on the quality characteristic under consideration. Finally, the upper and the

Mohammad Saber Fallah Nezhad; Seyed Taghi Akhavan Niaki

2010-01-01

89

Quantile regression for recurrent gap time data.  

PubMed

Evaluating covariate effects on gap times between successive recurrent events is of interest in many medical and public health studies. While most existing methods for recurrent gap time analysis focus on modeling the hazard function of gap times, a direct interpretation of the covariate effects on the gap times is not available through these methods. In this article, we consider quantile regression that can provide direct assessment of covariate effects on the quantiles of the gap time distribution. Following the spirit of the weighted risk-set method by Luo and Huang (2011, Statistics in Medicine 30, 301-311), we extend the martingale-based estimating equation method considered by Peng and Huang (2008, Journal of the American Statistical Association 103, 637-649) for univariate survival data to analyze recurrent gap time data. The proposed estimation procedure can be easily implemented in existing software for univariate censored quantile regression. Uniform consistency and weak convergence of the proposed estimators are established. Monte Carlo studies demonstrate the effectiveness of the proposed method. An application to data from the Danish Psychiatric Central Register is presented to illustrate the methods developed in this article. PMID:23489055

Luo, Xianghua; Huang, Chiung-Yu; Wang, Lan

2013-03-11

90

Radiosensitivity Enhancement by Celecoxib, a Cyclooxygenase (COX)-2 Selective Inhibitor, via COX2Dependent Cell Cycle Regulation on Human Cancer Cells Expressing Differential COX2 Levels  

Microsoft Academic Search

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotox- icity assays and radiation survival assays after treatment with celecoxib F radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or

You Keun Shin; Ji Sun Park; Hyun Seok Kim; Hyun Jung Jun; Gwi Eon Kim; Chang Ok Suh; Yeon Sook Yun; Hongryull Pyo

91

Cox2 is needed but not sufficient for apoptosis induced by Cox2 selective inhibitors in colon cancer cells  

Microsoft Academic Search

The role of Cox-2 in NSAID-induced apoptosis is debated. We studied the role of Cox-2 inhibition in apoptosis induced by a selective Cox-2 inhibitor, SC236 (a structural analogue of celecoxib) in two colon cancer cell lines, HT29 (expressing Cox-2 protein) and HCT116 (not expressing Cox-2 protein). Apoptosis was quantified by flow cytometry. SC236 0–75 µM decreased cell numbers and induced

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

2003-01-01

92

Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice  

PubMed Central

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-? 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.

Carey, Michelle A.; Bradbury, J. Alyce; Rebolloso, Yvette D.; Graves, Joan P.; Zeldin, Darryl C.; Germolec, Dori R.

2010-01-01

93

Are All COX2 Inhibitors Created Equal?  

Microsoft Academic Search

rostaglandins (PGs) are biologically active lipids de- rived from the cyclooxygenase (COX)-mediated me- tabolism of arachidonic acid. They are constitutively produced in certain tissues (eg, brain, gut, and kidney), and their synthesis is increased at sites of inflammation. Prosta- noids function as important mediators of inflammation and modulate a variety of physiological processes, including maintenance of gastric mucosal integrity, renal

Ingrid J. Chang; Raymond C. Harris

2010-01-01

94

Relative risk regression analysis of epidemiologic data.  

PubMed Central

Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events.

Prentice, R L

1985-01-01

95

Relative risk regression analysis of epidemiologic data.  

PubMed

Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events. PMID:4076087

Prentice, R L

1985-11-01

96

Unitary Response Regression Models  

ERIC Educational Resources Information Center

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

Lipovetsky, S.

2007-01-01

97

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

PubMed

Event-related potentials (ERPs) and magnetic fields (ERFs) are typically analyzed via ANOVAs on mean activity in a priori windows. Advances in computing power and statistics have produced an alternative, mass univariate analyses consisting of thousands of statistical tests and powerful corrections for multiple comparisons. Such analyses are most useful when one has little a priori knowledge of effect locations or latencies, and for delineating effect boundaries. Mass univariate analyses complement and, at times, obviate traditional analyses. Here we review this approach as applied to ERP/ERF data and four methods for multiple comparison correction: strong control of the familywise error rate (FWER) via permutation tests, weak control of FWER via cluster-based permutation tests, false discovery rate control, and control of the generalized FWER. We end with recommendations for their use and introduce free MATLAB software for their implementation. PMID:21895683

Groppe, David M; Urbach, Thomas P; Kutas, Marta

2011-09-06

98

Multivariate multiple regression analyses: a permutation method for linear models.  

PubMed

A multivariate extension of a univariate procedure for the analysis of experimental designs is presented. A Euclidean-distance permutation procedure is used to evaluate multivariate residuals obtained from a regression algorithm, also based on Euclidean distances. Applications include various completely randomized and randomized block experimental designs such as one-way, Latin square, factorial, nested, and split-plot designs, with and without covariates. Unlike parametric procedures, the only required assumption is the randomization of subjects to treatments. PMID:12353797

Mielke, Paul W; Berry, Kenneth J

2002-08-01

99

On internally corrected and symmetrized kernel estimators for nonparametric regression  

Microsoft Academic Search

We investigate the properties of a kernel-type multivariate regression estimator first proposed by Mack and Müller (Sankhya\\u000a 51:59–72, 1989) in the context of univariate derivative estimation. Our proposed procedure, unlike theirs, assumes that bandwidths of the\\u000a same order are used throughout; this gives more realistic asymptotics for the estimation of the function itself but makes\\u000a the asymptotic distribution more complicated.

Oliver B. Linton; David T. Jacho-Chávez

2010-01-01

100

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

Microsoft Academic Search

The present article reports studies to develop a univariate model to forecast the summer monsoon (June–August) rainfall over India. Based on the data pertaining to the period 1871–1999, the trend and stationarity within the time series have been investigated. After revealing the randomness and non-stationarity within the time series, the autoregressive integrated moving average (ARIMA) models have been attempted and

Surajit Chattopadhyay; Goutami Chattopadhyay

2010-01-01

101

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

NASA Astrophysics Data System (ADS)

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

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

2012-09-01

102

POSIX threads polynomials(PTPol): a scalable implementation of univariate arithmetic operations  

Microsoft Academic Search

In this paper, we describe the design of a C library named PTPol implementing arithmetic operations for univariate poly- nomials and report on practical experiments showing the relevance of using threads on recent multi-core computers. We show how to use eciently an API named OpenMP and POSIX Threads to achieve scalability. On multi-core archi- tectures, we obtain a speed-up equivalent

Mohab Safey El Din; Philippe Trebuchet

2007-01-01

103

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

PubMed Central

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

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

2008-01-01

104

Radionuclide concentrations in salt pans in the coastal area of Cox’s bazar, Bangladesh  

Microsoft Academic Search

Radionuclide concentrations of 226Ra, 232Th, 137Cs, 134Cs and 40K in samples of water, soil and salt from three gradients of salt pans (reservoir, condenser and crystalliser) in the coastal area of Cox’s Bazar, Bangladesh and in samples of refined salts were measured using ?-spectrometry. The activities of 226Ra in the salt pans were found to be in the range 3·18±1·02Bql-1

M. N. Alam; M. I. Chowdhury; M. Zafar; M. Kamal; S. Ghose; A. H. M. Kamal

1998-01-01

105

Logical and statistical fallacies in the use of cox regression models  

Microsoft Academic Search

Time-dependent covariates are an essential data analysis tool for modeling the effect of a study factor whose value changes during follow-up. However, survival analysis models can yield conclusions that are contrary to the truth if such time-dependent factors are not defined and used carefully. We outline some of the biases that can occur when time-dependent covariates are used improperly in

Robert A. Wolfe; Robert L. Strawderman

1996-01-01

106

Statistical methods for astronomical data with upper limits. II - Correlation and regression  

Microsoft Academic Search

Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for

T. Isobe; E. D. Feigelson; P. I. Nelson

1986-01-01

107

COX2 Inhibitors for the Prevention of Breast Cancer  

Microsoft Academic Search

The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is normally expressed predominantly in kidney and brain, and also has important roles in reproduction and inflammation. COX-2 misexpression has been observed in numerous human cancers, including the majority of colorectal cancers. Recently, COX-2 overexpression has been described in human breast cancer. COX-2 is present in about 40% of invasive breast carcinomas, particularly those

Louise R. Howe; Andrew J. Dannenberg

2003-01-01

108

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

PubMed Central

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

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

2011-01-01

109

Deficiency of Either Cyclooxygenase (COX)-1 or COX2 Alters Epidermal Differentiation and Reduces Mouse Skin Tumorigenesis  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1

Howard F. Tiano; Charles D. Loftin; Jackie Akunda; Christopher A. Lee; Judson Spalding; Alisha Sessoms; David B. Dunson; Eleanor G. Rogan; Scott G. Morham; Robert C. Smart; Robert Langenbach

2002-01-01

110

Estimating genomic breeding values and detecting QTL using univariate and bivariate models  

PubMed Central

Background Genomic selection is particularly beneficial for difficult or expensive to measure traits. Since multi-trait selection is an important tool to deal with such cases, an important question is what the added value is of multi-trait genomic selection. Methods The simulated dataset, including a quantitative and binary trait, was analyzed with four univariate and bivariate linear models to predict breeding values for juvenile animals. Two models estimated variance components with REML using a numerator (A), or SNP based relationship matrix (G). Two SNP based Bayesian models included one (BayesA) or two distributions (BayesC) for estimated SNP effects. The bivariate BayesC model sampled QTL probabilities for each SNP conditional on both traits. Genotypes were permuted 2,000 times against phenotypes and pedigree, to obtain significance thresholds for posterior QTL probabilities. Genotypes were permuted rather than phenotypes, to retain relationships between pedigree and phenotypes, such that polygenic effects could still be estimated. Results Correlations between estimated breeding values (EBV) of different SNP based models, for juvenile animals, were greater than 0.93 (0.87) for the quantitative (binary) trait. Estimated genetic correlation was 0.71 (0.66) for model G (A). Accuracies of breeding values of SNP based models were for both traits highest for BayesC and lowest for G. Accuracies of breeding values of bivariate models were up to 0.08 higher than for univariate models. The bivariate BayesC model detected 14 out of 32 QTL for the quantitative trait, and 8 out of 22 for the binary trait. Conclusions Accuracy of EBV clearly improved for both traits using bivariate compared to univariate models. BayesC achieved highest accuracies of EBV and was also one of the methods that found most QTL. Permuting genotypes against phenotypes and pedigree in BayesC provided an effective way to derive significance thresholds for posterior QTL probabilities.

2011-01-01

111

An uncertain regression model  

Microsoft Academic Search

Purpose – The purpose of this paper is to propose an uncertain regression model with an intrinsic error structure facilitated by an uncertain canonical process. Design\\/methodology\\/approach – This model is suitable for dealing with expert's knowledge ranging from small to medium size data of impreciseness. In order to have a rigorous mathematical treatment on the new regression model, this paper

Renkuan Guo; Danni Guo; YanHong Cui

2011-01-01

112

Lesson 6: Linear Regression  

NSDL National Science Digital Library

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

2011-01-01

113

BIAS IN ECOLOGICAL REGRESSION  

Microsoft Academic Search

Bias formulae are derived for ecological regression estima- tors. These formulae are useful for determining the direction and mag- nitude of bias in estimation. It is shown that when group cohesion is higher in areas with higher concentrations of group members and when polarization is higher in more homogeneous areas, ecological regression estimates of polarization will tend to be biased

STEPHEN ANSOLABEHERE; DOUGLAS RIVERS

114

Fuzzy Regression in Hydrology  

NASA Astrophysics Data System (ADS)

A general methodology for fuzzy regression is developed and illustrated by an actual hydrological case study. Fuzzy regression may be used whenever a relationship between variables is imprecise and/or data are inaccurate and/or sample sizes are insufficient. In such cases fuzzy regression may be used as a complement or an alternative to statistical regression analysis. In fuzzy regression, several "goodness of fit" criteria may be used such as the maximum average vagueness criterion and the prediction vagueness criterion. The technique is illustrated by means of a case study involving the relationship between soil electrical resistivity and hydraulic permeability. This relationship is imprecise and based on only a few data points. In the present case a curvilinear relationship is fitted using fuzzy regression with six calculated resistivities and six measured permeabilities. Prediction vagueness criteria appears to yield a more robust fuzzy regression than the maximum average vagueness criteria. Potential application areas of fuzzy regression in hydrology are discussed further. The methodology is relatively simple, and the results can be interpreted to provide a valuable hydrological decision-making aid.

Bardossy, Andras; Bogardi, Istvan; Duckstein, Lucien

1990-07-01

115

Correlation and Regression  

NSDL National Science Digital Library

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

Berger, Dale

2008-12-24

116

Prediction in Multiple Regression.  

ERIC Educational Resources Information Center

Presents the concept of prediction via multiple regression (MR) and discusses the assumptions underlying multiple regression analyses. Also discusses shrinkage, cross-validation, and double cross-validation of prediction equations and describes how to calculate confidence intervals around individual predictions. (SLD)

Osborne, Jason W.

2000-01-01

117

Morse-Smale Regression.  

PubMed

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

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

2013-01-01

118

Online multiple instance regression  

NASA Astrophysics Data System (ADS)

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

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

2013-09-01

119

Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis.  

PubMed

Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1 or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model. Reduced tumorigenesis was observed even though the levels of stable 7,12-dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX-deficient mice compared with wild-type mice. The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20-fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2-deficient mice, respectively, than in wild-type mice. Papillomas on the COX-deficient mice also displayed the premature onset of keratinocyte terminal differentiation. However, loricrin, a late marker of epidermal differentiation, was not significantly altered, suggesting that it was the early stages of keratinocyte differentiation that were primarily affected by COX deficiency. Because keratin 5, a keratin associated with basal cells, was detected differently in papillomas of COX-1-deficient as compared with COX-2-deficient mice, it appears that the isoforms do not have identical roles in papilloma development. Interestingly, apoptosis, a cellular process associated with nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not significantly altered in the epidermis or in papillomas of the COX-deficient mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation. PMID:12067981

Tiano, Howard F; Loftin, Charles D; Akunda, Jackie; Lee, Christopher A; Spalding, Judson; Sessoms, Alisha; Dunson, David B; Rogan, Eleanor G; Morham, Scott G; Smart, Robert C; Langenbach, Robert

2002-06-15

120

Cox and Giuli's Principles of Stellar Structure  

NASA Astrophysics Data System (ADS)

Cox and Guili's Principles of Stellar Structure has been the reference textbook for studies of the structure of stars for several decades. Its content and thoro ugh discussion of all relevant aspects of stellar physics make it a much needed tool for scholars and students. This new edition has been extended by four specialists and includes the most rec ent improvements relevant to the modelling and understanding of stars. New devel opments, such as results from the Hipparcos mission, the solar model and the inc lusion of particle diffusion in stellar models have been added to the original t ext.

Weiss, A.; Hillebrandt, W.; Thomas, H.-C.; Ritter, H.

121

Comparing the Characteristics of Gene Expression Profiles Derived by Univariate and Multivariate Classification Methods*  

PubMed Central

One application of gene expression arrays is to derive molecular profiles, i.e., sets of genes, which discriminate well between two classes of samples, for example between tumour types. Users are confronted with a multitude of classification methods of varying complexity that can be applied to this task. To help decide which method to use in a given situation, we compare important characteristics of a range of classification methods, including simple univariate filtering, penalised likelihood methods and the random forest. Classification accuracy is an important characteristic, but the biological interpretability of molecular profiles is also important. This implies both parsimony and stability, in the sense that profiles should not vary much when there are slight changes in the training data. We perform a random resampling study to compare these characteristics between the methods and across a range of profile sizes. We measure stability by adopting the Jaccard index to assess the similarity of resampled molecular profiles. We carry out a case study on five well-established cancer microarray data sets, for two of which we have the benefit of being able to validate the results in an independent data set. The study shows that those methods which produce parsimonious profiles generally result in better prediction accuracy than methods which don’t include variable selection. For very small profile sizes, the sparse penalised likelihood methods tend to result in more stable profiles than univariate filtering while maintaining similar predictive performance.

Zucknick, Manuela; Richardson, Sylvia; Stronach, Euan A.

2008-01-01

122

Univariate/Multivariate Genome-Wide Association Scans Using Data from Families and Unrelated Samples  

PubMed Central

As genome-wide association studies (GWAS) are becoming more popular, two approaches, among others, could be considered in order to improve statistical power for identifying genes contributing subtle to moderate effects to human diseases. The first approach is to increase sample size, which could be achieved by combining both unrelated and familial subjects together. The second approach is to jointly analyze multiple correlated traits. In this study, by extending generalized estimating equations (GEEs), we propose a simple approach for performing univariate or multivariate association tests for the combined data of unrelated subjects and nuclear families. In particular, we correct for population stratification by integrating principal component analysis and transmission disequilibrium test strategies. The proposed method allows for multiple siblings as well as missing parental information. Simulation studies show that the proposed test has improved power compared to two popular methods, EIGENSTRAT and FBAT, by analyzing the combined data, while correcting for population stratification. In addition, joint analysis of bivariate traits has improved power over univariate analysis when pleiotropic effects are present. Application to the Genetic Analysis Workshop 16 (GAW16) data sets attests to the feasibility and applicability of the proposed method.

Zhang, Lei; Pei, Yu-Fang; Li, Jian; Papasian, Christopher J.; Deng, Hong-Wen

2009-01-01

123

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

NASA Astrophysics Data System (ADS)

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

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

2011-11-01

124

Bayesian logistic regression analysis  

NASA Astrophysics Data System (ADS)

In this paper we present a Bayesian logistic regression analysis. It is found that if one wishes to derive the posterior distribution of the probability of some event, then, together with the traditional Bayes Theorem and the integrating out of nuissance parameters, the Jacobian transformation is an essential added ingredient. The application of the product rule gives the posterior of the unknown logistic regression coefficients. The Jacobian transformation then maps the posterior of these regression coefficients to the posterior of the corresponding probability of some event and some nuisance parameters. Finally, by way of the sumrule the nuissance parameters are integrated out.

van Erp, N.; van Gelder, P.

2013-08-01

125

Cox25 Teams Up with Mss51, Ssc1, and Cox14 to Regulate Mitochondrial Cytochrome c Oxidase Subunit 1 Expression and Assembly in Saccharomyces cerevisiae*  

PubMed Central

In the yeast Saccharomyces cerevisiae, mitochondrial cytochrome c oxidase (COX) biogenesis is translationally regulated. Mss51, a specific COX1 mRNA translational activator and Cox1 chaperone, drives the regulatory mechanism. During translation and post-translationally, newly synthesized Cox1 physically interacts with a complex of proteins involving Ssc1, Mss51, and Cox14, which eventually hand over Cox1 to the assembly pathway. This step is probably catalyzed by assembly chaperones such as Shy1 in a process coupled to the release of Ssc1-Mss51 from the complex. Impaired COX assembly results in the trapping of Mss51 in the complex, thus limiting its availability for COX1 mRNA translation. An exception is a null mutation in COX14 that does not affect Cox1 synthesis because the Mss51 trapping complexes become unstable, and Mss51 is readily available for translation. Here we present evidence showing that Cox25 is a new essential COX assembly factor that plays some roles similar to Cox14. A null mutation in COX25 by itself or in combination with other COX mutations does not affect Cox1 synthesis. Cox25 is an inner mitochondrial membrane intrinsic protein with a hydrophilic C terminus protruding into the matrix. Cox25 is an essential component of the complexes containing newly synthesized Cox1, Ssc1, Mss51, and Cox14. In addition, Cox25 is also found to interact with Shy1 and Cox5 in a complex that does not contain Mss51. These results suggest that once Ssc1-Mss51 are released from the Cox1 stabilization complex, Cox25 continues to interact with Cox14 and Cox1 to facilitate the formation of multisubunit COX assembly intermediates.

Fontanesi, Flavia; Clemente, Paula; Barrientos, Antoni

2011-01-01

126

Basic Multiple Regression  

NSDL National Science Digital Library

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

Lowry, Richard, 1940-

2008-06-25

127

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

SciTech Connect

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

Colleselli, Daniela [Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria); Bijuklic, Klaudija [Inflammation Research, Laboratory Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck (Austria); Mosheimer, Birgit A. [Inflammation Research, Laboratory Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck (Austria); Kaehler, Christian M. [Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria)]. E-mail: C.M.Kaehler@uibk.ac.at

2006-09-10

128

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

NASA Astrophysics Data System (ADS)

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

Ismail, A.; Hassan, Noor I.

2013-09-01

129

Analysis of Cross-Sectional Univariate Measurements for Family Dyads Using Linear Mixed Modeling  

PubMed Central

Outcome measurements from members of the same family are likely correlated. Such intrafamilial correlation (IFC) is an important dimension of the family as a unit but is not always accounted for in analyses of family data. This article demonstrates the use of linear mixed modeling to account for IFC in the important special case of univariate measurements for family dyads collected at a single point in time. Example analyses of data from partnered parents having a child with a chronic condition on their child's adaptation to the condition and on the family's general functioning and management of the condition are provided. Analyses of this kind are reasonably straightforward to generate with popular statistical tools. Thus, it is recommended that IFC be reported as standard practice reflecting the fact that a family dyad is more than just the aggregate of two individuals. Moreover, not accounting for IFC can affect the conclusions.

Knafl, George J.; Dixon, Jane K.; O'Malley, Jean P.; Grey, Margaret; Deatrick, Janet A.; Gallo, Agatha M.; Knafl, Kathleen A.

2010-01-01

130

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

NASA Astrophysics Data System (ADS)

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

Chattopadhyay, Surajit; Chattopadhyay, Goutami

2010-02-01

131

First Instances of Univariate and Tensor-product Multivariate Generalized Expo-Rational Finite Elements  

NASA Astrophysics Data System (ADS)

We consider a construction of finite elements (FE) which is, in some sense, dual to the construction of generalized expo-rational B-splines (GERBS)[1, 2]. The main result is the introduction of univariate and multivariate tensor-product GERBS-based FE which exhibit Hermite interpolatory properties. The derivation of these results is based on the theory of C?-smooth expo-rational B-splines (ERBS) and Ck-smooth, k = 0,1,2,... piecewise polynomial GERBS called Euler Beta-function B-splines. We provide visualization of the approximations of some model curves and surfaces using the new FE, as well as of the size and distribution of the error of these approximations.

Dechevsky, Lubomir T.; Zanaty, Peter

2011-12-01

132

Computing Confidence Bounds for Power and Sample Size of the General Linear Univariate Model  

PubMed Central

The power of a test, the probability of rejecting the null hypothesis in favor of an alternative, may be computed using estimates of one or more distributional parameters. Statisticians frequently fix mean values and calculate power or sample size using a variance estimate from an existing study. Hence computed power becomes a random variable for a fixed sample size. Likewise, the sample size necessary to achieve a fixed power varies randomly. Standard statistical practice requires reporting uncertainty associated with such point estimates. Previous authors studied an asymptotically unbiased method of obtaining confidence intervals for noncentrality and power of the general linear univariate model in this setting. We provide exact confidence intervals for noncentrality, power, and sample size. Such confidence intervals, particularly one-sided intervals, help in planning a future study and in evaluating existing studies.

Taylor, Douglas J.; Muller, Keith E.

2013-01-01

133

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

PubMed Central

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

2012-01-01

134

Micro-Raman Spectroscopy and Univariate Analysis for Monitoring Disease Follow-Up  

PubMed Central

Micro-Raman spectroscopy is a very promising tool for medical applications, thanks to its sensitivity to subtle changes in the chemical and structural characteristics of biological specimens. To fully exploit these promises, building a method of data analysis properly suited for the case under study is crucial. Here, a linear or univariate approach using a R2 determination coefficient is proposed for discriminating Raman spectra even with small differences. The validity of the proposed approach has been tested using Raman spectra of high purity glucose solutions collected in the 600 to 1,600 cm?1 region and also from solutions with two known solutes at different concentrations. After this validation step, the proposed analysis has been applied to Raman spectra from oral human tissues affected by Pemphigus Vulgaris (PV), a rare life-threatening autoimmune disease, for monitoring disease follow-up. Raman spectra have been obtained in the wavenumber regions from 1,050 to 1,700 cm?1 and 2,700 to 3,200 cm?1 from tissues of patients at different stages of pathology (active PV, under therapy and PV in remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage have been detected at 1,150–1,250 cm?1 (amide III) and 1,420–1,450 cm?1 (CH3 deformation) regions and around 1,650 cm?1 (amide I) and 2,930 cm?1 (CH3 symmetric stretch). The analysis of tissue Raman spectra by the proposed univariate method has allowed us to effectively differentiate tissues at different stages of pathology.

Camerlingo, Carlo; Delfino, Ines; Perna, Giuseppe; Capozzi, Vito; Lepore, Maria

2011-01-01

135

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

PubMed

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

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

2012-08-12

136

Simultaneous Multiple Response Regression and Inverse Covariance Matrix Estimation via Penalized Gaussian Maximum Likelihood  

PubMed Central

Multivariate regression is a common statistical tool for practical problems. Many multivariate regression techniques are designed for univariate response cases. For problems with multiple response variables available, one common approach is to apply the univariate response regression technique separately on each response variable. Although it is simple and popular, the univariate response approach ignores the joint information among response variables. In this paper, we propose three new methods for utilizing joint information among response variables. All methods are in a penalized likelihood framework with weighted L1 regularization. The proposed methods provide sparse estimators of conditional inverse co-variance matrix of response vector given explanatory variables as well as sparse estimators of regression parameters. Our first approach is to estimate the regression coefficients with plug-in estimated inverse covariance matrices, and our second approach is to estimate the inverse covariance matrix with plug-in estimated regression parameters. Our third approach is to estimate both simultaneously. Asymptotic properties of these methods are explored. Our numerical examples demonstrate that the proposed methods perform competitively in terms of prediction, variable selection, as well as inverse covariance matrix estimation.

Lee, Wonyul; Liu, Yufeng

2012-01-01

137

Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis.  

PubMed Central

Prostaglandins formed by the cyclooxygenase (COX) enzymes are important mediators of inflammation in arthritis. The contribution of the inducible COX-2 enzyme to inflammation in rat adjuvant arthritis was evaluated by characterization of COX-2 expression in normal and arthritic paws and by pharmacological inhibition of COX-2 activity. The injection of adjuvant induced a marked edema of the hind footpads with coincident local production of PGE2. PG production was associated with upregulation of COX-2 mRNA and protein in the affected paws. In contrast, the level of COX-1 mRNA was unaffected by adjuvant injection. TNF-alpha and IL-6 mRNAs were also increased in the inflamed paws as was IL-6 protein in the serum. Therapeutic administration of a selective COX-2 inhibitor, SC-58125, rapidly reversed paw edema and reduced the level of PGE2 in paw tissue to baseline. Interestingly, treatment with the COX-2 inhibitor also reduced the expression of COX-2 mRNA and protein in the paw. Serum IL-6 and paw IL-6 mRNA levels were also reduced to near normal levels by SC-58125. Furthermore, inhibition of COX-2 resulted in a reduction of the inflammatory cell infiltrate and decreased inflammation of the synovium. Notably, the antiinflammatory effects of SC-58125 were indistinguishable from the effects observed for indomethacin. These results suggest that COX-2 plays a prominent role in the inflammation associated with adjuvant arthritis and that COX-2 derived PGs upregulate COX-2 and IL-6 expression at inflammatory sites.

Anderson, G D; Hauser, S D; McGarity, K L; Bremer, M E; Isakson, P C; Gregory, S A

1996-01-01

138

Cyclooxygenase2 (COX2) in Inflammatory and Degenerative Brain Diseases  

Microsoft Academic Search

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

LUISA MINGHETTI

2004-01-01

139

The Cox2Specific Inhibitor Celecoxib Inhibits Adenylyl Cyclase  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known causes of acute renal insufficiency and gastropathy in patients with chronic inflammatory diseases. This action is presumed to result from nonselective inhibition of both constitutive and inducible forms of prostaglandin H synthases, also known as the cyclooxygenase enzymes (i.e., COX-1 amd COX-2). Celecoxib (Celebrex®) is a COX-2 enzyme inhibitor and has emerged as a

Shamsher S. Saini; Deborah L. Gessell-Lee; Johnny W. Peterson

2003-01-01

140

New insights into the role of COX 2 in inflammation  

Microsoft Academic Search

Cyclo-oxygenase (COX) is responsible for the synthesis of bioactive prostanoids, the inhibition of which serves as the basis for the mode of action of clinically used nonsteroidal anti-inflammatory drugs. While there were suggestions as early as the 1970s that an inducible isoform of COX exists, it was only in the early 1990s that COX 2 was identified, cloned and sequenced.

Derek W. Gilroy; Paul R. Colville-Nash

2000-01-01

141

Semiparametric Regression Pursuit  

PubMed Central

The semiparametric partially linear model allows flexible modeling of covariate effects on the response variable in regression. It combines the flexibility of nonparametric regression and parsimony of linear regression. The most important assumption in the existing methods for the estimation in this model is to assume a priori that it is known which covariates have a linear effect and which do not. However, in applied work, this is rarely known in advance. We consider the problem of estimation in the partially linear models without assuming a priori which covariates have linear effects. We propose a semiparametric regression pursuit method for identifying the covariates with a linear effect. Our proposed method is a penalized regression approach using a group minimax concave penalty. Under suitable conditions we show that the proposed approach is model-pursuit consistent, meaning that it can correctly determine which covariates have a linear effect and which do not with high probability. The performance of the proposed method is evaluated using simulation studies, which support our theoretical results. A real data example is used to illustrated the application of the proposed method.

Huang, Jian; Wei, Fengrong; Ma, Shuangge

2011-01-01

142

Latent Regression Analysis.  

PubMed

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

Tarpey, Thaddeus; Petkova, Eva

2010-07-01

143

COX-1 and -2 activity of rose hip.  

PubMed

The objective of this study was to investigate whether the clinically observed efficacy of rose hip in the treatment of osteoarthritis is due to inhibition of cyclooxygenase-1 and -2. Water, methanol, dichloromethane and hexane extracts of rose hip were tested for in vitro COX-1 and 2 activity. The organic solvent extracts showed good inhibition of both COX-1 and 2. The methanol extract was most active in both assays with IC(50) values of 12 microg/mL for COX-1 and 19 microg/mL for COX-2. The clinically observed effect might be due to inhibition of cyclooxygenase. PMID:17639563

Jäger, A K; Eldeen, I M S; van Staden, J

2007-12-01

144

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

PubMed

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. PMID:22708229

Khan, M; Fraser, A

2012-04-01

145

Illuminations: Least Squares Regression  

NSDL National Science Digital Library

Created by Illuminations: Resources for Teaching Mathematics, this unit plan contains nine lessons about interpreting the slope and y-intercept of least squares regression lines in the context of real-life data. The applet included allows students to plot the data and calculate the correlation coefficient and the equation of the regression line. Students will view the data in tabular, graphic, and algebraic form and will be able to discuss and display their work. This is a wonderful collection of interactive statistical lessons. They can easily be translated into classroom activities.

2010-01-01

146

Metamorphic geodesic regression.  

PubMed

We propose a metamorphic geodesic regression approach approximating spatial transformations for image time-series while simultaneously accounting for intensity changes. Such changes occur for example in magnetic resonance imaging (MRI) studies of the developing brain due to myelination. To simplify computations we propose an approximate metamorphic geodesic regression formulation that only requires pairwise computations of image metamorphoses. The approximated solution is an appropriately weighted average of initial momenta. To obtain initial momenta reliably, we develop a shooting method for image metamorphosis. PMID:23286131

Hong, Yi; Joshi, Sarang; Sanchez, Mar; Styner, Martin; Niethammer, Marc

2012-01-01

147

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

Microsoft Academic Search

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

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

2007-01-01

148

Deepest Regression in Analytical Chemistry  

Microsoft Academic Search

Recently the concept of regression depth has been introduced (1). The deepest regression (DR) is a method for linear regression which is defined as the fit with the best depth relative to the data. In this paper we explain the properties of the DR and give some applications of deepest regression in analytical chemistry which involve regression through the origin,

P. J. Rousseeuw; S. Van Aelst; B. Rambalib; J. Smeyers-Verbekeb

149

Expression of cyclooxygenase-2 (COX-2) in pituitary tumours  

PubMed Central

Summary Background Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours. Material/Methods We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size. Conclusions COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours.

Sokolowski, Grzegorz; Baldys-Waligorska, Agata; Trofimiuk, Malgorzata; Adamek, Dariusz; Hubalewska-Dydejczyk, Alicja; Golkowski, Filip

2012-01-01

150

QSAR analysis of diaryl COX-2 inhibitors: comparison of feature selection and train-test data selection methods.  

PubMed

QSAR analyses were performed on a series of trans-stilbenoid diaryl compounds for modeling their COX-2 inhibitory activities. The multivariate regression equations were developed with the selected independent variables using various feature selection methods. In addition, model training was done using different test-train data selection methods. The applicability of each variable and the test-train selection methods was investigated through the type and number of the selected significant descriptors as well as the statistical criteria of the developed model for each pair of feature and test-train selection methods. The goodness of fit and the statistical significance of 15 developed equations were evaluated using the correlation coefficient (R), the variance ratio (F), and the standard error of estimate (S.E.). The models were validated using the leave many out and the leave one out cross-validation methods. The mean percentage deviation (MPD(+/-SD)) was used as an accuracy criterion for checking the predicted activities. It was found that the developed models could predict the COX-2 and COX-1 inhibitory activities as well as the COX-2/COX-1 selectivity ratios producing the MPD values of 1.6(+/-0.8)%, 7.7(+/-5.6)%, and 16.9(+/-9.6)%, respectively. PMID:20332057

Soltani, Somaieh; Abolhasani, Hoda; Zarghi, Afshin; Jouyban, Abolghasem

2010-03-01

151

Explorations in Statistics: Regression  

ERIC Educational Resources Information Center

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

Curran-Everett, Douglas

2011-01-01

152

Minimax Ridge Regression Estimation.  

National Technical Information Service (NTIS)

The technique of ridge regression has become a popular tool for data analysts faced with a high degree of multicollinearity in their data. By using a ridge estimator, it was hoped that one could both stabilize the estimates (lower the condition number of ...

G. Casella

1977-01-01

153

ON SEGMENTED MULTIVARIATE REGRESSION  

Microsoft Academic Search

This paper concerns segmented multivariate regression models, models which have different linear forms in different subdomains of the domain of an in- dependent variable. Without knowing that number and their boundaries, we first estimate the number of these subdomains using a modified Schwarz criterion. The estimated number of regions proves to be weakly consistent under fairly general conditions. We then

Jian Liu; Shiying Wu; James V. Zidek

1997-01-01

154

Logistic Regression Diagnostics  

Microsoft Academic Search

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

Daryl Pregibon

1981-01-01

155

Bayesian ARTMAP for regression.  

PubMed

Bayesian ARTMAP (BA) is a recently introduced neural architecture which uses a combination of Fuzzy ARTMAP competitive learning and Bayesian learning. Training is generally performed online, in a single-epoch. During training, BA creates input data clusters as Gaussian categories, and also infers the conditional probabilities between input patterns and categories, and between categories and classes. During prediction, BA uses Bayesian posterior probability estimation. So far, BA was used only for classification. The goal of this paper is to analyze the efficiency of BA for regression problems. Our contributions are: (i) we generalize the BA algorithm using the clustering functionality of both ART modules, and name it BA for Regression (BAR); (ii) we prove that BAR is a universal approximator with the best approximation property. In other words, BAR approximates arbitrarily well any continuous function (universal approximation) and, for every given continuous function, there is one in the set of BAR approximators situated at minimum distance (best approximation); (iii) we experimentally compare the online trained BAR with several neural models, on the following standard regression benchmarks: CPU Computer Hardware, Boston Housing, Wisconsin Breast Cancer, and Communities and Crime. Our results show that BAR is an appropriate tool for regression tasks, both for theoretical and practical reasons. PMID:23665468

Sasu, L M; Andonie, R

2013-04-22

156

Beta Regression in R  

Microsoft Academic Search

The class of beta regression models is commonly used by practitioners to model variables that assume values in the standard unit interval (0, 1). It is based on the assumption that the dependent variable is beta-distributed and that its mean is related to a set of regressors through a linear predictor with unknown coefficients and a link function. The model

Francisco Cribari-Neto; Achim Zeileis

2010-01-01

157

Modern Regression Discontinuity Analysis  

ERIC Educational Resources Information Center

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

Bloom, Howard S.

2012-01-01

158

Inference in Linear Regression  

NSDL National Science Digital Library

This site, created by Michelle Lacey of Yale University, gives an explanation, a definition and an example of inference in linear regression. Topics include: confidence intervals for intercept and slope, significance tests, mean response, and prediction intervals. While brief, this is still a wonderful resource for any classroom studying statistics.

Lacey, Michelle

2009-11-27

159

Multiple Linear Regression  

NSDL National Science Digital Library

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

Lacey, Michelle

2009-11-30

160

Fourier Transform Infrared Spectroscopic Imaging and Multivariate Regression for Prediction of Proteoglycan Content of Articular Cartilage  

PubMed Central

Fourier Transform Infrared (FT-IR) spectroscopic imaging has been earlier applied for the spatial estimation of the collagen and the proteoglycan (PG) contents of articular cartilage (AC). However, earlier studies have been limited to the use of univariate analysis techniques. Current analysis methods lack the needed specificity for collagen and PGs. The aim of the present study was to evaluate the suitability of partial least squares regression (PLSR) and principal component regression (PCR) methods for the analysis of the PG content of AC. Multivariate regression models were compared with earlier used univariate methods and tested with a sample material consisting of healthy and enzymatically degraded steer AC. Chondroitinase ABC enzyme was used to increase the variation in PG content levels as compared to intact AC. Digital densitometric measurements of Safranin O –stained sections provided the reference for PG content. The results showed that multivariate regression models predict PG content of AC significantly better than earlier used absorbance spectrum (i.e. the area of carbohydrate region with or without amide I normalization) or second derivative spectrum univariate parameters. Increased molecular specificity favours the use of multivariate regression models, but they require more knowledge of chemometric analysis and extended laboratory resources for gathering reference data for establishing the models. When true molecular specificity is required, the multivariate models should be used.

Rieppo, Lassi; Rieppo, Jarno; Jurvelin, Jukka S.; Saarakkala, Simo

2012-01-01

161

Overexpression of Cox2 in Human Osteosarcoma Cells Decreases Proliferation and Increases Apoptosis  

Microsoft Academic Search

Overexpression of cyclooxygenase-2 (COX-2) is generally considered to promote tumorigenesis. To investigate a potential role of COX-2 in osteosarcoma, we overexpressed COX-2 in human osteosarcoma cells. Saos-2 cells deficient in COX-2 expression were retrovirally transduced or stably transfected with murine COX-2 cDNA. Functional expression of COX-2 was confirmed by Northern and Western analyses and prostaglandin production. Overexpression of COX-2 reduced

Zheng Xu; Shilpa Choudhary; Olga Voznesensky; Meenal Mehrotra; Monica Woodard; Marc Hansen; Harvey Herschman; Carol Pilbeam

2006-01-01

162

COX-2 inhibitors and their role in gynecology.  

PubMed

This review summarizes current knowledge about the roles of cyclooxygenases and prostaglandins in reproductive medicine. With the development of COX-2 specific inhibitors, new therapeutic options are available to obstetricians and gynecologists, offering better-tolerated alternatives to conventional NSAIDs. The analgesic effectiveness of COX-2 specific inhibitors is well established, and they are already in use in a range of painful conditions. Both celecoxib and valdecoxib are indicated for the treatment of primary dysmenorrhea, and may be effective in postoperative pain, including hysterectomy, and pain associated with endometriosis. There is also speculation that COX-2 specific inhibitors may be effective tocolytic agents without the risks to the fetus seen with conventional NSAIDs. The role of COX-2 in oncogenesis is also under investigation, and COX-2 specific inhibitors may eventually be used in the prevention and treatment of gynecologic malignancies. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the two types of cylooxygenase enzymes (COX), to list the effects and side effects of NSAIDs and COX-2 medications, and to outline the various changes in COX expression during pregnancy. PMID:12447099

Hayes, Ellen C; Rock, John A

2002-11-01

163

The double-edged sword of COX2 selective NSAIDs  

Microsoft Academic Search

THE LAUNCH OF THE CYCLOOXYGENASE-2 (COX-2) selective NSAIDs was based on 2 hypotheses: (1) the major adverse effects limiting the usefulness of nonselective NSAIDs are gastrointestinal in nature and (2) COX-2 selective NSAIDs are associ- ated with fewer gastrointestinal adverse effects than nonselective NSAIDs. At the time of the launch, neither of these hypotheses had been proven and, as docu-

James M. Wright

164

COX2 inhibitors: are they good, bad or ugly?  

Microsoft Academic Search

Arthritis and Hypertension are common co-morbid conditions affecting elderly adults. Hypertensive patients on antihypertensive medications can have destabilization of BP control and other cardiorenal events with the use of NSAIDs. The potential for similar interactions with COX-2 inhibitors is being explored. This study involves the effects of selective COX-2 inhibitor (Celecoxib) on renal functions and blood pressure. This is a

Munavvar Izhar; Elena Hung; George Bakris

2003-01-01

165

A Univariate Model of Calcium Release in the Dyadic Cleft of Cardiac Myocytes  

PubMed Central

Local calcium sparks in the dyadic cleft of cardiac myocytes are triggered by calcium influxes via L-type calcium channels (LCCs) located on the transverse tubule (TT) membrane, and subsequently controlled by the regeneration of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR). Calcium released from SR channels is known to be responsible for the sparks. Therefore, the activities of RyRs provide straightforward indication to the calcium concentration alteration. A method to study calcium signaling by analyzing RyR-gating statistics is described in the present study. Here we propose a univariate model with a simplified geometry of the dyadic cleft, which specifies the spatial localization of LCCs and RyRs to monitor the activity changes of RyRs. This model is used to explore two crucial aspects of local calcium signaling: the first is to disclose the tight control of calcium influxes via LCCs, and the second is to reveal the interactional impact of the self-regenerative RyRs. Patterns of active RyRs are rendered through numerous computational simulation experiments, manipulating the state initialization and the spatial localization of LCCs and RyRs to observe gating transition of RyRs.

Fan, Junjie; Yu, Zeyun

2010-01-01

166

Visual classification of very fine-grained sediments: Evaluation through univariate and multivariate statistics  

USGS Publications Warehouse

Classifying very fine-grained rocks through fabric elements provides information about depositional environments, but is subject to the biases of visual taxonomy. To evaluate the statistical significance of an empirical classification of very fine-grained rocks, samples from Devonian shales in four cored wells in West Virginia and Virginia were measured for 15 variables: quartz, illite, pyrite and expandable clays determined by X-ray diffraction; total sulfur, organic content, inorganic carbon, matrix density, bulk density, porosity, silt, as well as density, sonic travel time, resistivity, and ??-ray response measured from well logs. The four lithologic types comprised: (1) sharply banded shale, (2) thinly laminated shale, (3) lenticularly laminated shale, and (4) nonbanded shale. Univariate and multivariate analyses of variance showed that the lithologic classification reflects significant differences for the variables measured, difference that can be detected independently of stratigraphic effects. Little-known statistical methods found useful in this work included: the multivariate analysis of variance with more than one effect, simultaneous plotting of samples and variables on canonical variates, and the use of parametric ANOVA and MANOVA on ranked data. ?? 1980 Plenum Publishing Corporation.

Hohn, M. Ed.; Nuhfer, E. B.; Vinopal, R. J.; Klanderman, D. S.

1980-01-01

167

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

PubMed Central

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

Edwards, Darrin C.; Metz, Charles E.

2012-01-01

168

QSAR analysis of diaryl COX2 inhibitors: Comparison of feature selection and train-test data selection methods  

Microsoft Academic Search

QSAR analyses were performed on a series of trans-stilbenoid diaryl compounds for modeling their COX-2 inhibitory activities. The multivariate regression equations were developed with the selected independent variables using various feature selection methods. In addition, model training was done using different test-train data selection methods. The applicability of each variable and the test-train selection methods was investigated through the type

Somaieh Soltani; Hoda Abolhasani; Afshin Zarghi; Abolghasem Jouyban

2010-01-01

169

Overdispersion and Poisson Regression  

Microsoft Academic Search

This article discusses the use of regression models for count data. A claim is often made in criminology applications that\\u000a the negative binomial distribution is the conditional distribution of choice when for a count response variable there is evidence\\u000a of overdispersion. Some go on to assert that the overdisperson problem can be “solved” when the negative binomial distribution\\u000a is used

Richard Berk; John M. MacDonald

2008-01-01

170

Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death  

PubMed Central

Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive cyclooxygenase (COX)-2, overexpressed during carcinogenesis, has been a target for cancer prevention. To assess the potential link between chemopreventive agents, oxidative stress and COX-2, we studied the chemopreventive sulindac and nitric oxide-donating aspirin (NO-ASA). Both generated oxidative stress and induced COX-2 in various cell lines, more prominently in dying cells. Two antioxidants and an inhibitor of NADPH oxidase abrogated the induction of COX-2 and cell death. Exogenous xanthine/xanthine oxidase, which produce O2?·, had the same effect. Inhibition of caspases and cox-2 knockdown showed that COX-2 did not participate in reactive oxygen species (ROS) generation or cell death induction in response to NO-ASA. Our results support three potentially useful ideas: (i) the concept that ROS are a critical component of the action of chemopreventive agents; (ii) the notion that COX-2 may not be an ideal target for chemoprevention and (iii) the possibility that COX-2 may be overexpressed in cancer cells due to their state of oxidative stress. It is conceivable that, if further substantiated, these findings may inform the rational design of chemotherapeutic strategies, in particular the choice of agents in combination approaches.

Sun, Yu; Chen, Jie; Rigas, Basil

2009-01-01

171

Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death.  

PubMed

Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive cyclooxygenase (COX)-2, overexpressed during carcinogenesis, has been a target for cancer prevention. To assess the potential link between chemopreventive agents, oxidative stress and COX-2, we studied the chemopreventive sulindac and nitric oxide-donating aspirin (NO-ASA). Both generated oxidative stress and induced COX-2 in various cell lines, more prominently in dying cells. Two antioxidants and an inhibitor of NADPH oxidase abrogated the induction of COX-2 and cell death. Exogenous xanthine/xanthine oxidase, which produce O(2)(-)., had the same effect. Inhibition of caspases and cox-2 knockdown showed that COX-2 did not participate in reactive oxygen species (ROS) generation or cell death induction in response to NO-ASA. Our results support three potentially useful ideas: (i) the concept that ROS are a critical component of the action of chemopreventive agents; (ii) the notion that COX-2 may not be an ideal target for chemoprevention and (iii) the possibility that COX-2 may be overexpressed in cancer cells due to their state of oxidative stress. It is conceivable that, if further substantiated, these findings may inform the rational design of chemotherapeutic strategies, in particular the choice of agents in combination approaches. PMID:18952595

Sun, Yu; Chen, Jie; Rigas, Basil

2008-10-24

172

Shape regression machine.  

PubMed

We present a machine learning approach called shape regression machine (SRM) to segmenting in real time an anatomic structure that manifests a deformable shape in a medical image. Traditional shape segmentation methods rely on various assumptions. For instance, the deformable model assumes that edge defines the shape; the Mumford-Shah variational method assumes that the regions inside/outside the (closed) contour are homogenous in intensity; and the active appearance model assumes that shape/appearance variations are linear. In addition, they all need a good initialization. In contrast, SRM poses no such restrictions. It is a two-stage approach that leverages (a) the underlying medical context that defines the anatomic structure and (b) an annotated database that exemplifies the shape and appearance variations of the anatomy. In the first stage, it solves the initialization problem as object detection and derives a regression solution that needs just one scan in principle. In the second stage, it learns a nonlinear regressor that predicts the nonrigid shape from image appearance. We also propose a boosting regression approach that supports real time segmentation. We demonstrate the effectiveness of SRM using experiments on segmenting the left ventricle endocardium from an echocardiogram of an apical four chamber view. PMID:17633685

Zhou, Shaohua Kevin; Comaniciu, Dorin

2007-01-01

173

Modeling age-of-onset: Cox model with latent major gene effects  

SciTech Connect

Analysis of age-of-onset is a key factor in the segregation and linkage analysis of complex genetic traits, but is complicated by the censoring of unaffected individuals. Most previous work has used parametric distributional assumptions, but it is hard to characterize the distribution of age-of-onset by a single distribution. Other approaches discretize age-of-onset and use logistic regression to model incidence; this approach does not use the information fully. Frailty models have been used for age-of-oset in the biostatistics literature, but these models do not lend themselves to modeling the correlations due to genetic effects which segregate within a family. Here, we propose use of the Cox model with latent major gene effects; conditional on the major genotypes, Cox`s proportional hazards model is used for age-of-onset for each individual. This is a semiparametric model; we do not specify the baseline hazard function. Likelihood analysis of such models is restricted by the difficulty in evaluating of maximizing the likelihood, especially when data are available for some of the members of an extended pedigree. Markov chain Monte Carlo permits genotypic configurations to be realized from the posterior distributions given a current model and the observed data. Hence methods for likelihood analysis can be developed: Monte Carlo EM is used for estimation of the parameters and their variance-covariance matrix. Markers and observed covariates are easily incorporated into this analysis. We present the model, methods for likelihood analysis and the results of a simulation study. The results are comparable with those based on a Cox model with known genotypic dependence in a pedigree. An early-onset Alzheimer`s pedigree and some breast cancer pedigrees have been used as real data examples. Some possible extensions are also discussed.

Li, H.; Thompson, E.A. [Univ. of Washington, Seattle, WA (United States)

1994-09-01

174

Univariate and multivariate methods for chemical mapping of cervical cancer cells  

NASA Astrophysics Data System (ADS)

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

Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

2012-02-01

175

Orthogonal Regression: A Teaching Perspective  

ERIC Educational Resources Information Center

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

Carr, James R.

2012-01-01

176

Orthogonal Regression: A Teaching Perspective  

ERIC Educational Resources Information Center

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

Carr, James R.

2012-01-01

177

Orthogonal regression: a teaching perspective  

Microsoft Academic Search

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

James R. Carr

2011-01-01

178

Orthogonal regression: a teaching perspective  

Microsoft Academic Search

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

James R. Carr

2012-01-01

179

N-Caffeoyl serotonin as selective COX-2 inhibitor.  

PubMed

The inhibitory effects of the synthetic serotonin analogues (1-8) on COX (1 and 2) were evaluated. Two serotonin derivatives (4 and 8) showed inhibitory effect of COX (1 and 2). Especially, 4 exhibited excellent inhibitions on COX-2 with extremely high potency (IC(50)=42.5 ?M). The inhibitory activities of cinnamic acid derivatives and serotonin were evaluated to clarify whether inhibitory activities of compound 4 and 8 are due to cinnamic acid moiety or serotonin moiety. Caffeic acid and N-caffeoyl serotonin (4) exhibited selective inhibition of COX-2 compared to aspirin. Comparison caffeic acid with 4 suggested that the linkage of caffeic acid and serotonin enhance COX-2 inhibition. Comparison of structures of caffeic acid and sinapic acid implied that catechol moiety of cinnamic acid derivatives is a major contributing factor for selective inhibition of COX-2. The selective COX-2 inhibitory activity of compound 4 is significant and could be employed as drugs against inflammatory and allergy. PMID:22386242

Takahashi, Toshiyuki; Miyazawa, Mitsuo

2012-02-09

180

UNIVARIATE EFFECT OF ELEVATED CO2 OR O3 ON WATER RELATIONS OF SOYBEAN AND CORN LEAVES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Reported herein is the independent univariate effect of either atmospheric CO2 or O3 concentration on upper most sunlit leaf stomatal conductance (gs), transpiration rate (T), total water (TWP), osmotic (OWP) and resultant turgor (PWP) potentials, tissue concentration of osmotica (i.e., simple sugar...

181

UNIVARIATE EFFECT OF ELEVATED CO2 OR O3 ON WATER RELATIONS OF SOYBEAN AND CORN LEAVES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Reported herein is the independent univariate effect of either atmospheric CO2 or O3 concentration on upper most sunlit leaf stomatal conductance (gs), transpiration rate (T), total water (1W), osmotic (1") and resultant turgor (1P) potentials, tissue concentration of osmotica (i.e., simple sugars, ...

182

Characterization of Interfacial Chemistry of Adhesive/Dentin Bond Using FTIR Chemical Imaging With Univariate and Multivariate Data Processing  

PubMed Central

Fourier transform infrared (FTIR) chemical imaging can be used to investigate molecular chemical features of the adhesive/dentin interfaces. However, the information is not straightforward, and is not easily extracted. The objective of this study was to use multivariate analysis methods, principal component analysis and fuzzy c-means clustering, to analyze spectral data in comparison with univariate analysis. The spectral imaging data collected from both the adhesive/healthy dentin and adhesive/caries-affected dentin specimens were used and compared. The univariate statistical methods such as mapping of intensities of specific functional group do not always accurately identify functional group locations and concentrations due to more or less band overlapping in adhesive and dentin. Apart from the ease with which information can be extracted, multivariate methods highlight subtle and often important changes in the spectra that are difficult to observe using univariate methods. The results showed that the multivariate methods gave more satisfactory, interpretable results than univariate methods and were conclusive in showing that they can discriminate and classify differences between healthy dentin and caries-affected dentin within the interfacial regions. It is demonstrated that the multivariate FTIR imaging approaches can be used in the rapid characterization of heterogeneous, complex structure.

Wang, Yong; Yao, Xiaomei; Parthasarathy, Ranganathan

2008-01-01

183

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

Microsoft Academic Search

This paper presents some considerations about the use of adequate statistical techniques in the framework of the neuroelectromagnetic brain mapping. With the use of advanced EEG\\/MEG recording setup involving hundred of sensors, the issue of the protection against the type I errors that could occur during the execution of hundred of univariate statistical tests, has gained interest. In the present

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

2010-01-01

184

Regression for Proportion Data  

NASA Astrophysics Data System (ADS)

Many applications deal with the relative proportion of items that are assigned to a number of categories. In some of these applications, it is natural to model the measurements as having a multinomial distribution. Here we explore a one-to-one mapping that transforms proportion data to a vector of real numbers and show how to accurately approximate a multinomial distribution with a Gaussian distribution. Finally, we explore how Nadaraya-Watson and Gaussian process regression techniques can be adapted to deal with proportion data.

Center, Julian L.

2007-11-01

185

Expression of COX-1, COX-2, and inducible nitric oxide synthase protein in human gastric antrum with Helicobacter pylori infection.  

PubMed

For a better understanding of the regulation of prostaglandin and nitric oxide (NO) synthesis in circumstances in which the gastric mucosa is inflamed, we have examined the ex vivo production of NO and prostaglandin E2 and the protein expression of inducible nitric oxide synthase (iNOS) and 2 cyclo-oxygenase (COX) isoforms in gastric biopsies from nine Helicobacter pylori-infected patients with active gastritis and six Helicobacter pylori (HP)-negative patients. The results indicate a significant increased of NO and PGE2 in patients with HP infection compared with uninfected samples. These findings were paralleled by marked increases in iNOS and in COX-1 and COX-2 protein expression. Expression of iNOS and COX-2 protein was absent in the mucosa of HP-negative controls. We have demonstrated that iNOS protein is expressed in the gastric mucosa of patients with HP infection. It is likely that iNOS expression and the corresponding high release of NO may play an important role in gastric inflammation associated with HP infection. However, the expression of COX-1 and COX-2 and the parallel increase of prostaglandin E2 could imply that these factors could limit the extend of mucosal damage. In previous reports NO has been shown to stimulate the COX activity, so we think that the role of NO could be both in the regulation of normal function and in the genesis of diseases. PMID:10482283

Franco, L; Talamini, G; Carra, G; Doria, D

1999-08-01

186

Regression analysis and multivariate analysis.  

PubMed

Proper evaluation of data does not necessarily require the use of advanced statistical methods; however, such advanced tools offer the researcher the freedom to evaluate more complex hypotheses. This overview of regression analysis and multivariate statistics describes general concepts. Basic definitions and conventions are reviewed. The types of regression analysis are then discussed, including simple regression, multiple regression, multivariate multiple regression, and logistic regression. The various steps required to perform these analyses are described, and the advantages and disadvantages of each is detailed. PMID:8796937

Duleba, A J; Olive, D L

1996-05-01

187

Cancer Chemoprevention by Cyclooxygenase 2 (COX2) Blockade  

Microsoft Academic Search

Significant use of selective cyclooxygenase-2 (COX-2) blocking agents prescribed for the treatment of arthritis during 1999\\u000a to 2005 facilitates epidemiologic investigations to illuminate their chemopreventive effects against human cancer. We therefore\\u000a conducted a set of case control studies of selective COX-2 blocking agents to determine their chemopreventive potential for\\u000a the four major cancers: breast, prostate, colon, and lung. Newly diagnosed

RANDALL E. HARRIS; Joanne Beebe-Donk; GALAL A. ALSHAFIE

188

Skyrmion Lattice Domains in Fe1-xCoxSi  

Microsoft Academic Search

The strongly doped semiconductor Fe1-xCoxSi displays a dome of helimagnetic order for 0.05 <= x <= 0.7. We report small angle neutron scattering of the magnetic structure in the skyrmion lattice phase of Fe1-xCoxSi for x = 0.2 and magnetic field parallel to a crystallographic (100) direction. We observe twelve equally spaced maxima of scattering intensity on a ring, with

T. Adams; S. Mühlbauer; A. Neubauer; W. Münzer; F. Jonietz; R. Georgii; B. Pedersen; P. Böni; A. Rosch; C. Pfleiderer

2010-01-01

189

Characterization of Etoricoxib, a Novel, Selective COX2 Inhibitor  

Microsoft Academic Search

Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect

Aimee Dallob; Christopher J. Hawkey; Howard Greenberg; Nicholas Wight; Paul De Schepper; Scott Waldman; Peggy Wong; Lisa De Tora; Barry Gertz; Nancy Agrawal; John Wagner; Keith Gottesdiener

2003-01-01

190

Molecular and biochemical analysis of Saccharomyces cerevisiae cox1 mutants  

Microsoft Academic Search

We report on the molecular and biochemical analysis of a set of 13 respiratory deficient mutants of Saccharomyces cerevisiae which are specifically altered in COX1, the gene encoding the subunit Cox1p of cytochrome c oxidase. DNA sequence analysis shows that three are due to frameshift mutations, two to nonsense mutations, and eight to\\u000a missense mutations. All, except the missense mutant

Claire Lemaire; Sylviane Robineau; Pierre Netter

1998-01-01

191

Epigenetic deregulation of the COX pathway in cancer.  

PubMed

Inflammation is a major cause of cancer and may condition its progression. The deregulation of the cyclooxygenase (COX) pathway is implicated in several pathophysiological processes, including inflammation and cancer. Although, its targeting with nonsteroidal antiinflammatory drugs (NSAIDs) and COX-2 selective inhibitors has been investigated for years with promising results at both preventive and therapeutic levels, undesirable side effects and the limited understanding of the regulation and functionalities of the COX pathway compromise a more extensive application of these drugs. Epigenetics is bringing additional levels of complexity to the understanding of basic biological and pathological processes. The deregulation of signaling and biosynthetic pathways by epigenetic mechanisms may account for new molecular targets in cancer therapeutics. Genes of the COX pathway are seldom mutated in neoplastic cells, but a large proportion of them show aberrant expression in different types of cancer. A growing body of evidence indicates that epigenetic alterations play a critical role in the deregulation of the genes of the COX pathway. This review summarizes the current knowledge on the contribution of epigenetic processes to the deregulation of the COX pathway in cancer, getting insights into how these alterations may be relevant for the clinical management of patients. PMID:22580191

Cebola, Inês; Peinado, Miguel A

2012-05-03

192

Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors.  

PubMed

A series of novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors was prepared via treatment of various diaryl amides with tetrachlorosilane/sodium azide. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles contained a methylsulfonyl or sulfonamide group as COX-2 pharmacophore displayed only low inhibitory potency towards COX-2. Most potent compounds showed IC(50) values of 6 and 7 ?M for COX-2. All compounds showed IC(50) values greater 100 ?M for COX-1 inhibition. PMID:22341941

Al-Hourani, Baker Jawabrah; Sharma, Sai Kiran; Suresh, Mavanur; Wuest, Frank

2012-02-02

193

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

PubMed Central

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

Maisel, Tobias; Joseph, Stephanie; Mielke, Thorsten; Burger, Jorg; Schwarzinger, Stephan; Meyer, Ortwin

2012-01-01

194

Multiple Roles of the Cox20 Chaperone in Assembly of Saccharomyces cerevisiae Cytochrome c Oxidase  

PubMed Central

The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the intermembrane space. Processing is chaperoned by Cox20, an integral inner membrane protein whose hydrophilic domains are located in the intermembrane space, and Cox20 remains associated with mature, unassembled Cox2. The Cox2 C-tail domain is exported post-translationally by the highly conserved translocase Cox18 and associated proteins. We have found that Cox20 is required for efficient export of the Cox2 C-tail. Furthermore, Cox20 interacts by co-immune precipitation with Cox18, and this interaction requires the presence of Cox2. We therefore propose that Cox20 binding to Cox2 on the trans side of the inner membrane accelerates dissociation of newly exported Cox2 from the Cox18 translocase, promoting efficient cycling of the translocase. The requirement for Cox20 in cytochrome c oxidase assembly and respiratory growth is partially bypassed by yme1, mgr1 or mgr3 mutations, each of which reduce i-AAA protease activity in the intermembrane space. Thus, Cox20 also appears to stabilize unassembled Cox2 against degradation by the i-AAA protease. Pre-Cox2 leader peptide processing by Imp1 occurs in the absence of Cox20 and i-AAA protease activity, but is greatly reduced in efficiency. Under these conditions some mature Cox2 is assembled into cytochrome c oxidase allowing weak respiratory growth. Thus, the Cox20 chaperone has important roles in leader peptide processing, C-tail export, and stabilization of Cox2.

Elliott, Leah E.; Saracco, Scott A.; Fox, Thomas D.

2012-01-01

195

Ridge regression: Bonanza or beguilement?  

Microsoft Academic Search

Points out that ridge regression is an intriguing new toy for statistical estimation theory, but that it is just that––a toy that may someday evolve into a useful if limited tool; is still too fragile to do real work. Specifically, ridge regression can indeed improve on the accuracy of traditional estimates of regression parameters if background circumstances are right. But

William W. Rozeboom

1979-01-01

196

Regression with fuzzy random data  

Microsoft Academic Search

Different approaches to deal with regression analysis when the data are fuzzy are presented. It summarizes recent results and considers them in a more general context which allows to evaluate the different methods. Starting with necessary notions on regression and on fuzzy sets, three approaches are presented: at first a pure descriptive statistical approach, secondly statistical regression when the output

Wolfgang Näther

2006-01-01

197

Adaptive Regression and Ego Identity.  

ERIC Educational Resources Information Center

College students (n=71) completed inventory of adaptively regressive experiences and Identity Status Interview. Found that Moratorium status students (actively engaged in identity formation) showed greater disposition to adaptive regression than did individuals in other statuses. Findings support view that adaptive regression may serve function in…

Bilsker, Dan; Marcia, James E.

1991-01-01

198

Deepest regression in analytical chemistry  

Microsoft Academic Search

Recently the concept of regression depth has been introduced [J. Am. Stat. Assoc. 94 (1999) 388]. The deepest regression (DR) is a method for linear regression which is defined as the fit with the best depth relative to the data. In this paper we explain the properties of the DR and give some applications of DR in analytical chemistry which

P. J. Rousseeuw; S. Van Aelst; B. Rambali; J. Smeyers-Verbeke

2001-01-01

199

Change in nicotine-induced VEGF, PGE2 AND COX-2 expression following COX inhibition in human oral squamous cancer.  

PubMed

Cigarette smoke has been documented to be related to the development of cancer. However, the exact mechanism for the carcinogenic action of cigarette smoke is still unknown. Nicotine is recognized to be the major compound in cigarette smoke and has been suggested to play a role in oral cancer via a cyclooxygenase (COX)/ prostaglandin-dependent pathway. This study was designed to evaluate the action of nicotine in the oral cancer cell and to further examine whether COX-2 is responsible for expression of tumor-associated angiogenic vascular endothelial growth factor (VEGF) in vitro. Viability of human oral squamous cancer cells (BHY) was measured using MTT assay. Protein expression was determined by Western blot and immunoassay kits. We found that exposure of BHY cells to nicotine (200 µg/mL for 6 hours) resulted in 2.9-fold induction of COX-2 expression as well as a 4-fold increase in VEGF levels compared with a control group. Pretreatment with celecoxib inhibited nicotine-induced change in the expression of VEGF and COX-2. The results suggest that stimulation of COX-2 and VEGF expression can contribute as important factors in the tumorigenic action of nicotine in oral cancer progression. This effect can be blocked by celecoxib, suggesting an interaction of nicotine and COX-2 pathways. PMID:23394447

Salimi, Mona; Esfahani, Masoumeh; Habibzadeh, Narcis; Aslani, Hamid Reza; Amanzadeh, Amir; Esfandiary, Mehrangiz; Sedaghati, Bita; Bidgoli, Sepideh Arbabi; Ghahremani, Mohammad Hossein

2012-01-01

200

Probabilistically Valid Inference of Covariation From a Single x,y Observation When Univariate Characteristics Are Known.  

PubMed

Participants were asked to draw inferences about correlation from single x,y observations. In Experiment 1 statistically sophisticated participants were given the univariate characteristics of distributions of x and y and asked to infer whether a single x, y observation came from a correlated or an uncorrelated population. In Experiment 2, students with a variety of statistical backgrounds assigned posterior probabilities to five possible populations based on single x, y observations, again given knowledge of the univariate statistics. In Experiment 3, statistically naïve participants were given a problem analogous to that given in Experiment 1, framed verbally. Experiment 4 replicated Experiment 3 but added an "impossible to determine" response option. Models that rely on computing sample correlations make no predictions about these investigations. From a Bayesian perspective, participants' inferences in all four experiments tended to make probabilistically valid inferences as long as the single datum was directional. The results are discussed in light of the Brunswikian notion of vicarious functioning. PMID:21585467

Doherty, Michael E; Anderson, Richard B; Kelley, Amanda M; Albert, James H

2009-03-01

201

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

Microsoft Academic Search

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

Matthias Borowski; Karen Schettlinger; Ursula Gather

2009-01-01

202

Bayesian Spatial Quantile Regression  

PubMed Central

Tropospheric ozone is one of the six criteria pollutants regulated by the United States Environmental Protection Agency under the Clean Air Act and has been linked with several adverse health effects, including mortality. Due to the strong dependence on weather conditions, ozone may be sensitive to climate change and there is great interest in studying the potential effect of climate change on ozone, and how this change may affect public health. In this paper we develop a Bayesian spatial model to predict ozone under different meteorological conditions, and use this model to study spatial and temporal trends and to forecast ozone concentrations under different climate scenarios. We develop a spatial quantile regression model that does not assume normality and allows the covariates to affect the entire conditional distribution, rather than just the mean. The conditional distribution is allowed to vary from site-to-site and is smoothed with a spatial prior. For extremely large datasets our model is computationally infeasible, and we develop an approximate method. We apply the approximate version of our model to summer ozone from 1997–2005 in the Eastern U.S., and use deterministic climate models to project ozone under future climate conditions. Our analysis suggests that holding all other factors fixed, an increase in daily average temperature will lead to the largest increase in ozone in the Industrial Midwest and Northeast.

Reich, Brian J.; Fuentes, Montserrat; Dunson, David B.

2013-01-01

203

Bayesian Spatial Quantile Regression.  

PubMed

Tropospheric ozone is one of the six criteria pollutants regulated by the United States Environmental Protection Agency under the Clean Air Act and has been linked with several adverse health effects, including mortality. Due to the strong dependence on weather conditions, ozone may be sensitive to climate change and there is great interest in studying the potential effect of climate change on ozone, and how this change may affect public health. In this paper we develop a Bayesian spatial model to predict ozone under different meteorological conditions, and use this model to study spatial and temporal trends and to forecast ozone concentrations under different climate scenarios. We develop a spatial quantile regression model that does not assume normality and allows the covariates to affect the entire conditional distribution, rather than just the mean. The conditional distribution is allowed to vary from site-to-site and is smoothed with a spatial prior. For extremely large datasets our model is computationally infeasible, and we develop an approximate method. We apply the approximate version of our model to summer ozone from 1997-2005 in the Eastern U.S., and use deterministic climate models to project ozone under future climate conditions. Our analysis suggests that holding all other factors fixed, an increase in daily average temperature will lead to the largest increase in ozone in the Industrial Midwest and Northeast. PMID:23459794

Reich, Brian J; Fuentes, Montserrat; Dunson, David B

2012-01-01

204

Notch2-induced COX-2 expression enhancing gastric cancer progression.  

PubMed

Gastric carcinoma is one of the most common and mortal types of malignancy worldwide. To date, the mechanisms controlling its aggressiveness are not yet fully understood. Notch signal pathway can function as either an oncogene or a tumor suppressor in tumorigenesis. Four members (Notch1-4) of Notch receptors were found in mammals and each exhibits distinct roles in tumor progression. Previous study showed that the activated Notch1 receptor promoted gastric cancer progression through cyclooxygenase-2 (COX-2). This study addressed whether Notch2 signal pathway is also involved in gastric cancer progression. Constitutive expression of Notch2 intracellular domain (N2IC), the activated form of Notch2 receptor, promoted both cell proliferation and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. The colony formation, migration, invasion, and wound-healing abilities of SC-M1 cells were enhanced by N2IC expression, whereas these abilities were suppressed by Notch2 knockdown. Similarly, Notch2 knockdown inhibited cancer progressions of AGS and AZ521 gastric cancer cells. Expression of N2IC also caused epithelial-mesenchymal transition in SC-M1 cells. Furthermore, N2IC bound to COX-2 promoter and induced COX-2 expression through a CBF1-dependent manner in SC-M1 cells. The ability of N2IC to enhance tumor progression in SC-M1 cells was suppressed by knockdown of COX-2 or treatment with NS-398, a COX-2 inhibitor. Moreover, the suppression of tumor progression by Notch2 knockdown in SC-M1 cells was reversed by exogenous COX-2 or its major enzymatic product PGE(2) . Taken together, this study is the first to demonstrate that the Notch2-COX-2 signaling axis plays an important role in controlling gastric cancer progression. PMID:21976141

Tseng, Yun-Chien; Tsai, Yu-Hui; Tseng, Min-Jen; Hsu, Kai-Wen; Yang, Min-Chieh; Huang, Kuo-Hung; Li, Anna Fen-Yau; Chi, Chin-Wen; Hsieh, Rong-Hong; Ku, Hung-Hai; Yeh, Tien-Shun

2011-10-04

205

On the evolutionary origin of cyclooxygenase (COX) isozymes: characterization of marine invertebrate COX genes points to independent duplication events in vertebrate and invertebrate lineages.  

PubMed

In vertebrates, COX-1 and COX-2, two cyclooxygenase isozymes with different physiological functions and gene regulation, catalyze identical reactions in prostaglandin synthesis. It is still not understood why there are multiple forms of COX enzyme in the same cell type and when the evolutionary duplication of the COX gene occurred. Here we report the structure of two genes encoding for COX isozymes in the coral Gersemia fruticosa, the first non-vertebrate organism from which a cyclooxygenase was characterized. Both genes are about 20 kb in size and consist of nine exons. Intron/exon boundaries are well conserved between coral and mammalian COX genes. mRNAs of the previously reported G. fruticosa COX-A (GenBank trade mark accession number AY004222) and the novel COX-B share 94% sequence identity in the coding regions and less than 30% in the 5'- and 3'-untranslated region. Transcripts of both COX genes are detectable in coral cells, although the transcriptional level of COX-A is 2 orders of magnitude higher than COX-B. Expression of both coral genes in mammalian cells gave functional proteins with similar catalytic properties. By data base analyses we also detected and constructed different pairs of COX genes from the primitive chordates, Ciona savignyi and Ciona intestinalis. These two gene pairs encode proteins with 50% intra-species and only 70% cross-species sequence identity. Our results suggest that invertebrate COX gene pairs do not correspond to vertebrate COX-1 and COX-2 and are consistent with duplication of the COX gene having occurred independently in corals, ascidians, and vertebrates. It is evident that due to the importance and complexity of its regulatory role, COX has multiple isoforms in all organisms known to express it, and the genes encoding for the isozymes may to be regulated differently. PMID:14732711

Järving, Reet; Järving, Ivar; Kurg, Reet; Brash, Alan R; Samel, Nigulas

2004-01-19

206

Vascular COX-2 modulates blood pressure and thrombosis in mice.  

PubMed

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

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

2012-05-01

207

Synthesis and biological acitivity of annulated pyrazoles as selective COX-2 inhibitors. I.  

PubMed

A series of disubstituted 4,5-polymethylenepyrazoles were synthesized and evaluated their inhibitory activities against COX-2. Some compounds showed strong (0.3 nM) inhibitory activity on COX-2 and were found somewhat selective (up to 16) on COX-2 over COX-1. PMID:10489876

Kim, H H; Park, J G; Moon, T C; Chang, H W; Jahng, Y

1999-08-01

208

N-cyano sulfoximines: COX inhibition, anticancer activity, cellular toxicity, and mutagenicity.  

PubMed

From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and no mutagenic potential (as determined by an Ames assay). PMID:23225780

Park, Seong Jun; Baars, Hannah; Mersmann, Stefanie; Buschmann, Helmut; Baron, Jens Malte; Amann, Philipp M; Czaja, Katharina; Hollert, Henner; Bluhm, Kerstin; Redelstein, Regine; Bolm, Carsten

2012-12-06

209

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

PubMed

Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives. PMID:20379952

Gautam, Raju; Karkhile, Kailas V; Bhutani, Kamlesh K; Jachak, Sanjay M

2010-04-08

210

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

PubMed Central

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

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

2008-01-01

211

COX2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX2 inhibitor celecoxib  

Microsoft Academic Search

The regular use of various nonsteroidal anti-inflammatory drugs (NSAIDs) was shown to decrease the incidence of colorectal cancer. This effect is thought to be caused predominantly by inhibition of cyclooxygenase-2 (COX-2) and, subsequently, prostaglandin synthesis. However, recent studies have suggested that COX-independent pathways may contribute considerably to these antiproliferative effects. To evaluate the involvement of COX-dependent and COX- independent mechanisms

Sabine Grösch; Irmgard Tegeder; Ellen Niederberger; Lutz Bräutigam; Gerd Geisslinger

2001-01-01

212

NSAID inhibition of RGM1 gastric monolayer wound re-epithelialization: comparison of selective Cox2 versus non-selective Cox inhibitors  

Microsoft Academic Search

Clinical studies indicate that specific cyclooxygenase-2 (Cox-2) inhibitors are less ulcerogenic than their non-selective predecessors (e.g. indomethacin). However, Cox-2 inhibitors may also interfere with ulcer healing. Re-epithelialization is a crucial factor in both gastrointestinal mucosal injury and ulcer healing. This study was aimed to compare the effects of selective Cox-2 inhibitor (NS398) versus non-selective Cox inhibitor (indomethacin) on basal and

Andrew Q Giap; Andrzej Tarnawski; Neil T Hoa; Vimesh Akotia; Thomas Y Ma

2002-01-01

213

Regression on Quantile Residual Life  

PubMed Central

Summary A time-specific log-linear regression method on quantile residual lifetime is proposed. Under the proposed regression model, any quantile of a time-to-event distribution among survivors beyond a certain time point is associated with selected covariates under right censoring. Consistency and asymptotic normality of the regression estimator are established. An asymptotic test statistic is proposed to evaluate the covariate effects on the quantile residual lifetimes at a specific time point. Evaluation of the test statistic does not require estimation of the variance-covariance matrix of the regression estimators, which involves the probability density function of the survival distribution with censoring. Simulation studies are performed to assess finite sample properties of the regression parameter estimator and test statistic. The new regression method is applied to a breast cancer data set with long-term follow-up to estimate the patients’ median residual lifetimes, adjusting for important prognostic factors.

Jung, Sin-Ho; Jeong, Jong-Hyeon; Bandos, Hanna

2011-01-01

214

COX2 silencing inhibits cell proliferation in A549 cell  

Microsoft Academic Search

Objective  The aim of this study was to explore the effects on malignant proliferation of A549 cell by silencing cyclooxygenase (COX)-2.\\u000a \\u000a \\u000a \\u000a Methods  In the present study, we constructed three siRNA vectors producing small interference RNA. The siRNA vectors and the vacant\\u000a vectors were transfected into A549 cell with lipofectamine respectively and the transfected cell strains were constructed.\\u000a The change of COX-2 expression

Weiying Li; Wentao Yue; Lina Zhang; Xiaoting Zhao; Li Ma; Xuehui Yang; Chunyan Zhang; Yue Wang; Meng Gu

2011-01-01

215

Multifocal Fixed Drug Eruption with COX-2 Inhibitor-Celecoxib  

PubMed Central

Cyclooxygenase-2 (COX-2) inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs) for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE) with celecoxib which has not yet been reported in Indian settings.

Chugh, Shikha; Sarkar, Rashmi; Garg, Vijay K; Singh, Avninder; Keisham, Chitralekha

2013-01-01

216

Multifocal Fixed Drug Eruption with COX-2 Inhibitor-Celecoxib.  

PubMed

Cyclooxygenase-2 (COX-2) inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs) for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE) with celecoxib which has not yet been reported in Indian settings. PMID:23716804

Chugh, Shikha; Sarkar, Rashmi; Garg, Vijay K; Singh, Avninder; Keisham, Chitralekha

2013-03-01

217

Regression in Autistic Spectrum Disorders  

Microsoft Academic Search

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

Gerry A. Stefanatos

2008-01-01

218

PGE2 Production in Oral Cancer Cell Lines is COX2-dependent  

Microsoft Academic Search

It has been suggested that epithelial cyclooxygenase-2 (COX-2) promotes oral carcinogenesis and carcinoma malignancy through increased prostaglandin E2 (PGE2) production. Although oral squamous cell carcinomas (OSCC) often express COX-2, they may also produce PGE2 in a COX-1-dependent manner. We used 6 isolated cell lines to investigate which COX isoforms OSCC may use for PGE2 production. COX-1 and -2 expression patterns

C. Husvik; C. Khuu; M. Bryne; T. S. Halstensen

2009-01-01

219

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

Microsoft Academic Search

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

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

1996-01-01

220

[Comparative analysis of variability of three mitochondrial genes of cytochrome oxidase complex (cox1, cox2, and cox3) in wild and domestic carp (Cyprinus carpio L.)].  

PubMed

For the first time, we studied the polymorphism of three mitochondrial genes of the cytochrome oxidase complex (cox1, cox2, and cox3) in natural populations of wild carp living in the Volga, Amur, and Don River Basins, as well as in European Hungarian carp and two pedigree lines of Ropsha carp of domestic breeding. The highest level of nucleotide and haplotype diversity in the studied samples was detected for the cox1 gene (pi = 0.61, h = 100%). Two lines of the Ropsha carp (pi = 0.61, h = 100%) and the Far East population of Amur wild carp from Shershikh strait (Am: pi = 0.20, h = 70%) were the most polymorphic for three genes. The second sample of Amur wild carp from the Amur River (Ac), as well as the samples of Volga and Don wild carp and Hungarian carp had lower values of variability. The presence of two main genealogical lines of the wild carp and carp was demonstrated based on the total sequence of three genes, as well as the corresponding amino acid sequences in the studied area. One of these lines (line I) is typical of the sample of Amur wild carp (Am) and three members of the Ropsha carp. Line II is developed by sequences of Volga, Don, and Amur wild carp (Ac), as well as European Hungarian carp and seven other members of the Ropsha carp. Three to four sublines, which differ in nucleotide and amino acid substitutions, were found within the lines. Possible reasons for the origin of genomic variability in wild carp, as well as in European and Russian breeds of carp, are discussed. PMID:23516901

Torgunakova, O A; Egorova, T A; Semenova, S K

2012-12-01

221

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

PubMed Central

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

Font-Nieves, Miriam; Sans-Fons, M. Gloria; Gorina, Roser; Bonfill-Teixidor, Ester; Salas-Perdomo, Angelica; Marquez-Kisinousky, Leonardo; Santalucia, Tomas; Planas, Anna M.

2012-01-01

222

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

Microsoft Academic Search

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

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

2004-01-01

223

Penalized Regression with Ordinal Predictors  

Microsoft Academic Search

Ordered categorial predictors are a common case in regression modeling. In contrast to the case of ordinal response variables, ordinal predictors have been largely neglected in the literature. In this article penalized regression techniques are proposed. Based on dummy coding two types of penalization are explicitly developed; the first imposes a dierence penalty, the second is a ridge type refit-

Jan Gertheiss; Gerhard Tutz

2008-01-01

224

Logistic Regression: Concept and Application  

ERIC Educational Resources Information Center

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

Cokluk, Omay

2010-01-01

225

MACRO FOR ESTIMATING THE BOX-COX POWER TRANSFORMATION  

EPA Science Inventory

In their classic paper, Box and Cox (1964) demonstrated how a dependent variable could be transformed to satisfy simultaneously, assumptions implicit in the analysis of linear models. For the class of analyses in which the response of interest is positive and where no transformat...

226

COX-2 and c-kit expression in canine gliomas.  

PubMed

Gliomas are among the most common primary neural tumours of dogs. Cyclooxygenase-2 (COX-2) and c-kit overexpression are associated with increased aggressiveness of gliomas and decreased survival in human beings. COX-2 is the inducible form of cyclooxygenase, which catalyzes prostaglandin formation and may increase tumour proliferation and angiogenesis. C-kit is a tyrosine kinase receptor involved in normal cell physiology; c-kit is upregulated in some canine tumours. In this retrospective study, 20 canine gliomas were identified: 11 (55%) oligodendrogliomas, including 1 anaplastic variant; 1 (5%) oligoastrocytoma; and 8 (40%) astrocytomas, of which 2 were glioblastoma multiforme. None of the gliomas expressed COX-2. None of the gliomas were immunoreactive for c-kit, although all three high-grade tumours had intramural vascular expression. Consequently, COX-2 inhibitors would likely be ineffective against canine gliomas. C-kit inhibitors may have an anti-angiogenic effect in high-grade gliomas, but would likely be ineffective in low- and medium-grade tumours. PMID:22235799

Jankovsky, J M; Newkirk, K M; Ilha, M R; Newman, S J

2011-11-23

227

On nonsingular potentials of Cox-Thompson inversion scheme  

SciTech Connect

We establish a condition for obtaining nonsingular potentials using the Cox-Thompson inverse scattering method with one phase shift. The anomalous singularities of the potentials are avoided by maintaining unique solutions of the underlying Regge-Newton integral equation for the transformation kernel. As a by-product, new inequality sequences of zeros of Bessel functions are discovered.

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

2010-02-15

228

COX2 inhibitors: a story of greed, deception and death  

Microsoft Academic Search

In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over

Georges M. Halpern

2005-01-01

229

Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa  

PubMed Central

BACKGROUND AND AIMS—Constitutive cyclooxygenase (COX) 1 is believed to mediate prostaglandin dependent gastric protection. However, gastric mucosa contains cells capable of expressing inducible COX-2. We therefore investigated COX-1 and COX-2 expression, localisation, and activity in normal and abnormal human gastric mucosa.?METHODS—COX-1 and COX-2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis, and their contribution to prostaglandin (PG)E2 synthesis using selective enzyme inhibitors.?RESULTS—There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivity in some sections. Immunostaining was specifically abolished by antigen absorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 and COX-2 immunostaining was increased in Helicobacter pylori gastritis, particularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE2 synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucosa; p=0.017) which was significantly inhibited by COX-1 but not COX-2 inhibition. Increased COX-2 immunostaining in macrophages, endothelial cells, and myofibroblasts (with reduced epithelial expression) was seen at the rim of ulcers.?CONCLUSION—COX-2, as well as COX-1, is expressed by normal human gastric mucosa and is increased at the rim of ulcers. Although both are increased with H pylori, COX-1 contributes more than COX-2 to gastric PGE2 production.???Keywords: stomach; gastric mucosa; cyclooxygenases; Helicobacter pylori; ulceration; prostaglandins

Jackson, L; Wu, K; Mahida, Y; Jenkins, D; Hawkey, C

2000-01-01

230

Consistent Condom Use Increases the Regression Rate of Cervical Intraepithelial Neoplasia 2-3  

PubMed Central

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

Munk, Ane Cecilie; Gudlaugsson, Einar; Malpica, Anais; Fiane, Bent; L?vslett, Kjell I.; Kruse, Arnold-Jan; ?vestad, Irene Tveiteras; Voorhorst, Feja; Janssen, Emiel A. M.; Baak, Jan P. A.

2012-01-01

231

Comparison of methods for ordinal lens opacity data from atomic-bomb survivors: univariate worse-eye method and bivariate GEE method using global odds ratio  

Microsoft Academic Search

In analyses of bivariate ordered polytomous cataract data from atomic-bomb survivors, we compared two methods, the univariate\\u000a worse-eye method, and the bivariate generalized estimating equations (GEE’s) method using global odds ratio by Williamson\\u000a et al. (Journal of the American Statistical Association, 90, 1432–1437, 1995). When the association was large and only subject level covariates were used, model selection in the univariate

Eiji Nakashima; Kazuo Neriishi; Atsushi Minamoto

2008-01-01

232

Multiple Regression and Its Discontents  

ERIC Educational Resources Information Center

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

Snell, Joel C.; Marsh, Mitchell

2012-01-01

233

Variable Selection in Logistic Regression.  

National Technical Information Service (NTIS)

In many situations, we are interested in selection of important variables which are adequate for prediction under a logistic regression model. In this paper, some selection procedures based on the information theoretic criteria are proposed, and these pro...

Z. D. Bai P. R. Krishnaiah L. C. Zhao

1987-01-01

234

Multiple Correlation versus Multiple Regression.  

ERIC Educational Resources Information Center

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

Huberty, Carl J.

2003-01-01

235

Introduction to Simple Linear Regression  

NSDL National Science Digital Library

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

Dallal, Gerard E.

2009-01-23

236

Fuzzy Rank Linear Regression Model  

NASA Astrophysics Data System (ADS)

In this paper, we construct a fuzzy rank linear regression model using the rank transform (RT) method and least absolute deviation (LAD) method based on the ?-level sets of fuzzy numbers. The rank transform method is known to be efficient when the error distribution does not satisfy the conditions for normality and the method is not sensitive to outliers in the regression analysis. Some examples are given to compare the effectiveness of the proposed method with other existing methods.

Yoon, Jin Hee; Choi, Seung Hoe

237

A Box-Cox normal model for response times.  

PubMed

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. PMID:19187574

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

2009-01-30

238

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

PubMed

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

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

2012-05-01

239

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

NASA Astrophysics Data System (ADS)

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

Chattopadhyay, Surajit; Jhajharia, Deepak; Chattopadhyay, Goutami

2011-07-01

240

(MIS)COMMUNICATING COX2 CLINICAL TRIAL RISKS  

Microsoft Academic Search

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

Mark Hochhauser; Norman M. Goldfarb

241

Selective COX2 Inhibitors and Risk of Myocardial Infarction  

Microsoft Academic Search

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

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

2005-01-01

242

Students Speak With Gary Cox, EPIC Project Manager  

NASA Video Gallery

From NASA’s International Space Station Mission Control Center Gary Cox EPIC Project Manager, participates in a Digital Learning Network (DLN) event with students at South Effingham Middle School in Guyton, GA. The DLN connects students and teachers with NASA experts and education specialists using online communication technologies like video/web conferencing and webcasting. Register for free, interactive events listed in the catalog or watch the webcasts. http://dln.nasa.gov

Russell Todd D

2012-03-06

243

Modelling geomagnetic reversals as a Gaussian Cox Process  

NASA Astrophysics Data System (ADS)

The mean rate of reversal of the geomagnetic field, as recorded in the Geomagnetic Polarity Time Scale (GPTS), has long been an object of study. The significance of the apparent long-term variations in the mean rate of reversals - including the occurrence of superchrons - has been debated, as has the possible origins of these variations in external control of the geodynamo (e.g. by the time-varying boundary conditions imposed by mantle convection). Here we model the long-term variations in the reversal rate nonparametrically, in terms of an inhomogeneous Poisson process. Specifically, we consider a Gaussian Cox process, a type of doubly-stochastic Poisson process where the mean rate (or intensity) is modelled in terms of a Gaussian process. Such processes are amenable to likelihood-based inference using Bayesian Markov Chain Monte-Carlo (MCMC) methods, which we employ to provide posterior distributions of the model parameters. The specification of a Gaussian process requires a covariance function, relating the intensity at nearby times; crucially, however, the timescale of the covariance function is not prescribed, but appears as a model hyperparameter, whose posterior distribution is an important output of the analysis. For the geodynamo, this hyperparameter should robustly characterise the timescale of long-term variations. Two different types of Gaussian Cox process are considered: a Log Gaussian Cox Process, applied to binned reversal data; and a Sigmoidal Gaussian Cox Process, applied to the discrete reversal data using a technique involving latent variables. Different MCMC algorithms for sampling the posterior distribution of the model parameters are investigated for both types of process, to check (and to optimise) the convergence of the MCMC chains. This analysis is applied to different records of the GPTS, including those of Cande & Kent (1995) and Gradstein & Ogg (1996). The implications of this analysis for the geodynamo, and the possibility of comparable analysis of the output of numerical geodynamo simulations, are discussed.

Sarson, Graeme; Boys, Richard; Golightly, Andrew; Henderson, Daniel

2013-04-01

244

Preparation of 3-arylmethylindoles as selective COX2 inhibitors  

Microsoft Academic Search

The 3-arylmethylation of indoles using TMSOTf\\/Et3SiH with a wide variety of substituted benzaldehydes has been accomplished. Under these mild Lewis acid mediated reductive conditions, it was demonstrated that indoles bearing both 6-MeSO2 and 2-methyl substituents could be 3-arylmethylated in good to excellent yields to afford the corresponding 3-arylmethyl indoles, effective as selective COX-2 inhibitors. In addition, the viability of this

Jeffrey A Campbell; Viola Bordunov; Chris A Broka; John Dankwardt; Robert T Hendricks; James M Kress; Keith A. M Walker; Jin-Hai Wang

2004-01-01

245

Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors.  

PubMed

A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 1-(4-methylsulfonylphenyl)-3-(4-methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC(50)=0.11 microM) with a high COX-2 selectivity index (SI=203.6) comparable to the reference drug celecoxib (COX-2 IC(50)=0.06 microM; COX-2 SI=405). The structure-activity data acquired indicate that the urea moiety constitutes a suitable scaffold to design new acyclic 1,3-diarylurea derivatives with selective COX-2 inhibitory activity. PMID:18226898

Zarghi, Afshin; Kakhgi, Samaneh; Hadipoor, Atefeh; Daraee, Bahram; Dadrass, Orkideh G; Hedayati, Mehdi

2008-01-11

246

Limitations to benzene cancer risk assessment by Cox and Ricci  

SciTech Connect

Cox and Ricci estimated human cancer risks from exposure to benzene by applying the linearized multi-stage model (LMS) to data on tumor responses in male mice. The unique feature of their analysis was their use of internal measures of dose estimated using a physiologically based pharmokinetic (PBPK) model. It is the authors' opinion that the inclusion of all squamous cell carcinomas in the Cox and Ricci experiment was not the most appropriate animal tumor category for the analysis. In addition, the authors' feel that to develop a dose-response curve for humans, it is reasonable to model a tumor that is more closely related to the observed human cancer endpoint, which is leukemia. To determine how robust the risk estimates made by Cox and Ricci were to different animal endpoints, in this work their methods were applied to two additional endpoints in mice: malignant lymphoma and alveolar/bronchial carcinoma. The methodology produced a good statistical fit to both sets of data.

Crump, K.; Allen, B.; Clewell, H. (Clement International Corp., Ruston, LA (United States))

1993-04-01

247

COX-2 in cancer: Gordian knot or Achilles heel?  

PubMed Central

The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade, and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes, several of which are mediated by COX-2, approach the complexities of a “Gordian Knot.” We review evidence from our studies and from literature suggesting that cyclooxygenase-2 (COX-2) biology presents a nodal point in cancer biology and an “Achilles heel” of COX-2-dependent tumors.

Stasinopoulos, Ioannis; Shah, Tariq; Penet, Marie-France; Krishnamachary, Balaji; Bhujwalla, Zaver M.

2013-01-01

248

siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis.  

PubMed

Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (?-MSH)-induced melanin production. In addition, ?-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than ?-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and ?-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo. PMID:22506937

Kim, Ji Y; Shin, Jae Y; Kim, Miri R; Hann, Seung-Kyung; Oh, Sang H

2012-04-16

249

COX2 inhibitors block chemotherapeutic agent-induced apoptosis prior to commitment in hematopoietic cancer cells  

Microsoft Academic Search

Enzymatic inhibitors of pro-inflammatory cyclooxygenase-2 (COX-2) possess multiple anti-cancer effects, including chemosensitization. These effects are not always linked to the inhibition of the COX-2 enzyme. Here we analyze the effects of three COX-2 enzyme inhibitors (nimesulide, NS-398 and celecoxib) on apoptosis in different hematopoietic cancer models. Surprisingly, COX-2 inhibitors strongly prevent apoptosis induced by a panel of chemotherapeutic agents. We

Claudia Cerella; Cyril Sobolewski; Sébastien Chateauvieux; Estelle Henry; Michael Schnekenburger; Jenny Ghelfi; Mario Dicato; Marc Diederich

2011-01-01

250

Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX2 expression in mice  

Microsoft Academic Search

Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases owing to the finding that highly specific COX-2 inhibitors (i.e., Vioxx) increased the risk of myocardial infarction and stroke in chronic users. However, the specific impact of COX-2 expression in the intact

John M. Streicher; Kenichiro Kamei; Tomo-o Ishikawa; Harvey Herschman; Yibin Wang

2010-01-01

251

Cyclooxygenase2 (COX2) expression at the site of recent myocardial infarction: friend or foe?  

Microsoft Academic Search

Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia.Objective: To assess COX-2 expression at the site of recent myocardial infarction.Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10–60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate

A Abbate; D Santini; G G L Biondi-Zoccai; S Scarpa; F Vasaturo; G Liuzzo; R Bussani; F Silvestri; F Baldi; F Crea; L M Biasucci; A Baldi

2004-01-01

252

Overexpression of cyclooxygenase-2 (COX2) in human primitive neuroectodermal tumors: effect of celecoxib and rofecoxib  

Microsoft Academic Search

In this study the role of cyclooxygenase-2 (COX-2) in primitive neuroectodermal tumor (PNET) the most malignant brain tumors of childhood was investigated. COX-2 expression in human brain tumor biopsy samples (seven\\/seven) was about 6–8-fold higher than normal brain tissue and several PNET cell lines also express COX-2. The effect of selective COX-2 inhibitors, celecoxib and rofecoxib on the growth of

Ratnakar Patti; Kiranmai Gumired; Pallu Reddanna; Leslie N. Sutton; Peter C. Phillips; C. Damodar Reddy

2002-01-01

253

Diagnostics for multiple regression problems  

SciTech Connect

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

Daly, J.C.

1982-03-01

254

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

PubMed

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-PGF1? 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-PGF1?, 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. PMID:23874970

Kirkby, Nicholas S; Zaiss, Anne K; Urquhart, Paula; Jiao, Jing; Austin, Philip J; Al-Yamani, Malak; Lundberg, Martina H; MacKenzie, Louise S; Warner, Timothy D; Nicolaou, Anna; Herschman, Harvey R; Mitchell, Jane A

2013-07-09

255

Aspirin, but not the more selective cyclooxygenase (COX)-2 inhibitors meloxicam and SC 58125, aggravates postischaemic cardiac dysfunction, independent of COX function  

Microsoft Academic Search

Inhibition of cyclooxygenase (COX) might favour non-enzymatic formation of cardiodepressive isoprostanes from arachidonic acid by radicals generated during reperfusion. This could explain deleterious effects of acetylsalicylic acid (ASA) on cardiac function. We examined the influence of COX inhibition on myocardial function after low-flow ischaemia and reperfusion, employing either ASA (100 µmol\\/l), the partially selective COX-2 inhibitor meloxicam (0.3 µmol\\/l and

Bernhard Heindl; Bernhard F. Becker

2001-01-01

256

Sulfone COX2 inhibitors increase susceptibility of human LDL and plasma to oxidative modification: comparison to sulfonamide COX2 inhibitors and NSAIDs  

Microsoft Academic Search

Clinical investigations have demonstrated a link between use of the sulfone cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, and increased risk for atherothrombotic events. This increased risk was not observed for a sulfonamide COX-2 inhibitor (celecoxib), indicating a potential non-enzymatic mechanism for rofexocib. To test this hypothesis, we compared the independent effects of COX-2 inhibitors on human LDL oxidation, an important contributor to

Mary F. Walter; Robert F. Jacob; Charles A. Day; Rachel Dahlborg; Yujia Weng; R. Preston Mason

2004-01-01

257

Celecoxib Exhibits the Greatest Potency amongst Cyclooxygenase (COX) Inhibitors for Growth Inhibition of COX2-negative Hematopoietic and Epithelial Cell Lines1  

Microsoft Academic Search

Cyclooxygenase-2 (COX-2) is an important cellular target for both therapy and\\/or prevention of inflammatory disorders and cancer. The advent of selective COX-2 inhibitors now allows a more precise and safer treatment approach. The screening of an array of cancer cell lines for growth inhibitory effects of COX-2-selective and -nonselective inhibitors, including celecoxib (Celebrex) and rofecoxib (Vioxx), produced two un- anticipated

Chris Waskewich; Rosalyn D. Blumenthal; Honglan Li; Rhona Stein; David M. Goldenberg; Jack Burton

2002-01-01

258

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

PubMed

Triphala is an Ayurvedic herbal formulation consisting of equal parts of three myrobalans: Terminalia chebula, Terminalia bellerica and Emblica officinalis. We recently reported that chebulagic acid (CA) isolated from Terminalia chebula is a potent COX-2/5-LOX dual inhibitor. In this study, compounds isolated from Terminalia bellerica were tested for inhibition against COX and 5-LOX. One of the fractionated compounds showed potent inhibition against COX enzymes with no inhibition against 5-LOX. It was identified as gallic acid (GA) by LC-MS, NMR and IR analyses. We report here the inhibitory effects of GA, with an IC(50) value of 74 nM against COX-2 and 1500 nM for COX-1, showing ?20 fold preference towards COX-2. Further docking studies revealed that GA binds in the active site of COX-2 at the non-steroidal anti-inflammatory drug (NSAID) binding site. The carboxylate moiety of GA interacts with Arg120 and Glu524. Based on substrate dependent kinetics, GA was found to be a competitive inhibitor of both COX-1 and COX-2, with more affinity towards COX-2. Taken together, our studies indicate that GA is a selective inhibitor of COX-2. Being a small natural product with selective and reversible inhibition of COX-2, GA would form a lead molecule for developing potent anti-inflammatory drug candidates. PMID:20441561

Reddy, Tamatam Chandramohan; Aparoy, Polamarasetty; Babu, Neela Kishore; Kumar, Kotha Anil; Kalangi, Suresh Kumar; Reddanna, Pallu

2010-10-01

259

Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction.  

PubMed

Aspirin is a common preventative therapy in patients at risk for cardiovascular diseases, yet little is known about how aspirin protects the vasculature in hypercholesterolemia. The present study determines whether aspirin, nitric oxide-releasing aspirin (NCX-4016), a selective cyclooxygenase (COX)-1 inhibitor (SC560), or genetic deficiency of COX-1 prevents the inflammatory and prothrombogenic phenotype assumed by hypercholesterolemic (HC) venules. Aspirin or NCX-4016 (60 mg/kg) was administered orally for the last week of a 2-wk HC diet. COX-1-deficient (COX-1(-/-)) and wild-type (WT) mice were transplanted with WT (WT/COX-1(-/-)) or COX-1(-/-) (COX-1(-/-)/WT) bone marrow, respectively. HC-induced adhesion of platelets and leukocytes in murine intestinal venules, observed with intravital fluorescence microscopy, was greatly attenuated in aspirin-treated mice. Adhesion of aspirin-treated platelets in HC venules was comparable to untreated platelets, whereas adhesion of SC560-treated platelets was significantly attenuated. HC-induced leukocyte and platelet adhesion in COX-1(-/-)/WT chimeras was comparable to that in SC560-treated mice, whereas the largest reductions in blood cell adhesion were in WT/COX-1(-/-) chimeras. NCX-4016 treatment of platelet recipients or donors attenuated leukocyte and platelet adhesion independent of platelet COX-1 inhibition. Platelet- and endothelial cell-associated COX-1 promote microvascular inflammation and thrombogenesis during hypercholesterolemia, yet nitric oxide-releasing aspirin directly inhibits platelets independent of COX-1. PMID:17933963

Tailor, Anitaben; Wood, Katherine C; Wallace, John L; Specian, Robert D; Granger, D Neil

2007-10-12

260

COX1 and COX2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: An in vitro analysis  

Microsoft Academic Search

We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone

C. Beretta; G. Garavaglia; M. Cavalli

2005-01-01

261

A simulation study of finite-sample properties of marginal structural Cox proportional hazards models  

PubMed Central

Summary Motivated by a previously published study of HIV treatment, we simulated data subject to time-varying confounding affected by prior treatment to examine some finite-sample properties of marginal structural Cox proportional hazards models. We compared (a) unadjusted, (b) regression-adjusted, (c) unstabilized and (d) stabilized marginal structural (inverse probability-of-treatment [IPT] weighted) model estimators of effect in terms of bias, standard error, root mean squared error (MSE) and 95% confidence limit coverage over a range of research scenarios, including relatively small sample sizes and ten study assessments. In the base-case scenario resembling the motivating example, where the true hazard ratio was 0.5, both IPT-weighted analyses were unbiased while crude and adjusted analyses showed substantial bias towards and across the null. Stabilized IPT-weighted analyses remained unbiased across a range of scenarios, including relatively small sample size; however, the standard error was generally smaller in crude and adjusted models. In many cases, unstabilized weighted analysis showed a substantial increase in standard error compared to other approaches. Root MSE was smallest in the IPT-weighted analyses for the base-case scenario. In situations where time-varying confounding affected by prior treatment was absent, IPT-weighted analyses were less precise and therefore had greater root MSE compared with adjusted analyses. The 95% confidence limit coverage was close to nominal for all stabilized IPT-weighted but poor in crude, adjusted, and unstabilized IPT-weighted analysis. Under realistic scenarios, marginal structural Cox proportional hazards models performed according to expectations based on large-sample theory and provided accurate estimates of the hazard ratio.

Westreich, Daniel; Cole, Stephen R.; Schisterman, Enrique F.; Platt, Robert W.

2013-01-01

262

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

PubMed

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 (<1 mg Cu/kg diet) and one group receiving a diet containing adequate copper (6 mg Cu/kg diet) for 5 weeks. Hearts were removed, weighed, and non-myofibrillar proteins separated to analyze for levels of 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. PMID:20878365

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

2010-09-28

263

Regression models in physiological research.  

PubMed

Regression models play a significant role for appropriate interpretations of complex phenomena of biomedical sciences. In the present paper an attempt has been made to critically review the applications of regression models in physiological research pertaining to the solutions of various defence oriented problems of indirect estimation of human endurances, fitness, physical work capacity, energy expenditure at different work rates, body density and lean body mass from body measurements at high altitude, ventilatory 'norms' for wider age groups from physical characteristics, heat output and index finger temperature from ambient temperature, leg muscle volume and fat free mass from X-ray radiographs and stature, total body volume from anthropometric measurements, thermoregulatory efficiency at different environmental situations etc. These regression models are of practical significance for screening personnel in defence services, mines, industrial work, sports and the like. PMID:11372464

Verma, S S

2001-01-01

264

Estimating Regression Parameters in an Extended Proportional Odds Model.  

PubMed

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

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

2012-01-31

265

Estimating Regression Parameters in an Extended Proportional Odds Model  

PubMed Central

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

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

2012-01-01

266

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

PubMed Central

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

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

2012-01-01

267

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

PubMed

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

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

2013-02-04

268

Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX2) inhibitors  

Microsoft Academic Search

A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1\\/COX-2 isozyme inhibition structure–activity studies identified 1-(4-methylsulfonylphenyl)-3-(4-methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC50=0.11?M) with a high COX-2

Afshin Zarghi; Samaneh Kakhgi; Atefeh Hadipoor; Bahram Daraee; Orkideh G. Dadrass; Mehdi Hedayati

2008-01-01

269

Pharmacokinetics, COX2 specificity, and tolerability of supratherapeutic doses of rofecoxib in humans  

Microsoft Academic Search

Objective: Prostaglandin synthesis is catalyzed by a constitutive cyclo-oxygenase isoform (COX-1) and an inducible isoform (COX-2).\\u000a It is hypothesized that the analgesic and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (nonspecific COX-1\\/COX-2\\u000a inhibitors) such as ibuprofen principally derive from COX-2 inhibition. The purpose of this study was to evaluate steady-state\\u000a pharmacokinetics, biochemical selectivity and tolerability of rofecoxib (VioxxTM), characterized in vitro

M. Depré; E. Ehrich; A. Van Hecken; I. De Lepeleire; A. Dallob; P. Wong; A. Porras; B. J. Gertz; P. J. De Schepper

2000-01-01

270

A Logistic Regression Model for Predicting Axillary Lymph Node Metastases in Early Breast Carcinoma Patients  

PubMed Central

Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.

Xie, Fei; Yang, Houpu; Wang, Shu; Zhou, Bo; Tong, Fuzhong; Yang, Deqi; Zhang, Jiaqing

2012-01-01

271

Correlation Weights in Multiple Regression  

ERIC Educational Resources Information Center

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

Waller, Niels G.; Jones, Jeff A.

2010-01-01

272

Fungible Weights in Multiple Regression  

ERIC Educational Resources Information Center

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

Waller, Niels G.

2008-01-01

273

Linear Regression and Best Fit  

NSDL National Science Digital Library

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

Patel, Amar

2009-01-22

274

Regression Models of Atlas Appearance  

PubMed Central

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

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

2010-01-01

275

Bandwidth Choice for Nonparametric Regression  

Microsoft Academic Search

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

John Rice

1984-01-01

276

Regression, Prediction, and Model Building  

NSDL National Science Digital Library

This tutorial, created by Thomas W. McFarland of Nova Southeastern University, explains the theory and use of multiple regression and demonstrates it with an example on SAT scores and GPA. Data sets are provided in both SPSS and Minitab code. This is a good resource for both students and teachers interested in a more in-depth study of statistics.

Macfarland, Thomas W.

2009-09-04

277

Conditional knockout mouse for tissue-specific disruption of the cyclooxygenase-2 (Cox-2) gene.  

PubMed

Cyclooxygenase-2 (Cox-2) modulates many normal functions, and appears to play a role in a wide variety of pathophysiologic conditions. Cox-2 gene expression is induced in many different cell types, in response to many distinct stimuli. We generated a conditional knockout mouse in which critical exons of the Cox-2 gene are flanked with loxP sites. Cox-2(flox/flox) mice appear normal and are fertile. Recombination at the loxP sites, loss of Cox-2 protein expression, and prevention of induced PGE2 accumulation are observed in Cox-2(flox/flox) mouse embryo fibroblasts following infection with an adenovirus expressing CRE recombinase. In vivo recombination at the Cox-2(flox) allele was demonstrated in the liver of Cox-2(flox/flox) mice following intravenous injection of adenovirus expressing CRE recombinase. Spatially and temporally restricted elimination of the Cox-2 gene in Cox-2(flox/flox) conditional knockout mice should provide a valuable tool to analyze the cell type-specific role of Cox-2 in many disease models. PMID:16496341

Ishikawa, Tomo-O; Herschman, Harvey R

2006-03-01

278

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

PubMed Central

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

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

2013-01-01

279

Electron paramagnetic resonance in Zn1-xCoxO  

NASA Astrophysics Data System (ADS)

In this paper is reported the Electron Paramagnetic Resonance (EPR) studies in Zn1-xCoxO powder, with 0.01?x?0.05, at many temperatures (105-250 K). These samples were synthesized by the sol-gel method (citrate route). Results suggest that the ferromagnetism behavior of the materials is governed by ferromagnetic coupling among cobalt ions. For cobalt concentration higher than 3% were obtained mean size particle higher than 25 nm, measured by X-ray diffraction, and for this were also observed shallow free radical.

Acosta-Humánez, F.; Cogollo Pitalúa, R.; Almanza, O.

2013-03-01

280

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

PubMed Central

Background Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008) Conclusion H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus.

2009-01-01

281

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

PubMed

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

Frühwirth-Schnatter, Sylvia; Pyne, Saumyadipta

2010-01-27

282

Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells.  

PubMed

High exposure to cadmium is a risk factor for many neuronal diseases. Overexpression of cyclooxygenase (COX)-2 is linked to many neuroinflammatory and neoplastic diseases. We, herein, investigated the effect of cadmium on the expression of COX-2 in C6 rat glioma cells. Treatment with cadmium sulfate (cadmium) increased the expression of COX-2 mRNA. Remarkably, cadmium treatment further increased expression of not only the N-glycosylated COX-2 protein of 72 kDa but also the unglycosylated COX-2 of 66 kDa, as assessed by the unglycosylated COX-2 induced by tunicamycin or glucosamine, known inhibitors of COX-2 N-glycosylation. Of note, when translation was blocked in the presence of cycloheximide (CHX), levels of both N-glycosylated and unglycosylated COX-2 proteins induced by cadmium rapidly declined but the decline was prevented by MG132, a 26S proteasomal inhibitor. However, in the absence of CHX, cadmium induced and maintained expression of the unglycosylated COX-2 proteins. Pharmacological inhibition studies importantly demonstrated that the cadmium-mediated COX-2 transcriptional upregulation in C6 cells was not shown by exogenous glutathione (GSH) supplementation or treatment with inhibitors of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 MAPK and c-Jun N-terminal protein kinase-1/2 (JNK-1/2), respectively. Expression of COX-2 was not noted in C6 cells exposed to other heavy metals (cobalt or manganese). These results demonstrate that cadmium specifically induces expression of COX-2 through both transcriptional and co-translational (N-glycosylation) regulation in C6 cells in which the cadmium-induced COX-2 transcriptional upregulation is closely related to oxidative stress-dependent activation of the family of MAPKs and the cadmium-induced expression of both N-glycosylated and unglycosylated COX-2 proteins is proteasome- and translation-dependent. PMID:22767315

Park, Yu-Kyoung; Hong, Hua; Jang, Byeong-Churl

2012-07-03

283

Expression and translation of the COX-1b gene in human cells--no evidence of generation of COX-1b protein.  

PubMed

Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein, which is possibly related to different species-dependent lengths of intron 1, is controversially discussed. The human intron 1 comprises 94 bp, and the resulting frameshift at the intron 1-exon 2 junction creates a premature stop codon. Nevertheless, full-length human COX-1b protein expression, including translated intron 1 and the signal peptide, has been reported and was explained by a frameshift repair. In this study, the fate of COX-1b mRNA in a human overexpression system is analyzed. Independent of the hypothetical frameshift repair mechanism, the splicing of the COX-1b intron 1, resulting in COX-1 mRNA and removal of the signal peptide during protein maturation, with subsequent generation of a COX-1 protein is demonstrated. PMID:23362192

Reinauer, Christina; Censarek, Petra; Kaber, Gernot; Weber, Artur-Aron; Steger, Gerhard; Klamp, Thorsten; Schrör, Karsten

2013-06-01

284

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

Microsoft Academic Search

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

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

2003-01-01

285

Translocation and assembly of mitochondrially coded Saccharomyces cerevisiae cytochrome c oxidase subunit Cox2 by Oxa1 and Yme1 in the absence of Cox18.  

PubMed

Members of the Oxa1/YidC/Alb3 family of protein translocases are essential for assembly of energy-transducing membrane complexes. In Saccharomyces cerevisiae, Oxa1 and its paralog, Cox18, are required for assembly of Cox2, a mitochondrially encoded subunit of cytochrome c oxidase. Oxa1 is known to be required for cotranslational export of the Cox2 N-terminal domain across the inner mitochondrial membrane, while Cox18 is known to be required for post-translational export of the Cox2 C-tail domain. We find that overexpression of Oxa1 does not compensate for the absence of Cox18 at the level of respiratory growth. However, it does promote some translocation of the Cox2 C-tail domain across the inner membrane and causes increased accumulation of Cox2, which remains unassembled. This result suggests that Cox18 not only translocates the C-tail, but also must deliver it in a distinct state competent for cytochrome oxidase assembly. We identified respiring mutants from a cox18Delta strain overexpressing OXA1, whose respiratory growth requires overexpression of OXA1. The recessive nuclear mutations allow some assembly of Cox2 into cytochrome c oxidase. After failing to identify these mutations by methods based on transformation, we successfully located them to MGR1 and MGR3 by comparative hybridization to whole-genome tiling arrays and microarray-assisted bulk segregant analysis followed by linkage mapping. While Mgr1 and Mgr3 are known to associate with the Yme1 mitochondrial inner membrane i-AAA protease and to participate in membrane protein degradation, their absence does not appear to stabilize Cox2 under these conditions. Instead, Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 in the absence of Mrg1 or Mgr3, since respiratory growth and cytochrome c oxidase assembly in a cox18 mgr3 double-mutant strain overexpressing OXA1 is YME1 dependent. PMID:19307606

Fiumera, Heather L; Dunham, Maitreya J; Saracco, Scott A; Butler, Christine A; Kelly, Jessica A; Fox, Thomas D

2009-03-23

286

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

PubMed Central

Although there is clinical and historical evidence for a vivid relation between the vestibular and emotional systems, the neuroscientific underpinnings are poorly understood. The “spin doctors” of the nineteenth century used spinning chairs (e.g., Cox’s chair) to treat conditions of mania or elevated arousal. On the basis of a recent study on a hexapod motion-simulator, in this prototypic investigation we explore the impact of yaw stimulation on a spinning chair on mood states. Using a controlled experimental stimulation paradigm on a unique 3-D-turntable at the University of Zurich we included 11 healthy subjects and assessed parameters of mood states and autonomic nervous system activity. The Multidimensional Mood State Questionnaire and Visual Analog Scales (VAS) were used to assess changes of mood in response to a 100?s yaw stimulation. In addition heart rate was continuously monitored during the experiment. Subjects indicated feeling less “good,” “relaxed,” “comfortable,” and “calm” and reported an increased alertness after vestibular stimulation. However, there were no objective adverse effects of the stimulation. Accordingly, heart rate did not significantly differ in response to the stimulation. This is the first study in a highly controlled setting using the historical approach of stimulating the vestibular system to impact mood states. It demonstrates a specific interaction between the vestibular system and mood states and thereby supports recent experimental findings with a different stimulation technique. These results may inspire future research on the clinical potential of this method.

Winter, Lotta; Wollmer, M. Axel; Laurens, Jean; Straumann, Dominik; Kruger, Tillmann H. C.

2013-01-01

287

A new fuzzy regression algorithm.  

PubMed

A new fuzzy regression algorithm is described and compared with conventional ordinary and weighted least-squares and robust regression methods. The application of these different methods to relevant data sets proves that the performance of the procedure described in this paper exceeds that of the ordinary least-squares method and equals and often exceeds that of weighted or robust methods, including the two fuzzy methods proposed previously (Otto, M.; Bandemer, H., Chemom. Intell. Lab. Syst. 1986, 1, 71. Hu, Y.; Smeyers-Verbeke, J.; Massart, D. L. Chemom. Intell. Lab. Syst. 1990, 8, 143). Moreover, we emphasize the effectiveness and the generality of the two new criteria proposed in this paper for diagnosing the linearity of calibration lines in analytical chemistry. PMID:21619171

Pop, H F; Sârbu, C

1996-03-01

288

Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: Facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors  

PubMed Central

All nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) isozymes to different extents, which accounts for their anti-inflammatory and analgesic activities and their gastrointestinal side effects. We have exploited biochemical differences between the two COX enzymes to identify a strategy for converting carboxylate-containing NSAIDs into selective COX-2 inhibitors. Derivatization of the carboxylate moiety in moderately selective COX-1 inhibitors, such as 5,8,11,14-eicosatetraynoic acid (ETYA) and arylacetic and fenamic acid NSAIDs, exemplified by indomethacin and meclofenamic acid, respectively, generated potent and selective COX-2 inhibitors. In the indomethacin series, esters and primary and secondary amides are superior to tertiary amides as selective inhibitors. Only the amide derivatives of ETYA and meclofenamic acid inhibit COX-2; the esters are either inactive or nonselective. Inhibition kinetics reveal that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Site-directed mutagenesis of murine COX-2 indicates that the molecular basis for selectivity differs from the parent NSAIDs and from diarylheterocycles. Selectivity arises from novel interactions at the opening and at the apex of the substrate-binding site. Lead compounds in the present study are potent inhibitors of COX-2 activity in cultured inflammatory cells. Furthermore, indomethacin amides are orally active, nonulcerogenic, anti-inflammatory agents in an in vivo model of acute inflammation. Expansion of this approach can be envisioned for the modification of all carboxylic acid-containing NSAIDs into selective COX-2 inhibitors.

Kalgutkar, Amit S.; Crews, Brenda C.; Rowlinson, Scott W.; Marnett, Alan B.; Kozak, Kevin R.; Remmel, Rory P.; Marnett, Lawrence J.

2000-01-01

289

Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alpha-induced COX-2 but not constitutive COX-1 gene expression in HT-29 cells.  

PubMed Central

Cyclo-oxygenase (COX) is the key regulatory enzyme of the prostaglandin/eicosanoid pathway. While COX-1 is mostly constitutively expressed, the COX-2 isoform is inducible by proinflammatory cytokines. We used an adenoviral vector containing an NF-kappaB super-repressor (Ad5IkappaB) to investigate the role of NF-kappaB in tumour necrosis factor-alpha (TNF-alpha)-mediated COX-2 gene expression in a colonic epithelial cell line. COX-1 mRNA and protein were constitutively expressed in uninfected, control Ad5LacZ- or Ad5IkappaB-infected HT-29 cells with no apparent change following TNF-alpha exposure. COX-2 mRNA and protein expression was undetectable in unstimulated cells but was strongly up-regulated after TNF-alpha stimulation in uninfected and Ad5LacZ-infected HT-29 cells. This induction was prevented in Ad5IkappaB cells. TNF-alpha increased prostaglandin E2 production by 20-fold in Ad5LacZ-infected HT-29 cells compared with uninfected cells and was significantly inhibited in Ad5IkappaB-infected cells in agreement with the COX-2 mRNA findings. We conclude that NF-kappaB activation is critical in mediating COX-2, but not COX-1 gene expression in HT-29 cells. Selective inhibition of COX-2 expression with the NF-kappaB super-repressor may be useful in distinguishing the role of inducible versus constitutive prostaglandins in intestinal function and provides greater specificity than pharmacological inhibitors. Images Figure 1 Figure 2 Figure 3

Jobin, C; Morteau, O; Han, D S; Balfour Sartor, R

1998-01-01

290

COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure  

PubMed Central

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 tumour 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 analysed for COX-2; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood-dust at work in the past (88 %, 14/16). For smokers, 63 % (12/19) presented with SSC, whereas 64 % (7/11) of non-smokers displayed adenocarcinoma. COX-2 was expressed at high levels in adenocarcinoma as compared to SSC (p < 0,001). COX-2 expression showed significant association with occupational exposure to wood dust (p = 0.024), and with non-smoking status (p = 0.001). No statistically significant associations between the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components in the carcinogenesis process. In contrast, SCCs predominated among smokers and expressed COX-2 rarely; this may suggest at least partially different molecular mechanisms.

Holmila, Reetta; Cyr, Diane; Luce, Daniele; Heikkila, Pirjo; Dictor, Michael; Steiniche, Torben; Stjernvall, Tuula; Bornholdt, Jette; Wallin, Hakan; Wolff, Henrik; Husgafvel-Pursiainen, Kirsti

2008-01-01

291

Kernel estimation of regression functions  

Microsoft Academic Search

For the nonparametric estimation of regression functions with a one-dimensional design parameter, a new kernel estimate is\\u000a defined and shown to be superior to the one introduced by Priestley and Chao (1972). The results are not restricted to positive\\u000a kernels, but extend to classes of kernels satisfying certain moment conditions. An asymptotically valid solution for the boundary\\u000a problem, arising for

Theo Gasser; Hans-Georg Müller

292

Geometric characterization of planar regression  

Microsoft Academic Search

The geometric characterization of linear regression in terms of the ‘concentration ellipse’ by Galton [Galton, F., 1886, Family likeness in stature (with Appendix by Dickson, J.D.H.). Proceedings of the Royal Society of London, 40, 42–73.] and Pearson [Pearson, K., 1901, On lines and planes of closest fit to systems of points in space. Philosophical Magazine, 2, 559–572.] was extended to

Brian J. McCartin

2006-01-01

293

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

SciTech Connect

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

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

2007-07-12

294

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

PubMed

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

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

2013-08-12

295

Stretch-induced myoblast proliferation is dependent on the COX2 pathway  

SciTech Connect

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

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

2005-11-01

296

TNFalpha regulates renal COX-2 in the rat thick ascending limb (TAL).  

PubMed

We have examined cyclooxygenase (COX)-2-dependent mechanisms in preglomerular microvessels and the thick ascending limb (TAL). These renal structures are linchpins in the regulation of the renal circulation and extracellular fluid volume. Cytochrome P450 monooxygenases are the principal oxygenases in the TAL segment; however, COX-2 can be expressed in the TAL, as when challenged by angiotensin II. Glucocorticoids also affect the expression and activity of oxygenases in the TAL. Before adrenalectomy, <2% TAL cells expressed COX-2; after, >30% of TAL cells expressed COX-2. Recruitment of COX-2 is initiated in the renal cortex and proceeds to the medulla associated with: (1) COX-2 mRNA accumulation; (2) increased COX-2 expression; and (3) a two-fold increase in PGE2 production by cortical microsomes. These changes were nullified by dexamethasone. COX-2 mRNA, protein expression and PGE2 synthesis in the TAL are also increased in response to increased extracellular Ca2+. The Ca2+ sensing receptor is G-protein coupled and responds to changes in extracellular Ca2+ concentration by increasing protein kinase C activity to produce expression of COX-2. Thus, multiple signaling pathways contribute to COX-2 expression in TAL cells. PMID:14592548

Ferreri, Nicholas R; McGiff, John C; Vio, Carlos P; Carroll, Mairead A

2003-06-15

297

The Complex Interplay between COX-2 and Angiotensin II in Regulating Kidney Function  

PubMed Central

Purpose of Review Cyclooxygenase-2 (COX-2) plays a critical role in modulating deleterious actions of angiotensin II (Ang II) where there is an inappropriate activation of the renin-angiotensin system (RAS). This review discusses recent developments regarding the complex interactions by which COX-2 modulates the impact of an activated RAS on kidney function and blood pressure. Recent Findings Normal rats with increased COX-2 activity but with different intrarenal Ang II activity due to sodium restriction or chronic treatment with angiotensin converting enzyme (ACE) inhibitors showed similar responses to COX-2 selective inhibition (nimesulide) indicating independence from the intrarenal Ang II activity. COX-2 dependent maintenance of medullary blood flow was consistent and not dependent on dietary salt or ACE inhibition. In contrast, COX-2 influences on sodium excretion were contingent on the prevailing RAS activity. In chronic hypertensive models, COX-2 inhibition elicited similar reductions in kidney function but COX-2 metabolites contribute to rather than ameliorate the hypertension. Summary The maintenance of renal hemodynamics reflects direct and opposing effects of Ang II and COX-2 metabolites. The antagonism in water and electrolyte reabsorption is dependent on the prevailing intrarenal Ang II activity. The recent functional experiments demonstrate a beneficial modulation of Ang II by COX-2 except in the presence of inflammation promoted by hypertension, hyperglycemia and oxidative stress.

Green, Torrance; Gonzalez, Alexis A.; Mitchell, Kenneth D.; Navar, L. Gabriel

2012-01-01

298

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells  

PubMed Central

TNF and epidermal growth factor (EGF) are well-known stimuli of cyclooxygenase (COX)-2 expression, and TNF stimulates transactivation of EGF receptor (EGFR) signaling to promote survival in colon epithelial cells. We hypothesized that COX-2 induction and cell survival signaling downstream of TNF are mediated by EGFR transactivation. TNF treatment was more cytotoxic to COX-2?/? mouse colon epithelial (MCE) cells than wild-type (WT) young adult mouse colon (YAMC) epithelial cells or COX-1?/? cells. TNF also induced COX-2 protein and mRNA expression in YAMC cells, but blockade of EGFR kinase activity or expression inhibited COX-2 upregulation. TNF-induced COX-2 expression was reduced and absent in EGFR?/? and TNF receptor-1 (TNFR1) knockout MCE cells, respectively, but was restored upon expression of the WT receptors. Inhibition of mediators of EGFR transactivation, Src family kinases and p38 MAPK, blocked TNF-induced COX-2 protein and mRNA expression. Finally, TNF injection increased COX-2 expression in colon epithelium of WT, but not kinase-defective EGFRwa2 and EGFRwa5, mice. These data indicate that TNFR1-dependent transactivation of EGFR through a p38- and/or an Src-dependent mechanism stimulates COX-2 expression to promote cell survival. This highlights an EGFR-dependent cell signaling pathway and response that may be significant in colitis-associated carcinoma.

Hobbs, Stuart S.; Goettel, Jeremy A.; Liang, Dongchun; Yan, Fang; Edelblum, Karen L.; Frey, Mark R.; Mullane, Matthew T.

2011-01-01

299

A method for analyzing clustered interval-censored data based on Cox's model.  

PubMed

Methods for analyzing interval-censored data are well established. Unfortunately, these methods are inappropriate for the studies with correlated data. In this paper, we focus on developing a method for analyzing clustered interval-censored data. Our method is based on Cox's proportional hazard model with piecewise-constant baseline hazard function. The correlation structure of the data can be modeled by using Clayton's copula or independence model with proper adjustment in the covariance estimation. We establish estimating equations for the regression parameters and baseline hazards (and a parameter in copula) simultaneously. Simulation results confirm that the point estimators follow a multivariate normal distribution, and our proposed variance estimations are reliable. In particular, we found that the approach with independence model worked well even when the true correlation model was derived from Clayton's copula. We applied our method to a family-based cohort study of pandemic H1N1 influenza in Taiwan during 2009-2010. Using the proposed method, we investigate the impact of vaccination and family contacts on the incidence of pH1N1 influenza. PMID:22911905

Kor, Chew-Teng; Cheng, Kuang-Fu; Chen, Yi-Hau

2012-08-22

300

Nonlinear multiple imputation for continuous covariate within semiparametric Cox model: application to HIV data in Senegal.  

PubMed

Multiple imputation is commonly used to impute missing covariate in Cox semiparametric regression setting. It is to fill each missing data with more plausible values, via a Gibbs sampling procedure, specifying an imputation model for each missing variable. This imputation method is implemented in several softwares that offer imputation models steered by the shape of the variable to be imputed, but all these imputation models make an assumption of linearity on covariates effect. However, this assumption is not often verified in practice as the covariates can have a nonlinear effect. Such a linear assumption can lead to a misleading conclusion because imputation model should be constructed to reflect the true distributional relationship between the missing values and the observed values. To estimate nonlinear effects of continuous time invariant covariates in imputation model, we propose a method based on B-splines function. To assess the performance of this method, we conducted a simulation study, where we compared the multiple imputation method using Bayesian splines imputation model with multiple imputation using Bayesian linear imputation model in survival analysis setting. We evaluated the proposed method on the motivated data set collected in HIV-infected patients enrolled in an observational cohort study in Senegal, which contains several incomplete variables. We found that our method performs well to estimate hazard ratio compared with the linear imputation methods, when data are missing completely at random, or missing at random. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23712767

Mbougua, Jules Brice Tchatchueng; Laurent, Christian; Ndoye, Ibra; Delaporte, Eric; Gwet, Henri; Molinari, Nicolas

2013-05-28

301

Search Algorithms for Regression Test Case Prioritization  

Microsoft Academic Search

Regression testing is an expensive, but important, process. Unfortunately, there may be insufficient resources to allow for the reexecution of all test cases during regression testing. In this situation, test case prioritization techniques aim to improve the effectiveness of regression testing by ordering the test cases so that the most beneficial are executed first. Previous work on regression test case

Zheng Li; Mark Harman; Robert M. Hierons

2007-01-01

302

Regression Test Selection for C++ Software  

Microsoft Academic Search

Regression testing is an important but expensive software maintenance activity performed with the aim of providing condence in modied software. Regression test selection techniques reduce the cost of regression testing by selecting test cases for a modied program from a previously existing test suite. Many researchers have addressed the regression test selection problem for procedural language software, but few have

Gregg Rothermel; Mary Jean Harrold; Jeinay Dedhia

2000-01-01

303

Regression in individuals with Rett syndrome  

Microsoft Academic Search

Data on features of regression and pre-regression developmental history in a case series of 53 girls and women with Rett syndrome are presented. Consistent with the diagnostic criteria, hand skills and verbal or non-verbal communication skills were the most common skills lost during regression. Play and motor skills were also lost in half the cases. Regression most commonly occurred between

Tony Charman; Hilary Cass; Lucy Owen; Tony Wigram; Vicky Slonims; Alison Wisbeach; Sheena Reilly

2002-01-01

304

Tubuloglomerular feedback is decreased in COX-1 knockout mice after chronic angiotensin II infusion.  

PubMed

Prostaglandins (PGs), produced by two isoforms of cyclooxygenase (COX), COX-1 and COX-2, are important modulators of renal hemodynamics. COX-1 and COX-2 are expressed in the kidney often at distinct sites. Thromboxane (TxA(2)), PGE(2), and prostacyclin (PGI(2)) are the major PGs in the renal cortex of mice. Acute infusion of the vasoconstrictor ANG II increases COX-2-dependent PGE(2) and PGI(2). COX-2 is primarily expressed in the macula densa (MD), where several PG synthases are also expressed. We previously showed that MD COX-2 products modulate tubuloglomerular feedback (TGF) in the rat. Genetic deletion of COX-1 enhances COX-2 production of PGs, decreases renal and urinary PGs, and attenuates ANG II-induced hypertension. The present study tested the effects of chronic ANG II infusion on TGF in COX-1 knockout (KO) mice. Basal TGF was similar in COX-1 KO and wild-type (WT) mice. Chronic ANG II infusion increased TGF in WT mice (WT: 9.3 +/- 0.7 vs. WT + ANG II: 12.2 +/- 1.6 mmHg, P < 0.02). However, chronic ANG II decreased TGF in COX-1 KO mice (KO: 11.4 +/- 1.1 vs. KO + ANG II: 8.3 +/- 0.6 mmHg, P < 0.01). Pretreatment with the COX-2 inhibitor SC-58,236 in COX-1 KO mice prevented the ANG II-associated reduction in TGF (11.4 +/- 1.0 vs. 11.5 +/- 0.28 mmHg, not significant). Excretion of 6-keto-PGF(2alpha), the metabolite of PGI(2), was increased by ANG II infusion, whereas excretion of TxB(2), the stable metabolite of TxA(2), was not changed. ANG II infusion increased mean arterial pressure similarly in both WT and KO mice (WT: 93 +/- 2 vs. KO: 92 +/- 3 mmHg), but not in KO mice pretreated with SC-58,236 (85 +/- 2 mmHg). This study shows that COX-1-generated PGs partially mediate ANG II increases in TGF and that COX-2 PGs offset that effect. PMID:20107114

Araujo, Magali; Welch, William J

2010-01-27

305

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

Microsoft Academic Search

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

Keith N. Sircombe

2004-01-01

306

Bayesian dynamic regression models for interval censored survival data with application to children dental health.  

PubMed

Cox models with time-varying coefficients offer great flexibility in capturing the temporal dynamics of covariate effects on event times, which could be hidden from a Cox proportional hazards model. Methodology development for varying coefficient Cox models, however, has been largely limited to right censored data; only limited work on interval censored data has been done. In most existing methods for varying coefficient models, analysts need to specify which covariate coefficients are time-varying and which are not at the time of fitting. We propose a dynamic Cox regression model for interval censored data in a Bayesian framework, where the coefficient curves are piecewise constant but the number of pieces and the jump points are covariate specific and estimated from the data. The model automatically determines the extent to which the temporal dynamics is needed for each covariate, resulting in smoother and more stable curve estimates. The posterior computation is carried out via an efficient reversible jump Markov chain Monte Carlo algorithm. Inference of each coefficient is based on an average of models with different number of pieces and jump points. A simulation study with three covariates, each with a coefficient of different degree in temporal dynamics, confirmed that the dynamic model is preferred to the existing time-varying model in terms of model comparison criteria through conditional predictive ordinate. When applied to a dental health data of children with age between 7 and 12 years, the dynamic model reveals that the relative risk of emergence of permanent tooth 24 between children with and without an infected primary predecessor is the highest at around age 7.5, and that it gradually reduces to one after age 11. These findings were not seen from the existing studies with Cox proportional hazards models. PMID:23389549

Wang, Xiaojing; Chen, Ming-Hui; Yan, Jun

2013-02-07

307

COX-2 structural analysis and docking studies with gallic acid structural analogues.  

PubMed

Emblica officinalis is an ayurvedic herbal plant. The compounds isolated from this plant have good inhibitory effects against cyclooxygenase-2 (COX-2), among them gallic acid (GA) has the highest inhibitory effect. COX-2 (1.14.99.1) is an oxidoreductase having a role in prostaglandin biosynthesis, inflammatory responses and in cardiovascular events. COX-2 has gained special focus on research since past few decades. The sequence and structural studies reveals Mus musculus COX-2 shares the common conserved sequence and structural pattern with human COX-2. Molecular modeling and docking analysis with gallic acid and their structural analogues showed that 2-[(2E,4E)-hexa-2,4-dienyl]-3,4,5-trihydroxybenzoic acid, (3,4,5-trihydroxybenzoyl) 3,4,5-trihydroxybenzoate and 3-hydroxy-4-sulfooxybenzoic acid are more interactive and binding strongly than gallic acid at active site. Hence these three compounds should be considered as strong inhibitors for COX-2. PMID:23483789

Amaravani, M; Prasad, Nirmal K; Ramakrishna, Vadde

2012-12-10

308

Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo  

PubMed Central

Background and purpose: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. Experimental approach: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. Key results: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 × 10?11?M) than in distal specimens (EC50=7.4 × 10?10?M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. Conclusions and implications: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.

Chaignat, V; Danuser, H; Stoffel, M H; z'Brun, S; Studer, U E; Mevissen, M

2008-01-01

309

Box-Cox Mixed Logit Model for Travel Behavior Analysis  

NASA Astrophysics Data System (ADS)

To represent the behavior of travelers when they are deciding how they are going to get to their destination, discrete choice models, based on the random utility theory, have become one of the most widely used tools. The field in which these models were developed was halfway between econometrics and transport engineering, although the latter now constitutes one of their principal areas of application. In the transport field, they have mainly been applied to mode choice, but also to the selection of destination, route, and other important decisions such as the vehicle ownership. In usual practice, the most frequently employed discrete choice models implement a fixed coefficient utility function that is linear in the parameters. The principal aim of this paper is to present the viability of specifying utility functions with random coefficients that are nonlinear in the parameters, in applications of discrete choice models to transport. Nonlinear specifications in the parameters were present in discrete choice theory at its outset, although they have seldom been used in practice until recently. The specification of random coefficients, however, began with the probit and the hedonic models in the 1970s, and, after a period of apparent little practical interest, has burgeoned into a field of intense activity in recent years with the new generation of mixed logit models. In this communication, we present a Box-Cox mixed logit model, original of the authors. It includes the estimation of the Box-Cox exponents in addition to the parameters of the random coefficients distribution. Probability of choose an alternative is an integral that will be calculated by simulation. The estimation of the model is carried out by maximizing the simulated log-likelihood of a sample of observed individual choices between alternatives. The differences between the predictions yielded by models that are inconsistent with real behavior have been studied with simulation experiments.

Orro, Alfonso; Novales, Margarita; Benitez, Francisco G.

2010-09-01

310

Regulation of cell growth by selective COX2 inhibitors in oral carcinoma cell lines  

Microsoft Academic Search

Evidence indicates that NSAIDs that inhibit prostaglandin (PG) synthesis can reduce the incidence of colorectal cancers and that inhibition of cyclooxygenase-2 (COX-2) may be the underlying mechanism. The objective of this study was to investigate this putative mechanism by examining the effect of selective COX-2 inhibitors (Celebrex, DFU, NS-398) and COX-1 inhibitors (Aspirin) on the growth of two human oral

C. Y Yang; C. L Meng; C. L Liao; P. Y.-K Wong

2003-01-01

311

Radiosensitizing potential of the selective cyclooygenase-2 (COX2) inhibitor meloxicam on human glioma cells  

Microsoft Academic Search

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive\\u000a growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this\\u000a study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated\\u000a on human glioma cells in vitro. A panel

Irene V. Bijnsdorp; Jaap van den Berg; Gitta K. Kuipers; Laurine E. Wedekind; Ben J. Slotman; Johannes van Rijn; M. Vincent M. Lafleur; Peter Sminia

2007-01-01

312

Down-regulation of cyclooxygenase-2 (COX-2) by interleukin-1 receptor antagonist in human monocytes.  

PubMed Central

Cyclooxygenase (COX) is the key rate-limiting enzyme in the synthesis of prostanoids from arachidonic acid. Two isoforms of COX have been described in mammalian cells, referred to as cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutively expressed enzyme; COX-2 is an inducible enzyme that appears to be expressed in inflamed tissue and following exposure to growth factors or cytokines, such as interleukin-1 (IL-1). The aim of the present study was to test if the antagonism on the binding of IL-1 to its cell-surface receptor by human recombinant IL-1 receptor antagonist (hrIL-1ra) may control the COX mRNA expression and prostaglandin E2 (PGE2) production by human monocyte cultures. Northern blot studies showed that hrIL-ra (500 ng/ml) had a strong inhibitory effect on inducible COX activity. The effect was evident after 6 hr incubation (2.7-fold decrease of mRNA COX-2 transcripts); and about a threefold decrease at 24hr incubation. A non-significant effect was observed with COX-1 transcripts. Induced PGE2 production by monocyte cultures treated with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) was strongly inhibited in the presence of hrIL-1ra (500 ng/ml). In addition, a significant inhibition of COX-2 protein expression, as evaluated by Western blotting, was also observed. These data suggest that hrIL-1ra may be the key mediator in the down-regulation of the COX-2 inducible pathway. Images Figure 1 Figure 2 Figure 5 Figure 6

Porreca, E; Reale, M; Di Febbo, C; Di Gioacchino, M; Barbacane, R C; Castellani, M L; Baccante, G; Conti, P; Cuccurullo, F

1996-01-01

313

Primary Virtual and in vitro Bioassay Screening of Natural Inhibitors from Flavonoids against COX2  

Microsoft Academic Search

In this study, we reported the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2 092 flavonoids) using the iGEMDOCK software tool against the COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of COX-2. Centaureidin and luteolin were found to be the potential inhibitors of COX-2

Ya-Di LI; Christopher M. Frenz; Mian-Hua CHEN; Yu-Rong WANG; Feng-Juan LI; Cheng LUO; Ning LIANG; Hua YANG; Lars bohlin; Chang-Lu WANG

2011-01-01

314

Different COXindependent effects of the COX2 inhibitors etoricoxib and lumiracoxib  

Microsoft Academic Search

Etoricoxib and lumiracoxib are both highly selective COX-2 inhibitors. This drug class has recently been linked to severe side effects in particular within the cardiovascular system. The underlying signal transduction pathway is not clarified at the moment but different COX-independent mechanisms might contribute to wanted and unwanted effects of these drugs. Here, we investigated COX-2-independent effects of etoricoxib and lumiracoxib.

Ellen Niederberger; Christine Manderscheid; Gerd Geisslinger

2006-01-01

315

COX-2 is not required for the development of murine chronic pancreatitis.  

PubMed

Chronic pancreatitis is a severe inflammation of the pancreas associated with destruction of the parenchyma, fibrosis, and persistent abdominal pain. Cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandins, key mediators of the inflammatory response, are elevated in patients with chronic pancreatitis. Previous studies investigated COX-2 as a therapeutic target. These reports showed a reduced pathology in COX-2-deficient mice with a better outcome. Here we compared the role of COX-2 in acute and chronic pancreatic inflammation using the same COX-2(-/-) mouse model of cerulein-induced pancreatitis. In a setting of acute pancreatitis, juvenile COX-2(-/-) mice exhibited a reduced histopathological score compared with wild-type littermates; on the contrary, adult mice did not show any difference in the development of the disease. Similarly, in a setting of chronic pancreatitis induced over a period of 4 wk, adult mice of the two strains showed comparable histological score and collagen deposition. However, the abundance of mRNAs coding for profibrotic genes, such as collagen, ?-smooth muscle actin, and transforming growth factor-? was consistently lower in COX-2(-/-) mice. In addition, comparable histological scores and collagen deposition were observed in wild-type mice treated with a COX-2 inhibitor. We conclude that, in contrast to what was observed in the rat pancreatitis models, COX-2 has a limited and age-dependent effect on inflammatory processes in the mouse pancreas. These results suggest that COX-2 modulates the inflammatory process during the development of pancreatitis in a species-specific manner. Thus the pathophysiological roles of COX-2 and its therapeutic implications in patients with pancreatitis should be reexamined. PMID:21372163

Silva, Alberto; Weber, Achim; Bain, Martha; Reding, Theresia; Heikenwalder, Mathias; Sonda, Sabrina; Graf, Rolf

2011-03-03

316

Human COX6A1 gene: promoter analysis, cDNA isolation and expression in the monkey brain  

Microsoft Academic Search

The human COX6A1 gene encodes the ubiquitous isoform of cytochrome c oxidase (COX) subunit VIa (VIa-L), and is located in a CpG island on chromosome 12q24.2. We compared the COX6A1 gene with the published cDNA and several ESTs and concluded that subunit COX VIa-L is synthesized as a preprotein, as are other COX subunits. The same transcription start sites were

Margaret Wong-Riley; Aili Guo; Nancy J. Bachman; Margaret I. Lomax

2000-01-01

317

COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs  

Microsoft Academic Search

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of prostanoids by the enzyme cyclooxygenase (COX). Work in the past 15 years has shown that COX exists in two forms: COX1, which is largely associated with physiological functions, and COX2, which is largely associated with pathological functions. Heated debate followed the introduction of selective COX2 inhibitors around 5 years ago: do these

Jane A. Mitchell; Timothy D. Warner

2006-01-01

318

Regression of giant bullous emphysema.  

PubMed

Spontaneous resolution of bulla associated with infection or tumor is occasionally observed. However, resolution of progressively enlarging giant bullous emphysema (GBE) after medical therapy has not been reported. A 51-year-old man smoker with GBE on the right lung was referred to Samsung Medical Center for the consideration of bullectomy. A review of his medical records revealed that right-side bullous emphysema had been detected 4 years previously and it had progressively enlarged with a concomitant deterioration of lung function. Although he had a history of chronic asthma, he had never been treated on a regular basis. After combination therapy, including regular tiopropium, a salmeterol/flucatisone inhaler, a salbutamol inhaler as needed, and oral theophylline therapy, right side bulla showed marked regression. This regression of bulla was associated with an improved forced expiratory volume in one second and normalization of residual volume. This case serves as a reminder to clinicians that medical treatment for underlying diseases should precede surgical consideration in patients with GBE. PMID:20046002

Park, Hye Yun; Lim, Seong Yong; Park, Hye Kyeong; Park, So Young; Kim, Tae Sung; Suh, Gee Young

2010-01-01

319

Seizure susceptibility in immature brain due to lack of COX-2-induced PGF2?.  

PubMed

The immature brain is prone to seizure; however, the mechanism underlying this vulnerability has not been clarified. Febrile seizure is common in young children, and the use of non-steroidal anti-inflammatory drugs for febrile seizure is not recommended. In previous studies, we established that prostaglandin (PG) F2?, a product of cyclooxygenase (COX), acts as an endogenous anticonvulsant in the adult mouse. Therefore, we assumed that COX-2 activity was involved with seizure susceptibility in early life. In the present study, immature mice (postnatal day 9) were far more prone to kainic acid (KA)-induced seizures than mature mice (after postnatal day 35). Seizure activity began later in immature mice, but was more severe and was unaffected by a potent COX inhibitor, indomethacin; in contrast, indomethacin aggravated seizure activity in mature mice. Immature mouse brains exhibited little basal COX-2 expression and little KA-induced COX-2 induction, while KA-induced COX-2 expression and PGF2? release were prominent in mature brains. During brain development, COX expression was increased and glycosylated in an age-dependent manner, which was necessary for COX enzyme activity. Intracisternal PGF2? administration also reduced KA-induced seizure activity and mortality. Taken together, low COX activity and the resulting deficiency of PGF2? may be an essential cause of increased seizure susceptibility in the immature brain. PMID:24005111

Chung, Jee-In; Kim, A Young; Lee, Soo Hwan; Baik, Eun Joo

2013-09-01

320

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

PubMed

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

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

2011-10-01

321

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

SciTech Connect

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.

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

2005-11-01

322

Gastrointestinal safety of novel nonsteroidal antiinflammatory drugs: selective COX-2 inhibitors and beyond.  

PubMed

Nonsteroidal antiinflammatory drugs (NSAIDs) are frequently associated with adverse reactions, related to inhibition of cyclooxygenase (COX) in tissues where prostaglandins exert physiological effects, such as gastric mucosal defense and renal homeostasis. The discovery of two COX isoforms, namely COX-1 constitutively expressed in most tissues and COX-2 induced at sites of inflammation, led to the development of selective COX-2 inhibitors ("coxibs"), with the hope of significantly reducing the gastrointestinal toxicity associated with acute and chronic NSAID use. However, the increased knowledge of physiological roles of COX-2 enzyme in a variety of tissues, including stomach and kidney, together with the withdrawal from the market of rofecoxib and valdecoxib because of cardiovascular toxicity, have challenged the benefits of selective COX-2 inhibition. As a consequence, the interest for novel approaches has re-emerged; new therapeutic options, still under clinical evaluation, are represented by dual COX and 5-lipooxygenase (5-LOX) inhibitors, synthetic lipoxins, nitric oxide (NO)-releasing NSAIDs and, more recently, by NSAIDs releasing hydrogen sulphide (H2S). This review focuses upon the gastrointestinal (GI) safety of selective COX-2 inhibitors and of novel therapeutic strategies, in comparison with traditional NSAIDs. PMID:17933277

Coruzzi, Gabriella; Venturi, Nicola; Spaggiari, Silvana

2007-08-01

323

Principal component regression analysis with SPSS.  

PubMed

The paper introduces all indices of multicollinearity diagnoses, the basic principle of principal component regression and determination of 'best' equation method. The paper uses an example to describe how to do principal component regression analysis with SPSS 10.0: including all calculating processes of the principal component regression and all operations of linear regression, factor analysis, descriptives, compute variable and bivariate correlations procedures in SPSS 10.0. The principal component regression analysis can be used to overcome disturbance of the multicollinearity. The simplified, speeded up and accurate statistical effect is reached through the principal component regression analysis with SPSS. PMID:12758135

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

2003-06-01

324

Prognostic factors in childhood asthma: a logistic regression analysis.  

PubMed

Thirty-two factors related to childhood asthma were studied in 200 asthmatic children. Remission of asthma was defined as a period of at least 2 years free of asthma while receiving no treatment. Univariate analysis showed significant associations between persistence of asthma and perennial symptoms with an odds ratio (OR) of 2.5 (95% confidence intervals 1.2 to 5.5); sensitization to house dust mites OR 3.5 (1.2 to 9.6); sensitization to molds, OR 7.9 (2.9 to 21.6); sensitization to pollen, OR 4.8 (1.4 to 16.3); and sensitization to milk protein, OR 5.4 (1.8 to 15.9). There was a positive association of remission of asthma with good treatment compliance, OR 12.1 (1.6 to 91.6). A stepwise logistic regression analysis selected the variables: perennial symptoms (S: 0 = no, 1 = yes), length of follow-up time (T: number of months), treatment compliance (C: 0 = poor, 1 = good), sensitization to fungi (F: 0 to 4), and sensitization to milk protein (M: 0 to 4). The analysis yielded the following formula for calculation of probability of asthma remission P(R): [formula: see text] where S indicates perennial symptoms; T, follow-up time in months; C, compliance; F, allergy to fungi; and M, allergy to milk. PMID:8179234

Mazon, A; Nieto, A; Nieto, F J; Menendez, R; Boquete, M; Brines, J

1994-05-01

325

Improving Your Data Transformations: Applying the Box-Cox Transformation  

ERIC Educational Resources Information Center

|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…

Osborne, Jason W.

2010-01-01

326

Robust, Adaptive Functional Regression in Functional Mixed Model Framework.  

PubMed

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

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

2011-09-01

327

Robust, Adaptive Functional Regression in Functional Mixed Model Framework  

PubMed Central

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

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

2012-01-01

328

The 226Ra, 232Th and 40K activities in beach sand minerals and beach soils of Cox’s Bazar, Bangladesh  

Microsoft Academic Search

The radioactivity of 226Ra, 232Th and 40K in beach sand minerals from the Plant of the Beach Sand Exploitation Center (BSEC) and soils from the tourist zone of Cox’s Bazar, Bangladesh were measured using d?-ray spectrometry with the aim of estimating the radiation hazard as well as establishing a database for radioactivity levels of the Plant and the tourist area

M. N. Alam; M. I. Chowdhury; M. Kamal; S. Ghose; M. N. Islam; M. N. Mustafa; M. M. H. Miah; M. M. Ansary

1999-01-01

329

Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion  

PubMed Central

It is well established that dorsal root ganglion (DRG) cells synthesize prostaglandin. However, the role that prostaglandin plays in the inflammatory hyperalgesia of peripheral tissue has not been established. Recently, we have successfully established a technique to inject drugs (3 ?L) directly into the L5-DRG of rats, allowing in vivo identification of the role that DRG cell-derived COX-1 and COX-2 play in the development of inflammatory hyperalgesia of peripheral tissue. IL-1? (0.5 pg) or carrageenan (100 ng) was administered in the L5-peripheral field of rat hindpaw and mechanical hyperalgesia was evaluated after 3 h. Administration of a nonselective COX inhibitor (indomethacin), selective COX-1 (valeryl salicylate), or selective COX-2 (SC-236) inhibitors into the L5-DRG prevented the hyperalgesia induced by IL-1?. Similarly, oligodeoxynucleotide-antisense against COX-1 or COX-2, but not oligodeoxynucleotide-mismatch, decreased their respective expressions in the L5-DRG and prevented the hyperalgesia induced by IL-1? in the hindpaw. Immunofluorescence analysis demonstrated that the amount of COX-1 and COX-2, constitutively expressed in TRPV-1+ cells of the DRG, significantly increased after carrageenan or IL-1? administration. In addition, indomethacin administered into the L5-DRG prevented the increase of PKC? expression in DRG membrane cells induced by carrageenan. Finally, the administration of EP1/EP2 (7.5 ng) or EP4 (10 µg) receptor antagonists into L5-DRG prevented the hyperalgesia induced by IL-1? in the hindpaw. In conclusion, the results of this study suggest that the inflammatory hyperalgesia in peripheral tissue depends on activation of COX-1 and COX-2 in C-fibers, which contribute to the induction and maintenance of sensitization of primary sensory neurons.

Araldi, Dioneia; Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Vieira, Andre Schwambach; Athie, Maria Carolina Pedro; Figueiredo, Jozi Godoy; Duarte, Djane Braz; Tambeli, Claudia Herrera; Ferreira, Sergio Henrique; Parada, Carlos Amilcar

2013-01-01

330

Expression of COX -1 and -2 in a Clinical Model of Acute Inflammation  

PubMed Central

Cyclooxygenase (COX) plays an important role in the induction of pain and inflammation as well as the analgesic actions of NSAIDs and coxibs. This study evaluates the expression of the two isoforms COX-1 and COX-2 in a clinical model in which the surgical removal of impacted third molars is used to evaluate the analgesic activity of anti-inflammatory drugs. A 3 mm punch biopsy was performed on the oral mucosa overlying one impacted third molar immediately before extraction of two impacted lower third molars. After the second tooth was extracted, a second biopsy was performed adjacent to the surgical site either immediately after surgery, 30, 60 or 120 minutes after surgery. RNA was extracted from the biopsies and RT-PCR was performed to assess mRNA levels of COX-1, COX-2 and glyceraldehyde-3-phosphate dehydrogenase (G3PDH). The RT-PCR products in the biopsies were normalized to G3PDH and compared to baseline. COX-2 mRNA was progressively increased at 30, 60, and 120 minutes after surgery (P<0.05); COX-1 mRNA was transiently decreased at 60 minutes during the post-surgical period (P<0.05). The results demonstrate peripheral elevation of COX-2 following tissue injury, which may contribute to increased prostaglandin E2 at the site of injury, pain onset and the analgesic activity of both non-selective NSAIDs and selective COX-2 inhibitors. Perspective This clinical study uses a physiologically relevant model to determine the time course of expression of COX -1 and -2 in acute inflammation of the human oral mucosa. This study furthers our understanding of the contribution of the COX isoforms to acute pain.

Khan, Asma A.; Iadarola, Michael; Yang, Hsiu-Ying T.; Dionne, Raymond A.

2009-01-01

331

Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells.  

PubMed

Activation of mast cells by aggregation of their high-affinity IgE receptors stimulates prostaglandin (PG) D(2) synthesis and secretion. An immediate phase of PGD(2) synthesis, complete within 30 min, is followed by a delayed, second phase of PGD(2) production that reaches a maximum 4 to 8 h after activation. Activation of mast cells from COX-2 (-/-) mice stimulates the release of PGD(2) during the first 30 min, whereas activation of mast cells from COX-1 (-/-) mice does not generate any PGD(2) in the first 2 h. On the other hand, COX-2 (-/-) cells do not participate in delayed phase of PGD(2) synthesis, while COX-1 (-/-) cells secrete low levels of PGD(2) between 2 and 4 h after activation. These data demonstrate that (i) the first phase of PG synthesis is COX-1 dependent and (ii) the second, delayed phase of PG synthesis is dependent on activation-induced synthesis and activity of COX-2. PMID:10548515

Reddy, S T; Tiano, H F; Langenbach, R; Morham, S G; Herschman, H R

1999-11-01

332

Fuzzy Multiple Linear Regression: A Computational Approach.  

National Technical Information Service (NTIS)

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 ...

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

1992-01-01

333

Covariate Measurement Error in Logistic Regression.  

National Technical Information Service (NTIS)

In a logistic regression model when covariates are subject to measurement error the naive estimator, obtained by regressing on the observed covariates, is asymptotically biased. This document introduces a bias-adjusted estimator and two estimators appropr...

L. A. Stefanski R. J. Carroll

1985-01-01

334

Semiparametric regression during 2003-2007*  

PubMed Central

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

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

2010-01-01

335

A selective requirement for copper-dependent activation of cytochrome c oxidase by Cox17p  

Microsoft Academic Search

Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for cellular respiration and a defect in its function is associated with severe neonatal or infantile lactic acidosis and early death. Recently, we found that Cox17p is not only required for mitochondrial

Koichiro Kako; Akio Takehara; Hidenori Arai; Takashi Onodera; Yoshinori Takahashi; Hiroshi Hanagata; Yasumitsu Ogra; Hiroaki Takagi; Hiroko Kodama; Kazuo T. Suzuki; Eisuke Munekata; Akiyoshi Fukamizu

2004-01-01

336

Chamomile, a novel and selective COX2 inhibitor with anti-inflammatory activity  

Microsoft Academic Search

AimsInducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. Chamomile has long been used in traditional medicine for the treatment of inflammatory diseases. In this study we aimed to investigate whether chamomile interferes with the COX-2 pathway.

Janmejai K. Srivastava; Mitali Pandey; Sanjay Gupta

2009-01-01

337

Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.  

PubMed

Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype. PMID:23122588

Indrieri, Alessia; van Rahden, Vanessa Alexandra; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D'Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Zvulunov, Alex; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella

2012-11-01

338

Gastroprotective Agent Rebamipide Induces Cyclooxygenase2 (COX2) in Gastric Epithelial Cells  

Microsoft Academic Search

Cyclooxyngease-2 (COX-2) is a key enzyme in prostaglandin (PG) synthesis, and COX-2 induction plays an important role in the healing of gastric ulceration. Rebamipide is a gastroprotective agent and attenuates the activity of neutrophils. A number of reports have shown that rebamipide treatment increases PG production in the gastric mucosa {in vivo}. Although its clinical significance in ulcer healing has

Hiroaki Murata; Yuki Yabe; Shingo Tsuji; Masahiko Tsujii; Hai Ying Fu; Kayoko Asahi; Hiroshi Eguchi; Sunao Kawano; Norio Hayashi

2005-01-01

339

Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors  

PubMed Central

Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 203 possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.

Vernieri, Ermelinda; Gomez-Monterrey, Isabel; Grieco, Paolo; Musella, Simona; Bertamino, Alessia; Scognamiglio, Ilaria; Alcaro, Stefano; Ortuso, Francesco; Novellino, Ettore; Campiglia, Pietro

2013-01-01

340

Tench Coxe and the Right to Keep and Bear Arms, 1787-1823  

Microsoft Academic Search

Tench Coxe, a member of the second rank of this nation's Founders and a leading proponent of the Constitution and the Bill of Rights, wrote prolifically about the right to keep and bear arms. In this Article, the authors trace Coxe 's story, from his early writings in support of the Constitution, through his years of public service, to his

Stephen P. Halbrook; David B. Kopel

1999-01-01

341

Transactivation of EGFR by LPS Induces COX-2 Expression in Enterocytes  

PubMed Central

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC.

McElroy, Steven J.; Hobbs, Stuart; Kallen, Michael; Tejera, Noemi; Rosen, Michael J.; Grishin, Anatoly; Matta, Poojitha; Schneider, Claus; Upperman, Jeffrey; Ford, Henri; Polk, D. Brent; Weitkamp, Jorn-Hendrik

2012-01-01

342

Dietary Zinc Modulation of COX2 Expression and Lingual and Esophageal Carcinogenesis in Rats  

Microsoft Academic Search

Background: Cancer of the upper aerodigestive tract, includ- ing esophageal and tongue carcinomas, is a major cause of cancer deaths worldwide. Esophageal and tongue cancers have both been associated with dietary zinc deficiency (ZD), and cyclooxygenase (COX-2) is often overexpressed in these cancers. Using rat models, we examined whether zinc regu- lates COX-2 expression in these cancers. Method: Expression of

Louise Y. Y. Fong; Liang Zhang; Yubao Jiang; John L. Farber

2005-01-01

343

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

PubMed Central

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

2013-01-01

344

A generalized Osborn–Cox model for estimating fluxes in nonequilibrium stably stratified turbulent shear flows  

Microsoft Academic Search

This paper describes a nonsteady state generalization of the Osborn–Cox formulas for estimating diapycnal fluxes from microstructure measurements in evolving ocean turbulence. The analysis is based on the same homogeneous turbulence assumption employed in the Osborn–Cox model, but the time dependent terms neglected in their analysis are retained. The analysis is greatly simplified by the finding from laboratory and numerical

C. W. Van Atta

1999-01-01

345

Effect of COX-2 (PGE2) and IL-6 on Prostate Cancer Bone Metastases.  

National Technical Information Service (NTIS)

We hypothesized that (1) prostate cancer cells that express high levels of cyclooxygenase-2 (COX-2) and prostaglandin E2(PGE2) display enhanced bone targeting and (2) the level of expression of COX-2 and PGE2 in established bone metastases determines the ...

A. C. Levine

2008-01-01

346

Information, Learning, and Drug Diffusion: the Case of Cox2 Inhibitors  

Microsoft Academic Search

The recent withdrawal of Cox-2 Inhibitors has generated debate on the role of information in drug diffusion: can the market learn the efficacy of new drugs, or does it depend solely on manufacturer advertising and FDA updates? In this study, we use a novel data set to study the diffusion of three Cox-2 Inhibitors ? Celebrex, Vioxx and Bextra ?

Pradeep Chintadunta; Renna Jiang; Ginger Z. Jin

2008-01-01

347

Role of PPAR? in COX-2 activation in mycobacterial pulmonary inflammation  

PubMed Central

Preliminary studies show that intranasal (i.n.) administration of BCG in mice induces M1 activation of alveolar macrophages (MØ) that increase TNF-? production and cyclooxygenase-2 (COX-2) expression but reduce constitutive peroxisome proliferator-activated receptor gamma (PPAR?) expression. However, COX-2 is catalytically inactive for prostaglandin E2 release, unlike COX-2 active in M1 activation in vitro by BCG. In this study, we determined the role of PPAR? for BCG-induced M1 activation in vivo and in vitro. We found that treatment of mice with GW9662, a PPAR? antagonist, prior to i.n. BCG, partially restored PPAR? expression, and decreased TNF-? production and COX-2 expression. But COX-2 was still inactive. The decreased effects on TNF-? and COX-2 were also observed when alveolar MØ were treated in vitro with GW9662/BCG, but COX-2 was still active. Our results indicate that PPAR? up-regulates M1 activation of alveolar MØ, but inactive COX-2 formation is independent of PPAR? in mycobacterial pulmonary inflammation.

Kogiso, Mari; Shinohara, Tsutomu; Dorey, C. Kathleen; Shibata, Yoshimi

2012-01-01

348

Collapsibility of regression coefficients and its extensions  

Microsoft Academic Search

Collapsibility with respect to a measure of association implies that the measure of association can be obtained from the marginal model. We first discuss model collapsibility and collapsibility with respect to regression coefficients for linear regression models. For parallel regression models, we give simple and different proofs of some of the known results and obtain also certain new results. For

P. Vellaisamy; V. Vijay

2008-01-01

349

Structural Logistic Regression for Link Analysis  

Microsoft Academic Search

We present Structural Logistic Regression, an extension of logistic regression to modeling relational data. It is an integrated approach to building regression models from data stored in relational databases in which potential pre- dictors, both boolean and real-valued, are generated by structured search in the space of queries to the database, and then tested with statistical information crite- ria for

Alexandrin Popescul; Lyle H. Ungar

2003-01-01

350

Standards for Standardized Logistic Regression Coefficients  

ERIC Educational Resources Information Center

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

Menard, Scott

2011-01-01

351

Graphical Methods for Assessing Logistic Regression Models  

Microsoft Academic Search

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

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

1984-01-01

352

AUTOMATIC SMOOTHING FOR DISCONTINUOUS REGRESSION FUNCTIONS  

Microsoft Academic Search

This article proposes an automatic smoothing method for recovering dis- continuous regression functions. The method models the target regression function with a series of disconnected cubic regression splines which partition the function's domain. In this way discontinuity points can be incorporated in a fitted curve simply as the boundary points between adjacent splines. Three objective criteria are constructed and compared

Thomas C. M. Lee

2002-01-01

353

Developmental Regression in Autism Spectrum Disorders  

ERIC Educational Resources Information Center

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

Rogers, Sally J.

2004-01-01

354

GRASP: generalized regression analysis and spatial prediction  

Microsoft Academic Search

We present generalized regression analysis and spatial prediction (GRASP) conceptually as a method for producing spatial predictions using statistical models, and introduce and demonstrate a specific implementation in Splus that facilitates the process. We put forward GRASP as a new name encapsulating an existing concept that aims at making spatial predictions using generalized regression analysis. Regression modeling is used to

Anthony Lehmann; Jacob McC Overton; John R Leathwick

2002-01-01

355

Inference on the Quantile Regression Process  

Microsoft Academic Search

Quantile regression is gradually evolving into a comprehensive approach to the statistical analysis of linear and nonlinear response models for conditional quantile functions. Just as classical linear regression methods based on minimizing sums of squared residuals enable one to estimate models for conditional mean functions, quantile regression methods based on minimizing asymmetrically weighted {\\\\it absolute} residuals offer a mechanism for

Roger Koenker

2000-01-01

356

Insights into regression testing [software testing  

Microsoft Academic Search

A problem facing those conducting maintenance testing is to identify proper test classes. The notion of regression testability is introduced as a way to measure the ease of retesting. Both the program design and the test plan design may affect the regression testability of a program. The testing set, testing number, regression number and stable and workable metrics are developed

Hareton K. N. Leung; Lee White

1989-01-01

357

Urinary tract obstruction induces transient accumulation of COX-2-derived prostanoids in kidney tissue  

PubMed Central

Inhibitors of cyclooxygenase (COX)-2 prevent suppression of aquaporin-2 and reduce polyuria in the acute phase after release of bilateral ureteral obstruction (BUO). We hypothesized that BUO leads to COX-2-mediated local accumulation of prostanoids in inner medulla (IM) tissue. To test this, rats were subjected to BUO and treated with selective COX-1 or COX-2 inhibitors. Tissue was examined at 2, 6, 12, and 24 h after BUO. COX-2 protein abundance increased in IM 12 and 24 h after onset of BUO but did not change in cortex. COX-1 did not change at any time points in any region. A full profile of all five primary prostanoids was obtained by mass spectrometric determination of PGE2, PGF2?, 6-keto-PGF1?, PGD2, and thromboxane (Tx) B2 concentrations in kidney cortex/outer medulla and IM fractions. IM concentration of PGE2, 6-keto-PGF1?, and PGF2? was increased at 6 h BUO, and PGE2 and PGF2? increased further at 12 h BUO. TxB2 increased after 12 h BUO. 6-keto-PGF1? remained significantly increased after 24 h BUO. The COX-2 inhibitor parecoxib lowered IM PGE2, TxB2, 6-keto-PGF1?, and PGF2? below vehicle-treated BUO and sham rats at 6, 12 and, 24 h BUO. The COX-1 inhibitor SC-560 lowered PGE2, PGF2?, and PGD2 in IM compared with untreated 12 h BUO, but levels remained significantly above sham. In cortex tissue, PGE2 and 6-keto-PGF1? concentrations were elevated at 6 h only. In conclusion, COX-2 activity contributes to the transient increase in prostacyclin metabolite 6-keto-PGF1? and TxB2 concentration in the kidney IM, and COX-2 is the predominant isoform that is responsible for accumulation of PGE2 and PGF2? with minor, but significant, contributions from COX-1. PGD2 synthesis is mediated exclusively by COX-1. In BUO, therapeutic interventions aimed at the COX-prostanoid pathway should target primarily COX-2.

N?rregaard, Rikke; Jensen, Boye L; Topcu, Sukru Oguzkan; Wang, Guixian; Schweer, Horst; Nielsen, S?ren

2010-01-01

358

Urinary tract obstruction induces transient accumulation of COX-2-derived prostanoids in kidney tissue.  

PubMed

Inhibitors of cyclooxygenase (COX)-2 prevent suppression of aquaporin-2 and reduce polyuria in the acute phase after release of bilateral ureteral obstruction (BUO). We hypothesized that BUO leads to COX-2-mediated local accumulation of prostanoids in inner medulla (IM) tissue. To test this, rats were subjected to BUO and treated with selective COX-1 or COX-2 inhibitors. Tissue was examined at 2, 6, 12, and 24 h after BUO. COX-2 protein abundance increased in IM 12 and 24 h after onset of BUO but did not change in cortex. COX-1 did not change at any time points in any region. A full profile of all five primary prostanoids was obtained by mass spectrometric determination of PGE(2), PGF(2alpha), 6-keto-PGF(1alpha), PGD(2), and thromboxane (Tx) B(2) concentrations in kidney cortex/outer medulla and IM fractions. IM concentration of PGE(2), 6-keto-PGF(1alpha), and PGF(2alpha) was increased at 6 h BUO, and PGE(2) and PGF(2alpha) increased further at 12 h BUO. TxB(2) increased after 12 h BUO. 6-keto-PGF(1alpha) remained significantly increased after 24 h BUO. The COX-2 inhibitor parecoxib lowered IM PGE(2,) TxB(2), 6-keto-PGF(1alpha), and PGF(2alpha) below vehicle-treated BUO and sham rats at 6, 12 and, 24 h BUO. The COX-1 inhibitor SC-560 lowered PGE(2), PGF(2alpha), and PGD(2) in IM compared with untreated 12 h BUO, but levels remained significantly above sham. In cortex tissue, PGE(2) and 6-keto-PGF(1alpha) concentrations were elevated at 6 h only. In conclusion, COX-2 activity contributes to the transient increase in prostacyclin metabolite 6-keto-PGF(1alpha) and TxB(2) concentration in the kidney IM, and COX-2 is the predominant isoform that is responsible for accumulation of PGE(2) and PGF(2alpha) with minor, but significant, contributions from COX-1. PGD(2) synthesis is mediated exclusively by COX-1. In BUO, therapeutic interventions aimed at the COX-prostanoid pathway should target primarily COX-2. PMID:20147610

Nørregaard, Rikke; Jensen, Boye L; Topcu, Sukru Oguzkan; Wang, Guixian; Schweer, Horst; Nielsen, Søren; Frøkiaer, Jørgen

2010-02-10

359

Model Selection for Cox Models with Time-Varying Coefficients  

PubMed Central

Summary Cox models with time-varying coefficients offer great flexibility in capturing the temporal dynamics of covariate effects on right censored failure times. Since not all covariate coefficients are time-varying, model selection for such models presents an additional challenge, which is to distinguish covariates with time-varying coefficient from those with time-independent coefficient. We propose an adaptive group lasso method that not only selects important variables but also selects between time-independent and time-varying specifications of their presence in the model. Each covariate effect is partitioned into a time-independent part and a time-varying part, the latter of which is characterized by a group of coefficients of basis splines without intercept. Model selection and estimation are carried out through a fast, iterative group shooting algorithm. Our approach is shown to have good properties in a simulation study that mimics realistic situations with up to 20 variables. A real example illustrates the utility of the method.

Yan, Jun; Huang, Jian

2011-01-01

360

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

PubMed

Although there is clinical and historical evidence for a vivid relation between the vestibular and emotional systems, the neuroscientific underpinnings are poorly understood. The "spin doctors" of the nineteenth century used spinning chairs (e.g., Cox's chair) to treat conditions of mania or elevated arousal. On the basis of a recent study on a hexapod motion-simulator, in this prototypic investigation we explore the impact of yaw stimulation on a spinning chair on mood states. Using a controlled experimental stimulation paradigm on a unique 3-D-turntable at the University of Zurich we included 11 healthy subjects and assessed parameters of mood states and autonomic nervous system activity. The Multidimensional Mood State Questionnaire and Visual Analog Scales (VAS) were used to assess changes of mood in response to a 100?s yaw stimulation. In addition heart rate was continuously monitored during the experiment. Subjects indicated feeling less "good," "relaxed," "comfortable," and "calm" and reported an increased alertness after vestibular stimulation. However, there were no objective adverse effects of the stimulation. Accordingly, heart rate did not significantly differ in response to the stimulation. This is the first study in a highly controlled setting using the historical approach of stimulating the vestibular system to impact mood states. It demonstrates a specific interaction between the vestibular system and mood states and thereby supports recent experimental findings with a different stimulation technique. These results may inspire future research on the clinical potential of this method. PMID:24133463

Winter, Lotta; Wollmer, M Axel; Laurens, Jean; Straumann, Dominik; Kruger, Tillmann H C

2013-10-15

361

Synthesis and selective cyclooxygenase-2 (COX2) inhibitory activity of a series of novel bicyclic pyrazoles  

Microsoft Academic Search

Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3-oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human whole blood (HWB). Several of the compounds were found to be novel and selective COX-2 inhibitors, the most potent and selective being 1-(5-cyclohexyl (2H,3H-pyrazolo[5,1-b]-1,3-oxazolidin-6-yl)-4-(methylsulfonyl)benzene, 7a (IC5o for COX-1>100 ?M; for COX-2=1.3 ?M).

Ramani R. Ranatunge; David S. Garvey; David R. Janero; L. Gordon Letts; Allison M. Martino; Madhavi G. Murty; Stewart K. Richardson; Delano V. Young; Irina S. Zemetseva

2004-01-01

362

The use of Cox-2 and PPAR? signaling in anti-cancer therapies  

PubMed Central

Increased production of the pro-inflammatory enzyme cyclooxygenase-2 (Cox-2) and altered expression and activity of peroxisome proliferator-activated receptor ? (PPAR?) have been observed in many malignancies. Both the PPAR? ligands and the Cox-2 inhibitors possess anti-inflammatory and anti-neoplastic effects in vitro and have been assessed for their therapeutic potential in several pre-clinical and clinical studies. Recently, multiple interactions between PPAR? and Cox-2 signaling pathways have been revealed. Understanding of the cross-talk between PPAR? and Cox-2 might provide important novel strategies for the effective treatment and/or prevention of cancer. This article summarizes recent achievements involving the functional interactions between the PPAR? and Cox-2 signaling pathways and discusses the implications of such interplay for clinical use.

KNOPFOVA, LUCIA; SMARDA, JAN

2010-01-01

363

A single mutation in the first transmembrane domain of yeast COX2 enables its allotopic expression.  

PubMed

During the course of evolution, a massive reduction of the mitochondrial genome content occurred that was associated with transfer of a large number of genes to the nucleus. To further characterize factors that control the mitochondrial gene transfer/retention process, we have investigated the barriers to transfer of yeast COX2, a mitochondrial gene coding for a subunit of cytochrome c oxidase complex. Nuclear-recoded Saccharomyces cerevisiae COX2 fused at the amino terminus to various alternative mitochondrial targeting sequences (MTS) fails to complement the growth defect of a yeast strain with an inactivated mitochondrial COX2 gene, even though it is expressed in cells. Through random mutagenesis of one such hybrid MTS-COX2, we identified a single mutation in the first Cox2 transmembrane domain (W56 --> R) that (i) results in the cellular expression of a Cox2 variant with a molecular mass indicative of MTS cleavage, which (ii) supports growth of a cox2 mutant on a nonfermentable carbon source, and that (iii) partially restores cytochrome c oxidase-specific respiration by the mutant mitochondria. COX2(W56R) can be allotopically expressed with an MTS derived from S. cerevisiae OXA1 or Neurospora crassa SU9, both coding for hydrophobic mitochondrial proteins, but not with an MTS derived from the hydrophilic protein Cox4. In contrast to some other previously transferred genes, allotopic COX2 expression is not enabled or enhanced by a 3'-UTR that localizes mRNA translation to the mitochondria, such as yeast ATP2(3)('-UTR). Application of in vitro evolution strategies to other mitochondrial genes might ultimately lead to yeast entirely lacking the mitochondrial genome, but still possessing functional respiratory capacity. PMID:20194738

Supekova, Lubica; Supek, Frantisek; Greer, John E; Schultz, Peter G

2010-03-01

364

Role of COX-2 in tumor progression and survival of head and neck squamous cell carcinoma  

PubMed Central

Inhibition of cyclooxygenase-2 (COX-2) pathways may have significant implications for the prevention and treatment of head and neck squamous cell carcinoma (HNSCC). COX-2 is overexpressed in both premalignant lesions and invasive HNSCC. We examined COX-2 expression by immunohistochemistry in normal tissues, different stages of premalignant lesions, and carcinoma in-situ (CIS). We also evaluated the correlation between COX-2 expression and clinical characteristics of HNSCC patients. Tissue specimens were obtained from: premalignant lesions from 25 subjects enrolled in a biochemoprevention trial; tumor samples collected at diagnosis from 38 HNSCC patients enrolled in an induction chemotherapy trial; and normal control tissues from 10 non-cancer, non-smoking subjects. COX-2 was expressed in early and intermediate stages of premalignant lesions, increasing first in the basal and parabasal layers, then lower spinous, and upper spinous layers. This correlation was noted in normal epithelium (p<0.0001), histologically normal in-field samples (p<0.0001), low-grade dysplasia (p=0.024), and moderate-grade dysplasia (p=0.009), but was lost in the majority of high-grade dysplasia/CIS (p=0.896). COX-2 expression was also noted to increase progressively through the early stages of premalignancy, and to decrease in severe/CIS stage and invasive carcinoma. COX-2 expression in tumors from patients treated with induction chemotherapy was correlated with overall survival after controlling for clinical variables. These findings elucidate the differential expression pattern of COX-2 in stages of head and neck premalignant lesions and invasive carcinoma, supporting the rationale for COX-2 inhibition as an important strategy for cancer chemoprevention. Further validation of COX-2 expression is needed in prospective ongoing chemoprevention trials.

Saba, Nabil F.; Choi, Misun; Muller, Susan; Shin, Hyung Ju C.; Tighiouart, Mourad; Papadimitrakopoulou, Vassiliki A; El-Naggar, Adel K; Khuri, Fadlo R.; Chen, Zhuo (Georgia); Shin, Dong M.

2010-01-01

365

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

PubMed Central

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

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

2012-01-01

366

On cluster-wise fuzzy regression analysis.  

PubMed

Since Tanaka et al. (1982) proposed a study of linear regression analysis with a fuzzy model, fuzzy regression analysis has been widely studied and applied in a variety of substantive areas. Regression analysis in the case of heterogeneity of observations is commonly presented in practice. The authors' main goal is to apply fuzzy clustering techniques to fuzzy regression analysis. Fuzzy clustering is used to overcome the heterogeneous problem in the fuzzy regression model. They present the cluster-wise fuzzy regression analysis in two approaches: the two-stage weighted fuzzy regression and the one-stage generalized fuzzy regression. The two-stage procedure extends the results of Jajuga (1986) and Diamond (1988). The one-stage approach is created by embedding fuzzy clusterings into the fuzzy regression model fitting at each step of procedure. This kind of embedding in the one-stage procedure is more effective since the structure of regression line shape encountered in the data set is taken into account at each iteration of the algorithm. Numerical results give evidence that the one-stage procedure can be highly recommended in cluster-wise fuzzy regression analysis. PMID:18255835

Yang, M S; Ko, C H

1997-01-01

367

A Survey of UML Based Regression Testing  

NASA Astrophysics Data System (ADS)

Regression testing is the process of ensuring software quality by analyzing whether changed parts behave as intended, and unchanged parts are not affected by the modifications. Since it is a costly process, a lot of techniques are proposed in the research literature that suggest testers how to build regression test suite from existing test suite with minimum cost. In this paper, we discuss the advantages and drawbacks of using UML diagrams for regression testing and analyze that UML model helps in identifying changes for regression test selection effectively. We survey the existing UML based regression testing techniques and provide an analysis matrix to give a quick insight into prominent features of the literature work. We discuss the open research issues like managing and reducing the size of regression test suite, prioritization of the test cases that would be helpful during strict schedule and resources that remain to be addressed for UML based regression testing.

Fahad, Muhammad; Nadeem, Aamer

368

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

PubMed

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

McCarty, Mark F

2011-10-15

369

Cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) expression in human pituitary macroadenomas.  

PubMed

Macroadenomas are tumors of the pituitary gland and are considered almost to be always benign and curable. The clinical manifestations of a pituitary tumor depend on the hormone secreted by the tumor as well as on the pattern of tumor growth within the sella turcica. Current trends attempt to target new molecular markers that also may serve as potential therapeutic targets. Cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are upregulated in a number of epithelial tumors. No published reports exist about expression of COX-2 in pituitary macroadenomas, and only a few reports with differing results exist concerning EGFR expression in pituitary macroadenomas. This study sought to determine whether a relationship exists between COX-2 and EGFR expression and pituitary macroadenomas. Thirty specimens of pituitary macroadenomas were evaluated after being identified in the surgical pathology database of Thomas Jefferson University Hospital. The hematoxylin and eosin-stained slides were reviewed, and the representative paraffin blocks containing the index case were chosen and immunohistochemically stained for COX-2 and EGFR expression. The COX-2 and EGFR-stained slides were reviewed and an immunohistochemical score was calculated and analyzed. The pituitary macroadenomas were classified on the basis of hormone expression: none (nonsecreting), minor (nondominant, plurihormonal), single (dominant nonplurihormonal), or plurihormonal (dominant plurihormonal). The hormonal classification was then analyzed for association with COX-2 expression. COX-2 expression was significantly associated with plurihormonal pituitary macroadenomas (p value 0.03). COX-2 expression was significantly associated with expression of luteinizing hormone (p value 0.007) and with expression of thyroid-stimulating hormone (TSH) (p value 0.04). Additionally, COX-2 expression was significantly associated with single-hormone of pituitary adenoma (p value 0.049). The expression of COX-2 in 100% of the normal autopsy pituitary glands establishes an additional central nervous system location of COX-2 expression. EGFR was not expressed in any of the pituitary macroadenomas. The expression of COX-2 in plurihormonal pituitary macroadenomas, particularly those secreting TSH, may be a potential target for treatment in addition to surgical and/or radiotherapy treatment in these benign but clinically significant tumors. COX-2 is expressed in normal autopsy pituitary tissue. PMID:12902861

Bloomer, Courtnay W; Kenyon, Lawrence; Hammond, Elizabeth; Hyslop, Terry; Andrews, David W; Curran, Walter J; Dicker, Adam P

2003-08-01

370

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

PubMed Central

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

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

2011-01-01

371

Comparing the Effects of COX and Non-COX-inhibiting NSAIDs on Enhancement of Apoptosis and Inhibition of Aberrant Crypt Foci Formation in a Rat Colorectal Cancer Model.  

PubMed

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

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

2013-09-01

372

Predictive Distribution of Regression Vector and Residual Sum of Squares for Normal Multiple Regression Model  

Microsoft Academic Search

This article proposes predictive inference for the multiple regression model with independent normal errors. The distributions of the sample regression vector (SRV) and the residual sum of squares (RSS) for the model are derived by using invariant differentials. Also, the predictive distributions of the future regression vector (FRV) and the future residual sum of squares (FRSS) for the future regression

Shahjahan Khan

2005-01-01

373

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

PubMed Central

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

Cunliffe, Michael

2011-01-01

374

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice.  

PubMed

A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation-induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this. PMID:19127021

Vardeh, Daniel; Wang, Dairong; Costigan, Michael; Lazarus, Michael; Saper, Clifford B; Woolf, Clifford J; Fitzgerald, Garret A; Samad, Tarek A

2009-01-05

375

Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities  

PubMed Central

Inhibitors selective for prostaglandin G/H synthase-2 (PGHS-2) (known colloquially as COX-2) were designed to minimize gastrointestinal complications of traditional NSAIDs — adverse effects attributed to suppression of COX-1–derived PGE2 and prostacyclin (PGI2). Evidence from 2 randomized controlled-outcome trials (RCTs) of 2 structurally distinct selective inhibitors of COX-2 supports this hypothesis. However, 5 RCTs of 3 structurally distinct inhibitors also indicate that such compounds elevate the risk of myocardial infarction and stroke. The clinical information is biologically plausible, as it is compatible with evidence that inhibition of COX-2–derived PGI2 removes a protective constraint on thrombogenesis, hypertension, and atherogenesis in vivo. However, the concept of simply tipping a “balance” between COX-2–derived PGI2 and COX-1–derived platelet thromboxane is misplaced. Among the questions that remain to be addressed are the following: (a) whether this hazard extends to all or some of the traditional NSAIDs; (b) whether adjuvant therapies, such as low-dose aspirin, will mitigate the hazard and if so, at what cost; (c) whether COX-2 inhibitors result in cardiovascular risk transformation during chronic dosing; and (d) how we might identify individuals most likely to benefit or suffer from such drugs in the future.

Grosser, Tilo; Fries, Susanne; FitzGerald, Garret A.

2006-01-01

376

Isolation of linoleic and alpha-linolenic acids as COX-1 and -2 inhibitors in rose hip.  

PubMed

Rose hip has previously shown clinical efficacy in the treatment of osteoarthritis, and organic solvent extracts of rose hip have showed inhibition of cyclooxygenase-1 and -2. A petroleum ether extract of rose hip was fractioned by VLC on silica; on a C-18 column and by HPLC. Each step was COX-1/2 activity-guided. The bioassay-guided fractionation led to the isolation of linoleic acid (the IC50 for COX-1 was 85 microm and 0.6 microM for COX-2) and alpha-linolenic acid (the IC50 for COX-1 was 52 microM and 12 microM for COX-2). The COX-2/COX-1 ratio was 0.007 for linoleic acid and 0.2 for alpha-linolenic acid. Linoleic acid and alpha-linolenic acid contribute to the COX-1 and -2 inhibitory activity of rose hip. PMID:18389471

Jäger, A K; Petersen, K N; Thomasen, G; Christensen, S Brøgger

2008-07-01

377

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

Microsoft Academic Search

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

Roman A. Barraza; Eric M. Poeschla

2006-01-01

378

COX-2 inhibitors block chemotherapeutic agent-induced apoptosis prior to commitment in hematopoietic cancer cells.  

PubMed

Enzymatic inhibitors of pro-inflammatory cyclooxygenase-2 (COX-2) possess multiple anti-cancer effects, including chemosensitization. These effects are not always linked to the inhibition of the COX-2 enzyme. Here we analyze the effects of three COX-2 enzyme inhibitors (nimesulide, NS-398 and celecoxib) on apoptosis in different hematopoietic cancer models. Surprisingly, COX-2 inhibitors strongly prevent apoptosis induced by a panel of chemotherapeutic agents. We selected U937 cells as a model of sensitive cells for further studies. Here, we provide evidence that the protective effect is COX-independent. No suppression of the low basal prostaglandin (PG)E(2) production may be observed upon treatment by COX-2 inhibitors. Besides, the non-active celecoxib analog 2,5-dimethyl-celecoxib is able to protect from apoptosis as well. We demonstrate early prevention of the stress-induced apoptotic signaling, prior to Bax/Bak activation. This preventive effect fits with an impairment of the ability of chemotherapeutic agents to trigger apoptogenic stress. Accordingly, etoposide-induced DNA damage is strongly attenuated in the presence of COX-2 inhibitors. In contrast, COX-2 inhibitors do not exert any anti-apoptotic activity when cells are challenged with physiological stimuli (anti-Fas, TNF? or Trail) or with hydrogen peroxide, which do not require internalization and/or are not targeted by chemoresistance proteins. Altogether, our findings show a differential off-target anti-apoptotic effect of COX-2 inhibitors on intrinsic vs. extrinsic apoptosis at the very early steps of intracellular signaling, prior to commitment. The results imply that an exacerbation of the chemoresistance phenomena may be implicated. PMID:21745461

Cerella, Claudia; Sobolewski, Cyril; Chateauvieux, Sébastien; Henry, Estelle; Schnekenburger, Michael; Ghelfi, Jenny; Dicato, Mario; Diederich, Marc

2011-06-24

379

Soman Increases Neuronal COX-2 Levels: Possible Link between Seizures and Protracted Neuronal Damage  

PubMed Central

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

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

2010-01-01

380

LY294002 inhibits glucocorticoid-induced COX2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism  

Microsoft Academic Search

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

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

2008-01-01

381

Design and synthesis of new 1,3-benzthiazinan-4-one derivatives as selective cyclooxygenase (COX2) inhibitors  

Microsoft Academic Search

A new group of 1, 3-benthiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were evaluated for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1\\/COX-2 inhibition studies identified 3-(p-fluoropheny)-2-(4-methylsulfonylphenyl)-1,3-benzthiazinan-4-one (7b) as a potent (IC50=0.05?M) and selective (selectivity index=259) COX-2 inhibitor.

Afshin Zarghi; Tannaz Zebardast; Bahram Daraie; Mehdi Hedayati

2009-01-01

382

Design and synthesis of new 1,3-benzthiazinan-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors.  

PubMed

A new group of 1, 3-benthiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were evaluated for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition studies identified 3-(p-fluoropheny)-2-(4-methylsulfonylphenyl)-1,3-benzthiazinan-4-one (7b) as a potent (IC(50)=0.05 microM) and selective (selectivity index=259) COX-2 inhibitor. PMID:19596198

Zarghi, Afshin; Zebardast, Tannaz; Daraie, Bahram; Hedayati, Mehdi

2009-06-27

383

Bayesian random-effects threshold regression with application to survival data with nonproportional hazards.  

PubMed

In epidemiological and clinical studies, time-to-event data often violate the assumptions of Cox regression due to the presence of time-dependent covariate effects and unmeasured risk factors. An alternative approach, which does not require proportional hazards, is to use a first hitting time model which treats a subject's health status as a latent stochastic process that fails when it reaches a threshold value. Although more flexible than Cox regression, existing methods do not account for unmeasured covariates in both the initial state and the rate of the process. To address this issue, we propose a Bayesian methodology that models an individual's health status as a Wiener process with subject-specific initial state and drift. Posterior inference proceeds via a Markov chain Monte Carlo methodology with data augmentation steps to sample the final health status of censored observations. We apply our method to data from melanoma patients with nonproportional hazards and find interesting differences from a similar model without random effects. In a simulation study, we show that failure to account for unmeasured covariates can lead to inaccurate estimates of survival probabilities. PMID:19828558

Pennell, Michael L; Whitmore, G A; Ting Lee, Mei-Ling

2009-10-14

384

NSAID inhibition of RGM1 gastric monolayer wound re-epithelialization: comparison of selective Cox-2 versus non-selective Cox inhibitors.  

PubMed

Clinical studies indicate that specific cyclooxygenase-2 (Cox-2) inhibitors are less ulcerogenic than their non-selective predecessors (e.g. indomethacin). However, Cox-2 inhibitors may also interfere with ulcer healing. Re-epithelialization is a crucial factor in both gastrointestinal mucosal injury and ulcer healing. This study was aimed to compare the effects of selective Cox-2 inhibitor (NS398) versus non-selective Cox inhibitor (indomethacin) on basal and basic fibroblast growth factor (bFGF) - stimulated gastric wound re-epithelialization. In-vitro epithelial wounds were created in confluent monolayers of RGM1 rat gastric epithelial cells by a razor blade scrape. Following wounding there was a significant re-epithelialization by 24 hrs. Indomethacin (0.25 mM and 0.5 mM) significantly inhibited basal wound re-epithelialization in a dose dependent manner. In contrast, selective Cox-2 inhibitor NS398 did not inhibit the basal re-epithelialization process. Basic FGF treatment produced significant enhancement of wound re-epitheliazation at the various concentrations [10, 20, 30, 40, 50 and 70 ng/ml] studied. Both indomethacin and NS398 inhibited bFGF stimulated wound re-epithelialization, with indomethacin having a greater inhibitory effect. The extent of NS398 inhibition was limited to the bFGF-stimulated component, whereas indomethacin inhibition extended to both the bFGF-stimulated and the basal re-epithelialization components. These findings indicate that specific Cox-2 inhibitor (NS398) does not interfere with the basal re-epithelialization but significantly inhibits the bFGF - stimulated re-epithelialization, whereas indomethacin interferes with both the basal as well as the bFGF-stimulated wound re-epithelialization. PMID:12138016

Giap, Andrew Q; Tarnawski, Andrzej; Hoa, Neil T; Akotia, Vimesh; Ma, Thomas Y

2002-05-10

385

Population Shape Regression from Random Design Data  

Microsoft Academic Search

Regression analysis is a powerful tool for the study of changes in a dependent variable as a function of an independent regressor\\u000a variable, and in particular it is applicable to the study of anatomical growth and shape change. When the underlying process\\u000a can be modeled by parameters in a Euclidean space, classical regression techniques (Hardle, Applied Nonparametric Regression,\\u000a 1990; Wand

Bradley C. Davis; P. Thomas Fletcher; Elizabeth Bullitt; Sarang C. Joshi

2010-01-01

386

A flexible support vector machine for regression  

Microsoft Academic Search

In this paper, a novel regression algorithm coined flexible support vector regression is proposed. We first model the insensitive\\u000a zone in classic support vector regression, respectively, by its up- and down-bound functions and then give a kind of generalized\\u000a parametric insensitive loss function (GPILF). Subsequently, based on GPILF, we propose an optimization criterion such that\\u000a the unknown regressor and its

Xiaobo ChenJian; Jian Yang; Jun Liang

387

Regression depth and support vector machine  

Microsoft Academic Search

The regression depth method (RDM) proposed by Rousseeuw and Hubert [RH99] plays an important role in the area of robust regression for a continuous response variable. Christmann and Rousseeuw [CR01] showed that RDM is also useful for the case of binary regression. Vapnik?s convex risk minimization principle [Vap98] has a dominating role in statistical machine learning theory. Important special cases

Andreas Christmann

2004-01-01

388

Involvement of COX2 in VEGF-induced angiogenesis via P38 and JNK pathways in vascular endothelial cells  

Microsoft Academic Search

Objective: Cyclooxygenase-2 (COX-2) is induced by hypoxic stimuli and is also involved in the process of angiogenesis. We previously demonstrated that vascular endothelial growth factor (VEGF) is one of the principal factors produced by hypoxic myocytes and is responsible for the induction of COX-2 expression in endothelial cells. Yet the signaling pathways by which VEGF modulates COX-2 gene expression are

GuiFu Wu; Jincai Luo; Jamal S. Rana; Roger Laham; Frank W. Sellke; Jian Li

389

Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency  

PubMed Central

We have created a mouse model with an isolated cytochrome c oxidase (COX) deficiency by disrupting the COX10 gene in skeletal muscle. Missense mutations in COX10 have been previously associated with mitochondrial disorders. Cox10p is a protoheme:heme-O-farnesyl transferase required for the synthesis of heme a, the prosthetic group of the catalytic center of COX. COX10 conditional knockout mice were generated by crossing a LoxP-tagged COX10 mouse with a transgenic mouse expressing cre recombinase under the myosin light chain 1f promoter. The COX10 knockout mice were healthy until approximately 3 months of age when they started developing a slowly progressive myopathy. Surprisingly, even though COX activity in COX10 KO muscles was <5% of control muscle at 2.5 months, these muscles were still able to contract at 80–100% of control maximal forces and showed only a 10% increase in fatigability, and no signs of oxidative damage or apoptosis were detected. However, the myopathy worsened with time, particularly in female animals. This COX10 KO mouse allowed us to correlate the muscle function with residual COX activity, an estimate that can help predict the progression pattern of human mitochondrial myopathies.

Diaz, Francisca; Thomas, Christine K.; Garcia, Sofia; Hernandez, Dayami; Moraes, Carlos T.

2009-01-01

390

Hybrid fuzzy regression with trapezoidal fuzzy data  

NASA Astrophysics Data System (ADS)

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

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

2011-12-01

391

Quantile regression applied to spectral distance decay  

USGS Publications Warehouse

Remotely sensed imagery has long been recognized as a powerful support for characterizing and estimating biodiversity. Spectral distance among sites has proven to be a powerful approach for detecting species composition variability. Regression analysis of species similarity versus spectral distance allows us to quantitatively estimate the amount of turnover in species composition with respect to spectral and ecological variability. In classical regression analysis, the residual sum of squares is minimized for the mean of the dependent variable distribution. However, many ecological data sets are characterized by a high number of zeroes that add noise to the regression model. Quantile regressions can be used to evaluate trend in the upper quantiles rather than a mean trend across the whole distribution of the dependent variable. In this letter, we used ordinary least squares (OLS) and quantile regressions to estimate the decay of species similarity versus spectral distance. The achieved decay rates were statistically nonzero (p < 0.01), considering both OLS and quantile regressions. Nonetheless, the OLS regression estimate of the mean decay rate was only half the decay rate indicated by the upper quantiles. Moreover, the intercept value, representing the similarity reached when the spectral distance approaches zero, was very low compared with the intercepts of the upper quantiles, which detected high species similarity when habitats are more similar. In this letter, we demonstrated the power of using quantile regressions applied to spectral distance decay to reveal species diversity patterns otherwise lost or underestimated by OLS regression. ?? 2008 IEEE.

Rocchini, D.; Cade, B. S.

2008-01-01

392

Effect of COX-2 Inhibitors on the Aromatase Gene Expression in Human Breast Cancer.  

National Technical Information Service (NTIS)

Aromatase (CYP-19) is responsible for estrogen biosynthesis within breast tumor tissue. Aromatase and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancer, and increased levels of prostaglandin (PG) activates the CYP19 promotor and incre...

C. L. Shapiro W. Burak R. Brueggemeier

2003-01-01

393

Novel single base pair COX III subunit deletion of mitochondrial DNA associated with rhabdomyolysis.  

PubMed

A high number of cytochrome c oxidase (COX)-negative muscle fibres (approximately 45%) without ragged red fibres was found in a 27-year-old male patient with a single unprovoked episode of severe rhabdomyolysis. There was no family history of neuromuscular disorder and sequencing revealed a novel COX III single base pair deletion (MT-CO3{NC_012920.1}:m.[9559delC]). The deletion creates a frame shift and downstream termination codon affecting the last 136 amino acids (MT-CO3{YP_003024032.1}:p.[Pro118GlnfsX124]). The heteroplasmic mutation load in muscle was approximately 58% and single COX-negative fibres harboured significantly greater levels of mutant mitochondrial DNA than COX-positive fibres. PMID:21163656

Marotta, Rosetta; Chin, Judy; Kirby, Denise M; Chiotis, Maria; Cook, Mark; Collins, Steven J

2010-12-15

394

Celebration of the contributions of Art Cox to stellar pulsation interpretations  

SciTech Connect

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

Castor, J.I.

1997-10-02

395

A method for vibratome sectioning of Golgi–Cox stained whole rat brain  

Microsoft Academic Search

A method for impregnating the whole rat brain with Golgi–Cox stain and sectioning with the vibratome is described. The method is simple, inexpensive and provides good resolution of dendrites and spines.

Robbin Gibb; Bryan Kolb

1998-01-01

396

Cox2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium glutamate-induced obese rats  

Microsoft Academic Search

AimsThe purpose of the present work was to investigate the effect of cyclooxygenase-2 (COX-2) inhibition on the cardiovascular and inflammatory aspects promoted by monosodium glutamate (MSG)-induced obesity in rats.

N. V. Cunha; S. B. de Abreu; C. Panis; S. Grassiolli; F. A. Guarnier; R. Cecchini; T. L. Mazzuco; P. Pinge-Filho; M. C. Martins-Pinge

2010-01-01

397

An observational study of the discrediting of COX-2 NSAIDs in Australia: Vioxx or class effect?  

PubMed Central

Background When a medicine such as rofecoxib (Vioxx) is withdrawn, or a whole class of medicines discredited such as the selective COX-2 inhibitors (COX-2s), follow-up of impacts at consumer level can be difficult and costly. The Australian Longitudinal Study on Women's Health provides a rare opportunity to examine individual consumer medicine use following a major discrediting event, the withdrawal of rofecoxib and issuing of safety warnings on the COX-2 class of medicines. The overall objective of this paper was to examine the impact of this discrediting event on dispensing of the COX-2 class of medicines, by describing medicine switching behaviours of older Australian women using rofecoxib in September 2004; the uptake of other COX-2s; and the characteristics of women who continued using a COX-2. Methods Participants were concessional beneficiary status women from the Older cohort (born 1921-26) of the Australian Longitudinal Study on Women's Health who consented to linkage to Pharmaceutical Benefits Scheme data, with at least one rofecoxib prescription dispensed in the 12 months before rofecoxib withdrawal. A prescription was defined as one dispensing occasion. Women were grouped by rofecoxib pattern of use: continuous (nine or more prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) or non-continuous (eight or less prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) users. Incidence rate per 100,000 person days and incidence risk ratio described uptake of alternate medicines, following rofecoxib withdrawal. Kaplan-Meier curves described differences in uptake patterns by medicine and pattern of rofecoxib use. Patterns of use of COX-2s in the next 100 days after first COX-2 uptake were described. Results Medicine switches and pattern of medicines uptake differed significantly depending upon whether a woman was a continuous or non-continuous rofecoxib user prior to rofecoxib discrediting. Continuous rofecoxib users overwhelmingly switched to another COX-2 and remained continuing COX-2 users for at least 100 days post-switch. Conclusions The typical switching behaviour of this group of women suggests that the issues leading to the discrediting of rofecoxib were not seen as a COX-2 class effect by prescribers to this high use group of consumers.

2011-01-01

398

Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor.  

PubMed

Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel treatment. Co-administration of paclitaxel and etodolac in both cell lines resulted in decreased rhodamine 123 efflux. The actual concentration of intracellular paclitaxel in OMC-2P cells was significantly lower than that in OMC-2 cells treated with paclitaxel alone and was significantly increased after co-administration of paclitaxel and etodolac. These findings suggest that paclitaxel resistance may be associated with COX-2 and MDR1 expression in cancer cells. Co-administration of COX-2 inhibitors and paclitaxel may have a key role in modulating or overcoming paclitaxel resistance in endometrial cancers. PMID:24100466

Hasegawa, Kiyoshi; Ishikawa, Kunimi; Kawai, Satoshi; Torii, Yutaka; Kawamura, Kyoko; Kato, Rina; Tsukada, Kazuhiko; Udagawa, Yasuhiro

2013-10-08

399

Cyclooxygenase-2 (COX-2) expression in high-risk premalignant oral lesions.  

PubMed

Emerging data indicate a link between genetic instability and up-regulation of cyclooxygenase-2 (COX-2). To see if individuals at high risk of oral cancer are candidates for treatment with selective COX-2 inhibitors (coxibs), levels of COX-2 expression in healthy, premalignant and cancerous oral mucosa were compared with the occurrence of DNA ploidy status as a genetic risk marker of oral cancer. COX-2 gene product was evaluated immunohistochemically in 30 healthy persons, in 22 patients with dysplastic lesions without previous or concomitant carcinomas, and in 29 patients with oral carcinomas. The immunohistochemical findings were verified by western blotting. COX-2 expression was correlated to DNA content as a genetic risk marker of oral cancer. COX-2 was up-regulated from healthy to premalignant to cancerous oral mucosa. Thus, COX-2 expression was found in 1 case of healthy oral mucosa (3%). All specimens from healthy mucosa had a normal DNA content. In patients with premalignancies. In 29 patients with oral carcinomas, cyclooxygenase-2 expression was observed in 26 (88%), and aneuploidy was observed in 25 cases (94%, P=0.04). Notably, of 22 patients with dysplastic lesions, COX-2 was exclusively expressed in a subgroup of nine patients (41%) identified to be at high risk of cancer by the aberrant DNA content of their lesions. Seven of these patients were followed for 5 years or more. An oral carcinoma developed in six of them (85%; P=0.02). These findings emphasize the need to determine whether coxibs can reduce the risk of oral cancer in patients with high-risk precancerous lesions. PMID:12747975

Sudbø, Jon; Ristimäki, Ari; Sondresen, Jan Erik; Kildal, Wanja; Boysen, Morten; Koppang, Hanna S; Reith, Albrecht; Risberg, Björn; Nesland, Jahn M; Bryne, Magne

2003-07-01

400

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

Microsoft Academic Search

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

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

2002-01-01

401

Modulation of COX2 expression by statins in human monocytic cells  

Microsoft Academic Search

Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and throm- boxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reduc- tases and cholesterol synthesis, which block the expres- sion of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2

Aida Habib; Ishraq Shamseddeen; Mona S. Nasrallah; Tania Abi Antoun; Georges Nemer; Jacques Bertoglio; Rami Badreddine; Kamal F. Badr

2007-01-01

402

Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX2 during carcinogenesis  

Microsoft Academic Search

Patients with (previous) head and neck cancer (HNC) are at high risk for developing second squamous cell cancer of the oesophagus. The role of cyclooxygenase-2 (COX-2) in oesophageal squamous carcinogenesis has not yet been investigated in this high-risk group. Therefore, this study examined COX-2 mRNA and protein expression in oesophageal biopsies and resected tissues of 44 HNC patients. The evaluation

K Maaser; P Däubler; B Barthel; B Heine; B von Lampe; H Stein; B Hoffmeister; H Scherer; H Scherübl

2003-01-01

403

COX2 polymorphisms and the risk for head and neck cancer in white patients  

Microsoft Academic Search

BACKGROUND: Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on head and neck carcinogenesis. METHODS: Blood from 431 white patients with oral, pharyngeal, or laryngeal

Wilbert H. M. Peters; Martin Lacko; Rene H. M. te Morsche; Adri C. Voogd; Michael B. Oude Ophuis; Johannes J. Manni

2009-01-01

404

Novel single base pair COX III subunit deletion of mitochondrial DNA associated with rhabdomyolysis  

Microsoft Academic Search

A high number of cytochrome c oxidase (COX)-negative muscle fibres (approximately 45%) without ragged red fibres was found in a 27-year-old male patient with a single unprovoked episode of severe rhabdomyolysis. There was no family history of neuromuscular disorder and sequencing revealed a novel COX III single base pair deletion (MT-CO3{NC_012920.1}:m.[9559delC]).The deletion creates a frame shift and downstream termination codon

Rosetta Marotta; Judy Chin; Denise M. Kirby; Maria Chiotis; Mark Cook; Steven J. Collins

2011-01-01

405

Human fecal water inhibits COX-2 in colonic HT-29 cells: role of phenolic compounds.  

PubMed

The inducible enzyme cyclooxygenase-2 (COX-2) plays a major role in the regulation of inflammation and possibly in the development of colon cancer. The aim of the present study was to screen for COX-2 inhibitors in samples of fecal water (the aqueous phase of feces) and investigate whether phenolic compounds are responsible for any observed effects on COX-2. Volunteers (n = 20) were recruited and asked to supply a 24-h stool sample. Fecal water samples were prepared and analyzed by GC-MS for their content of phenolic compounds. These samples were also evaluated for their effects on COX-2 protein levels (Western blot) and prostaglandin (PG)E2 production in tumor necrosis-alpha-stimulated HT-29 cells and pure enzymatic activity in a COX-2-catalyzed prostaglandin biosynthesis in vitro assay. The major phenolic compounds identified were phenylpropionic acid, phenylacetic acid, cinnamic acid, and benzoic acid derivatives. Of 13 fecal water samples analyzed, 12 significantly decreased PGE2 production (range 5.4-39.7% inhibition, P-value < 0.05) compared with control cells and 13 of 14 samples analyzed decreased COX-2 protein levels in HT-29 cells (19-63% inhibition). Of the 20 fecal water samples, 2 also weakly inhibited enzymatic activity of purified COX-2 (22-24% inhibition). Three compounds identified in fecal water, 3-phenylpropionic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, decreased the protein level at 250 micromol/L (15-62% inhibition). This study shows for the first time that human fecal water contains components that can affect both the COX-2 protein level and enzymatic activity. PMID:16177193

Karlsson, Pernilla C; Huss, Ulrika; Jenner, Andrew; Halliwell, Barry; Bohlin, Lars; Rafter, Joseph J

2005-10-01

406

Wnt\\/beta-Catenin Signaling Enhances Cyclooxygenase2 (COX2) Transcriptional Activity in Gastric Cancer Cells  

Microsoft Academic Search

BackgroundIncreased expression of the cyclooxygenase-2 enzyme (COX2) is one of the main characteristics of gastric cancer (GC), which is a leading cause of death in the world, particularly in Asia and South America. Although the Wnt\\/?-catenin signaling pathway has been involved in the transcriptional activation of the COX2 gene, the precise mechanism modulating this response is still unknown.Methodology\\/Principal FindingsHere we

Felipe Nuñez; Soraya Bravo; Fernando Cruzat; Martín Montecino; Giancarlo V. de Ferrari; Moray Campbell

2011-01-01

407

Briarane diterpenes diminish COX-2 expression in human colon adenocarcinoma cells.  

PubMed

Exploration of a soft coral (Briareum sp.) from Vanuatu led to the isolation of three new briaranes, designated brialalepolides A (1), B (2), and C (3). Compounds 2 and 3 reduced the expression of COX-2 in human colon adenocarcinoma cells, as well as in murine macrophage cells. This is significant because the metabolic products of COX-2 have been implicated in the pathogenesis of colon cancer and other diseases. PMID:21438584

Joyner, P Matthew; Waters, Amanda L; Williams, Russell B; Powell, Douglas R; Janakiram, Naveena B; Rao, Chinthalapally V; Cichewicz, Robert H

2011-03-25

408

Autometallographic enhancement of the Golgi-Cox staining enables high resolution visualization of dendrites and spines  

Microsoft Academic Search

We present a method for autometallographic (AMG) enhancement of the Golgi-Cox staining enabling high resolution visualization\\u000a of dendrites and spines. The method is cheaper and more flexible than conventional enhancement procedures performed with commercial\\u000a photographic developers. The staining procedure is thoroughly described and we demonstrate with qualitative and quantitative\\u000a data, how histological tissue sectioning, Golgi-Cox immersion time and different AMG

Dariusz Orlowski; Carsten R. Bjarkam

2009-01-01

409

Single crystal growth and superconductivity of Ca(Fe1-xCox)2As2  

SciTech Connect

We report the single crystal growth of Ca(Fe1-xCox)2As2 (0 <= x <= 0.082) from Sn flux. The temperature-composition phase diagram is mapped out based on the magnetic susceptibility and electrical transport measurements. Phase diagram of Ca(Fe1-xCox)2As2 is qualitatively different from those of Sr and Ba, it could be due to both the charge doping and structural tuning effects associated with Co substitution.

Hu, Rongwei; Ran, Sheng; Budko, Serguei; Straszheim, Warren E.; Canfield, Paul C.

2012-05-18

410

COX2 over-expression correlates with VEGF and tumour angiogenesis in canine mammary cancer  

Microsoft Academic Search

This study was designed to investigate the possible roles of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in canine mammary cancer angiogenesis. Immunohistochemistry was performed on 70 tumours (28 benign and 42 malignant) in order to detect COX-2 and VEGF expression. Microvessel density (MVD) was determined by CD31 immunolabelling to assess tumour angiogenesis.There was a significantly higher expression of

Felisbina L. Queiroga; Isabel Pires; Margarida Parente; Hugo Gregório; Carlos S. Lopes

2011-01-01

411

Information, learning, and drug diffusion: The case of Cox2 inhibitors  

Microsoft Academic Search

The recent withdrawal of Cox-2 Inhibitors has generated debate on the role of information in drug diffusion: can the market\\u000a learn the efficacy of new drugs, or does it depend solely on manufacturer advertising and FDA updates? In this study, we use\\u000a a novel data set to study the role of learning in the diffusion of three Cox-2 Inhibitors—Celebrex, Vioxx

Pradeep K. Chintagunta; Renna Jiang; Ginger Z. Jin

2009-01-01

412

Effects of RNA editing on the coxI evolution and phylogeny reconstruction  

Microsoft Academic Search

CoxI genomic and cDNA sequences from gymnosperms and angiosperms were used to study the effects of RNA editing on gene evolution\\u000a and phylogenyre construction. In six gymnosperms harboring edited coxI gene the number of nucleotide substitutions at 1st, 2nd and 3rd codon positions was similar. In contrast, in angiosperms, the number of nucleotide substitutions at 1st and 2nd codon positions

Alfred E. Szmidt; Meng-Zhu Lu; Xiao-Ru Wang

2001-01-01

413

Selective COX2 inhibition and cardiovascular effects: a review of the rofecoxib development program  

Microsoft Academic Search

Cyclo-oxygenase-2 (COX-2) inhibitors appear to alter the balance of vasoactive eicosanoids (prostacyclin and thromboxane) and to suppress the inflammatory mediators implicated in the progression of atherogenesis and ischemic myocardial injury. Neutral, harmful, and beneficial cardiovascular (CV) effects have all been postulated to result from these changes. Investigations conducted with rofecoxib, a selective COX-2 inhibitor, have substantially contributed to our understanding

Matthew R Weir; Rhoda S Sperling; Alise Reicin; Barry J Gertz

2003-01-01

414

Going against the flow: the impact of PHARMAC not funding COX2 inhibitors for chronic arthritis  

Microsoft Academic Search

COX-2 inhibitors have come under a lot of scrutiny lately, with questions raised regarding class effects and the risk-benefit of these pharmaceuticals. From 1999 to 2003 the New Zealand Pharmaceutical Management Agency (PHARMAC) evaluated the evidence on COX-2 inhibitors, including their efficacy, cost-effectiveness and budgetary impact. In September 2003 PHARMAC decided not to list celecoxib, rofecoxib and meloxicam on the

Rachel Grocott; Scott Metcalfe

2005-01-01

415

COX2 and beyond: approaches to prostaglandin inhibition in human disease  

Microsoft Academic Search

Selective inhibitors of cyclooxygenase (COX)-2 afford relief from pain and inflammation. They could also prove useful in the chemoprevention of cancer and are being investigated in a range of neurological diseases. This novel class of drug is less likely to cause gastric ulceration than traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, plausible mechanisms have been proposed whereby COX-2 inhibitors could cause

Garret A. FitzGerald

2003-01-01

416

Comparison of partial least squares regression and principal component regression for pelvic shape prediction.  

PubMed

This paper studied two different regression techniques for pelvic shape prediction, i.e., the partial least square regression (PLSR) and the principal component regression (PCR). Three different predictors such as surface landmarks, morphological parameters, or surface models of neighboring structures were used in a cross-validation study to predict the pelvic shape. Results obtained from applying these two different regression techniques were compared to the population mean model. In almost all the prediction experiments, both regression techniques unanimously generated better results than the population mean model, while the difference on prediction accuracy between these two regression methods is not statistically significant (?=0.01). PMID:23174420

Schumann, Steffen; Nolte, Lutz-P; Zheng, Guoyan

2012-11-20

417

Reducing Regression Test Size by Exclusion  

Microsoft Academic Search

Operational software is constantly evolving. Regression testing is used to identify the unintended consequences of evolutionary changes. As most changes affect only a small proportion of the system, the challenge is to ensure that the regression test set is both safe (all relevant tests are used) and inclusive (only relevant tests are used). Previous approaches to reducing test sets struggle

Keith Gallagher; Tracy Hall; Sue Black

2007-01-01

418

Implementing Variable Selection Techniques in Regression.  

ERIC Educational Resources Information Center

Variable selection techniques in stepwise regression analysis are discussed. In stepwise regression, variables are added or deleted from a model in sequence to produce a final "good" or "best" predictive model. Stepwise computer programs are discussed and four different variable selection strategies are described. These strategies include the…

Thayer, Jerome D.

419

Multinomial logit PLS regression of compositional data  

Microsoft Academic Search

This paper studies the discriminant modeling method for the constrained data. We propose the multinomial logit partial least squares (ML-PLS) regression of compositional data by implementing the ML-PLS regression method on the centered logratio (clr) transformed data. And the model presents the following advantages: i) compared to the additive logratio (alr) transformation of the compositional data, the clr transformed variables

Jie Meng

2010-01-01

420

Covariate Measurement Error in Logistic Regression  

Microsoft Academic Search

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

Leonard A. Stefanski; Raymond J. Carroll

1985-01-01

421

Population Shape Regression From Random Design Data  

Microsoft Academic Search

Regression analysis is a powerful tool for the study of changes in a dependent variable as a function of an in- dependent regressor variable, and in particular it is ap- plicable to the study of anatomical growth and shape change. When the underlying process can be modeled by parameters in a Euclidean space, classical regression tech- niques (13, 34) are

Bradley C. Davis; P. Thomas Fletcher; Elizabeth Bullitt; Sarang C. Joshi

2007-01-01

422

Bootstrap Bartlett Adjustment in Seemingly Unrelated Regression  

Microsoft Academic Search

Seemingly unrelated regression (SUR) is a method introduced by Zellner (1962) for estimating several regression equations simultaneously, a common and important problem in econometrics. This article considers hypothesis testing in SUR using the log-likelihood ratio (LLR) test. Although the asymptotic distribution of this statistic is well known, substantial departures occur in samples of the size commonly employed by economists. Significance

David M. Rocke

1989-01-01

423

Stepwise versus Hierarchical Regression: Pros and Cons  

ERIC Educational Resources Information Center

Multiple regression is commonly used in social and behavioral data analysis. In multiple regression contexts, researchers are very often interested in determining the "best" predictors in the analysis. This focus may stem from a need to identify those predictors that are supportive of theory. Alternatively, the researcher may simply be interested…

Lewis, Mitzi

2007-01-01

424

Principal Components Regression in Exploratory Statistical Research  

Microsoft Academic Search

Regression upon principal components of the percentage points of the income and education distributions for 1950 census tracts in the city of Chicago led to the estimation of “beta coefficient profiles” for television receiver and refrigerator ownership, for central heating system usage, and for a measure of dwelling unit overcrowding. The betas are standardized coefficients of regression of a dependent

William F. Massy

1965-01-01

425

A linear regression with unobserved dependent variables  

Microsoft Academic Search

Let (?,X) be a random vector such that E(X|?) = ? and Var(x|?) a + b? + c? for some known constants a, b and c. Assume X1,…,Xn are independent observations which have the same distribution as X. Let t(X) be the linear regression of ? on X. The linear empirical Bayes estimator is used to approximate the linear regression

Kai F Yu

1988-01-01

426

Bayesian adaptive nonparametric M-regression  

Microsoft Academic Search

Nonparametric regression has been popularly used in curve fitting, signal denosing, and image processing. In such applications, the underlying functions (or signals) may vary irregularly, and it is very common that data are contaminated with outliers. Adaptive and robust techniques are needed to extract clean and accurate information. In this paper, we develop adaptive nonparametric M-regression with a Bayesian approach.

Colin Chen

2009-01-01

427

Deblurring Using Regularized Locally Adaptive Kernel Regression  

Microsoft Academic Search

Kernel regression is an effective tool for a variety of image processing tasks such as denoising and interpolation . In this paper, we extend the use of kernel regression for deblurring applications. In some earlier examples in the literature, such nonparametric deblurring was suboptimally performed in two sequential steps, namely denoising followed by deblurring. In contrast, our optimal solution jointly

Hiroyuki Takeda; Sina Farsiu; Peyman Milanfar

2008-01-01

428

Active learning for logistic regression: an evaluation  

Microsoft Academic Search

Which active learning methods can we expect to yield good performance in learning binary and multi-category logistic regression classi- fiers? Addressing this question is a natural first step in providing robust so- lutions for active learning across a wide variety of exponential models includ- ing maximum entropy, generalized linear, log-linear, and conditional random field models. For the logistic regression model

Andrew I. Schein; Lyle H. Ungar

2007-01-01

429

Illustration of Regression towards the Means  

ERIC Educational Resources Information Center

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

Govindaraju, K.; Haslett, S. J.

2008-01-01

430

Wavelet Regression By Cross-Validation  

Microsoft Academic Search

This paper is about using wavelets for regression. The main aim of the paper is to introduce and develop a cross-validation method for selecting a wavelet regression threshold that produces good estimates with respect to L2 error. The selected threshold determines which coefficients to keep in an orthogonal wavelet expansion of noisy data and acts in a similar way to

G. p. Nason

1994-01-01

431

Survey Design under the Regression Superpopulation Model  

Microsoft Academic Search

The construction of sample designs and estimators under a linear regression superpopulation model is considered. The anticipated variance, the variance of the predictor computed with respect to the sampling design and the superpopulation model, is used as a criterion for evaluating probability designs and model-unbiased predictors. Regression predictors that are model unbiased and design consistent are constructed.

Cary T. Isaki; Wayne A. Fuller

1982-01-01

432

Regression-Based Summarization of Email Conversations  

Microsoft Academic Search

In this paper we present a regression-based machine learning approach to email thread summarization. The regression model is able to take advantage of multi- ple gold-standard annotations for training purposes, in contrast to most work with binary classiers. We also investigate the usefulness of novel features such as speech acts. This paper also introduces a newly created and publicly available

Jan Ulrich; Giuseppe Carenini; Gabriel Murray; Raymond T. Ng

2009-01-01

433

Choosing between Logistic Regression and Discriminant Analysis  

Microsoft Academic Search

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

Sandra Wilson

1978-01-01

434

Illustration of Regression towards the Means  

ERIC Educational Resources Information Center

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

Govindaraju, K.; Haslett, S. J.

2008-01-01

435

Fast regression estimates of missing data  

Microsoft Academic Search

A recent comparison of methods for estimating missing data concluded that when there is sufficient redundancy to justify using a more elaborate method than the mean of each variable, the principal components and regression methods are equally good and superior to the other methods investigated. Principal components was preferred because of its tremendous computational savings over the regression method. This

Raymond F. Koopman

1976-01-01

436

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

Microsoft Academic Search

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

A. Zarghi; S. Arfaei; R. Ghodsi

437

Thyroid hormone regulates renocortical COX-2 and PGE2 expression in the late gestation fetal sheep.  

PubMed

Cyclooxygenase 2 (COX-2) is important for development of the fetal kidney. Precisely how renal COX-2 expression is regulated in fetal life is unclear. The hypothesis that thyroid hormone positively regulates COX-2 and PGE(2) levels in the late gestation fetal kidney cortex was tested. Sham, thyroidectomized (TX), and TX + thyroid hormone replacement (R) fetal sheep were studied. TX was performed at 120 days gestational age (dGA). TX + R fetuses were continuously infused with thyroxine from 3 days after surgery until study completion. Fetal kidney cortex was obtained at 137 dGA for measurement of renal cyclooxygenase type-2 (COX-2) protein and PGE(2) metabolites. Renocortical COX-2 and PGE(2) levels were significantly lower in TX compared with sham and TX + R fetuses. There were no differences between sham and TX + R fetuses. These findings demonstrate that thyroid hormone positively regulates renal COX-2 and PGE(2) expression in the late gestation fetal sheep kidney. PMID:18579848

Carey, Luke C; Valego, Nancy K; Chen, Kai; Rose, James C

2008-07-01

438

Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity  

PubMed Central

Aims Inducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. Chamomile has long been used in traditional medicine for the treatment of inflammatory diseases. In this study we aimed to investigate whether chamomile interferes with the COX-2 pathway. Main Methods We used lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as an in vitro model for our studies. Key Findings Chamomile treatment inhibited the release of LPS-induced prostaglandin E(2) in RAW 264.7 macrophages. This effect was found to be due to inhibition of COX-2 enzyme activity by chamomile. In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. The non-steroidal anti-inflammatory drug, sulindac and a specific COX-2 inhibitor, NS398, were shown to act similarly in LPS-activated RAW 264.7 cells. Our data suggest that chamomile works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs. Significance These findings add a novel aspect to the biological profile of chamomile which might be important for understanding the usefulness of aqueous chamomile extract in the form of tea in preventing inflammation and cancer.

Srivastava, Janmejai K; Pandey, Mitali; Gupta, Sanjay

2009-01-01

439

Regression of Environmental Noise in LIGO data  

NASA Astrophysics Data System (ADS)

We address the problem of noise regression in the output of gravitational-wave interferometers us