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1

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

Microsoft Academic Search

The Cox regression model for censored survival data specifies that covariates have a proportional effect on the hazard function of the life-time distribution of an individual. In this paper we discuss how this model can be extended to a model where covariate processes have a proportional effect on the intensity process of a multivariate counting process. This permits a statistical

P. K. Andersen; R. D. Gill

1982-01-01

2

Cox regression model for dissecting genetic architecture of survival time.  

PubMed

Common quantitative trait locus (QTL) mapping methods fail to analyze survival traits of skewed normal distributions. As a result, some mapping methods for survival traits have been proposed based on survival analysis. Under a single QTL model, however, those methods perform poorly in detecting multiple QTLs and provide biased estimates of QTL parameters. For sparse oversaturated model used to map survival time loci, the least absolute shrinkage and selection operator (LASSO) for Cox regression model can be employed to efficiently shrink most of genetic effects to zero. Then, a few non-zero genetic effects are re-estimated and statistically tested using the standard maximum Cox partial likelihood method. Simulation shows that the proposed method has higher statistic power for QTL detection than that of the LASSO for logarithmic linear model or the interval mapping based on Cox model, although it somewhat underestimates QTL effects. Especially, computational speed of the method is very fast. An application of this method illustrates mapping main effect and interacting QTLs for heading time in the North American Barley Genome Mapping Project. PMID:25311647

Jiang, Dan; Wang, Hongwei; Li, Jiahan; Wu, Yang; Fang, Ming; Yang, Runqing

2014-12-01

3

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

ERIC Educational Resources Information Center

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

Chen, Chau-Kuang

2005-01-01

4

Robust Regression Analysis of Copy Number Variation Data based on a Univariate Score  

PubMed Central

Motivation The discovery that copy number variants (CNVs) are widespread in the human genome has motivated development of numerous algorithms that attempt to detect CNVs from intensity data. However, all approaches are plagued by high false discovery rates. Further, because CNVs are characterized by two dimensions (length and intensity) it is unclear how to order called CNVs to prioritize experimental validation. Results We developed a univariate score that correlates with the likelihood that a CNV is true. This score can be used to order CNV calls in such a way that calls having larger scores are more likely to overlap a true CNV. We developed cnv.beast, a computationally efficient algorithm for calling CNVs that uses robust backward elimination regression to keep CNV calls with scores that exceed a user-defined threshold. Using an independent dataset that was measured using a different platform, we validated our score and showed that our approach performed better than six other currently-available methods. Availability cnv.beast is available at http://www.duke.edu/~asallen/Software.html. PMID:24516529

Satten, Glen A.; Allen, Andrew S.; Ikeda, Morna; Mulle, Jennifer G.; Warren, Stephen T.

2014-01-01

5

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

6

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

PubMed

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

Kong, Shengchun; Nan, Bin

2014-01-01

7

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

PubMed Central

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

Kong, Shengchun; Nan, Bin

2013-01-01

8

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

9

Using trajectories from a bivariate growth curve as predictors in a Cox regression model.  

PubMed

An important research objective in most psychiatric clinical trials of maintenance treatment is to find predictors of recurrence of illness. In those trials, patients are first admitted into an open treatment period also called acute treatment. If they respond to the treatment and are considered to have stable remission from the illness, they enter the second phase of the trial where they are randomized into different arms of the 'maintenance treatments'. Often, more than one response variable is measured longitudinally in the acute treatment phase to monitor treatment responses. Trajectories of these response measures are believed to have predictive ability for recurrences in the maintenance phase of the trial. By using a bivariate growth curve from two such longitudinal measures, we developed a method to use the estimated trajectories of each subject in a Cox regression model to predict recurrence in the maintenance phase. To adjust for the parameter estimation errors, we applied a full likelihood approach based on the conditional expectations of the predictors. Simulation studies indicate that the estimation error corrected estimators for the Cox model parameters are less biased when compared to the naive regression estimators without accounting for these errors. The uniqueness of this method lies in estimating trajectories from bivariate unequally spaced longitudinal response measures. An illustrative example is provided with data from a maintenance treatment trial for major depression in an elderly population. Visual Fortran 90 programs were developed to implement the algorithm. PMID:16612837

Dang, Qianyu; Mazumdar, Sati; Anderson, Stewart J; Houck, Patricia R; Reynolds, Charles F

2007-02-20

10

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

PubMed Central

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

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

2014-01-01

11

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

PubMed Central

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

2014-01-01

12

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

E-print Network

. INTRODUCTION Privacy-preserving data mining (PPDM) is a research area that focuses on the incorporationPrivacy-Preserving Cox Regression for Survival Analysis Shipeng Yu, Glenn Fung, Romer Rosales Department of Radiation Oncology (Maastro), GROW Research Institute, University Hospital Maastricht

Rosales, Rómer E.

13

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

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

14

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

15

MULCOX2: a general computer program for the Cox regression analysis of multivariate failure time data.  

PubMed

Multivariate failure time data is commonly encountered in biomedicine, because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. MULCOX2 implements a general statistical methodology for analyzing such data. This approach formulates the marginal distributions of multivariate failure times by Cox proportional hazards models without specifying the nature of dependence among related failure times. The baseline hazard functions for the marginal models may be identical or different. A variety of statistical inference can be made regarding the effects of (possibly time-dependent) covariates on the failure rates. Although designed primarily for the marginal approach, MULCOX2 is general enough to implement several alternative methods. The program runs on any computer with a FORTRAN compiler. The running time is minimal. Two illustrative examples are provided. PMID:8261775

Lin, D Y

1993-08-01

16

Including network knowledge into Cox regression models for biomarker signature discovery.  

PubMed

Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step toward a better personalized medicine. During the last decade various methods have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Most of these methods focus on classification problems, that is learn a model from data that discriminates patients into distinct clinical groups. Far less has been published on approaches that predict a patient's event risk. In this paper, we investigate eight methods that integrate network information into multivariable Cox proportional hazard models for risk prediction in breast cancer. We compare the prediction performance of our tested algorithms via cross-validation as well as across different datasets. In addition, we highlight the stability and interpretability of obtained gene signatures. In conclusion, we find GeneRank-based filtering to be a simple, computationally cheap and highly predictive technique to integrate network information into event time prediction models. Signatures derived via this method are highly reproducible. PMID:24430933

Fröhlich, Holger

2014-03-01

17

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

PubMed

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

Armstrong, R A

2014-01-01

18

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

PubMed Central

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

Armstrong, R. A.

2014-01-01

19

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 distribution…

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

2012-01-01

20

Regression  

NSDL National Science Digital Library

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

Laval, Philippe B.

2009-02-27

21

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

PubMed Central

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

2014-01-01

22

Regression  

NSDL National Science Digital Library

In this activity, students click on a coordinate plane to plot points and view the best-fit line for those points. Students can also adjust their own fit line to test their skills at predicting the best-fit line. This activity allows students to explore linear regression and the correlation coefficient, r. This activity includes supplemental materials, including background information about the topics covered, a description of how to use the application, and exploration questions for use with the java applet.

2010-01-01

23

Regression  

Microsoft Academic Search

\\u000a The rather curious name regression was given to a statistical methodology by British scientist Sir Francis Galton, who analyzed the heights of sons and the\\u000a average heights of their parents. From his observations, Galton (Fig. 16.1a) concluded that sons of very tall (or short) parents\\u000a were generally taller (shorter) than average, but not as tall (short) as their parents. The

Brani Vidakovic

24

Cox Regression for Survey Data  

Cancer.gov

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

25

Univariate time series forecasting algorithm validation  

NASA Astrophysics Data System (ADS)

Forecasting is a complex process which requires expert tacit knowledge in producing accurate forecast values. This complexity contributes to the gaps between end users and expert. Automating this process by using algorithm can act as a bridge between them. Algorithm is a well-defined rule for solving a problem. In this study a univariate time series forecasting algorithm was developed in JAVA and validated using SPSS and Excel. Two set of simulated data (yearly and non-yearly); several univariate forecasting techniques (i.e. Moving Average, Decomposition, Exponential Smoothing, Time Series Regressions and ARIMA) and recent forecasting process (such as data partition, several error measures, recursive evaluation and etc.) were employed. Successfully, the results of the algorithm tally with the results of SPSS and Excel. This algorithm will not just benefit forecaster but also end users that lacking in depth knowledge of forecasting process.

Ismail, Suzilah; Zakaria, Rohaiza; Muda, Tuan Zalizam Tuan

2014-12-01

26

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. PMID:15115874

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

27

Global temperature predictability through univariate empirical modeling  

NASA Astrophysics Data System (ADS)

Temperature prediction in atmospheric science research has emphasized dynamical prediction models which use primitive equations and computational methods. For the extended-range (more than two-week) predictions and long- term predictions, the performance of dynamical models developed up to now in general is inferior to that of empirical models which use a historical data base to extract the hidden information. Univariate empirical prediction models are developed in this research for possible operational purposes. The brightness temperature anomalies from the Microwave Sounding Units (MSUs) on board the National Oceanic and Atmospheric Administration (NOAA) satellites are selected as the data base for global temperature prediction modeling. The emphasis is on data analysis and possible operational extended-range forecasts by one-dimensional time-series (global mean temperature anomalies) prediction models, two-dimensional (zonal mean temperature anomalies) prediction models and three- dimensional (global spherical variations of temperature anomalies) prediction models, respectively. In the one- dimensional linear prediction model, tropospheric temperature anomalies, which show more complicated phenomena than in other layers, are forecast. A multi- regression model is developed using monthly mean temperature anomalies. In the multi-regression model, Fourier spectrum analysis is used to investigate the possible physical relation on each atmospheric variable. The univariate Auto Regressive Integrated Moving Average (ARIMA) method is followed with the same data. Three- month lead global mean temperature anomaly prediction by the multi-regression model has a correlation of 0.72 with actual observations during 20-month test periods. The ARIMA model has an average correlation of 0.61 during twelve-month forecasts. In non-linear prediction models, analog methods are adopted to investigate the possibility of the extended- range prediction using daily mean brightness temperature anomalies. The statistical average skill score by correlation coefficients of the prediction with respect to the idealized observational data is about 0.3 for the 200-day prediction. The relatively short-term prediction skills show lower correlation but small mean square errors. For the theoretical establishment of the predictability, the ideas from dynamical systems (Lorenz model) are applied to the real MSU observational data. After the proposition on the predictability for the given data is established, possible operational models are developed for the given prediction ranges within a certain error bound. In two-dimensional models, tropospheric and stratospheric temperature anomalies are analyzed and forecast using daily MSU data. In two-dimensional predictions, two models are developed. In three-dimensional (monthly, gridpoint) predictions, lower-tropospheric, mid-tropospheric and lower- stratospheric temperature anomalies are forecast. Structural variations are emphasized in the analysis. Similar to the two-dimensional model, one-dimensional techniques are selected in the prediction model with additional mathematical manipulations. The univariate prediction model performs its forecasting economically. The results of each univariate empirical prediction model applied on the case studies, even though generalization is not possible now, show encouraging results for operational use. (Abstract shortened by UMI.)

Yoon, Chul Soon

1998-11-01

28

Matt Cox Oral History  

E-print Network

Oral history interview with Matt Cox conducted by Emily Stratton in Lawrence, Kansas, on July 16, 2013. This interview features Matt Cox, the planter and lead pastor of EastLake Community Church. EastLake Community Church ...

Cox, Matt; Stratton, Emily

2013-07-16

29

VC-Dimension of Univariate Decision Trees.  

PubMed

In this paper, we give and prove the lower bounds of the Vapnik-Chervonenkis (VC)-dimension of the univariate decision tree hypothesis class. The VC-dimension of the univariate decision tree depends on the VC-dimension values of its subtrees and the number of inputs. Via a search algorithm that calculates the VC-dimension of univariate decision trees exhaustively, we show that our VC-dimension bounds are tight for simple trees. To verify that the VC-dimension bounds are useful, we also use them to get VC-generalization bounds for complexity control using structural risk minimization in decision trees, i.e., pruning. Our simulation results show that structural risk minimization pruning using the VC-dimension bounds finds trees that are more accurate as those pruned using cross validation. PMID:25594983

Yildiz, Olcay Taner

2015-02-01

30

Properties of Generalized Univariate Hypergeometric Functions  

Microsoft Academic Search

Based on Spiridonov's analysis of elliptic generalizations of the Gauss hypergeometric function, we develop a common framework for 7-parameter families of generalized elliptic, hyperbolic and trigonometric univariate hypergeometric functions. In each case we derive the symmetries of the generalized hypergeometric function under the Weyl group of type E 7 (elliptic, hyperbolic) and of type E 6 (trigonometric) using the appropriate

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

2007-01-01

31

Univariate normalization of bispectrum using Hölder's inequality.  

PubMed

Considering that many biological systems including the brain are complex non-linear systems, suitable methods capable of detecting these non-linearities are required to study the dynamical properties of these systems. One of these tools is the third order cummulant or cross-bispectrum, which is a measure of interfrequency interactions between three signals. For convenient interpretation, interaction measures are most commonly normalized to be independent of constant scales of the signals such that its absolute values are bounded by one, with this limit reflecting perfect coupling. Although many different normalization factors for cross-bispectra were suggested in the literature these either do not lead to bounded measures or are themselves dependent on the coupling and not only on the scale of the signals. In this paper we suggest a normalization factor which is univariate, i.e., dependent only on the amplitude of each signal and not on the interactions between signals. Using a generalization of Hölder's inequality it is proven that the absolute value of this univariate bicoherence is bounded by zero and one. We compared three widely used normalizations to the univariate normalization concerning the significance of bicoherence values gained from resampling tests. Bicoherence values are calculated from real EEG data recorded in an eyes closed experiment from 10 subjects. The results show slightly more significant values for the univariate normalization but in general, the differences are very small or even vanishing in some subjects. Therefore, we conclude that the normalization factor does not play an important role in the bicoherence values with regard to statistical power, although a univariate normalization is the only normalization factor which fulfills all the required conditions of a proper normalization. PMID:24975293

Shahbazi, Forooz; Ewald, Arne; Nolte, Guido

2014-08-15

32

Cellulose I crystallinity determination using FT–Raman spectroscopy: univariate and multivariate methods  

Microsoft Academic Search

Two new methods based on FT–Raman spectroscopy, one simple, based on band intensity ratio, and the other using a partial least\\u000a squares (PLS) regression model, are proposed to determine cellulose I crystallinity. In the simple method, crystallinity in\\u000a cellulose I samples was determined based on univariate regression that was first developed using the Raman band intensity\\u000a ratio of the 380

Umesh P. AgarwalRichard; Richard S. Reiner; Sally A. Ralph

2010-01-01

33

Covariate Measurement Error in the Cox Model: A Simulation Study  

Microsoft Academic Search

When a continuous covariate measured with error is used as a predictor in a survival analysis using the Cox proportional hazards model [Cox, D. R. (1972). Regression models and life tables (with discussion). J. R. Statist. Soc. Ser. B 34:187–220], the parameter estimate is usually biased. In a simulation study, we compared alternative approaches to account for additive measurement error

Kenneth Liu; Roslyn A. Stone; Sati Mazumdar; Patricia R. Houck; Charles F. Reynolds III

2004-01-01

34

An Artificial Immune Univariate Marginal Distribution Algorithm  

NASA Astrophysics Data System (ADS)

Hybridization is an extremely effective way of improving the performance of the Univariate Marginal Distribution Algorithm (UMDA). Owing to its diversity and memory mechanisms, artificial immune algorithm has been widely used to construct hybrid algorithms with other optimization algorithms. This paper proposes a hybrid algorithm which combines the UMDA with the principle of general artificial immune algorithm. Experimental results on deceptive function of order 3 show that the proposed hybrid algorithm can get more building blocks (BBs) than the UMDA.

Zhang, Qingbin; Kang, Shuo; Gao, Junxiang; Wu, Song; Tian, Yanping

35

Properties of Generalized Univariate Hypergeometric Functions  

Microsoft Academic Search

Based on Spiridonov’s analysis of elliptic generalizations of the Gauss hypergeometric function, we develop a common framework\\u000a for 7-parameter families of generalized elliptic, hyperbolic and trigonometric univariate hypergeometric functions. In each\\u000a case we derive the symmetries of the generalized hypergeometric function under the Weyl group of type E\\u000a 7 (elliptic, hyperbolic) and of type E\\u000a 6 (trigonometric) using the appropriate

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

2007-01-01

36

From Univariate to Multivariate Uncertainty Calculation  

E-print Network

The Guide to the Expression of Uncertainty in Measurement (GUM) mainly deals with measurement models having only a single output quantity. However, in many cases more than one output quantity is required, where all of them are related to a common set of input quantities. In order to evaluate the measurement uncertainties associated with estimated expectations of these output quantities, the uncertainty propagation as treated in the GUM requires an appropriate extension. This article will introduce the concept of the multivariate uncertainty calculation as an extension of the univariate uncertainty calculation.

Krystek, Michael P

2010-01-01

37

Dennis Cox, USGS Volunteer  

USGS Multimedia Gallery

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

38

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

39

Univariate Distribution Relationships Lawrence M. LEEMIS and Jacquelyn T. MCQUESTON  

E-print Network

Univariate Distribution Relationships Lawrence M. LEEMIS and Jacquelyn T. MCQUESTON Probability distributions are traditionally treated separately in introductory mathematical statistics textbooks. A figure is pre- sented here that shows properties that individual distributions possess and many

Leemis, Larry

40

Futures versus univariate forecast of crude oil prices  

Microsoft Academic Search

A simple univariate model is employed to generate an unbiased and (weakly) efficient forecast of the crude oil spot price. In terms of predictive information, however, this univariate forecast is inferior to the futures price for one-month-ahead contracts. This observation may suggest that the futures price of crude oil, while unbiased, tends to be semi-strongly efficient. Copyright 2005 Organization of

Salah Abosedra

2005-01-01

41

Analgesia and COX-2 inhibition.  

PubMed

While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE2 levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB2 at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE2 is temporally related to NSAID analgesia. PMID:11695255

Dionne, R A; Khan, A A; Gordon, S M

2001-01-01

42

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

PubMed Central

Background The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. Methods We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). Results The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p?=?0.037), lower CDH-1 mRNA expression (p?=?0.020), and advanced T-classification (p?=?0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p?=?0.041). Conclusions These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC. PMID:24887090

2014-01-01

43

COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin  

PubMed Central

Background Some studies have found worse prognosis among COX-2 expressing breast cancers. Aspirin and NSAIDs inhibit COX-2. Three studies, including ours, have reported a survival advantage among women with breast cancer who take either aspirin or NSAIDs. We hypothesized that in the Nurses’ Health Study (NHS), COX-2 expression would be associated with worse prognosis, and aspirin use would be associated with better survival particularly among women with COX-2 positive tumors. Methods We studied 2,001 women with invasive breast cancers stained for COX-2 by immunohistochemistry. Tumor prognostic factors were from medical records. Aspirin use was assessed at least 12 months after diagnosis and updated. Cause of death was from death certificates. Statistical analyses included logistic regression of prognostic factors with COX-2 status as the outcome, and proportional hazards regression with breast cancer death as the outcome. Results Tumor COX-2 expression was associated with higher diagnostic stage. Compared with stage I, the RR(95% CI) for stages II-IV were 1.16(0.93–1.45), 1.68(1.27–2.22), and 1.76(0.93–3.32). COX-2 expression was associated with lobular compared with ductal histology, (1.40[1.02–1.92]), and estrogen receptor positive compared with negative (2.22[1.66–2.95]). The RR(95% CI) of breast cancer death for current aspirin use was similar for women with COX-2 positive and negative tumors; 0.64(0.43–0.96) and 0.57(0.44–0.74) respectively. Conclusions In the NHS, COX-2 breast cancer expression was associated with higher stage at diagnosis. The survival benefit associated with aspirin use did not differ by COX-2 status. Impact COX-2 breast cancer expression is associated with worse prognosis. If aspirin truly impacts breast cancer survival, it is not solely via COX-2. PMID:21728052

Holmes, Michelle D.; Chen, Wendy Y.; Schnitt, Stuart J.; Collins, Laura; Colditz, Graham A.; Hankinson, Susan E.; Tamimi, Rulla M.

2012-01-01

44

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

PubMed

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

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

2014-02-20

45

Bounded optimal knots for regression splines  

Microsoft Academic Search

Using a B-spline representation for splines with knots seen as free variables, the approxima- tion to data by splines improves greatly. The main limitations are the presence of too many local optima in the univariate regression context, and it becomes even worse in multivariate additive modeling. When the number of knots is a priori 9xed, we present a simple algorithm

Nicolas Molinari; Robert Sabatier

46

Tests of the Specification of Univariate and Bivariate Ordered Probit  

Microsoft Academic Search

This note presents tests of the specification of univariate and bivariate ordered probit. The test is sensitive to deviations from either normality or the exogeneity of the explanatory variables. As an example, the ownership of dogs and televisions, both sources of time-intensive entertainment, is studied. The specification for dogs is not rejected, the specification for televisions is rejected at the

J. S. Butler; Patrali Chatterjee

1997-01-01

47

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

ERIC Educational Resources Information Center

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

Shapiro, Jonathan

48

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

ERIC Educational Resources Information Center

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

Burdenski, Thomas K., Jr.

49

Maximum Likelihood and Minimum Distance Applied to Univariate Mixture Distributions.  

ERIC Educational Resources Information Center

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

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

50

A Root Isolation Algorithm for Sparse Univariate Polynomials  

E-print Network

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

Paris-Sud XI, Université de

51

Censored Regression Trend Analyses for Ambient Water Quality Data  

E-print Network

Censored Regression Trend Analyses for Ambient Water Quality Data Gordon K. Smyth 1 , Melanie Cox 2 regression; logistic distribution; regression splines; seasonal trends. 1 Introduction Water is a very to increasing levels of development and support approximately 75% of the population. Management of water

Smyth, Gordon K.

52

Regression Revisited  

Microsoft Academic Search

Sir Francis Galton introduced median regression and the use of the quantile function to describe distributions. Very early on the tradition moved to mean regression and the universal use of the Normal distribution, either as the natural 'error' distribution or as one forced by transformation. Though the introduction of 'quantile regression' refocused attention on the shape of the variability about

Warren Gilchrist

2008-01-01

53

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

2013-01-01

54

Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation.  

PubMed

Prostanoid production depends on the activity of two cyclooxygenase (COX) isoforms. It is appreciated that COX-1 plays a role in physiological processes, whereas COX-2 acts in pathological conditions. However their roles, particularly roles of COX-1, have not yet been fully established in inflammation. Here, we examined the effects of COX inhibitors, having differential isoform selectivity, on the late phase of rat carrageenin-induced pleurisy to elucidate the role of COX-2 expressed in the draining lymph nodes and found substantial contribution of COX-1-product(s). Protein and mRNA of COX-2 were detectable with Western blotting analysis and reverse-transcription polymerase chain reaction (RT-PCR) analysis in parathymic lymph nodes, peaking at 48 h after induction of pleurisy. Microsomal prostaglandin E synthase (mPGES)-1 was detectable by immunohistochemical analysis in cells with dendritic processes, a morphological characteristic similar to that of COX-2 expressing cells. Although aspirin, indomethacin and a COX-1 inhibitor, ketorolac, significantly decreased the volume of pleural exudate, they did not affect the levels of COX-2 and mPGES-1 in the lymph node 24 h after induction of pleurisy. In contrast, COX-2 inhibitors, nimesulide and NS-398, had no effect on the exudate volume, but they increased the number of COX-2- and mPGES-1-expressing cells and extension of their dendritic processes with significant increase in the COX-2 level, which were antagonised by ketorolac. These results suggest that COX-2-expressing cells may negatively self-regulate their functions by producing PGE2 via mPGES-1: migration into the draining lymph node and their differentiation. Moreover, COX-1- and COX-2-derived prostanoids may play differential or sometimes antagonistic roles in the late phase of acute inflammation. PMID:17258197

Nakano, Masashi; Denda, Naoyuki; Matsumoto, Misako; Kawamura, Michiko; Kawakubo, Yasuaki; Hatanaka, Ko; Hiramoto, Yoshisuke; Sato, Yu-ichi; Noshiro, Makoto; Harada, Yoshiteru

2007-03-22

55

COX-2 Inhibitors and Gastric Cancer  

PubMed Central

The evidence that cyclooxygenase-2 (COX-2) is upregulated and plays an important role in carcinogenesis of gastric cancer has triggered the topic of COX-2 inhibitors as chemopreventive agents for gastric cancer. Studies find that COX-2 inhibitors are associated not only with chemoprophylactic effects, but also with chemotherapeutic potentials in gastric cancer. Both COX-dependent and COX-independent pathways have a role in the anticancer efficiency of COX-2 inhibitors. However, enthusiasm is thwarted by the potential toxicity, that is, gastrointestinal toxicity of nonselective COX-2 inhibitors and cardiovascular risk of selective COX-2 inhibitors. Therefore, more studies are needed to develop new targeted antitumor agents (such as prostaglandin E receptor antagonist) and to define fundamental questions such as optimal treatment regimens, integration of cotherapy, and careful selection of candidates. PMID:25371669

Wang, Zhen; Chen, Jun-qiang; Liu, Jin-lu

2014-01-01

56

External validation of a Cox prognostic model: principles and methods  

PubMed Central

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

2013-01-01

57

Univariate approximate integration via nested Taylor multivariate function decomposition  

NASA Astrophysics Data System (ADS)

This work is based on the idea of nesting one or more Taylor decompositions in the remainder term of a Taylor decomposition of a function. This provides us with a better approximation quality to the original function. In addition to this basic idea each side of the Taylor decomposition is integrated and the limits of integrations are arranged in such a way to obtain a universal [0;1] interval without losing from the generality. Thus a univariate approximate integration technique is formed at the cost of getting multivariance in the remainder term. Moreover the remainder term expressed as an integral permits us to apply Fluctuationlessness theorem to it and obtain better results.

Gürvit, Ercan; Baykara, N. A.

2014-12-01

58

ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.  

PubMed

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

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

2013-06-01

59

Selectivity in analytical chemistry: Two interpretations for univariate methods.  

PubMed

Selectivity is extremely important in analytical chemistry but its definition is elusive despite continued efforts by professional organizations and individual scientists. This paper shows that the existing selectivity concepts for univariate analytical methods broadly fall in two classes: selectivity concepts based on measurement error and concepts based on response surfaces (the response surface being the 3D plot of the univariate signal as a function of analyte and interferent concentration, respectively). The strengths and weaknesses of the different definitions are analyzed and contradictions between them unveiled. The error based selectivity is very general and very safe but its application to a range of samples (as opposed to a single sample) requires the knowledge of some constraint about the possible sample compositions. The selectivity concepts based on the response surface are easily applied to linear response surfaces but may lead to difficulties and counterintuitive results when applied to nonlinear response surfaces. A particular advantage of this class of selectivity is that with linear response surfaces it can provide a concentration independent measure of selectivity. In contrast, the error based selectivity concept allows only yes/no type decision about selectivity. PMID:25476364

Dorkó, Zsanett; Verbi?, Tatjana; Horvai, George

2015-01-15

60

The pathways for intelligible speech: multivariate and univariate perspectives.  

PubMed

An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400-2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486-2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local "searchlights" and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing. PMID:23585519

Evans, S; Kyong, J S; Rosen, S; Golestani, N; Warren, J E; McGettigan, C; Mourão-Miranda, J; Wise, R J S; Scott, S K

2014-09-01

61

Simple Regression  

Microsoft Academic Search

\\u000a Over a century ago Sir Francis Galton investigated the manner in which a son’s height depended on that of the father. He showed\\u000a that the heights of tall fathers’ sons were distributed about a value somewhat less than that of their father. The paper was\\u000a entitled “Regression towards mediocrity in hereditary stature”, and the word regression has stayed with the

David J. Saville; Graham R. Wood

62

Logistic Regression  

NASA Astrophysics Data System (ADS)

The logistic regression originally is intended to explain the relationship between the probability of an event and a set of covariables. The model's coefficients can be interpreted via the odds and odds ratio, which are presented in introduction of the chapter. The observations are possibly got individually, then we speak of binary logistic regression. When they are grouped, the logistic regression is said binomial. In our presentation we mainly focus on the binary case. For statistical inference the main tool is the maximum likelihood methodology: we present the Wald, Rao and likelihoods ratio results and their use to compare nested models. The problems we intend to deal with are essentially the same as in multiple linear regression: testing global effect, individual effect, selection of variables to build a model, measure of the fitness of the model, prediction of new values… . The methods are demonstrated on data sets using R. Finally we briefly consider the binomial case and the situation where we are interested in several events, that is the polytomous (multinomial) logistic regression and the particular case of ordinal logistic regression.

Grégoire, G.

2014-01-01

63

Forecasting electricity usage using univariate time series models  

NASA Astrophysics Data System (ADS)

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

Hock-Eam, Lim; Chee-Yin, Yip

2014-12-01

64

Stabilization of Cox1p intermediates by the Cox14p-Coa3p complex  

PubMed Central

Cox14p and Coa3p have been shown to regulate translation of the mitochondrial COX1 mRNA and to be required for assembly of cytochrome oxidase. We present evidence that Cox14p and Coa3p stabilize previously identified Cox1p intermediates and that in the absence of either protein, Cox1p aggregates with itself and other mitochondrial gene products, including cytochrome b, Var1p and Cox2p. Our evidence suggests that Cox1p assembly intermediates are in close proximity to other mitochondrially translated proteins and that an important function of Cox14p and Coa3p is to prevent Cox1 from entering into unproductive aggregation pathways. PMID:23434581

McStay, Gavin P.; Su, Chen Hsien; Tzagoloff, Alexander

2013-01-01

65

Clinical pharmacology of selective COX-2 inhibitors.  

PubMed

The discovery of cyclooxygenase (COX)-2 has provided the rationale for the development of a new class of nonsteroidal antiinflammatory drugs (NSAIDs), the selective COX-2 inhibitors (denominated coxibs), with the aim of reducing the gastrointestinal (GI) toxicity associated with the administration of NSAIDs by virtue of COX-1 sparing. Rofecoxib and celecoxib are the first selective COX-2 inhibitors approved by the FDA and EMEA for the treatment of rheumatoid arthritis (RA), osteoarthritis (OA) and for relief of acute pain. Rofecoxib has been shown to spare COX-1 activity ex vivo, in platelets and gastric mucosa, when administered at therapeutic doses or above. In a large clinical trial, COX-2 inhibitors have been demonstrated to halve the incidence of serious upper GI events vs a nonselective NSAID. Recently, other selective COX-2 inhibitors with different COX-1/COX-2 selectivity and pharmacokinetic features have been developed, i.e. valdecoxib, parecoxib, etoricoxib and lumiracoxib. The improved biochemical selectivity of valdecoxib vs celecoxib in vitro (COX-1/COX-2 ratio: 60 vs 30, respectively) may be clinically relevant leading to an improved GI safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib, showing only a slightly higher COX-2 selectivity than rofecoxib in vitro (COX-1/COX-2 ratio: 344 vs 272, respectively), has been reported to cause a similar specific COX-2 inhibition ex vivo that should translate into comparable GI safety. Lumiracoxib, the most selective COX-2 inhibitor in vitro (COX-1/COX-2 ratio: 400), is the only acidic coxib. It has been hypothesized that this pecular chemical feature may lead to an enhanced concentration in inflammatory sites that may translate into an improved clinical efficacy. The results of clinical trials have shown that coxibs have a comparable clinical efficacy and renal toxicity and an improved GI safety vs nonselective NSAIDs. Whether the different pharmacodynamic and pharmacokinetics features of the various coxibs will produce detectable differences in efficacy and toxicity remains to be evaluated in appropriate comparative randomized clinical studies. PMID:14552704

Capone, M L; Tacconelli, S; Sciulli, M G; Patrignani, P

2003-01-01

66

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. PMID:19025609

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

2008-01-01

67

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. PMID:24133463

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

2013-01-01

68

Detecting and Dealing with Outliers in Univariate and Multivariate Contexts.  

ERIC Educational Resources Information Center

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

Wiggins, Bettie Caroline

69

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

70

The Cox3p assembly module of yeast cytochrome oxidase.  

PubMed

Yeast cytochrome oxidase (COX) was previously inferred to assemble from three modules, each containing one of the three mitochondrially encoded subunits and a different subset of the eight nuclear gene products that make up this respiratory complex. Pull-down assays of pulse-labeled mitochondria enabled us to characterize Cox3p subassemblies that behave as COX precursors and contain Cox4p, Cox7p, and Cox13p. Surprisingly, Cox4p is a constituent of two other complexes, one of which was previously proposed to be an intermediate of Cox1p biogenesis. This suggests that Cox4p, which contacts Cox1p and Cox3p in the holoenzyme, can be incorporated into COX by two alternative pathways. In addition to subunits of COX, some Cox3p intermediates contain Rcf1p, a protein associated with the supercomplex that stabilizes the interaction of COX with the bc1 (ubiquinol-cytochrome c reductase) complex. Finally, our results indicate that although assembly of the Cox1p module is not contingent on the presence of Cox3p, the converse is not true, as none of the Cox3p subassemblies were detected in a mutant blocked in translation of Cox1p. These studies support our proposal that Cox3p and Cox1p are separate assembly modules with unique compositions of ancillary factors and subunits derived from the nuclear genome. PMID:24478450

Su, Chen-Hsien; McStay, Gavin P; Tzagoloff, Alexander

2014-04-01

71

The Cox3p assembly module of yeast cytochrome oxidase  

PubMed Central

Yeast cytochrome oxidase (COX) was previously inferred to assemble from three modules, each containing one of the three mitochondrially encoded subunits and a different subset of the eight nuclear gene products that make up this respiratory complex. Pull-down assays of pulse-labeled mitochondria enabled us to characterize Cox3p subassemblies that behave as COX precursors and contain Cox4p, Cox7p, and Cox13p. Surprisingly, Cox4p is a constituent of two other complexes, one of which was previously proposed to be an intermediate of Cox1p biogenesis. This suggests that Cox4p, which contacts Cox1p and Cox3p in the holoenzyme, can be incorporated into COX by two alternative pathways. In addition to subunits of COX, some Cox3p intermediates contain Rcf1p, a protein associated with the supercomplex that stabilizes the interaction of COX with the bc1 (ubiquinol-cytochrome c reductase) complex. Finally, our results indicate that although assembly of the Cox1p module is not contingent on the presence of Cox3p, the converse is not true, as none of the Cox3p subassemblies were detected in a mutant blocked in translation of Cox1p. These studies support our proposal that Cox3p and Cox1p are separate assembly modules with unique compositions of ancillary factors and subunits derived from the nuclear genome. PMID:24478450

Su, Chen-Hsien; McStay, Gavin P.; Tzagoloff, Alexander

2014-01-01

72

Estimation with Univa.ria.te "Mixed Case" Interval Censored Data  

E-print Network

of \\Vashington Seattle, Washington, 98195 USA #12;#12;Estimation with Univariate "Mixed Case" Interval Censored Data Shuguang Song The Boeing Company Abstract: In this paper, we study the Nonparametric MaximumEstimation with Univa.ria.te "Mixed Case" Interval Censored Data by Shuguang Song The Boeing

Washington at Seattle, University of

73

Bootstrapping to Test for Nonzero Population Correlation Coefficients Using Univariate Sampling  

ERIC Educational Resources Information Center

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

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

2007-01-01

74

Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial.  

PubMed

COX-2(cyclooxygenase-2) has sparked a surge in pharmaceutical interest since its discovery at the beginning of the 1990s. Several COX-2 selective inhibitors that avoid gastrointestinal side effects have been successfully launched into the market in recent years. The first selective COX-2 inhibitor, celecoxib, entered the market in December 1998 [corrected] However, there are a few organs that physiologically and functionally express COX-2, particularly the glomeruli of the kidney and the cortex of the brain. Inhibition of COX-2 expression in these organs possibly causes heart attack and stroke in long-term COX-2 inhibitor users. Recently, a USA Food and Drug Agency (FDA) advisory panel re-evaluated COX-2 inhibitors and unanimously concluded that the entire class of COX-2 inhibitors increase the risk of cardiovascular problems. Thus the use of COX-2 inhibitors is still controversial, and there is a challenge for not only pharmacologists, but also the pharmaceutical industry, to develop improved painkilling and anti-inflammatory drugs. This may involve exploring a new generation of COX-2 inhibitors with different inhibitory mechanisms through computer-aided design, screening different sources of inhibitors with lower selectivity, or seeking completely new targets. Synthetic COX-2 inhibitors have high selectivity and the advantage of irreversible inhibition, whereas naturally derived COX-2 inhibitors have lower selectivity and fewer side effects, with the medical effects in general not being as striking as those achieved using synthetic inhibitors. This review discusses the mechanism of COX-2 inhibitor therapy and a possible new way of exploration in the development of anti-inflammatory, analgetic, and antipyretic drugs. PMID:16038624

Luo, Cheng; He, Ming-liang; Bohlin, Lars

2005-08-01

75

COX-2 inhibitors and cardiovascular risk.  

PubMed

The development of drugs that selectively inhibit cyclooxygenase-2 (COX-2) demonstrates translational research from bench to bedside based on underlying knowledge of micro-cellular structure and function. However, theoretical concerns about potentially prothrombotic effects of selective COX-2 inhibitors coupled with observations of increased cardiovascular risk have produced significant consternation and lead to the withdrawal of two of these agents from the market. A number of questions remain unanswered. It appears clear that both selective and non-selective COX inhibitors are associated with increases in blood pressure. In addition, blood pressure is often increased after starting nonsteroidal therapy, and we know that even small increases in blood pressure in subjects with pre-existing vascular disease are associated with substantial increases in the risk of cardiovascular morbidity. Given this line of reasoning, one might hypothesize that the observed increases in the risk of cardiovascular events associated with COX-inhibitors are largely due to increases in blood pressure in populations of subjects who are already at high risk. But can we generalize that the adverse cardiovascular effects observed for rofecoxib and valdecoxib are sufficient to indict the entire class of COX-2 inhibitors, or is this not a class effect, but dependent upon the degree of COX-2 selectivity? In either case, it seems prudent to recommend that subjects who are at higher risk for a cardiovascular event and receiving a COX-inhibitor should also be treated with low dose ASA with close follow up of blood pressure and efficacious use of anti-hypertensive medications. Finally, modest dietary salt restriction may help lessen the effects of COX-inhibitors on blood pressure. PMID:17612050

Salzberg, Daniel J; Weir, Matthew R

2007-01-01

76

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

PubMed Central

Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1?-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. PMID:25664986

Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V.

2015-01-01

77

Regression: A Bibliography.  

ERIC Educational Resources Information Center

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

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

78

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

79

NSAIDs: gastroprotection or selective COX-2 inhibitor?  

PubMed

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and cost-effective use of these drugs in the palliative care population. PMID:15198117

Dickman, Andrew; Ellershaw, John

2004-05-01

80

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. PMID:24098505

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

2013-01-01

81

Fuzzy Regression in Hydrology  

Microsoft Academic Search

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

Andras Bardossy; Istvan Bogardi; Lucien Duckstein

1990-01-01

82

An appreciation of Richard Threlkeld Cox  

NASA Astrophysics Data System (ADS)

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

Tribus, Myron

2002-05-01

83

Segmented Regressions and Causality (with applications to macroeconomic time series)  

Microsoft Academic Search

The segmented regression approach described in Bianchi (1993a,b) is applied in this paper to pairs of time series, with the aim of establishing empirical relationships and directions of causality between variables. The approach is based on the asumption of regime shifts in univariate time series occurring infrequently over time. Cause-effect relationships are established on the basis of the timing of

Marco BIANCHI

1993-01-01

84

Epidermal COX-2 induction following ultraviolet irradiation: suggested mechanism for the role of COX-2 inhibition in photoprotection.  

PubMed

The cyclooxygenase isoforms, COX-1 and COX-2, are involved in the biosynthesis of prostaglandin E2, a major prostaglandin involved in epidermal homeostasis and repair. Cancer originating in the epidermis can develop when keratinocyte proliferation and apoptosis become dysregulated, resulting in sustained epidermal hyperplasia. COX-2 inhibitors, which demonstrate significant in vivo selectivity relative to COX-1, suppress both ultraviolet-induced epidermal tumor development and progression, suggesting that prostaglandin regulation of keratinocyte biology is involved in the pathogenesis of epidermal neoplasia. In this study, we characterized the expression of COX-1 and COX-2, as well as keratinocyte proliferation, differentiation, and apoptosis, following acute ultraviolet irradiation in the hairless SKH-1 mouse. Following acute ultraviolet exposure, COX-2 expression was predominantly induced in the basal keratinocyte layer coincident with an increase in keratinocyte proliferation and apoptosis. The role of COX-2 was further evaluated using a selective COX-2 inhibitor, SC-791, as well as the traditional nonsteroidal COX inhibitor, indomethacin. Following acute ultraviolet irradiation, inhibition of COX-2 with either inhibitor decreased epidermal keratinocyte proliferation. Likewise, keratinocyte apoptosis was increased with COX-2 inhibition, particularly in the proliferating basal keratinocyte layer. There was also a modest inhibition of keratinocyte differentiation. These data suggest that COX-2 expression is probably necessary for keratinocyte survival and proliferation occurring after acute ultraviolet irradiation. We hypothesize that selective COX-2 inhibition, as described herein, may lead to enhanced removal of ultraviolet-damaged keratinocytes, thereby decreasing malignant transformation in the epidermis. PMID:14632205

Tripp, Catherine S; Blomme, Eric A G; Chinn, Kevin S; Hardy, Medora M; LaCelle, Peter; Pentland, Alice P

2003-10-01

85

INFORMATION TRANSMISSION AND STEGANOGRAPHY Ingemar J. Cox  

E-print Network

INFORMATION TRANSMISSION AND STEGANOGRAPHY Ingemar J. Cox , Ton Kalker , Georg Pakura and Mathias Scheel ABSTRACT Recently there has been strong interest in developing models of steganography based. INTRODUCTION The history of steganography can be traced back thousands of years, examples of which

Cox, Ingemar J.

86

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. PMID:16519514

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

2008-01-01

87

Structure–activity relationship of indomethacin analogues for MRP-1, COX1 and COX2 inhibition  

Microsoft Academic Search

We report the screening of analogues of indomethacin to investigate the structure–activity relationship (SAR) of indomethacin-mediated multidrug resistance associated protein-1 (MRP-1) inhibition. By examining the activities of compounds with minor variations of the parent structure, we were able to separate MRP-1, glutathione-S-transferase (GST), cyclooxygenase (COX)-1 and COX-2 inhibitory activities. Combination cytotoxicity assays were utilised to identify agents which possess synergistic

S Touhey; R O'Connor; S Plunkett; A Maguire; M Clynes

2002-01-01

88

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-

89

The Mizon-Richard encompassing test for the Cox and Aalen additive hazards models.  

PubMed

The Cox hazards model (Cox, 1972, Journal of the Royal Statistical Society, Series B34, 187-220) for survival data is routinely used in many applied fields, sometimes, however, with too little emphasis on the fit of the model. A useful alternative to the Cox model is the Aalen additive hazards model (Aalen, 1980, in Lecture Notes in Statistics-2, 1-25) that can easily accommodate time changing covariate effects. It is of interest to decide which of the two models that are most appropriate to apply in a given application. This is a nontrivial problem as these two classes of models are nonnested except only for special cases. In this article we explore the Mizon-Richard encompassing test for this particular problem. It turns out that it corresponds to fitting of the Aalen model to the martingale residuals obtained from the Cox regression analysis. We also consider a variant of this method, which relates to the proportional excess model (Martinussen and Scheike, 2002, Biometrika 89, 283-298). Large sample properties of the suggested methods under the two rival models are derived. The finite-sample properties of the proposed procedures are assessed through a simulation study. The methods are further applied to the well-known primary biliary cirrhosis data set. PMID:17608786

Martinussen, Torben; Aalen, Odd O; Scheike, Thomas H

2008-03-01

90

Monocytes stimulate COX2 expression in pancreatic cancer cells  

Microsoft Academic Search

COX-2 is an enzyme that modulates human pancreatic cancer (PaCa) cell survival, proliferation, and tumor metastasis. 60–80% of human PaCa express COX-2. However, the regulation of COX-2 expression in PaCa cells is not clear. We hypothesize that inflammatory cell infiltrate—namely monocytes\\/macrophages found commonly in PaCa—regulates the expression and activity of COX-2. The human histiocytic lymphoma cell line U937 was terminally

G. Eibl; Y. Okada; H. A. Reber; T. E. Rix; J. P. Duffy; O. J. Hines

2003-01-01

91

Fault detection of univariate non-Gaussian data with Bayesian network  

E-print Network

Fault detection of univariate non-Gaussian data with Bayesian network Sylvain Verron, Teodor.verron@univ-angers.fr Abstract--The purpose of this article is to present a new method for fault detection with Bayesian network. The interest of this method is to propose a new structure of Bayesian network allowing to detect a fault

Paris-Sud XI, Université de

92

Measuring Unexpected Hospital Demand: The Application of a Univariate Model to Public Hospitals in Greece  

Microsoft Academic Search

The accurate forecasting of hospital demand is an important issue in many countries. The author applied a univariate model using hospital daily emergency admissions of 10 public hospitals in Athens, Greece, during the period 2001–2005. Unexpected demand varied considerably among hospital units in Greece, and its volatility over time was low. Managerial and organizational characteristics of the hospital, the easy

Zoe Boutsioli

2009-01-01

93

Improved DCT-based method for online detection of oscillations in univariate time series$  

E-print Network

Improved DCT-based method for online detection of oscillations in univariate time series$ Jiandong of applying the discrete cosine transform (DCT)-based method for oscillation detection. An improved DCT & Singhal, 2005), the discrete cosine transform (DCT)-based method (Li, Wang, Huang, & Lu, 2010

Wang, Jiandong

94

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

95

COX-2 inhibitors: pharmacological data and adverse effects.  

PubMed

The nonsteroidal anti-inflammatory drugs (NSAIDs) cover a wide range of selectivity, from the nonselective cyclooxygenase (COX) inhibitors to the preferential COX-2, and the newest coxibs, selective COX-2, with 1000-fold selectivities for COX-2. Coxibs belong to the distinct classes of sulphonamides, methylsulphones, and phenylacetic acid derivatives. The affinity of an inhibitor for COX-1 and COX-2 determinates its relative selectivity. Minor changes in the amino acid structure between the 2 enzymes results in different forms of their active sites. However, the primitive hypothesis of a dualism between an isoform totally inducible (COX-2) and the other isoform constitutive (COX-1) was not completely true. Thus, also selective COX-2 inhibitors have been shown to interact with gastrointestinal, renal, and cardiovascular systems. New insights into pharmacological data and side effect profile of coxibs have been reported in this review. They may reduce gastrointestinal-related risks, but when administered with low-dose aspirin, they could create an ulcerogenic dual-COX inhibitor. Moreover, by inhibiting COX-2, they could delay ulcer healing. Similarly to traditional NSAIDs, coxibs compromise the glomerular filtration rate in patients at increased risk, and may cause peripheral oedema and hypertension. According to the traditional ''COX-2 hypothesis'', they should not impair efficacy of coagulation. However, in combination with an oral anticoagulant they increase the International Normalized Ratio (INR) and, in some cases, cause bleeding. The altered balance between prostacyclin and thromboxane, due to selective inhibition of COX-2 without reducing COX-1, could promote a prothrombotic state and explain the observed increased cardiovascular risk. Finally, the role of COX-2 expression in the ischemic preconditioning mechanism and the recent discovery of a pro-oxidant activity of sulphones has been analysed. PMID:16012420

Mattia, C; Coluzzi, F

2005-01-01

96

Cox-2 inhibitors: today and tomorrow.  

PubMed

The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory pathways led to the development of specific Cox-2 inhibitors, the coxibs. These agents include the currently available celecoxib and rofecoxib and such second-generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic advantage of coxibs is founded primarily in their lack of significant gastrointestinal (GI) side effects. Clinical trials have demonstrated the efficacy of coxibs to be completely comparable with traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit ratios with these agents compared with traditional NSAIDs, related to their reduced GI complication profiles and lower indirect costs associated with disability. Although several clinical questions remain (eg, use with low-dose aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the emergence and clinical utility of coxibs is likely to continue on the basis of their efficacy and relative GI safety advantage. Although newer, more specific Cox-2 inhibitors may alter the choice, it is likely that this class of anti-inflammatories will become (if they have not already) the drugs of first choice in the treatment of acute pain, chronic pain, and most rheumatic conditions in the 21st century. In addition to the treatment of rheumatic conditions, it is possible that coxibs will also be of clinical utility in protection against malignant transformation and Alzheimer disease. PMID:12003372

McMurray, Robert W; Hardy, Kenneth J

2002-04-01

97

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

NASA Astrophysics Data System (ADS)

A statistical framework is introduced that resolves important problems with the interpretation and use of traditional Horton regression statistics. The framework is based on a univariate regression model that leads to an alternative expression for Horton ratio, connects Horton regression statistics to distributional simple scaling, and improves the accuracy in estimating Horton plot parameters. The model is used to examine data for drainage area A and mainstream length L from two groups of basins located in different physiographic settings. Results show that confidence intervals for the Horton plot regression statistics are quite wide. Nonetheless, an analysis of covariance shows that regression intercepts, but not regression slopes, can be used to distinguish between basin groups. The univariate model is generalized to include n > 1 dependent variables. For the case where the dependent variables represent ln A and ln L, the generalized model performs somewhat better at distinguishing between basin groups than two separate univariate models. The generalized model leads to a modification of Hack's law where L depends on both A and Strahler order ?. Data show that ? plays a statistically significant role in the modified Hack's law expression.

Furey, Peter R.; Troutman, Brent M.

2008-12-01

98

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

USGS Publications Warehouse

A statistical framework is introduced that resolves important problems with the interpretation and use of traditional Horton regression statistics. The framework is based on a univariate regression model that leads to an alternative expression for Horton ratio, connects Horton regression statistics to distributional simple scaling, and improves the accuracy in estimating Horton plot parameters. The model is used to examine data for drainage area A and mainstream length L from two groups of basins located in different physiographic settings. Results show that confidence intervals for the Horton plot regression statistics are quite wide. Nonetheless, an analysis of covariance shows that regression intercepts, but not regression slopes, can be used to distinguish between basin groups. The univariate model is generalized to include n > 1 dependent variables. For the case where the dependent variables represent ln A and ln L, the generalized model performs somewhat better at distinguishing between basin groups than two separate univariate models. The generalized model leads to a modification of Hack's law where L depends on both A and Strahler order ??. Data show that ?? plays a statistically significant role in the modified Hack's law expression. ?? 2008 Elsevier B.V.

Furey, P.R.; Troutman, B.M.

2008-01-01

99

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

PubMed Central

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

Frautschy, Sally A.

2015-01-01

100

Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria  

PubMed Central

Regulation of eukaryotic cytochrome oxidase assembly occurs at the level of Cox1 translation, its central mitochondria-encoded subunit. Translation of COX1 messenger RNA is coupled to complex assembly in a negative feedback loop: the translational activator Mss51 is thought to be sequestered to assembly intermediates, rendering it incompetent to promote translation. In this study, we identify Coa3 (cytochrome oxidase assembly factor 3; Yjl062w-A), a novel regulator of mitochondrial COX1 translation and cytochrome oxidase assembly. We show that Coa3 and Cox14 form assembly intermediates with newly synthesized Cox1 and are required for Mss51 association with these complexes. Mss51 exists in equilibrium between a latent, translational resting, and a committed, translation-effective, state that are represented as distinct complexes. Coa3 and Cox14 promote formation of the latent state and thus down-regulate COX1 expression. Consequently, lack of Coa3 or Cox14 function traps Mss51 in the committed state and promotes Cox1 synthesis. Our data indicate that Coa1 binding to sequestered Mss51 in complex with Cox14, Coa3, and Cox1 is essential for full inactivation. PMID:20876281

Mick, David U.; Vukotic, Milena; Piechura, Heike; Meyer, Helmut E.; Warscheid, Bettina; Deckers, Markus

2010-01-01

101

The Reasons for Nursing Home Entry in an Adult Day Care Population: Caregiver Reports Versus Regression Results  

Microsoft Academic Search

This article aims to compare reasons for nursing home entry determined through a regression of baseline predictors to relatives’ perceptions of reasons for entry. Participants included 201 community-residing members of 5 senior day care centers in Maryland. Through a prospective design, statistical predictors using Cox regressions were compared to the relatives’ reports of reasons for nursing home entry. These reports

Jiska Cohen-Mansfield; Philip W. Wirtz

2009-01-01

102

Syst. Zool., 36(4):398-400, 1987 Univariate Analyses of Morphometric Variation Do Not Emulate the  

E-print Network

Syst. Zool., 36(4):398-400, 1987 Univariate Analyses of Morphometric Variation Do Not Emulate was to evaluate empirically whether the commonly used univariate ANOVAs emulate the multi- variate results. Our emulated the results of the MANOVAs. Generally speaking, Willig et al. (1986) tested the null hypothesis

Willig, Michael

103

Statistical methods for astronomical data with upper limits. I - Univariate distributions  

NASA Technical Reports Server (NTRS)

The statistical treatment of univariate censored data is discussed. A heuristic derivation of the Kaplan-Meier maximum-likelihood estimator from first principles is presented which results in an expression amenable to analytic error analysis. Methods for comparing two or more censored samples are given along with simple computational examples, stressing the fact that most astronomical problems involve upper limits while the standard mathematical methods require lower limits. The application of univariate survival analysis to six data sets in the recent astrophysical literature is described, and various aspects of the use of survival analysis in astronomy, such as the limitations of various two-sample tests and the role of parametric modelling, are discussed.

Feigelson, E. D.; Nelson, P. I.

1985-01-01

104

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

PubMed Central

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 family-wise 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

2014-01-01

105

Censored quantile regression with recursive partitioning-based weights.  

PubMed

Censored quantile regression provides a useful alternative to the Cox proportional hazards model for analyzing survival data. It directly models the conditional quantile of the survival time and hence is easy to interpret. Moreover, it relaxes the proportionality constraint on the hazard function associated with the popular Cox model and is natural for modeling heterogeneity of the data. Recently, Wang and Wang (2009. Locally weighted censored quantile regression. Journal of the American Statistical Association 103, 1117-1128) proposed a locally weighted censored quantile regression approach that allows for covariate-dependent censoring and is less restrictive than other censored quantile regression methods. However, their kernel smoothing-based weighting scheme requires all covariates to be continuous and encounters practical difficulty with even a moderate number of covariates. We propose a new weighting approach that uses recursive partitioning, e.g. survival trees, that offers greater flexibility in handling covariate-dependent censoring in moderately high dimensions and can incorporate both continuous and discrete covariates. We prove that this new weighting scheme leads to consistent estimation of the quantile regression coefficients and demonstrate its effectiveness via Monte Carlo simulations. We also illustrate the new method using a widely recognized data set from a clinical trial on primary biliary cirrhosis. PMID:23975800

Wey, Andrew; Wang, Lan; Rudser, Kyle

2014-01-01

106

A Clinical Study of Isolated Aortic Valve Replacement: A Univariate Analysis of Risk Factors  

Microsoft Academic Search

Between 1979 and 1990, 190 patients underwent isolated aortic valve replacement at Seoul National University Hospital in Korea. There were 11 (5.8%) in-hospital deaths. Univariate analysis identified advanced age (p = 0.026), preoperative serum GOT or GPT greater than 40 IU\\/1 (p < 0.001, p = 0.003), NYHA Class III or IV (p = 0.029), preoperative mean pulmonary arterial pressure

Wook Sung Kim; Jeong Ryul Lee; Ki Bong Kim; Sook Whan Sung; Hyuk Ahn; Yong Jin Kim; Hurn Chae; Joo Hyun Kim; Joon Ryang Rho; Chong Whan Kim; Kyung Phill Suh; Young Kyun Lee

1993-01-01

107

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

108

Analysis of Type I Error Rates of Univariate and Multivariate Procedures in Repeated Measures Designs  

Microsoft Academic Search

We compared the robustness of univariate and multivariate statistical procedures to control Type I error rates when the normality and homocedasticity assumptions were not fulfilled. The procedures we evaluated are the mixed model adjusted by means of the SAS Proc Mixed module, and Bootstrap-F approach, Brown–Forsythe multivariate approach, Welch–James multivariate approach, and Welch–James multivariate approach with robust estimators. The results

Pablo Livacic-Rojas; Guillermo Vallejo; Paula Fernández

2010-01-01

109

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

PubMed

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

Raharjo, Sentot Joko; Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah

2014-01-01

110

Apoptotic effects of two COX-2 inhibitors on breast adenocarcinoma cells through COX-2 independent pathway.  

PubMed

Recently, much effort has been directed toward the search for compounds that influence apoptosis and to understand their mechanisms of action. Cyclooxygenase (COX)-2 inhibitors may induce apoptosis through the COX-2-independent mechanism via a mitochondrial pathway. In view of the reported antiproliferative activities of two COX-2 inhibitor derivatives (1, 2) in breast cancer cells (MCF-7), the present study was undertaken to evaluate the potential of these compounds to induce apoptosis and unravel the associated mechanisms. The apoptotic activities of the two compounds were assessed using flow cytometry, fluorescence microscope, and Western blot analysis. Compounds 1 and 2-treated MCF-7 cells revealed the apoptotic cell death, as confirmed by the changes in nuclear morphology and the increased annexin-V/PI staining. Elevation of Bax to Bcl-2 ratio and activation of caspase-3 were found to be associated with the initiation of apoptosis induced by compound 1. Further investigation showed that compounds 1 and 2 inhibited NF-?B, FHC, and ERK activation, while no dramatic change was revealed in c-Myc and EGR-1 levels. Our data suggest that induction of apoptosis by compounds 1 and 2 is not associated with COX-2 expression and occurs through the NF-?B pathway, which sequentially inhibits P-ERK and FHC expression. PMID:25142612

Norouzi, Mahnaz; Norouzi, Shaghayegh; Amini, Mohsen; Amanzadeh, Amir; Irian, Saeed; Salimi, Mona

2015-01-01

111

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

PubMed Central

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

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

2009-01-01

112

Potential cardiovascular effects of COX-2 selective nonsteroidal antiinflammatory drugs.  

PubMed

The newly developed nonsteroidal antiinflammatory drugs (NSAIDs) that selectively inhibit cyclooxygenase-2 (COX-2), are effective against pain and inflammation and appear to have less gastrointestinal toxicity than conventional NSAIDs. Their COX-2 selectivity, however, has raised concerns regarding their cardiovascular safety, since they do not inhibit COX-1, the isoform of the enzyme that is active in thrombosis and vasoconstriction. At this point there is no conclusive evidence that COX-2 inhibitors cause ischemic vascular events, because retrospective post hoc analyses conflict one another, and no specific randomized trials have yet been done. Renal effects, edema and hypertension appear to be similar between conventional NSAIDs and COX-2-selective inhibitors. Aspirin is still required for patients with cardiovascular risk who are prescribed a COX-2-selective inhibitor. PMID:14649387

Fowles, Robert E

2003-01-01

113

Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition.  

PubMed

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

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

2010-03-23

114

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

E-print Network

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

Parzen, Michael

115

Prognostic impact of COX-2 in non-small cell lung cancer: A comprehensive compartment-specific evaluation of tumor and stromal cell expression.  

PubMed

Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n?=?1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n?=?616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC. PMID:25449785

Mattsson, Johanna S M; Bergman, Bengt; Grinberg, Marianna; Edlund, Karolina; Marincevic, Millaray; Jirström, Karin; Pontén, Fredrik; Hengstler, Jan G; Rahnenführer, Jörg; Karlsson, Mats G; Karlsson, Christina; Helenius, Gisela; Botling, Johan; Micke, Patrick; Gulyas, Miklos

2015-01-28

116

Diarylheterocycle core ring features effect in selective COX-1 inhibition.  

PubMed

The COX-1 isoenzyme plays a significant role in a variety of diseases, as it catalyzes the bioprocesses behind many health problems. Among the diarylheterocycle class of COX inhibitors, the isoxazole ring has been widely used as a central heterocycle for the preparation of potent and selective COX-1 inhibitors such as P6 [3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole]. The role of the isoxazole nucleus in COX-1 inhibitor selectivity has been clarified by preparing a set of new diarylheterocycles with various heterocycle cores. Replacement of isoxazole with isothiazole or pyrazole gave a drastic decrease in COX-1 inhibitory activity, whereas the introduction of an electron-donating group (EDG) on the N-aryl pyrazole allowed recovery of COX-1 inhibitory activity and selectivity. The EDG-equipped 5-(furan-2-yl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (17) selectively inhibits COX-1 activity (IC(50) =3.4 ?M; 28% COX-2 inhibition at 50 ?M), in contrast to its inactive analogue, 3-(furan-2-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole, which does not bear the methoxy EDG. Molecular docking studies of compound 17 into the binding site of COX-1 shed light on its binding mode. PMID:22278975

Perrone, Maria Grazia; Vitale, Paola; Malerba, Paola; Altomare, Angela; Rizzi, Rosanna; Lavecchia, Antonio; Di Giovanni, Carmen; Novellino, Ettore; Scilimati, Antonio

2012-04-01

117

Explorations in statistics: regression  

NSDL National Science Digital Library

This article explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive connection. Regression helps us answer three questions: does some variable Y depend on another variable X; if so, what is the nature of the relationship between Y and X; and for some value of X, what value of Y do we predict? Residual plots are an essential component of a thorough regression analysis: they help us decide if our statistical regression model of the relationship between Y and X is appropriate.

PhD Douglas Curran-Everett (National Jewish Medical and Research Center Div. Biostatistics, Depts. Prev. Med./Biometrics, Physiology/Biophys)

2011-12-01

118

The heme a synthase Cox15 associates with cytochrome c oxidase assembly intermediates during Cox1 maturation.  

PubMed

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

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

2013-10-01

119

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

PubMed Central

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

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

2013-01-01

120

Improved Regression Calibration  

ERIC Educational Resources Information Center

The likelihood for generalized linear models with covariate measurement error cannot in general be expressed in closed form, which makes maximum likelihood estimation taxing. A popular alternative is regression calibration which is computationally efficient at the cost of inconsistent estimation. We propose an improved regression calibration…

Skrondal, Anders; Kuha, Jouni

2012-01-01

121

Exponential possibility regression analysis  

Microsoft Academic Search

This paper aims at giving the application of possibility theory based on exponential distributions to regression analysis. A general outline of the possibility theory is illustrated by exponential possibility distributions. It is shown that possibility analysis is well corresponding to statistical analysis. Using exponential possibility analysis, we propose possibility regression analysis which is suitable for rough phenomena arising from social

H. Tanaka; H. Ishibuchi; S. Yoshikawa

1995-01-01

122

Morse-Smale Regression  

PubMed Central

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.

2012-01-01

123

DISCUSS: Regression and Correlation  

NSDL National Science Digital Library

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

Hunt, Neville; Nicholson, James; Tyrrell, Sidney

2009-04-24

124

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

125

Support Vector Regression for Censored Data (SVRc): A Novel Tool for Survival Analysis  

Microsoft Academic Search

A crucial challenge in predictive modeling for survival analysis is managing censored observations in the data. The Cox proportional hazards model is the standard tool for the analysis of continuous censored survival data. We propose a novel machine learning algorithm, support vector regression for censored data (SVRc) for improved analysis of medical survival data. SVRc leverages the high-dimensional capabilities of

Faisal M. Khan; Valentina Bayer Zubek

2008-01-01

126

Verified computation of a disc containing exactly k roots of a univariate nonlinear function  

NASA Astrophysics Data System (ADS)

It is well known that it is an ill-posed problem to decide whether a function has a multiple root. For example, an arbitrarily small perturbation of a real polynomial may change a double real root into two distinct real or complex roots. In this paper we describe a computational method for the verified computation of a complex disc to contain exactly k roots of a univariate nonlinear function. The function may be given by some program. Computational results using INTLAB, the Matlab toolbox for reliable computing, demonstrate properties and limits of the method.

Rump, Siegfried M.; Oishi, Shin'ichi

127

Alveolate and chlorophycean mitochondrial cox2 genes split twice independently  

Microsoft Academic Search

The mitochondrial gene for COXII is typically encoded in the organelle genome, however in some members of two unrelated groups, Apicomplexa and Chlorophyceae, cox2 is split into two genes, and both are encoded in the nucleus. Rare genomic changes (RGCs) have acquired popularity as phylogenetic markers, and accordingly this rearrangement of cox2 has been used to infer a possible source

Ross F. Waller; Patrick J. Keeling

2006-01-01

128

CURRICULUM VITAE L. Clarke Cox, Ph.D.  

E-print Network

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

Guenther, Frank

129

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. PMID:23077613

Maisel, Tobias; Joseph, Stephanie; Mielke, Thorsten; Bürger, Jörg; Schwarzinger, Stephan; Meyer, Ortwin

2012-01-01

130

Characterization of the univariate and multivariate techniques on the analysis of simulated and fMRI datasets with visual task  

Microsoft Academic Search

Current analytical techniques applied to functional MRI (fMRI) data may be generally divided into two parts: univariate and multivariate techniques. It is therefore our attempt to evaluate and intercompare their respective algorithms on simulated and fMRI visual task data sets. In this study, the two representative univariate approaches, including the correlation and the specified-resolution wavelet analytical methods, and three multivariate

C. L. Chen; T. H. Wu; Y. T. Wu; Y. H. Huang; J. S. Lee

2003-01-01

131

Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro.  

PubMed

The present study was aimed to test the possible cyclooxygenase (COX)-1/COX-2 selectivity of the old analgesic drug phenacetin and its metabolite p-phenetidine, which exhibits high renal toxicity. Paracetamol (acetaminophen), the main metabolite of phenacetin with low renal toxicity, and indomethacin were selected as reference compounds. Collagen-stimulated platelet thromboxane B2 (TxB2) production and phorbol 12-myristate-13-acetate (PMA)-induced neutrophil prostaglandin E2 (PGE2) synthesis were used as indicators for COX-1 and COX-2 activity, respectively. Phenacetin was even less potent than paracetamol to reduce the production of both TxB2 and PGE2, and no clear preference for either of the COX-enzymes was seen. P-phenetidine was a more potent inhibitor, already at nanomolar level, of the synthesis of these prostanoids than indomethacin and showed some preference to COX-2 inhibition. Somewhat higher, micromolar, concentrations of p-phenetidine also reduced COX-2 expression in neutrophils. We suggest that the very potent inhibitory activity of p-phenetidine on PGE2 synthesis combined with the reduction of COX-2 expression could explain the renal papillary necrosis in phenacetin kidney. PMID:14592552

Kankuri, Esko; Solatunturi, Erkka; Vapaatalo, Heikki

2003-06-15

132

Comparing the characteristics of gene expression profiles derived by univariate and multivariate classification methods.  

PubMed

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. PMID:18312212

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

2008-01-01

133

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

NASA Technical Reports Server (NTRS)

Sturm's Theorem is a well-known result in real algebraic geometry that provides a function that computes the number of roots of a univariate polynomial in a semiopen interval. This paper presents a formalization of this theorem in the PVS theorem prover, as well as a decision procedure that checks whether a polynomial is always positive, nonnegative, nonzero, negative, or nonpositive on any input interval. The soundness and completeness of the decision procedure is proven in PVS. The procedure and its correctness properties enable the implementation of a PVS strategy for automatically proving existential and universal univariate polynomial inequalities. Since the decision procedure is formally verified in PVS, the soundness of the strategy depends solely on the internal logic of PVS rather than on an external oracle. The procedure itself uses a combination of Sturm's Theorem, an interval bisection procedure, and the fact that a polynomial with exactly one root in a bounded interval is always nonnegative on that interval if and only if it is nonnegative at both endpoints.

Narkawicz, Anthony J.; Munoz, Cesar A.

2014-01-01

134

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

135

Understanding logistic regression analysis  

PubMed Central

Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed. PMID:24627710

Sperandei, Sandro

2014-01-01

136

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

137

Regression versus No Regression in the Autistic Disorder: Developmental Trajectories  

ERIC Educational Resources Information Center

Developmental regression is a complex phenomenon which occurs in 20-49% of the autistic population. Aim of the study was to assess possible differences in the development of regressed and non-regressed autistic preschoolers. We longitudinally studied 40 autistic children (18 regressed, 22 non-regressed) aged 2-6 years. The following developmental…

Bernabei, P.; Cerquiglini, A.; Cortesi, F.; D' Ardia, C.

2007-01-01

138

Multivariate Regression with Calibration*  

PubMed Central

We propose a new method named calibrated multivariate regression (CMR) for fitting high dimensional multivariate regression models. Compared to existing methods, CMR calibrates the regularization for each regression task with respect to its noise level so that it is simultaneously tuning insensitive and achieves an improved finite-sample performance. Computationally, we develop an efficient smoothed proximal gradient algorithm which has a worst-case iteration complexity O(1/?), where ? is a pre-specified numerical accuracy. Theoretically, we prove that CMR achieves the optimal rate of convergence in parameter estimation. We illustrate the usefulness of CMR by thorough numerical simulations and show that CMR consistently outperforms other high dimensional multivariate regression methods. We also apply CMR on a brain activity prediction problem and find that CMR is as competitive as the handcrafted model created by human experts.

Liu, Han; Wang, Lie; Zhao, Tuo

2014-01-01

139

Reliability and Regression Analysis  

NSDL National Science Digital Library

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

Lane, David M.

2009-02-17

140

Regression analysis with longitudinal measurements  

E-print Network

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.3.Bayesian regression . . . . . . . . . . . . . . . . . . . . . . 9 A. Regression for continuous response . . . . . . . . . . . 9 B. Regression for binary response . . . . . . . . . . . . . 10 2.4.Parametric regression analysis on cardiotoxic... . . . . . . . . . . . . . . . . . . 49 B. Nonparametric regression . . . . . . . . . . . . . . . . 51 5.4.Model diagnostics . . . . . . . . . . . . . . . . . . . . . . . 53 5.5.Simulation study . . . . . . . . . . . . . . . . . . . . . . . 55 5.6.Longitudinal study of cardiotoxicity...

Ryu, Duchwan

2005-08-29

141

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

142

p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-?B complexes  

PubMed Central

Deregulated expression of COX-2 has been causally linked to development, progression, and outcome of several types of human cancer. We describe a novel fundamental level of transcriptional control of COX-2 expression. Using primary human mammary epithelial cells and monocyte/macrophage cell lines, we show that the chromatin boundary/insulator factor CTCF establishes an open chromatin domain and induces expression of a long non-coding RNA within the upstream promoter region of COX-2. Upon induction of COX-2 expression, the lncRNA associates with p50, a repressive subunit of NF-?B, and occludes it from the COX-2 promoter, potentially facilitating interaction with activation-competent NF-?B p65/p50 dimers. This enables recruitment of the p300 histone acetyltransferase, a domain-wide increase in histone acetylation and assembly of RNA Polymerase II initiation complexes. Our findings reveal an unexpected mechanism of gene control by lncRNA-mediated repressor occlusion and identify the COX-2-lncRNA, PACER, as a new potential target for COX-2-modulation in inflammation and cancer. DOI: http://dx.doi.org/10.7554/eLife.01776.001 PMID:24843008

Krawczyk, Michal; Emerson, Beverly M

2014-01-01

143

p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-?B complexes.  

PubMed

Deregulated expression of COX-2 has been causally linked to development, progression, and outcome of several types of human cancer. We describe a novel fundamental level of transcriptional control of COX-2 expression. Using primary human mammary epithelial cells and monocyte/macrophage cell lines, we show that the chromatin boundary/insulator factor CTCF establishes an open chromatin domain and induces expression of a long non-coding RNA within the upstream promoter region of COX-2. Upon induction of COX-2 expression, the lncRNA associates with p50, a repressive subunit of NF-?B, and occludes it from the COX-2 promoter, potentially facilitating interaction with activation-competent NF-?B p65/p50 dimers. This enables recruitment of the p300 histone acetyltransferase, a domain-wide increase in histone acetylation and assembly of RNA Polymerase II initiation complexes. Our findings reveal an unexpected mechanism of gene control by lncRNA-mediated repressor occlusion and identify the COX-2-lncRNA, PACER, as a new potential target for COX-2-modulation in inflammation and cancer.DOI: http://dx.doi.org/10.7554/eLife.01776.001. PMID:24843008

Krawczyk, Michal; Emerson, Beverly M

2014-01-01

144

Mass Univariate Analysis of Event-Related Brain Potentials/Fields II: Simulation Studies  

PubMed Central

Mass univariate analysis is a relatively new approach for the study of ERPs/ERFs. It consists of many statistical tests and one of several powerful corrections for multiple comparisons. Multiple comparison corrections differ in their power and permissiveness. Moreover, some methods are not guaranteed to work or may be overly sensitive to uninteresting deviations from the null hypothesis. Here we report the results of simulations assessing the accuracy, permissiveness, and power of six popular multiple comparison corrections (permutation-based control of the family-wise error rate: FWER, weak control of FWER via cluster-based permutation tests, permutation based control of the generalized FWER, and three false discovery rate control procedures) using realistic ERP data. In addition, we look at the sensitivity of permutation tests to differences in population variance. These results will help researchers apply and interpret these procedures. PMID:21895684

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

2014-01-01

145

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. PMID:22164077

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

2011-01-01

146

Regularized fuzzy clusterwise ridge regression  

Microsoft Academic Search

Fuzzy clusterwise regression has been a useful method for investigating cluster-level heterogeneity of observations based\\u000a on linear regression. This method integrates fuzzy clustering and ordinary least-squares regression, thereby enabling to estimate\\u000a regression coefficients for each cluster and fuzzy cluster memberships of observations simultaneously. In practice, however,\\u000a fuzzy clusterwise regression may suffer from multicollinearity as it builds on ordinary least-squares regression.

Hye Won Suk; Heungsun Hwang

2010-01-01

147

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

PubMed Central

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

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

2014-01-01

148

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

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

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

149

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

150

Practical Session: Logistic Regression  

NASA Astrophysics Data System (ADS)

An exercise is proposed to illustrate the logistic regression. One investigates the different risk factors in the apparition of coronary heart disease. It has been proposed in Chapter 5 of the book of D.G. Kleinbaum and M. Klein, "Logistic Regression", Statistics for Biology and Health, Springer Science Business Media, LLC (2010) and also by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr341.pdf). This example is based on data given in the file evans.txt coming from http://www.sph.emory.edu/dkleinb/logreg3.htm#data.

Clausel, M.; Grégoire, G.

2014-01-01

151

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

152

Molecular dynamics simulations of arachidonic acid complexes with COX-1 and COX-2: insights into equilibrium behavior.  

PubMed

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

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

2006-03-14

153

HIF-1?/COX-2 expression and mouse brain capillary remodeling during prolonged moderate hypoxia and subsequent re-oxygenation.  

PubMed

Dynamic microvascular remodeling maintains an optimal continuous supply of oxygen and nutrients to the brain to account for prolonged environmental variations. The objective of this study was to determine the relative time course of capillary regression during re-oxygenation after exposure to prolonged moderate hypoxia and expression of the primary signaling factors involved in the process. Four-month old male C57BL/6 mice were housed and maintained in a hypobaric chamber at 290 Torr (0.4 atm) for 21 days and allowed to recover at normoxia (room air) for up to 21 days. The mice were either decapitated or perfused in-situ and brain samples collected were either homogenized for Western blot analysis or fixed and embedded in paraffin for immunohistochemistry. Hypoxia inducible factor-1? (HIF-1?), vascular endothelial growth factor (VEGF) and erythropoietin (EPO) expression were increased during hypoxic exposure and diminished during subsequent re-oxygenation. However, cyclooxygenase-2 (COX-2) and angiopoietin-2 (Ang-2) were both elevated during hypoxia as well as subsequent re-oxygenation. Significantly increased capillary density at the end of the 3rd week of hypoxia regressed back toward normoxic baseline as the duration of re-oxygenation continued. In conclusion, elevated COX-2 and Ang-2 expression during hypoxia where angiogenesis occurs and re-oxygenation, when micro-vessels regress, identifies these proteins as vascular remodeling molecules crucial for angioplasticity. PMID:24796880

Benderro, Girriso F; LaManna, Joseph C

2014-06-20

154

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

2013-10-01

155

Multivariate Adaptive Regression Splines  

Microsoft Academic Search

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

Jerome H. Friedman

1991-01-01

156

Mechanisms of neuroblastoma regression.  

PubMed

Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

Brodeur, Garrett M; Bagatell, Rochelle

2014-12-01

157

Mechanisms of neuroblastoma regression  

PubMed Central

Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

Brodeur, Garrett M.; Bagatell, Rochelle

2014-01-01

158

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 connection.…

Curran-Everett, Douglas

2011-01-01

159

Calculating a Stepwise Ridge Regression.  

ERIC Educational Resources Information Center

Although methods for using ordinary least squares regression computer programs to calculate a ridge regression are available, the calculation of a stepwise ridge regression requires a special purpose algorithm and computer program. The correct stepwise ridge regression procedure is given, and a parallel FORTRAN computer program is described.…

Morris, John D.

1986-01-01

160

Prostaglandin-mediated control of rat brain kynurenic acid synthesis--opposite actions by COX-1 and COX-2 isoforms.  

PubMed

Kynurenic acid (KYNA), an endogenous glutamate-receptor antagonist preferentially blocking NMDA-receptors, has analgesic properties and has also been implicated in the pathophysiology of schizophrenia. Recently, the non-steroid anti-inflammatory drug (NSAID) diclofenac was found to increase rat brain KYNA. Here, we analyze whether cyclooxygenase (COX)-1 or COX-2 modulate the levels of rat brain KYNA. The non-selective COX-inhibitor diclofenac (50 mg/kg, i.p.) or indomethacin (50 mg/kg, i.p.), a non-selective inhibitor with a preferential selectivity for COX-1, produced an elevation in brain KYNA. In contrast, the COX-2 selective inhibitors parecoxib (25 mg/kg, i.p.) or meloxicam (5 mg/kg, i.p.) decreased brain KYNA. Both elevation and lowering of brain KYNA by indomethacin or parecoxib, respectively, were prevented by the prostaglandin E1/E2 agonist misoprostol (1 mg/kg, s.c.). It is proposed that increased brain KYNA formation induced by NSAIDs displaying an inhibitory action on COX-1 contribute to their analgesic efficacy as well as to their psychiatric side effects. PMID:15517427

Schwieler, L; Erhardt, S; Erhardt, C; Engberg, G

2005-07-01

161

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

PubMed Central

Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq??(1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods. PMID:25506389

Chu, Ge-Jin; Liang, Yong; Wang, Jia-Xuan

2014-01-01

162

Unified univariate and multivariate random field theory Keith J. Worsley12  

E-print Network

, Francesco Tomaiuolo4 , Jason Lerch2 1 Department of Mathematics and Statistics, and 2 Montreal Neurological: vector deformations to warp an MRI image to an atlas standard, diffusion in several different directions, age, gender, or disease state. The simplest approach is to use a multivariate multiple regression

Worsley, Keith

163

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

164

Sparse partial least squares regression for simultaneous dimension reduction and variable selection  

PubMed Central

Partial least squares regression has been an alternative to ordinary least squares for handling multicollinearity in several areas of scientific research since the 1960s. It has recently gained much attention in the analysis of high dimensional genomic data. We show that known asymptotic consistency of the partial least squares estimator for a univariate response does not hold with the very large p and small n paradigm. We derive a similar result for a multivariate response regression with partial least squares. We then propose a sparse partial least squares formulation which aims simultaneously to achieve good predictive performance and variable selection by producing sparse linear combinations of the original predictors. We provide an efficient implementation of sparse partial least squares regression and compare it with well-known variable selection and dimension reduction approaches via simulation experiments. We illustrate the practical utility of sparse partial least squares regression in a joint analysis of gene expression and genomewide binding data. PMID:20107611

Chun, Hyonho; Kele?, Sündüz

2010-01-01

165

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

PubMed

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

Schnabel, Thomas; Musso, Maurizio; Tondi, Gianluca

2014-01-01

166

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

NASA Astrophysics Data System (ADS)

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

Žilinskas, Antanas; Žilinskas, Julius

2015-04-01

167

Fast Censored Linear Regression  

PubMed Central

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

HUANG, YIJIAN

2013-01-01

168

Performance Assessment of Industrial Linear Controllers in Univariate Control Loops for Both Set Point Tracking and Load  

E-print Network

variance of control errors as performance benchmark for PID controllers. Besides the variance-based indices for stochastic disturbances, there are some performance indices for PID controllers to reject deterministicPerformance Assessment of Industrial Linear Controllers in Univariate Control Loops for Both Set

Wang, Jiandong

169

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

ERIC Educational Resources Information Center

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

Starns, Jeffrey J.; Ratcliff, Roger

2008-01-01

170

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

NASA Astrophysics Data System (ADS)

Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision.

Moustafa, Azza Aziz; Salem, Hesham; Hegazy, Maha; Ali, Omnia

2015-02-01

171

Synthesis, biological evaluation, and docking studies of novel heterocyclic diaryl compounds as selective COX-2 inhibitors.  

PubMed

Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan, 2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring were synthesized and their in vitro inhibitory activities on COX-1 and COX-2 isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan derivative 6b was identified as potent COX inhibitor with selectivity toward COX-1 (COX-1 IC(50)=0.061 microM and COX-2 IC(50)=0.325 microM; selectivity index (SI)=0.19). Among the 1H-pyrazole derivatives, 11b was found to be a potent COX-2 inhibitor, about 38 times more potent than Rofecoxib (COX-2 IC(50)=0.011 microM and 0.398 microM, respectively), but showed no selectivity for COX-2 isoform. Compound 11c demonstrated strong and selective COX-2 inhibitory activity (COX-1 IC(50)=1 microM, COX-2 IC(50)=0.011 microM; SI= approximately 92). Molecular docking studies of compounds 6b and 11b-d into the binding sites of COX-1 and COX-2 allowed to shed light on the binding mode of these novel COX inhibitors. PMID:20692174

Eren, Gökçen; Unlü, Serdar; Nuñez, Maria-Teresa; Labeaga, Luis; Ledo, Francisco; Entrena, Antonio; Bano?lu, Erden; Costantino, Gabriele; Sahin, M Fethi

2010-09-01

172

Orthogonale lineare regression: Stichprobenparameter  

Microsoft Academic Search

Das Problem der othogonalen linearen Regression [1, 2], durch eine Menge vonn PunktenPi (xi,yi) ?R×R eine Ausgleichsgeradeg so zu legen, daß der orthogonale Abstand dieser PunktePi von der Geradeng im quadratischen Mittel minimal wird, kann sehr einfach gelöst werden, wenn man jedem PunktPi die komplexe Zahlzi=xi+jyi zuordnet. Der zugehörige Algorithmus wird in FORTRAN IV angegeben.

U. Kasack

1974-01-01

173

Clinical pharmacology of novel selective COX-2 inhibitors.  

PubMed

Novel coxibs (i.e. etoricoxib, valdecoxib, parecoxib and lumiracoxib) with enhanced biochemical cyclooxygenase (COX)-2 selectivity over that of rofecoxib and celecoxib have been recently developed. They have the potential advantage to spare COX-1 activity, thus reducing gastrointestinal toxicity, even when administered at high doses to improve efficacy. They are characterized by different pharmacodynamic and pharmacokinetics features. The higher biochemical selectivity of valdecoxib than celecoxib, evidenced in vitro, may be clinically relevant leading to an improved gastrointestinal safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib shows only a slightly improved COX-2 selectivity than rofecoxib, a highly selective COX-2 inhibitor that has been reported to halve the incidence of serious gastrointestinal toxicity compared to nonselective nonsteroidal antiinflammatory drugs (NSAIDs). Lumiracoxib, the most selective COX-2 inhibitor in vitro, is the only acidic coxib. The hypothesis that this chemical property may lead to an increased and persistent drug accumulation in inflammatory sites and consequently to an improved clinical efficacy, however, remains to be verified. Several randomized clinical studies suggest that the novel coxibs have comparable efficacy to nonselective NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and acute pain, but they share similar renal side-effects. The apparent dose-dependence of renal toxicity may limit the use of higher doses of the novel coxibs for improved efficacy. Large-size randomized clinical trials are ongoing to define the gastrointestinal and cardiovascular safety of the novel coxibs. PMID:14965322

Tacconelli, S; Capone, M L; Patrignani, P

2004-01-01

174

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

PubMed Central

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

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

2014-01-01

175

Exploring the cyclooxygenase 2 (COX2)/15d-?(12,14)PGJ(2) system in hamster Sertoli cells: regulation by FSH/testosterone and relevance to glucose uptake.  

PubMed

We have previously described a stimulatory effect of testosterone on cyclooxygenase 2 (COX2) expression and prostaglandin (PG) synthesis, and the involvement of PGs in the modulation of testosterone production in Leydig cells of the seasonal breeder Syrian hamster. In this study, we investigated the existence of a COX2/PGs system in hamster Sertoli cells, its regulation by testosterone and FSH, and its effect on glucose uptake. COX2 expression was observed in Sertoli cells of both reproductively active and inactive adult hamsters. Testosterone and the plasma membrane-impermeable testosterone-BSA significantly induced COX2 expression, mitogen activated protein kinases 1/2 (MAPK1/2) phosphorylation and 15d-?(12,14)PGJ(2) production in Sertoli cells purified from photoperiodically regressed hamsters. These actions were abolished by the antiandrogen bicalutamide and by the inhibitor of MAPK kinase (MEK1/2) U0126, suggesting that testosterone exerts its stimulatory effect on COX2/PGs through a non-classical mechanism that involves the presence of androgen receptors and MAPK1/2 activation. FSH also stimulated COX2/PGs via MAPK1/2 phosphorylation. FSH and testosterone stimulate, whereas 15d-?(12,14)PGJ(2) via PPAR? inhibits, [2,6-(3)H]-2-deoxy-d-glucose ([(3)H]-2-DOG) uptake. Meloxicam, a selective COX2 inhibitor, further increases [(3)H]-2-DOG uptake in the presence of FSH or testosterone. Thus, in addition to their positive effect, FSH and testosterone may also exert an indirect negative regulation on glucose uptake which involves the COX2/15d-?(12,14)PGJ(2)/PPAR? system. Overall, these results demonstrate the presence of a COX2/PG system in hamster Sertoli cells which might act as a local modulator of FSH and testosterone actions. PMID:22974512

Matzkin, María Eugenia; Pellizzari, Eliana Herminia; Rossi, Soledad Paola; Calandra, Ricardo Saúl; Cigorraga, Selva Beatriz; Frungieri, Mónica Beatriz

2012-11-01

176

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

PubMed

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

Jiao, Jing; Mikulec, Carol; Ishikawa, Tomo-o; Magyar, Clara; Dumlao, Darren S; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey

2014-06-01

177

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

2010-10-01

178

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. PMID:16519515

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

2008-01-01

179

The effects of the Cox maze procedure on atrial function  

PubMed Central

Objective The effects of the Cox maze procedure on atrial function remain poorly defined. The purpose of this study was to investigate the effects of a modified Cox maze procedure on left and right atrial function in a porcine model. Methods After cardiac magnetic resonance imaging, 6 pigs underwent pericardiotomy (sham group), and 6 pigs underwent a modified Cox maze procedure (maze group) with bipolar radiofrequency ablation. The maze group had preablation and immediate postablation left and right atrial pressure–volume relations measured with conductance catheters. All pigs survived for 30 days. Magnetic resonance imaging was then repeated for both groups, and conductance catheter measurements were repeated for the right atrium in the maze group. Results Both groups had significantly higher left atrial volumes postoperatively. Magnetic resonance imaging–derived reservoir and booster pump functional parameters were reduced postoperatively for both groups, but there was no difference in these parameters between the groups. The maze group had significantly higher reduction in the medial and lateral left atrial wall contraction postoperatively. There was no change in immediate left atrial elastance or in the early and 30-day right atrial elastance after the Cox maze procedure. Although the initial left atrial stiffness increased after ablation, right atrial diastolic stiffness did not change initially or at 30 days. Conclusions Performing a pericardiotomy alone had a significant effect on atrial function that can be quantified by means of magnetic resonance imaging. The effects of the Cox maze procedure on left atrial function could only be detected by analyzing segmental wall motion. Understanding the precise physiologic effects of the Cox maze procedure on atrial function will help in developing less-damaging lesion sets for the surgical treatment of atrial fibrillation. PMID:19026812

Voeller, Rochus K.; Zierer, Andreas; Lall, Shelly C.; Sakamoto, Shun–ichiro; Chang, Nai–Lun; Schuessler, Richard B.; Moon, Marc R.; Damiano, Ralph J.

2010-01-01

180

Support vector interval regression networks for interval regression analysis  

Microsoft Academic Search

In this paper, the support vector interval regression networks (SVIRNs) are proposed for the interval regression analysis. The SVIRNs consist of two radial basis function networks. One network identifies the upper side of data interval, and the other network identifies the lower side of data intervals. Because the support vector regression (SVR) approach is equivalent to solving a linear constrained

Jin-tsong Jeng; Chen-chia Chuang; Shun-feng Su

2003-01-01

181

Female children with autism spectrum disorder: an insight from mass-univariate and pattern classification analyses.  

PubMed

Several studies on structural MRI in children with autism spectrum disorders (ASD) have mainly focused on samples prevailingly consisting of males. Sex differences in brain structure are observable since infancy and therefore caution is required in transferring to females the results obtained for males. The neuroanatomical phenotype of female children with ASD (ASDf) represents indeed a neglected area of research. In this study, we investigated for the first time the anatomic brain structures of a sample entirely composed of ASDf (n=38; 2-7 years of age; mean=53 months; SD=18) with respect to 38 female age and non verbal IQ matched controls, using both mass-univariate and pattern classification approaches. The whole brain volumes of each group were compared using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure, allowing us to build a study-specific template. Significantly more gray matter (GM) was found in the left superior frontal gyrus (SFG) in ASDf subjects compared to controls. The GM segments obtained in the VBM-DARTEL preprocessing are also classified with a support vector machine (SVM), using the leave-pair-out cross-validation protocol. Then, the recursive feature elimination (SVM-RFE) approach allows for the identification of the most discriminating voxels in the GM segments and these prove extremely consistent with the SFG region identified by the VBM analysis. Furthermore, the SVM-RFE map obtained with the most discriminating set of voxels corresponding to the maximum Area Under the Receiver Operating Characteristic Curve (AUC(max)=0.80) highlighted a more complex circuitry of increased cortical volume in ASDf, involving bilaterally the SFG and the right temporo-parietal junction (TPJ). The SFG and TPJ abnormalities may be relevant to the pathophysiology of ASDf, since these structures participate in some core atypical features of autism. PMID:21896334

Calderoni, Sara; Retico, Alessandra; Biagi, Laura; Tancredi, Raffaella; Muratori, Filippo; Tosetti, Michela

2012-01-16

182

Statistical Models Nonlinear Regression I  

E-print Network

mediocrity in hereditary stature". Journal of the Anthropological Institute 15 (1886), 246-263. Sir Francis Galton, 1822-1911 Nonlinear Regression · Parametric regression models general structure · Nonlinear

183

Combining Information from Related Regressions  

E-print Network

Combining Information from Related Regressions Francesca Dominici, Giovanni Parmigiani, Kenneth H for combining information from several regression studies, each considering only a subset of the variables of interest. Our approach uses a combination of Bayesian hierarchical modeling and data augmentation

West, Mike

184

Dual, but not selective, COX-1 and COX-2 inhibitors, attenuate acetic acid-evoked bladder irritation in the anaesthetised female cat.  

PubMed

Non-selective cyclooxygenase (COX) inhibitors exert effects on lower urinary tract function in several species. The exact contributions of COX-1 and COX-2 isozymes have not been studied much. The present studies investigated the effects of non- and selective COX inhibitors on bladder irritation in the cat.Chloralose-anaesthetised female cats were catheterised through the bladder dome for cystometric evaluation of bladder responses to intravesical infusion of saline or acetic acid. Bladder capacity, voiding efficiency, threshold pressure, and reflex-evoked bladder contraction amplitude and duration were measured. The cat COX selectivity of the doses of inhibitors examined was determined using an in vitro whole-blood assay and analysis of plasma levels. Pretreatment with indomethacin or ketoprofen (non-selective COX inhibitors; 0.3 mg kg(-1) i.v.) inhibited acetic acid-evoked irritation (characterised by a decrease in bladder capacity in vehicle pretreated animals). FR-122047 (selective COX-1 inhibitor), NS-398 and nimesulide (selective COX-2 inhibitors; 1 and 3 mg kg(-1) i.v.) had no effects on bladder irritation. Analysis of plasma levels of the doses examined and determination of COX-1 and COX-2 inhibition in cat whole blood confirmed the reported selectivity of these compounds in this species. The present studies suggest that dual COX inhibition is required to attenuate acetic acid-evoked bladder irritation in the cat. PMID:16547526

Wibberley, Alexandra; McCafferty, Gerald P; Evans, Christopher; Edwards, Richard M; Hieble, J Paul

2006-05-01

185

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

PubMed Central

Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE?/?/COX-2?/? mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE?/?/COX-2?/? mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs. PMID:24887395

Kirkby, Nicholas S.; Lundberg, Martina H.; Wright, William R.; Warner, Timothy D.; Paul-Clark, Mark J.; Mitchell, Jane A.

2014-01-01

186

Computational methods for local regression  

Microsoft Academic Search

Local regression is a nonparametric method in which the regression surface is estimated by fitting parametric functions locally in the space of the predictors using weighted least squares in a moving fashion similar to the way that a time series is smoothed by moving averages. Three computational methods for local regression are presented. First, fast surface fitting and evaluation is

William S. Cleveland; E. Grosse

1991-01-01

187

Two-step Regression Quantiles  

Microsoft Academic Search

We propose a new version of the regression ?-quantile in the linear regression model, ordering the residuals with respect to an initial R-estimate of the slope parameter. In this way we obtain a consistent estimator of (?0 + F ?1(?) ,? 1 ,...,? p)? , asymptotically equivalent to the regression ?-quantile of Koenker and Bassett. The result is extended to

Jana Jureckova

188

Regularized matrix regression  

PubMed Central

Summary Modern technologies are producing a wealth of data with complex structures. For instance, in two-dimensional digital imaging, flow cytometry and electroencephalography, matrix-type covariates frequently arise when measurements are obtained for each combination of two underlying variables. To address scientific questions arising from those data, new regression methods that take matrices as covariates are needed, and sparsity or other forms of regularization are crucial owing to the ultrahigh dimensionality and complex structure of the matrix data. The popular lasso and related regularization methods hinge on the sparsity of the true signal in terms of the number of its non-zero coefficients. However, for the matrix data, the true signal is often of, or can be well approximated by, a low rank structure. As such, the sparsity is frequently in the form of low rank of the matrix parameters, which may seriously violate the assumption of the classical lasso. We propose a class of regularized matrix regression methods based on spectral regularization. A highly efficient and scalable estimation algorithm is developed, and a degrees-of-freedom formula is derived to facilitate model selection along the regularization path. Superior performance of the method proposed is demonstrated on both synthetic and real examples. PMID:24648830

Zhou, Hua; Li, Lexin

2014-01-01

189

In vivo endothelial interaction between ACE and COX inhibitors.  

PubMed

Here we studied the mechanism of thrombolytic response (THR) induced by angiotensin converting enzyme (ACE-I) in vivo in anaesthetised Wistar rats with extracorporeal circulation. Intravenous injections of ACE-Is, i.e. perindopril or quinapril at non-hypotensive doses of 3-30 microg kg(-1) produced a dose-dependent thrombolysis that was associated with a parallel rise in arterial blood levels of 6-keto-PGF(1 alpha), but not those of TXB(2) or PGE(2). L-NAME at a dose of 5 mg kg(-1) affected significantly neither ACE-I-induced thrombolysis nor prostacyclinemia; however, the pre-treatment with icatibant (0.1-0.5 mg kg(-1)) abolished both effects. The selective COX-1 inhibitor, SC 560 (100-300 microg kg(-1) i.v.), or a would be selective COX-3 inhibitor--paracetamol (acetaminophen, 1-3 mg kg(-1)), both agents induced a transient thrombolysis and slightly potentiated thrombolysis by ACE-Is. In contrast, selective COX-2 inhibitors (rofecoxib>celecoxib>nimesulide>NS 398) were thrombogenic, and abolished THR and rise in 6-keto-PGF(1 alpha) induced by ACE-Is. Summing up, in our in vivo bioassay system ACE-Is such as quinapril, perindopril or captopril at non-hypotensive doses evoke THR that is mediated by endogenous bradykinin and prostacyclin derived from endothelial COX-2. PMID:15626595

Gryglewski, R J; Chlopicki, S; Swies, J

2005-02-01

190

English, Media, and Information in the Post-Cox Era.  

ERIC Educational Resources Information Center

This paper discusses the Cox Committee for English (England) proposals and suggests some theoretical and practical approaches to teaching about the exchange of information through a media education perspective, especially news reporting. Findings are based on research into approaches to media education presented in a series of broadcast radio…

Hart, Andrew

191

PREVALENCE OF GENERALIZED LAVER DIAMOND SEAN D. COX  

E-print Network

PREVALENCE OF GENERALIZED LAVER DIAMOND SEAN D. COX Abstract. Viale [15] introduced the notion() is quite prevalent in models of set theory; in particular: (1) L satisfies + Lav() whenever is a successor with the weaker and its 2-cardinal variants--that the principle Lav() is quite prevalent in models of set theory

192

Fuzzy Hexagonal Automata and Snowflakes Angela M. Coxe  

E-print Network

Fuzzy Hexagonal Automata and Snowflakes Angela M. Coxe Lafayette College, Box 8916, Easton, PA There is a common perception that snowflakes are 6-sided and a common quip that "no two snowflakes are alike". The 6 of snowflakes. Introduction As early as 1611 Kepler wrote about the mystery of the six-symmetry of snowflakes

Reiter, Clifford A.

193

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

E-print Network

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

Grissino-Mayer, Henri D.

194

Enhanced ID Pit Sizing Using Multivariate Regression Algorithm  

NASA Astrophysics Data System (ADS)

EPRI is funding a program to enhance and improve the reliability of inside diameter (ID) pit sizing for balance-of plant heat exchangers, such as condensers and component cooling water heat exchangers. More traditional approaches to ID pit sizing involve the use of frequency-specific amplitude or phase angles. The enhanced multivariate regression algorithm for ID pit depth sizing incorporates three simultaneous input parameters of frequency, amplitude, and phase angle. A set of calibration data sets consisting of machined pits of various rounded and elongated shapes and depths was acquired in the frequency range of 100 kHz to 1 MHz for stainless steel tubing having nominal wall thickness of 0.028 inch. To add noise to the acquired data set, each test sample was rotated and test data acquired at 3, 6, 9, and 12 o'clock positions. The ID pit depths were estimated using a second order and fourth order regression functions by relying on normalized amplitude and phase angle information from multiple frequencies. Due to unique damage morphology associated with the microbiologically-influenced ID pits, it was necessary to modify the elongated calibration standard-based algorithms by relying on the algorithm developed solely from the destructive sectioning results. This paper presents the use of transformed multivariate regression algorithm to estimate ID pit depths and compare the results with the traditional univariate phase angle analysis. Both estimates were then compared with the destructive sectioning results.

Krzywosz, Kenji

2007-03-01

195

Stochastic modelling of temperatures affecting the in situ performance of a solar-assisted heat pump: The univariate approach  

Microsoft Academic Search

Univariate stochastic modeling, using Box-Jenkins methods, is carried out for three air temperatures which can influence the performance of a solar-assisted heat pump system. In this system, external ambient air (the low grade source) is pre-heated by the conventional tiled roof of an occupied domestic residence. The air then crosses the evaporator of an electrically driven split heat pump which

D. L. Loveday; C. Craggs

1992-01-01

196

EGF receptor and COX-1/COX-2 enzyme proteins as related to corresponding mRNAs in human per-operative biopsies of colorectal cancer  

PubMed Central

Background Cyclooxygenase (COX) and epidermal growth factor receptor (EGFR) activities promote progression of colorectal cancer. Combined treatment against these targets has not been more effective than single treatments alone. Therefore, our aim was to analyze relationships between COX and EGFR in peroperative colorectal tumor biopsies. Method Tumor and colon mucosa tissue were collected at primary intended curative operations in patients according to well-recognized statistical distributions of tumor stages in colorectal cancer. COX-1, COX-2 and EGFR content in tumor and colon mucosa tissue were quantified by western blot and Q-PCR. Results COX-2 protein appeared as two bands, one at 66 kDa in almost all tumor and mucosa samples and one at 74 kDa in 73% of the tumors and in 23% of the mucosa samples. Tumor COX-2 mRNA was not different from the content in mucosa samples, while COX-2 protein was increased in tumor tissue (p < 0.0003). A correlation between 74 kDa COX-2 protein and COX-2 mRNA occurred in tumor tissue, with significantly increasing COX-2 mRNA across tumor stages. EGFR mRNA content was lower in tumor tissue (p < 0.0001), while EGFR protein was similar in tumor and mucosa samples. COX-2 and EGFR proteins showed a positive correlation in mucosa, while a negative correlation occurred in tumor tissue. Tumor tissue with high COX-2 74 kDa protein lacked EGFR protein. Conclusion Our present results are compatible with the theory that COX-2 and EGFR signalling pathways are inversely related in colorectal cancer tissue. This may explain why combinatorial clinical treatments have been less rewarding. PMID:24171795

2013-01-01

197

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

2008-02-15

198

Mountain C-Regressions in Comparing Fuzzy C-Regressions  

Microsoft Academic Search

In fuzzy clustering, the fuzzy c-mean (FCM) is a most used algorithm. The embedding of FCM into switching regressions, called the fuzzy c-regression (FCR), was proposed by Hathaway and Bezdek in 1993. However, these FCRs always heavily depend on the initial values. In this paper, we propose mountain c-regressions (MCR) to solve the initial-value problem where the MCR is based

Miin-shen Yang; Kuo-lung Wu; June-nan Hsieh

2007-01-01

199

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. PMID:23379851

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

2012-01-01

200

The Bradykinin B2 receptor is required for full expression of renal COX2 and renin  

Microsoft Academic Search

Angiotensin converting enzyme (ACE) inhibition leads to increased levels of bradykinin, cyclooxygenase-2 (COX-2), and renin. Since bradykinin stimulates prostaglandin release, renin synthesis may be regulated through a kinin-COX-2 pathway. To test this hypothesis, we examined the impact of bradykinin B2 receptor (B2R) gene disruption in mice on kidney COX-2 and renin gene expression. Kidney COX-2 mRNA and protein levels were

John D. Imig; Xueying Zhao; Sheyla R. Orengo; Susana Dipp; Samir S. El-Dahr

2003-01-01

201

Hepatic Ischemia and Reperfusion Injury in the Absence of Myeloid Cell-Derived COX-2 in Mice  

PubMed Central

Cyclooxygenase-2 (COX-2) is a mediator of hepatic ischemia and reperfusion injury (IRI). While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2?M/?M) to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2?M/?M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2?M/?M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2?M/?M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2?M/?M and WT mice. COX-2?M/?M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9) expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2?M/?M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s) other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype. PMID:24819536

Duarte, Sergio; Kato, Hiroyuki; Kuriyama, Naohisa; Suko, Kathryn; Ishikawa, Tomo-o; Busuttil, Ronald W.; Herschman, Harvey R.; Coito, Ana J.

2014-01-01

202

RESEARCH ARTICLE Open Access Multiple recent horizontal transfers of the cox1  

E-print Network

has been acquired via some 80 separate plant-to-plant transfer events among 833 diverse angiosperms. Despite strong overall incongruence of cox1 intron phylogeny with angiosperm phylogeny, two that is extended relative to all previously recognized CCTs in angiosperm cox1. Re-examination of all published cox

Olmstead, Richard

203

Linear regression in astronomy. II  

NASA Astrophysics Data System (ADS)

A wide variety of least-squares linear regression procedures used in observational astronomy, particularly investigations of the cosmic distance scale, are presented and discussed. The classes of linear models considered are (1) unweighted regression lines, with bootstrap and jackknife resampling; (2) regression solutions when measurement error, in one or both variables, dominates the scatter; (3) methods to apply a calibration line to new data; (4) truncated regression models, which apply to flux-limited data sets; and (5) censored regression models, which apply when nondetections are present. For the calibration problem we develop two new procedures: a formula for the intercept offset between two parallel data sets, which propagates slope errors from one regression to the other; and a generalization of the Working-Hotelling confidence bands to nonstandard least-squares lines. They can provide improved error analysis for Faber-Jackson, Tully-Fisher, and similar cosmic distance scale relations.

Feigelson, Eric D.; Babu, Gutti J.

1992-09-01

204

Polynomial Regression on Riemannian Manifolds  

E-print Network

In this paper we develop the theory of parametric polynomial regression in Riemannian manifolds and Lie groups. We show application of Riemannian polynomial regression to shape analysis in Kendall shape space. Results are presented, showing the power of polynomial regression on the classic rat skull growth data of Bookstein as well as the analysis of the shape changes associated with aging of the corpus callosum from the OASIS Alzheimer's study.

Hinkle, Jacob; Fletcher, P Thomas; Joshi, Sarang

2012-01-01

205

Mountain c-regressions method  

Microsoft Academic Search

Since Quandt [The estimation of the parameters of a linear regression system obeying two separate regimes, Journal of the American Statistical Association 53 (1958) 873–880] initiated the research on 2-regressions analysis, switching regression had been widely studied and applied in psychology, economics, social science and music perception. In fuzzy clustering, the fuzzy c-means (FCM) is the most commonly used algorithm.

Kuo-lung Wu; Miin-shen Yang; June-nan Hsieh

2010-01-01

206

Celecoxib exhibits the greatest potency amongst cyclooxygenase (COX) inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines.  

PubMed

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 unanticipated findings. Firstly, the antiproliferative effects of celecoxib were noted to be of very similar magnitude for both hematopoietic and epithelial cancer cell lines. Most hematopoietic cell lines had no detectable COX-2 expression by reverse transcription-PCR, and none expressed COX-2 protein. In addition, COX-2-negative epithelial lines were found to have IC50s for celecoxib that were very similar to their COX-2+ counterparts. Thus, important antiproliferative effects were observed that were independent of both the cell lineage and COX-2 status. Secondly, it was also observed that COX-2 inhibitor drugs, celecoxib and rofecoxib, with similar COX-2-selectivity and clinical efficacy for inflammatory indications, differed significantly in their in vitro antiproliferative effects on cancer cell lines. IC50s of 35-65 microM were observed for celecoxib across this entire panel of cell lines. Finally, no difference in the mode or degree of cytotoxicity was apparent between cell lines, because similar levels of apoptosis were observed in COX-2+ and -negative cell lines after treatment with celecoxib, with correspondingly lower levels after rofecoxib treatment. These data are important in that they provide the first direct comparison of epithelial and hematopoietic cancer cell lines, as well as a direct comparison of the in vitro anticancer effects of the two clinically available COX-2 inhibitors. PMID:11929821

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

2002-04-01

207

LC-MS/MS Confirms That COX-1 Drives Vascular Prostacyclin Whilst Gene Expression Pattern Reveals Non-Vascular Sites of COX-2 Expression  

PubMed Central

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.

2013-01-01

208

Inhibition of COX1 activity and COX2 expression by 3-(4?-geranyloxy-3?-methoxyphenyl)-2- trans propenoic acid and its semi-synthetic derivatives  

Microsoft Academic Search

Oxyprenylated naturally occurring cinnamic acids displayed efficient and promising biological activities. Aim of this study was to characterize the effects of 3-(4?-geranyl-3?-methoxy)phenyl-2-trans propenoic acid and its selected semi-synthetic analogues, on COX-2 expression and activity, and on COX-1 activity, in purified systems or in whole cell systems. The anti-inflammatory activity of title compounds (1) was tested as inhibition of COX-2 on

Salvatore Genovese; Massimo Curini; Paolo Gresele; Teresa Corazzi; Francesco Epifano

2011-01-01

209

Error bounds in cascading regressions  

USGS Publications Warehouse

Cascading regressions is a technique for predicting a value of a dependent variable when no paired measurements exist to perform a standard regression analysis. Biases in coefficients of a cascaded-regression line as well as error variance of points about the line are functions of the correlation coefficient between dependent and independent variables. Although this correlation cannot be computed because of the lack of paired data, bounds can be placed on errors through the required properties of the correlation coefficient. The potential meansquared error of a cascaded-regression prediction can be large, as illustrated through an example using geomorphologic data. ?? 1985 Plenum Publishing Corporation.

Karlinger, M.R.; Troutman, B.M.

1985-01-01

210

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

211

Laser-induced breakdown spectroscopy of steel: a comparison of univariate and multivariate calibration methods.  

PubMed

Laser-induced breakdown spectroscopy (LIBS) was carried out on twenty-three low to high alloy steel samples to quantify their concentrations of chromium, nickel, and manganese. LIBS spectral data were correlated to known concentrations of the samples and three calibration methods were compared. A standard LIBS calibration technique using peak area integration normalized by an internal standard was compared to peak area integration normalized by total light and the multivariate statistical technique of partial least squares. For the partial least squares analysis, the PLS-1 algorithm was used, where a predictive model is generated for each element separately. Partial least squares regression coefficients show that the algorithm correctly identifies the atomic emission peaks of interest for each of the elements. Predictive capabilities of each calibration approach were quantified by calculating the standard and relative errors of prediction. The performance of partial least squares is on par with using iron as an internal standard but has the key advantage that it can be applied to samples where the concentrations of all elements are unknown. PMID:20149276

Stipe, Christopher B; Hensley, Brian D; Boersema, Jeffrey L; Buckley, Steven G

2010-02-01

212

Precision Efficacy Analysis for Regression.  

ERIC Educational Resources Information Center

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

Brooks, Gordon P.

213

A general regression neural network  

Microsoft Academic Search

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

Donald F. Specht

1991-01-01

214

Active set support vector regression  

Microsoft Academic Search

This paper presents active set support vector regression (ASVR), a new active set strategy to solve a straightforward reformulation of the standard support vector regression problem. This new algorithm is based on the successful ASVM algorithm for classification problems, and consists of solving a finite number of linear equations with a typically large dimensionality equal to the number of points

David R. Musicant; Alexander Feinberg

2004-01-01

215

Estimation in semiparametric spatial regression  

Microsoft Academic Search

Nonparametric methods have been very popular in the last couple of decades in time series and regression, but no such development has taken place for spatial models. A rather obvious reason for this is the curse of dimensionality. For spatial data on a grid evaluating the conditional mean given its closest neighbors requires a four-dimensional nonparametric regression. In this paper

Jiti Gao; Zudi Lu; Dag Tjøstheim

2006-01-01

216

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

217

Regular spliceosomal introns are invasive in Chlamydomonas reinhardtii: 15 introns in the recently relocated mitochondrial cox2 and cox3 genes.  

PubMed

In the unicellular green alga, Chlamydomonas reinhardtii, cytochrome oxidase subunit 2 (cox2) and 3 (cox3) genes are missing from the mitochondrial genome. We isolated and sequenced a BAC clone that carries the whole cox3 gene and its corresponding cDNA. Almost the entire cox2 gene and its cDNA were also determined. Comparison of the genomic and the corresponding cDNA sequences revealed that the cox3 gene contains as many as nine spliceosomal introns and that cox2 bears six introns. Putative mitochondria targeting signals were predicted at each N terminal of the cox genes. These spliceosomal introns were typical GT-AG-type introns, which are very common not only in Chlamydomonas nuclear genes but also in diverse eukaryotic taxa. We found no particular distinguishing features in the cox introns. Comparative analysis of these genes with the various mitochondrial genes showed that 8 of the 15 introns were interrupting the conserved mature protein coding segments, while the other 7 introns were located in the N-terminal target peptide regions. Phylogenetic analysis of the evolutionary position of C. reinhardtii in Chlorophyta was carried out and the existence of the cox2 and cox3 genes in the mitochondrial genome was superimposed in the tree. This analysis clearly shows that these cox genes were relocated during the evolution of Chlorophyceae. It is apparent that long before the estimated period of relocation of these mitochondrial genes, the cytosol had lost the splicing ability for group II introns. Therefore, at least eight introns located in the mature protein coding region cannot be the direct descendant of group II introns. Here, we conclude that the presence of these introns is due to the invasion of spliceosomal introns, which occurred during the evolution of Chlorophyceae. This finding provides concrete evidence supporting the "intron-late" model, which rests largely on the mobility of spliceosomal introns. PMID:11675593

Watanabe, K I; Ohama, T

2001-01-01

218

The second generation of COX-2 inhibitors: what advantages do the newest offer?  

PubMed

The discovery of two cyclooxygenase (COX)-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prostanoid production, led to the development of new non-steroidal anti-inflammatory drugs (NSAIDs), the selective COX-2 inhibitors, promising minimal NSAID-typical toxicity with full anti-inflammatory efficacy. So far, the strategy of selective COX-2 inhibition has been successful. Selective COX-2 inhibitors have significantly less gastrotoxicity and no effects on platelet aggregation. However, with regard to renal adverse events, selective COX-2 inhibitors do not offer a clinically relevant advantage over non-selective inhibitors. Moreover, concerns over the cardiovascular risk of selective COX-2 inhibitors have recently been raised. The second generation of COX-2 inhibitors with higher COX-2 selectivity was developed with the promise of further reduction of NSAID-typical adverse effects. The leading compounds are valdecoxib, parecoxib, etoricoxib and lumaricoxib. At the present time they have proven efficacy for the treatment of pain and inflammation. Parecoxib as a parenteral, highly selective COX-2 inhibitor has the potential to become the NSAID of choice for treatment of postoperative pain. In clinical trials, valdecoxib, parecoxib, etoricoxib and lumaricoxib have caused no more endoscopic ulcers than placebo. However, to date, no data on the clinically relevant endpoints perforation, symptomatic ulcer and bleeding are available. Furthermore, no definite conclusions on renal and cardiovascular safety are possible. Current evidence points to a marginal, if any, gain of safety compared with the first generation of COX-2 inhibitors. However, trials with the new COX-2 inhibitors offer the chance to address these open questions of highly selective COX-2 inhibition; that is, thrombogenic risk, sodium and water retention, and interference with tissue repair, in particular, healing of mucosal damage. PMID:12487621

Stichtenoth, Dirk O; Frölich, Jürgen C

2003-01-01

219

Practical Session: Simple Linear Regression  

NASA Astrophysics Data System (ADS)

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

Clausel, M.; Grégoire, G.

2014-01-01

220

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

NASA Technical Reports Server (NTRS)

Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for the slope of a regression line. Monte Carlo simulations demonstrate that survival analysis is reliable in determining correlations between luminosities at different bands. Survival analysis is applied to CO emission in infrared galaxies, X-ray emission in radio galaxies, H-alpha emission in cooling cluster cores, and radio emission in Seyfert galaxies.

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

1986-01-01

221

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

NASA Astrophysics Data System (ADS)

Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for the slope of a regression line. Monte Carlo simulations demonstrate that survival analysis is reliable in determining correlations between luminosities at different bands. Survival analysis is applied to CO emission in infrared galaxies, X-ray emission in radio galaxies, H-alpha emission in cooling cluster cores, and radio emission in Seyfert galaxies.

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

1986-07-01

222

Ridge regression. [RIDGE, for backward solution to multiple regression problems and ridge regression solution for full model, in FORTRAN  

Microsoft Academic Search

Ridge Regression is a description of a new multiple regression program. This program provides for a backward solution to multiple regression problems and will give the ridge regression solution for the full model. This document has been designed for users of the ridge regression program.

Iman

1977-01-01

223

Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression.  

PubMed

Cyclooxygenase (COX) inhibitors have suppressive effects on several types of cancer cells including prostate cancer. In this study, we considered the potential COX-inhibitory activity of a unique anti-inflammatory herbal preparation (Zyflamend; New Chapter, Inc., Brattleboro, VT) and analyzed its effects on the human prostate cancer cell line LNCaP. COX inhibitory activity of Zyflamend was determined by a spectrophotometric-based assay using purified ovine COX-1 and COX-2 enzymes. Effects of Zyflamend on LNCaP cell growth and apoptosis in vitro were assessed by cell counting, Western blot detection of poly ADP-ribose polymerase (PARP) cleavage, and measurement of caspase-3 activity in treated and control cell extracts. Western blotting techniques were conducted to determine the effects of this herbal preparation on the expression of the cell signaling proteins, p21, androgen receptor (AR), phospho-protein kinase C (pPKC)(alpha/beta), and phospho (p)Stat3. The phospohorylation status of several signal transduction phosphoproteins was profiled using a high-throughput phosphoprotein screening assay in treated cells and compared to controls. Zyflamend dramatically decreased COX-1 and COX-2 enzymatic activity. Elevated p21 expression coincided with attenuated cell growth following treatment of LNCaP cells with Zyflamend. PARP cleavage fragments were evident, and caspase-3 activity was upregulated over the control indicating the ability of Zyflamend to induce apoptosis of these cells. Androgen receptor expression levels declined by 40%, and decreases were observed in the active forms of Stat3 and PKC(alpha/beta) in Zyflamend-treated LNCaP cells. Zyflamend inhibited both COX-1 and COX-2 enzymatic activities, suppressed cell growth, and induced apoptosis in LNCaP cells. However, our data suggests that the effects are likely due to COX-independent mechanisms potentially involving enhanced expression of p21 and reduced expression of AR, pStat3, and pPKC(alpha/beta). PMID:16201851

Bemis, Debra L; Capodice, Jillian L; Anastasiadis, Aristotelis G; Katz, Aaron E; Buttyan, Ralph

2005-01-01

224

[Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats].  

PubMed

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition. PMID:12136686

Laudanno, O M; Piombo, Gabriela; Cesolari, J A M; Godoy, Alicia; Rocaspana, Adriana; Aramberry, L

2002-05-01

225

Defining the COX inhibitor selectivity of NSAIDs: implications for understanding toxicity.  

PubMed

The hypothesis that the anti-inflammatory activity of NSAIDs derives from COX inhibition is well established. It also underpins the accepted mechanism of the gastrointestinal and renal toxicity of NSAIDs. However, in terms of NSAID-induced cardiovascular toxicity, is COX inhibition then guilty by association? Multiple experimental models of COX-1/COX-2 inhibition have enabled ranking of the relative inhibitory activity of NSAIDs. Inhibition is expressed as an IC(50) value and the index of COX selectivity as the ratio of the IC(50) value for COX-2 and COX-1. These data informed the 'imbalance hypothesis' that the cardiovascular risk of NSAIDs results from an imbalance in the detrimental actions of COX-1-derived thromboxane A(2) and the beneficial actions of COX-2-derived prostacyclin (PGI(2)). Data derived from in vitro models used to generate NSAID IC(50) values are discussed in the context of the difficulties in defining COX selectivity and hence understanding the toxicity of NSAIDs in current clinical use. PMID:22111779

Knights, Kathleen M; Mangoni, Arduino A; Miners, John O

2010-11-01

226

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

PubMed Central

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

2013-01-01

227

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

PubMed

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

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

2014-10-01

228

Bootstrapping a change-point Cox model for survival data  

PubMed Central

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

Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

2014-01-01

229

US Defense Intelligence Agency (DIA) Scoops Cox Report  

NSDL National Science Digital Library

In light of the Final Report of the Select Committee on US National Security and Military/ Commercial Concerns with the People's Republic of China, or the Cox Report, the National Security Archive (NSA), located at George Washington University, has released a Defense Estimative Brief published by the US Defense Intelligence Agency in April 1984. The four-page brief, obtained by the NSA through a Freedom of Information Act request, details Chinese efforts to enhace its nuclear capability through "overt contact with US scientists and technology, and the covert acquisition of US technology."

230

Regression analysis Dependent variable (WMMY)  

E-print Network

;64 65 #12;66 Multiple Linear Regression 67 Example ­ Acid rain in Norwegian lakes Data from a study of the influence of acid rain on Norwegian lakes, made in 1986. Totally 1005 lakes were studied. In this example

Langseth, Helge

231

Linear Regression of BMD Scanners  

NSDL National Science Digital Library

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

Vu Bioengineering Ret Program

232

Abstract Expression Grammar Symbolic Regression  

NASA Astrophysics Data System (ADS)

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

Korns, Michael F.

233

Efficient Structured Support Vector Regression  

Microsoft Academic Search

\\u000a Support Vector Regression (SVR) has been a long standing problem in machine learning, and gains its popularity on various\\u000a computer vision tasks. In this paper, we propose a structured support vector regression framework by extending the max-margin\\u000a principle to incorporate spatial correlations among neighboring pixels. The objective function in our framework considers\\u000a both label information and pairwise features, helping to

Ke Jia; Lei Wang; Nianjun Liu

2010-01-01

234

Basis Selection for Wavelet Regression  

NASA Technical Reports Server (NTRS)

A wavelet basis selection procedure is presented for wavelet regression. Both the basis and the threshold are selected using cross-validation. The method includes the capability of incorporating prior knowledge on the smoothness (or shape of the basis functions) into the basis selection procedure. The results of the method are demonstrated on sampled functions widely used in the wavelet regression literature. The results of the method are contrasted with other published methods.

Wheeler, Kevin R.; Lau, Sonie (Technical Monitor)

1998-01-01

235

Regression Discontinuity Designs in Epidemiology  

PubMed Central

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

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

2014-01-01

236

Clinical features, survival times and COX-1 and COX-2 expression in cats with transitional cell carcinoma of the urinary bladder treated with meloxicam.  

PubMed

Records of 11 cats with transitional cell carcinoma of the urinary bladder, which had been treated with meloxicam, were reviewed for signalment, duration of clinical signs prior to diagnosis, results of diagnostic imaging, whether or not concurrent surgery was performed and survival. Immunohistochemical expression of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) was assessed in the tumours of seven cats. Tumour location varied greatly. The cats had a mean age of 13 years. Three cats had a previous diagnosis of feline idiopathic cystitis of up to 2008 days duration. Ten of the cats showed clinical improvement (reduction of haematuria and/or dysuria), with a mean survival time (MST) of 311 days (range 10-1064); 1-year survival of 50%. All seven bladders assessed for COX staining were COX-1 positive and five were COX-2 positive. The MST for the COX-2-positive cats was 123 days, the MST for the COX-2-negative cases was 375 days. PMID:22408147

Bommer, Nicholas X; Hayes, Alison M; Scase, Timothy J; Gunn-Moore, Danièlle A

2012-08-01

237

Probiotics Regulate the Expression of COX2 in Intestinal Epithelial Cells  

Microsoft Academic Search

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

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

2008-01-01

238

Multiple testing and data adaptive regression: an application to HIV-1 sequence data.  

PubMed

Analysis of viral strand sequence data and viral replication capacity could potentially lead to biological insights regarding the replication ability of HIV-1. Determining specific target codons on the viral strand will facilitate the manufacturing of target-specific antiretrovirals. Various algorithmic and analysis techniques can be applied to this application. In this paper, we apply two techniques to a data set consisting of 317 patients, each with 282 sequenced protease and reverse transcriptase codons. The first application is recently developed multiple testing procedures to find codons which have significant univariate associations with the replication capacity of the virus. A single-step multiple testing procedure (Pollard and van der Laan 2003) method was used to control the family wise error rate (FWER) at the five percent alpha level as well as the application of augmentation multiple testing procedures to control the generalized family wise error (gFWER) or the tail probability of the proportion of false positives (TPPFP). We also applied a data adaptive multiple regression algorithm to obtain a prediction of viral replication capacity based on an entire mutant/non-mutant sequence profile. This is a loss-based, cross-validated Deletion/Substitution/Addition regression algorithm (Sinisi and van der Laan 2004), which builds candidate estimators in the prediction of a univariate outcome by minimizing an empirical risk. These methods are two separate techniques with distinct goals used to analyze this structure of viral data. PMID:16646861

Birkner, Merrill D; Sinisi, Sandra E; van der Laan, Mark J

2005-01-01

239

A proportional hazards regression model with change-points in the baseline function.  

PubMed

In this article, we consider a new regression model for counting processes under a proportional hazards assumption. This model is motivated by the need of understanding the evolution of the booking process of a railway company. The main novelty of the approach consists in assuming that the baseline hazard function is piecewise constant, with unknown times of jump (these times of jump are estimated from the data as model parameters). Hence, the parameters of the model can be separated into two different types: parameters that measure the influence of the covariates, and parameters from a multiple change-point model for the baseline. Cox's semiparametric regression can be seen as a limit case of our model. We develop an iterative procedure to estimate the different parameters, and a test procedure that allows to perform change-point detection in the baseline. Our technique is supported by simulation studies and a real data analysis, which show that our model can be a reasonable alternative to Cox's regression model, particularly in the presence of tied event times. PMID:23054240

Oueslati, Abdullah; Lopez, Olivier

2013-01-01

240

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

PubMed

We present a new SAS macro %pshreg that can be used to fit a proportional subdistribution hazards model for survival data subject to competing risks. Our macro first modifies the input data set appropriately and then applies SAS's standard Cox regression procedure, PROC PHREG, using weights and counting-process style of specifying survival times to the modified data set. The modified data set can also be used to estimate cumulative incidence curves for the event of interest. The application of PROC PHREG has several advantages, e.g., it directly enables the user to apply the Firth correction, which has been proposed as a solution to the problem of undefined (infinite) maximum likelihood estimates in Cox regression, frequently encountered in small sample analyses. Deviation from proportional subdistribution hazards can be detected by both inspecting Schoenfeld-type residuals and testing correlation of these residuals with time, or by including interactions of covariates with functions of time. We illustrate application of these extended methods for competing risk regression using our macro, which is freely available at: http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/statistical-software/pshreg, by means of analysis of a real chronic kidney disease study. We discuss differences in features and capabilities of %pshreg and the recent (January 2014) SAS PROC PHREG implementation of proportional subdistribution hazards modelling. PMID:25572709

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

2015-02-01

241

Selective COX-1 inhibition as a target of theranostic novel diarylisoxazoles.  

PubMed

Cyclooxygenase(COX)-1 role in some diseases is increasingly studied. 3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a highly selective cyclooxygenase-1 inhibitor, was used as a "lead" to design new isoxazoles (2a-m), differently selective towards COX-1. Those isoxazoles might be useful as novel theranostic agents and also to better clarify COX-1 role in the human physiology and diseases. 2a-m were prepared in fair to good yields developing suitable synthetic strategies. They were evaluated in vitro for their COX-inhibitory activity and selectivity. Structure-activity relationship studies of the novel set of diarylisoxazoles allowed to identify new key determinants for COX-1 selectivity, and to uncover compounds appropriate for a deep pharmacokinetic and pharmacodynamic investigation. 3-(5-Chlorofuran-2yl)-4-phenylisoxazol-5-amine (2f) was the most active compound of the series, its inhibitory activity was assessed in purified enzyme (COX-1 IC?? = 1.1 ?M; COX-2 IC?? > 50 ?M) and in the ovarian cancer cell line (OVCAR-3) expressing only COX-1 (IC?? = 0.58 ?M). Furthermore, the high inhibitory potency of 2f was rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-1 binding site. We found critical interactions between the inhibitor and constriction residues R120 and Y355 at the base of the active site, as well as with S530 at the top of the side pocket. PMID:24531199

Vitale, Paola; Perrone, Maria Grazia; Malerba, Paola; Lavecchia, Antonio; Scilimati, Antonio

2014-03-01

242

COX-2 selective inhibitors cardiac toxicity: getting to the heart of the matter.  

PubMed

On September 30, 2004, Merck and Co. voluntary withdrew rofecoxib (Vioxx) from the market due to increased risk of cardiovascular events associated with the drug. This raised some issues. It is unclear whether the cardiac toxicities associated with rofecoxib isare due to its high COX-2 selectivity. Rofecoxib is the most specific COX-2 inhibitor among the first generation of the class, i.e., negligible COX-1 inhibitory effect. In addition to the gastrointestinal side effects, COX-1 inhibition is known to offer cardioprotection. This is one of the main present indications of aspirin-like drugs. It is plausible that the COX-2 inhibition is associated with altered homeostasis that is compensated with the cardioprotection effect of COX-1 inhibition that patients receive either through the less COX-2 selectivity of other NSAIDs or through co-administration of low dose aspirin. In addition, the cardiac toxicity of rofecoxib could be due to its unique chemical structure, its pharmacokinetics and tissue distribution, and/or the presence of toxic metabolites. Nevertheless, one cannot ignore the public need for NSAIDs with less gastrointestinal side effects than the traditional drugs. However, based on some available indirect evidence, and unless more clear-cut data become available, the use of highly COX-2 selective NSAIDs without the use of a suitable COX-1 inhibitor, (e.g., low dose aspirin) may be best avoided. This may be particularly relevant to the chronic use of these drugs. PMID:15576013

Davies, Neal M; Jamali, Fakhreddin

2004-10-29

243

Copper conjugates of nimesulide Schiff bases targeting VEGF, COX and Bcl-2 in pancreatic cancer cells.  

PubMed

Copper conjugates of Schiff base derivatives of nimesulide (1), a well-known cyclooxygenase-2 (COX-2) inhibitor, were synthesized, structurally characterized and evaluated for their COX selectivity indices and cytotoxicities on pancreatic tumor, BxPC-3 (COX-2 positive) and MiaPaCa (COX-2 negative) cell lines. Copper conjugates exhibit distorted square planar geometries as revealed by the single crystal X-ray structure determination of Cu(L1)(2) and show significant growth inhibition in both cell lines (IC50 values 3-26 microM for COX-2 positive and 5-9 microM for COX-2 negative cell line) than the parent nimesulide (35 microM for COX-2 positive and >100 microM for COX-2 negative cell line). The mechanistic pathway for the biological activity involves inhibition of vascular endothelial growth factor (VEGF) and COX inhibition, as well as down regulation of antiapoptotic Bcl-2 and Bcl-(XL) proteins. PMID:17689613

Ambike, Vinita; Adsule, Shreelekha; Ahmed, Fakhara; Wang, Zhiwei; Afrasiabi, Zahra; Sinn, Ekkehard; Sarkar, Fazlul; Padhye, Subhash

2007-10-01

244

5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis  

PubMed Central

Cyclooxygenase-2(COX-2) overexpression promotes inflammation and tumorigenesis. COX-2 expression in response to diverse stimuli is tightly controlled to avoid persistent overexpression. 5-methoxyindole metabolites of L-tryptophan represent a new class of compounds that control COX-2 expression at the transcriptional level. Two of the metabolites, the newly discovered 5-methoxytryptophan (5-MTP, also known as cytoguardin) and N-acetyl 5-methoxytryptamine (melatonin) are the focus of this review. 5-MTP is produced by mesenchymal cells such as fibroblasts via 5-hydroxytryptophan (5-HTP). It inhibits COX-2 transcriptional activation induced by diverse proinflammatory and mitogenic factors. Cancer cells are deficient in cytoguardin production which contributes to COX-2 overexpression. Fibroblast-generated 5-MTP is capable of restoring the control of COX-2 overexpression in cancer cells. 5-MTP blocks cancer cell migration and invasion in vitro and inhibits tumor growth and cancer metastasis in a xenograft model. Melatonin possesses similar COX-2 suppressing and anti-cancer properties albeit at supra-pharmacological concentrations. By contrast, 5-hydroxyindole metabolites of L-tryptophan such as 5-hydroxytryptamine (serotonin), 5-hydroxytryptophol and other serotonin catabolites do not control COX-2 expression. 5-hydroxytryptophan inhibits COX-2 expression through conversion to 5-MTP. The physiological relevance of 5-MTP as an endogenous regulator of inflammation and cancer metastasis remains to be investigated. On the other hand, 5-methoxyindole metabolites of tryptophan are valuable lead compounds for development of new anti-inflammatory drugs and cancer chemoprevention. PMID:24589238

2014-01-01

245

Chapter 2: Mechanistic Aspects of COX-2 Expression in Colorectal Neoplasia  

PubMed Central

The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states and a large amount of evidence has demonstrated constitutive COX-2 expression to be a contributing factor promoting colorectal cancer (CRC). Various genetic, epigenetic, and inflammatory pathways have been identified to be involved in the etiology and development of CRC. Alteration in these pathways can influence COX-2 expression at multiple stages of colon carcinogenesis allowing for elevated prostanoid biosynthesis to occur in the tumor microenvironment. In normal cells, COX-2 expression levels are potently regulated at the post-transcriptional level through various RNA sequence elements present within the mRNA 3?-untranslated region(3?UTR). A conserved AU-rich element(ARE) functions to target COX-2 mRNA for rapid decay and translational inhibition through association with various RNA-binding proteins to influence the fate of COX-2 mRNA. Specific microRNAs bind regions within the COX-2 3?UTR and control COX-2 expression. In this chapter, we discuss novel insights in the mechanisms of altered posttranscriptional regulation of COX-2 in CRC and how this knowledge may be used to develop novel strategies for cancer prevention and treatment. PMID:22893198

Dixon, Dan A.; Blanco, Fernando F.; Bruno, Annalisa; Patrignani, Paola

2012-01-01

246

Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships  

PubMed Central

Non-steroidal anti-inflammatory drugs (NSAIDs) are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though that more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (rofecoxib, celecoxib, valdecoxibetc.) were developed as safer NSAIDs with improved gastric safety profile. However, the recent market removal of some COXIBs such as rofecoxib due to its adverse cardiovascular side effects clearly encourages the researchers to explore and evaluate alternative templates with COX-2 inhibitory activity. Recognition of new avenues for selective COX-2 inhibitors in cancer chemotherapy and neurological diseases such as Parkinson and Alzheimer’s diseases still continues to attract investigations on the development of COX-2 inhibitors. This review highlights the various structural classes of selective COX-2 inhibitors with special emphasis on their structure-activity relationships. PMID:24250402

Zarghi, Afshin; Arfaei, Sara

2011-01-01

247

What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis.  

PubMed

Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI data are analyzed and interpreted. Many studies now report both MVPA results and results from standard univariate voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA results can be sensitive to latent multidimensional representations and processes whereas univariate voxel-wise analysis cannot, one conclusion that is often drawn when MVPA and univariate results differ is that the activation patterns underlying MVPA results contain a multidimensional code. In the current study, we conducted simulations to formally test this assumption. Our findings reveal that MVPA tests are sensitive to the magnitude of voxel-level variability in the effect of a condition within subjects, even when the same linear relationship is coded in all voxels. We also find that MVPA is insensitive to subject-level variability in mean activation across an ROI, which is the primary variance component of interest in many standard univariate tests. Together, these results illustrate that differences between MVPA and univariate tests do not afford conclusions about the nature or dimensionality of the neural code. Instead, targeted tests of the informational content and/or dimensionality of activation patterns are critical for drawing strong conclusions about the representational codes that are indicated by significant MVPA results. PMID:24768930

Davis, Tyler; LaRocque, Karen F; Mumford, Jeanette A; Norman, Kenneth A; Wagner, Anthony D; Poldrack, Russell A

2014-08-15

248

Logistic regression for dichotomized counts.  

PubMed

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

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

2014-05-26

249

Regression Verification Using Impact Summaries  

NASA Technical Reports Server (NTRS)

Regression verification techniques are used to prove equivalence of syntactically similar programs. Checking equivalence of large programs, however, can be computationally expensive. Existing regression verification techniques rely on abstraction and decomposition techniques to reduce the computational effort of checking equivalence of the entire program. These techniques are sound but not complete. In this work, we propose a novel approach to improve scalability of regression verification by classifying the program behaviors generated during symbolic execution as either impacted or unimpacted. Our technique uses a combination of static analysis and symbolic execution to generate summaries of impacted program behaviors. The impact summaries are then checked for equivalence using an o-the-shelf decision procedure. We prove that our approach is both sound and complete for sequential programs, with respect to the depth bound of symbolic execution. Our evaluation on a set of sequential C artifacts shows that reducing the size of the summaries can help reduce the cost of software equivalence checking. Various reduction, abstraction, and compositional techniques have been developed to help scale software verification techniques to industrial-sized systems. Although such techniques have greatly increased the size and complexity of systems that can be checked, analysis of large software systems remains costly. Regression analysis techniques, e.g., regression testing [16], regression model checking [22], and regression verification [19], restrict the scope of the analysis by leveraging the differences between program versions. These techniques are based on the idea that if code is checked early in development, then subsequent versions can be checked against a prior (checked) version, leveraging the results of the previous analysis to reduce analysis cost of the current version. Regression verification addresses the problem of proving equivalence of closely related program versions [19]. These techniques compare two programs with a large degree of syntactic similarity to prove that portions of one program version are equivalent to the other. Regression verification can be used for guaranteeing backward compatibility, and for showing behavioral equivalence in programs with syntactic differences, e.g., when a program is refactored to improve its performance, maintainability, or readability. Existing regression verification techniques leverage similarities between program versions by using abstraction and decomposition techniques to improve scalability of the analysis [10, 12, 19]. The abstractions and decomposition in the these techniques, e.g., summaries of unchanged code [12] or semantically equivalent methods [19], compute an over-approximation of the program behaviors. The equivalence checking results of these techniques are sound but not complete-they may characterize programs as not functionally equivalent when, in fact, they are equivalent. In this work we describe a novel approach that leverages the impact of the differences between two programs for scaling regression verification. We partition program behaviors of each version into (a) behaviors impacted by the changes and (b) behaviors not impacted (unimpacted) by the changes. Only the impacted program behaviors are used during equivalence checking. We then prove that checking equivalence of the impacted program behaviors is equivalent to checking equivalence of all program behaviors for a given depth bound. In this work we use symbolic execution to generate the program behaviors and leverage control- and data-dependence information to facilitate the partitioning of program behaviors. The impacted program behaviors are termed as impact summaries. The dependence analyses that facilitate the generation of the impact summaries, we believe, could be used in conjunction with other abstraction and decomposition based approaches, [10, 12], as a complementary reduction technique. An evaluation of our regression verification technique shows that our approach is capable of leveragin

Backes, John; Person, Suzette J.; Rungta, Neha; Thachuk, Oksana

2013-01-01

250

Interquantile Shrinkage in Regression Models.  

PubMed

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

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

2013-01-01

251

Choquistic Regression: Generalizing Logistic Regression using the Choquet Integral  

E-print Network

of predictive accuracy. Keywords: logistic regression, Choquet integral, monotone classification, attribute) classification [1]. In fact, this method is not only interesting from a statistical point of view, but also quite of cancer, and each model violating this constraint will not be considered as faithful and hence be refused

Hüllermeier, Eyke

252

Bayesian variable selection in regression  

SciTech Connect

This paper is concerned with the selection of subsets of ''predictor'' variables in a linear regression model for the prediction of a ''dependent'' variable. We take a Bayesian approach and assign a probability distribution to the dependent variable through a specification of prior distributions for the unknown parameters in the regression model. The appropriate posterior probabilities are derived for each submodel and methods are proposed for evaluating the family of prior distributions. Examples are given that show the application of the Bayesian methodology. 23 refs., 3 figs.

Mitchell, T.J.; Beauchamp, J.J.

1987-01-01

253

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. PMID:23401543

Araldi, Dionéia; Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Vieira, André Schwambach; Athié, Maria Carolina Pedro; Figueiredo, Jozi Godoy; Duarte, Djane Braz; Tambeli, Claudia Herrera; Ferreira, Sérgio Henrique; Parada, Carlos Amilcar

2013-01-01

254

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

PubMed Central

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

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

2014-01-01

255

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

PubMed

Nepodin and chrysophanol, isolated from Rumex nepalensis roots, showed significant cyclooxygenase (COX) inhibitory activity. To further optimize these lead molecules and study structure activity relationship (SAR), eighteen derivatives of nepodin and nine derivatives of chrysophanol were synthesized and evaluated for COX-1 and COX-2 inhibitory potential. Among the synthesized compounds, four nepodin (1f, 1g, 1h and 1i) and three chrysophanol (2e, 2f and 2h) derivatives displayed more pronounced COX-2 inhibition than their respective lead molecule. Further, compounds 1f, 1g, 2e and 2h exhibited better anti-inflammatory activity than ibuprofen in carrageenan-induced rat paw edema assay. Taking into account the in vitro and in vivo results, molecular docking and in silico prediction of ADMET properties of compounds were carried out respectively. PMID:24763362

Grover, Jagdeep; Kumar, Vivek; Singh, Vikram; Bairwa, Khemraj; Sobhia, M Elizabeth; Jachak, Sanjay M

2014-06-10

256

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

PubMed Central

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

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

2012-01-01

257

L1 penalized estimation in the Cox proportional hazards model.  

PubMed

This article presents a novel algorithm that efficiently computes L(1) penalized (lasso) estimates of parameters in high-dimensional models. The lasso has the property that it simultaneously performs variable selection and shrinkage, which makes it very useful for finding interpretable prediction rules in high-dimensional data. The new algorithm is based on a combination of gradient ascent optimization with the Newton-Raphson algorithm. It is described for a general likelihood function and can be applied in generalized linear models and other models with an L(1) penalty. The algorithm is demonstrated in the Cox proportional hazards model, predicting survival of breast cancer patients using gene expression data, and its performance is compared with competing approaches. An R package, penalized, that implements the method, is available on CRAN. PMID:19937997

Goeman, Jelle J

2010-02-01

258

Developing Stochastic Deep Drainage Surfaces In Cox's Creek Catchment  

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

259

Synthesis and biological evaluation of linear phenylethynylbenzenesulfonamide regioisomers as cyclooxygenase-1/-2 (COX-1/-2) inhibitors.  

PubMed

A group of regioisomeric phenylethynylbenzenesulfonamides possessing a COX-2 SO2NH2 pharmacophore at the para-, meta- or ortho-position of the C-1 phenyl ring, in conjunction with a C-2 substituted-phenyl (H, OMe, OH, Me, F) group, were synthesized and evaluated as inhibitors of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isozymes. The target 1,2-diphenylacetylenes were synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. In vitro COX-1/-2 isozyme inhibition structure-activity data showed that COX-1/-2 inhibition and the COX selectivity index (SI) are sensitive to the regioisomeric placement of the COX-2 SO2NH2 pharmacophore where the COX-2 potency order for the benzenesulfonamide regioisomers was generally meta>para and ortho. Among this group of compounds, the in vitro COX-1/-2 isozyme inhibition studies identified 3-(2-phenylethynyl)benzenesulfonamide (10a) as a COX-2 inhibitor (COX-2 IC50=0.45 microM) with a good COX-2 selectivity (COX-2 SI=70). In contrast, 2-[2-(3-fluorophenyl)ethynyl]benzenesulfonamide (11c) possessing a SO2NH2 COX-2 pharmacophore at the ortho-position of the C-1 phenyl ring exhibited COX-1 inhibition and selectivity (COX-1 IC50=3.6 microM). A molecular modeling study where 10a was docked in the binding site of COX-2 shows that the meta-SO2NH2 COX-2 pharmacophore was inserted inside the COX-2 secondary pocket (Arg513, Phe518, Val523, and His90). Similar docking of 10a within the COX-1 binding site shows that the meta-SO2NH2 pharmacophore is unable to interact with the respective amino acid residues in COX-1 that correspond to those near the secondary pocket in COX-2 due to the presence of the larger Ile523 in COX-1 that replaces Val523 in COX-2. PMID:16635574

Anana, Raymond; Rao, P N Praveen; Chen, Qiao-Hong; Knaus, Edward E

2006-08-01

260

Structure-activity relationship of indomethacin analogues for MRP-1, COX-1 and COX-2 inhibition. identification of novel chemotherapeutic drug resistance modulators.  

PubMed

We report the screening of analogues of indomethacin to investigate the structure-activity relationship (SAR) of indomethacin-mediated multidrug resistance associated protein-1 (MRP-1) inhibition. By examining the activities of compounds with minor variations of the parent structure, we were able to separate MRP-1, glutathione-S-transferase (GST), cyclooxygenase (COX)-1 and COX-2 inhibitory activities. Combination cytotoxicity assays were utilised to identify agents which possess synergistic potential in MRP-1-expressing cell lines. MRP-1 Inside Out Vesicles (IOVs) were utilised to demonstrate the ability of the indomethacin analogues to inhibit the pump directly. Most of the indomethacin analogues active as MRP-1 inhibitors were poor GST inhibitors when compared with the GST-inhibitory activity of indomethacin. Two of the MRP-1 inhibitory analogues were found to have no COX-1 inhibitory activity and low COX-2 inhibitory activity, suggesting potentially reduced clinical toxicity. One MRP-1 inhibitory indomethacin analogue was also found to have low COX-1 inhibitory activity, but significant COX-2 inhibitory activity, making this analogue again interesting in terms of low potential toxicity, but with the possibility of direct inhibitory effects on tumour growth. PMID:12142058

Touhey, S; O'Connor, R; Plunkett, S; Maguire, A; Clynes, M

2002-08-01

261

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

262

Nonlinear regression Gordon K. Smyth  

E-print Network

that the function f satisfies the first-order differential equation f x, q x D cf x, q 5 for some constant c. Physical processes can often be modelled by higher-order differential equations, leading to higher-order of the differential equation. See, for example, [3, Chapter 6] or [9, Chapter 8]. #12;2 Nonlinear regression Another

Smyth, Gordon K.

263

Weighting Regressions by Propensity Scores  

ERIC Educational Resources Information Center

Regressions can be weighted by propensity scores in order to reduce bias. However, weighting is likely to increase random error in the estimates, and to bias the estimated standard errors downward, even when selection mechanisms are well understood. Moreover, in some cases, weighting will increase the bias in estimated causal parameters. If…

Freedman, David A.; Berk, Richard A.

2008-01-01

264

Fuzzy Class Logistic Regression Analysis  

Microsoft Academic Search

Distribution mixtures are used as models to analyze grouped data. The estimation of parameters is an important step for mixture distributions. The latent class model is generally used as the analysis of mixture distributions for discrete data. In this paper, we consider the parameter estimation for a mixture of logistic regression models. We know that the expectation maximization (EM) algorithm

Miin-shen Yang; Hwei-ming Chen

2004-01-01

265

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

266

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

267

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.

268

Precision and Recall for Regression  

Microsoft Academic Search

Cost sensitive prediction is a key task in many real world applications. Most existing research in this area deals with classification problems. This paper addresses a related regression problem: the prediction of rare extreme values of a continuous variable. These values are often regarded as outliers and removed from posterior analysis. However, for many applications (e.g. in finance, meteorology, biology,

Luis Torgo; Rita Ribeiro

2009-01-01

269

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

270

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

PubMed

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

Blobaum, Anna L; Uddin, Md Jashim; Felts, Andrew S; Crews, Brenda C; Rouzer, Carol A; Marnett, Lawrence J

2013-05-01

271

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

272

Non-COX-2 targets and cancer: Expanding the molecular target repertoire of chemoprevention  

Microsoft Academic Search

Chemoprevention represents a highly promising approach for the control of cancer. That nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other cancers has led to novel approaches to cancer prevention. The known inhibitory effect of NSAIDs on the eicosanoid pathway prompted mechanistic and drug development work focusing on cyclooxygenase (COX), culminating in clinical trials of cyclooxygenase 2 (COX-2) inhibitors for cancer

Khosrow Kashfi; Basil Rigas

2005-01-01

273

Mutations in COX7B Cause Microphthalmia with Linear Skin Lesions, an Unconventional Mitochondrial Disease  

PubMed Central

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

2012-01-01

274

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

275

Interval regression by tolerance analysis approach  

Microsoft Academic Search

In interval linear regression analysis, we are given crisp or interval data and we are to determine appropriate interval regression parameters. There are various methods for interval regression; many of them possess the property that while some of the resulting interval regression parameters are very wide, the other parameters are crisp. This drawback is the main limiting factor for such

Milan Hladík; Michal ?erný

276

Identification of COX inhibitors in the hexane extract of Japanese horse chestnut (Aesculus turbinata) seeds.  

PubMed

Japanese horse chestnut (Aesculus turbinata) seed extract inhibits the activity of cyclooxygenase (COX), but its active constituents have not been identified. In the present study, COX inhibitors were isolated from the hexane extract of this seed by means of 4 steps of liquid chromatography and were identified by gas chromatography/mass spectrometry and nuclear magnetic resonance. The COX inhibitors in the extract of Japanese horse chestnut seeds were identified as linoleic acid, linolenic acid, and oleic acid. Their efficacies were in the following order: linolenic acid = linoleic acid > oleic acid. These active constituents are C18 unsaturated fatty acids; stearic acid, a C18 saturated fatty acid, had no activity. Linolenic acid and linoleic acid had high selectivity toward COX-2 (selectivity index = 10), whereas oleic acid had no selectivity. Considering the efficacy and yield of each fatty acid, linoleic acid may be the principal COX inhibitor in this seed. PMID:17675801

Sato, Itaru; Kofujita, Hisayoshi; Tsuda, Shuji

2007-07-01

277

Synthesis, biological activity and molecular modeling studies of novel COX-1 inhibitors.  

PubMed

Synthesis of new potential COX-1 and/or COX-2 inhibitors, derivatives of 1,1-di-(3-carboxyphenyl)ethane, their biological activity, docking results on COX-1 enzyme and absorption, distribution, metabolism, excretion (ADME) properties are presented. In addition to known interactions between ketoprofen and ibuprofen, leading NSAID agents and COX-1 active site, the possibility of formation of additional interactions is explored. Interactions with Ala527, and with one of the water molecules situated within the active site are identified. Molecular mechanics and DFT calculations for studied compounds have revealed free rotation around two central bonds (C1-C3' and C1-C3"), making them flexible, thus easier to enter and adjust to the active site. Further modifications of core structure have been undertaken to optimize biological activity and ADME properties. As a result, two of the compounds are indicated as novel COX-1 inhibitors. PMID:14987823

Marti?, Miljen; Tati?, Iva; Markovi?, Stribor; Kujundzi?, Nedjeljko; Kostrun, Sanja

2004-02-01

278

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. PMID:22308015

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

2012-01-01

279

Cox-2 inhibitory effects of naturally occurring and modified fatty acids.  

PubMed

In the search for new cyclooxygenase-2 (COX-2) selective inhibitors, the inhibitory effects of naturally occurring fatty acids and some of their structural derivatives on COX-2-catalyzed prostaglandin biosynthesis were investigated. Among these fatty acids, linoleic acid (LA), alpha-linolenic acid (alpha-LNA), myristic acid, and palmitic acid were isolated from a CH(2)Cl(2) extract of the plant Plantago major by bioassay-guided fractionation. Inhibitory effects of other natural, structurally related fatty acids were also investigated: stearic acid, oleic acid, pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Further, the inhibitory effects of these compounds on COX-2- and COX-1-catalyzed prostaglandin biosynthesis was compared with the inhibition of some synthesized analogues of EPA and DHA with ether or thioether functions. The most potent COX-2-catalyzed prostaglandin biosynthesis inhibitor was all-(Z)-5-thia-8,11,14,17-eicosatetraenoic acid (2), followed by EPA, DHA, alpha-LNA, LA, (7E,11Z,14Z,17Z)-5-thiaeicosa-7,11,14,17-tetraenoic acid, all-(Z)-3-thia-6,9,12,15-octadecatetraenoic acid, and (5E,9Z,12Z,15Z,18Z)-3-oxaheneicosa-5,9,12,15,18-pentaenoic acid, with IC(50) values ranging from 3.9 to180 microM. The modified compound 2 and alpha-LNA were most selective toward COX-2, with COX-2/COX-1 ratios of 0.2 and 0.1, respectively. This study shows that several of the natural fatty acids as well as all of the semisynthetic thioether-containing fatty acids inhibited COX-2-catalyzed prostaglandin biosynthesis, where alpha-LNA and compound 2 showed selectivity toward COX-2. PMID:11421736

Ringbom, T; Huss, U; Stenholm, A; Flock, S; Skattebøl, L; Perera, P; Bohlin, L

2001-06-01

280

Binary data regression: Weibull distribution  

NASA Astrophysics Data System (ADS)

The problem of estimation in binary response data has receivied a great number of alternative statistical solutions. Generalized linear models allow for a wide range of statistical models for regression data. The most used model is the logistic regression, see Hosmer et al. [6]. However, as Chen et al. [5] mentions, when the probability of a given binary response approaches 0 at a different rate than it approaches 1, symmetric linkages are inappropriate. A class of models based on Weibull distribution indexed by three parameters is introduced here. Maximum likelihood methods are employed to estimate the parameters. The objective of the present paper is to show a solution for the estimation problem under the Weibull model. An example showing the quality of the model is illustrated by comparing it with the alternative probit and logit models.

Caron, Renault; Polpo, Adriano

2009-12-01

281

Average linear least squares regression  

Microsoft Academic Search

Summary We describe an algorithm and a corresponding FORTRAN subroutine for finding a regression vectorx withn components such that\\u000a$$F(x) = \\\\sum\\\\limits_{i = 1}^s {w_i \\\\left\\\\| {A_i x - b_i } \\\\right\\\\|}$$\\u000a is minimized, where ?.? denotes the Euclidean norm,Wi>0,Ai are design matrices withmi rows andn columns, andbi are observation vectors withmi components (i=1,...,s).

H. Späth; F. R. Germany

1986-01-01

282

Logistic Regression Longitudinal Data Analysis  

E-print Network

the other predictors fixed. 2 ej represents the odds ratio associated with a unit change in xj , holding The above logistic regression model can be rewritten in terms of odds ratio as, p(x) 1 - p(x) = e0+1x = e0 (e1 )x . e0 is the odds of success when x = 0. For a unit change in x, the odds of success changes

Bardsley, John

283

Clinical use and pharmacological properties of selective COX-2 inhibitors.  

PubMed

Selective COX-2 inhibitors (coxibs) are approved for the relief of acute pain and symptoms of chronic inflammatory conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). They have similar pharmacological properties but a slightly improved gastrointestinal (GI) safety profile if compared to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, long-term use of coxibs can be associated with an increased risk for cardiovascular (CV) adverse events (AEs). For this reason, two coxibs were withdrawn from the market. Currently celecoxib, etoricoxib, and lumiracoxib are used. These three coxibs differ in their chemical structure and selectivity for COX-2, which might explain some of their pharmacological features. Following oral administration, the less lipophilic celecoxib has a lower bioavailability (20-40%) than the other two coxibs (74-100%). All are eliminated by hepatic metabolism involving mainly CYP2C9 (celecoxib, lumiracoxib) and CYP3A4 (etoricoxib). Elimination half-life varies from 5 to 8 h (lumiracoxib), 11 to 16 h (celecoxib) and 19 to 32 h (etoricoxib). In patients with liver disease, plasma levels of celecoxib and etoricoxib are increased about two-fold. Clinical efficacies of the coxibs are comparable to tNSAIDs. There is an ongoing discussion about whether the slightly better GI tolerability (which is lost if acetylsalicylic acid is coadministered) of the coxibs is offset by their elevated risks for CV AEs (also seen with tNSAIDs other than naproxen), which apparently increase with dose and duration of exposure. In addition, the higher costs for coxibs (if compared to tNSAIDs, even when a "gastroprotective" proton pump inhibitor is coadministered) should be taken into consideration, if a coxib will be selected for certain patients with a high risk for GI complications. For such treatment, the lowest effective dose should be used for a limited time. Monitoring of kidney function and blood pressure appears advisable. It is hoped that further controlled studies can better define the therapeutic place of the coxibs. PMID:17999057

Shi, Shaojun; Klotz, Ulrich

2008-03-01

284

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

2009-08-01

285

N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation.  

PubMed

A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R'=H, CH(2)Ph, COPh) substituent in conjunction with a C-3 -C=HN-C(6)H(4)-4-X (X=F, Me, CF(3), Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R(1)=CH(2)Ph, X=F), 17 (R(1)=CH(2)Ph, X=CF(3)), 18 (R(1)=COPh, X=F) and 20 (R(1)=COPh, X=CF(3)) were identified as effective and selective COX-2 inhibitors (COX-2 IC(50)'s=0.32-0.84 ?M range; COX-2 selectivity index (SI)=113 to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20) emerged as the most potent (COX-1 IC(50) >100 ?M; COX-2 IC(50)=0.32 ?M) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC(50)=0.13 ?M; COX-2 IC(50)=6.9 ?M, COX-2 SI=0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF(3) substituent attached to the CN spacer is positioned near the secondary pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded (N···NH=2.85 Å) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387. PMID:22361134

Kaur, Jatinder; Bhardwaj, Atul; Huang, Zhangjian; Knaus, Edward E

2012-03-15

286

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

NASA Technical Reports Server (NTRS)

Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.

Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.

1996-01-01

287

Extension of Cox Proportional Hazard Model for Estimation of Interrelated Age-Period-Cohort Effects on Cancer Survival  

PubMed Central

In the frame of the Cox proportional hazard (PH) model, a novel two-step procedure for estimating age-period-cohort (APC) effects on the hazard function of death from cancer was developed. In the first step, the procedure estimates the influence of joint APC effects on the hazard function, using Cox PH regression procedures from a standard software package. In the second step, the coefficients for age at diagnosis, time period and birth cohort effects are estimated. To solve the identifiability problem that arises in estimating these coefficients, an assumption that neighboring birth cohorts almost equally affect the hazard function was utilized. Using an anchoring technique, simple procedures for obtaining estimates of interrelated age at diagnosis, time period and birth cohort effect coefficients were developed. As a proof-of-concept these procedures were used to analyze survival data, collected in the SEER database, on white men and women diagnosed with LC in 1975–1999 and the age at diagnosis, time period and birth cohort effect coefficients were estimated. The PH assumption was evaluated by a graphical approach using log-log plots. Analysis of trends of these coefficients suggests that the hazard of death from LC for a given time from cancer diagnosis: (i) decreases between 1975 and 1999; (ii) increases with increasing the age at diagnosis; and (iii) depends upon birth cohort effects. The proposed computing procedure can be used for estimating joint APC effects, as well as interrelated age at diagnosis, time period and birth cohort effects in survival analysis of different types of cancer. PMID:21552491

Mdzinarishvili, Tengiz; Gleason, Michael X.; Kinarsky, Leo; Sherman, Simon

2011-01-01

288

Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and mononuclear cells by NSAIDS and Cox 2 inhibitors  

Microsoft Academic Search

A range of NSAIDs and reported Cox 2 selective compounds were tested in human freshly isolated platelets and LPS-stimulated mononuclear cells to determine their potency and selectivity as inhibitors of constitutive (presumably Cox 1) and inducible (presumably Cox 2) cyclooxygenase respectively. All compounds tested were either equipotent at inhibiting constitutive and inducible cyclooxygenase or were selective for the inducible form.

C. J. Grossman; J. Wiseman; F. S. Lucas; M. A. Trevethick; P. J. Birch

1995-01-01

289

COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model.  

PubMed

Cyclooxygenases (COXs) are involved in choroidal neovascularization (CNV). However, the relative contribution of COX-1 and -2 to CNV has not been determined. In this study, the expression of COX-2 was investigated in CNVs in a murine laser-induced model. Subsequently, we found that experimental CNV expressed COX-2, most remarkably around the highly vascularized lesions. To examine the effect of COX-2 inhibition on CNV, etodolac, a non-steroidal anti-inflammatory drug with a high COX-2 selectivity, was tested on murine CNV model. The results demonstrated that the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared to the control eyes following etodolac administration. The area of CNV lesions, as examined using histological sections and choroidal flatmounts at day 7, demonstrated that the average size of the CNV lesions was significantly reduced in the etodolac-treated eyes compared to the control eyes. Together, our results demonstrated that selective COX-2 inhibition suppresses CNV. PMID:15530415

Takahashi, Hidenori; Yanagi, Yasuo; Tamaki, Yasuhiro; Uchida, Saiko; Muranaka, Kimimasa

2004-12-10

290

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

PubMed Central

In a previous study, we found that intracerebral administration of excitotoxin (RS)-(tetrazole-5yl) glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox). In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2) in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection. PMID:24971026

An, Ying; Belevych, Natalya; Wang, Yufen; Zhang, Hao; Nasse, Jason S; Herschman, Harvey; Chen, Qun; Tarr, Andrew; Liu, Xiaoyu; Quan, Ning

2014-01-01

291

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

PubMed Central

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.

2009-01-01

292

Molecular dynamics simulations of arachidonic acid-derived pentadienyl radical intermediate complexes with COX-1 and COX-2: insights into oxygenation regio- and stereoselectivity.  

PubMed

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

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

2006-03-14

293

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

2013-01-01

294

Magnetic Properties of Zn1-xCoxO Nanoparticles.  

NASA Astrophysics Data System (ADS)

Zn1-xCoxO nanoparticles have been synthesized at various concentrations of Co2+ doping (0.005 ? x ? 0.15) by wet chemical method. Particle size was ranging from 34 - 45 nm. The magnetic moment increases from x = 0.005 and 0.01 sample to x = 0.04 sample drastically showing a value of magnetic moment as high as 8.54 ?B/Cations and then decreases for x = 0.09 and 0.15 values of Co2+ doping. There is almost paramagnetic behaviour for x = 0.005 and 0.01 Co2+ doped samples. The x = 0.04 sample shows ferromagnetic ordering. Ferromagnetic behaviour decreases for x = 0.09 and 0.15 samples as the antiferromagnetic interaction dominates at higher Co2+ doping concentrations. To probe the source of magnetism, we have undertaken photolu-minescence studies also which revealed the presence of oxygen and Zinc vacancies along with other defects.

Singh, Ningthoujam Surajkumar; Singh, Shougaijam Dorendrajit; Bandyopadhyay, Sujit Kumar

295

Using multivariate adaptive regression splines to estimate subadult age from diaphyseal dimensions.  

PubMed

Subadult age estimation is considered the most accurate parameter estimated in a subadult biological profile, even though the methods are deficient and the samples from which they are based are inappropriate. The current study addresses the problems that plague subadult age estimation and creates age estimation models from diaphyseal dimensions of modern children. The sample included 1,310 males and females between the ages of birth and 12 years. Eighteen diaphyseal length and breadth measurements were obtained from Lodox Statscan radiographic images generated at two institutions in Cape Town, South Africa, between 2007 and 2012. Univariate and multivariate age estimation models were created using multivariate adaptive regression splines. k-fold cross-validated 95% prediction intervals (PIs) were created for each model, and the precision of each model was assessed. The diaphyseal length models generated the narrowest PIs (2 months to 6 years) for all univariate models. The majority of multivariate models had PIs that ranged from 3 months to 5 and 6 years. Mean bias approximated 0 for each model, but most models lost precision after 10 years of age. Univariate diaphyseal length models are recommended for younger children, whereas multivariate models are recommended for older children where the inclusion of more variables minimized the size of the PIs. If diaphyseal lengths are not available, multivariate breadth models are recommended. The present study provides applicable age estimation formulae and explores the advantages and disadvantages of different subadult age estimation models using diaphyseal dimensions. Am J Phys Anthropol 154:376-386, 2014. © 2014 Wiley Periodicals, Inc. PMID:24782395

Stull, Kyra E; L'Abbé, Ericka N; Ousley, Stephen D

2014-07-01

296

Stepwise Regression. [For forward or backward solution to multiple regression problems, in FORTRAN  

Microsoft Academic Search

STEPWISE Regression is a description of a new multiple regression program. This program will provide for either a forward or backward solution to multiple regression problems. This document is designed for users of the STEPWISE program.

Iman

1976-01-01

297

2-Acetoxyverecynarmin C, a new briarane COX inhibitory diterpenoid from Pennatula aculeata.  

PubMed

A new briarane-type diterpenoid, named 2-acetoxyverecynarmin C, was isolated from the methanolic extract of an octocoral, Pennatula aculeata, that exhibited cyclooxygenase (COX) inhibitory activity. The structure of the compound was elucidated by ESI-HRMS, 1D and 2D NMR spectroscopy and comparison of the measured spectral data with those reported in the literature. The relative stereochemistry at chiral carbons was established from 2D NOESY experiments. 2-Acetoxyverecynarmin C is a tricyclic compound containing a furan ring at C-7,8 of a briarane skeleton. 2-Acetoxyverecynarmin C showed moderate inhibitory activity in in vitro COX-1 and COX-2 assays. PMID:25233592

Bahl, Anu; Jachak, Sanjay M; Palaniveloo, Kishneth; Ramachandram, Tulasiramanan; Vairappan, Charles S; Chopra, Harish K

2014-08-01

298

Effect of nonsteroidal anti-inflammatory drugs with varying extent of COX-2-COX-1 selectivity on urinary sodium and potassium excretion in the rat.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) have different selectivity to inhibit cyclooxygenase-1 (COX-1) and COX-2. Treatment with NSAIDs has been associated with kidney side effects. We compared the effect of a selected group of NSAIDs with different COX-2--COX-1 selectivities on urinary sodium and potassium excretion in rats. Each treatment with rofecoxib, celecoxib, meloxicam, diclofenac, and flurbiprofen (30, 120, 9, 30, and 125 mg/kg, respectively) and placebo was administered orally once daily for 4 days. Urine was collected 0-8 h after each dose. Urinary sodium and potassium excretion and urine flow rate were compared with placebo. As compared with placebo, rofecoxib, celecoxib, diclofenac, and flurbiprofen significantly reduced excretion rate of sodium (rofecoxib, 0.28 +/- 0.02 vs. 0.41 +/- 0.03; celecoxib, 0.23 +/- 0.03 vs. 0.48 +/- 0.04; diclofenac, 0.09 +/- 0.02 vs. 0.46 +/- 0.03; and flurbiprofen, 0.11 +/- 0.02 vs. 0.47 +/- 0.02 micromol/(min x 100 g)) and potassium (rofecoxib, 0.55 +/- 0.04 vs. 0.68 +/- 0.04; celecoxib, 0.50 +/- 0.06 vs. 0.72 +/- 0.06; diclofenac, 0.26 +/- 0.05 vs. 0.67 +/- 0.04; and flurbiprofen, 0.35 +/- 0.05 vs. 0.62 +/- 0.03 micromol/ (min x 100 g)). Rofecoxib and flurbiprofen significantly reduced urine flow rate. Meloxicam had no significant effect on either sodium and potassium excretion or on the urine flow rate. At the examined dosage level, no relationship was found between reported COX-2--COX-1 selectivity and urinary electrolytes excretion. PMID:15759054

Harirforoosh, Sam; Jamali, Fakhreddin

2005-01-01

299

Block-Quantized Support Vector Ordinal Regression  

Microsoft Academic Search

Support vector ordinal regression (SVOR) is a recently proposed ordinal regression (OR) algorithm. Despite its theoretical and empirical success, the method has one major bottleneck, which is the high computational complexity. In this brief, we propose a both practical and theoretical guaranteed algorithm, block-quantized support vector ordinal regression (BQSVOR), where we approximate the kernel matrix K with [(K)tilde] that is

Bin Zhao; Fei Wang; Changshui Zhang

2009-01-01

300

Bayesian Unimodal Density Regression for Causal Inference  

ERIC Educational Resources Information Center

Karabatsos and Walker (2011) introduced a new Bayesian nonparametric (BNP) regression model. Through analyses of real and simulated data, they showed that the BNP regression model outperforms other parametric and nonparametric regression models of common use, in terms of predictive accuracy of the outcome (dependent) variable. The other,…

Karabatsos, George; Walker, Stephen G.

2011-01-01

301

Gene Expression Signature for Spontaneous Cancer Regression  

Microsoft Academic Search

Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms lead- ing to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aiming to enhance the patient's natural immunity against melanoma have yet to meet their expectations. Reasons for failure

Florian Rambow; Guillaume Piton; Stephan Bouet; Jean-Jaques Leplat; Sylvain Baulande; Angelique Marrau; Mark Stam; Vratislav Horak; Silvia Vincent-Naulleau

302

A neural network approach to ordinal regression  

Microsoft Academic Search

Ordinal regression is an important type of learning, which has properties of both classification and regression. Here we describe an effective approach to adapt a traditional neural network to learn ordinal categories. Our approach is a generalization of the perceptron method for ordinal regression. On several benchmark datasets, our method (NNRank) outperforms a neural network classificatio n method. Compared with

Jianlin Cheng; Zheng Wang; Gianluca Pollastri

2008-01-01

303

Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3?-UTR  

PubMed Central

Two cyclooxygenase (COX) enzymes, COX-1 and COX-2, are present in human cells. While COX-1 is constitutively expressed, COX-2 is inducible and up-regulated in response to many signals. Since increased transcriptional activity accounts for only part of COX-2 up-regulation, we chose to explore other RNA processing mechanisms in the regulation of this gene. Previously, we showed that COX-2 is regulated by alternative polyadenylation, and that the COX-2 proximal polyadenylation signal contains auxiliary upstream sequence elements (USEs) that are very important in efficient polyadenylation. To explore trans-acting protein factors interacting with these cis-acting RNA elements, we performed pull-down assays with HeLa nuclear extract and biotinylated RNA oligonucleotides representing COX-2 USEs. We identified PSF, p54nrb, PTB, and U1A as proteins specifically bound to the COX-2 USEs. We further explored their participation in polyadenylation using MS2 phage coat protein-MS2 RNA binding site tethering assays, and found that tethering any of these four proteins to the COX-2 USE mutant RNA can compensate for these cis-acting elements. Finally, we suggest that these proteins (p54nrb, PTB, PSF, and U1A) may interact as a complex since immunoprecipitations of the transfected MS2 fusion proteins coprecipitate the other proteins. PMID:17507659

Hall-Pogar, Tyra; Liang, Songchun; Hague, Lisa K.; Lutz, Carol S.

2007-01-01

304

hCOA3 Stabilizes Cytochrome c Oxidase 1 (COX1) and Promotes Cytochrome c Oxidase Assembly in Human Mitochondria*  

PubMed Central

Cytochrome c oxidase (COX) or complex IV of the mitochondrial respiratory chain plays a fundamental role in energy production of aerobic cells. In humans, COX deficiency is the most frequent cause of mitochondrial encephalomyopathies. Human COX is composed of 13 subunits of dual genetic origin, whose assembly requires an increasing number of nuclear-encoded accessory proteins known as assembly factors. Here, we have identified and characterized human CCDC56, an 11.7-kDa mitochondrial transmembrane protein, as a new factor essential for COX biogenesis. CCDC56 shares sequence similarity with the yeast COX assembly factor Coa3 and was termed hCOA3. hCOA3-silenced cells display a severe COX functional alteration owing to a decreased stability of newly synthesized COX1 and an impairment in the holoenzyme assembly process. We show that hCOA3 physically interacts with both the mitochondrial translation machinery and COX structural subunits. We conclude that hCOA3 stabilizes COX1 co-translationally and promotes its assembly with COX partner subunits. Finally, our results identify hCOA3 as a new candidate when screening for genes responsible for mitochondrial diseases associated with COX deficiency. PMID:23362268

Clemente, Paula; Peralta, Susana; Cruz-Bermudez, Alberto; Echevarría, Lucía; Fontanesi, Flavia; Barrientos, Antoni; Fernandez-Moreno, Miguel A.; Garesse, Rafael

2013-01-01

305

Robust nonlinear regression in applications  

PubMed Central

SUMMARY Robust statistical methods, such as M-estimators, are needed for nonlinear regression models because of the presence of outliers/influential observations and heteroscedasticity. Outliers and influential observations are commonly observed in many applications, especially in toxicology and agricultural experiments. For example, dose response studies, which are routinely conducted in toxicology and agriculture, sometimes result in potential outliers, especially in the high dose groups. This is because response to high doses often varies among experimental units (e.g., animals). Consequently, this may result in outliers (i.e., very low values) in that group. Unlike the linear models, in nonlinear models the outliers not only impact the point estimates of the model parameters but can also severely impact the estimate of the information matrix. Note that, the information matrix in a nonlinear model is a function of the model parameters. This is not the case in linear models. In addition to outliers, heteroscedasticity is a major concern when dealing with nonlinear models. Ignoring heteroscedasticity may lead to inaccurate coverage probabilities and Type I error rates. Robustness to outliers/influential observations and to heteroscedasticity is even more important when dealing with thousands of nonlinear regression models in quantitative high throughput screening assays. Recently, these issues have been studied very extensively in the literature (references are provided in this paper), where the proposed estimator is robust to outliers/influential observations as well as to heteroscedasticity. The focus of this paper is to provide the theoretical underpinnings of robust procedures developed recently.

Lim, Changwon; Sen, Pranab K.; Peddada, Shyamal D.

2014-01-01

306

Role of Surf1 in heme recruitment for bacterial COX biogenesis.  

PubMed

Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a highly complex process involving subunits encoded both in the nuclear and the organellar genome; in addition, a large number of assembly factors participate in this process. The soil bacterium Paracoccus denitrificans is an interesting alternative model for the study of COX biogenesis events because the number of chaperones involved is restricted to an essential set acting in the metal centre formation of oxidase, and the high degree of sequence homology suggests the same basic mechanisms during early COX assembly. Over the last years, studies on the P. denitrificans Surf1 protein shed some light on this important assembly factor as a heme a binding protein associated with Leigh syndrome in humans. Here, we summarise our current knowledge about Surf1 and its role in heme a incorporation events during bacterial COX biogenesis. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID:21945856

Hannappel, Achim; Bundschuh, Freya A; Ludwig, Bernd

2012-06-01

307

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

PubMed Central

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

Dadiboyena, Sureshbabu; Nefzi, Adel

2011-01-01

308

Students Speak With Gary Cox, EPIC Project Manager - Duration: 19:52.  

NASA Video Gallery

From NASAâ??s International Space Station Mission Control Center Gary Cox EPIC Project Manager, participates in a Digital Learning Network (DLN) event with students at South Effingham Middle School...

309

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. PMID:22114865

2011-01-01

310

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

PubMed Central

Background This study was designed to examine a novel role of COX-2/PGE2 signaling as a regulator of PTPRJ expression in endothelial cells. Methods A bioinformatics analysis of a whole genome array was carried out to search for regulators of PTPRJ expression in endothelial cells. PTPRJ expression was also measured in endothelial cells derived from a balloon injury-induced neointimal hyperplasia model in male New Zealand Rabbits. Changes in PTPRJ expression in HUVEC cells was examined by RT-PCR and western blotting after transfection of COX-2 plasmids or treatment with varying concentrations of a COX-2 inhibitor. Results A significant correlation was identified between COX-2 and PTPRJ in GSE39264 (Pearson correlation coefficient ?=??0.87; n?=?22; P<0.01, two-tailed). PTPRJ expression was reduced during the progression of neointimal hyperplasia after balloon injury, which correlated with an increase in COX-2 expression. In HUVECs, after transfection with 1 µg/ml, 0.5 µg/ml, or 0.25 µg/ml COX-2 plasmids, PTPRJ protein expression was reduced to 0.60- (±0.08), 0.75- (±0.09), and 0.88- (±0.04) fold, respectively, while mRNA expression was reduced to 0.15- (±0.03), 0.26- (±0.05), and 0.47- (±0.09) fold, respectively. After treatment of HUVECs with 10 µmol/L or 20 µmol/L celecoxib, the reduction in PTPRJ expression induced by COX-2 over-expression was not only rescued but in fact increased by 2.05-fold (±0.28) and 3.34-fold (±0.37), respectively, compared with control. Conclusions Our results suggest that COX-2/PGE2 signaling may function as a negative regulator of PTPRJ expression in endothelial cells both in vivo and vitro. PMID:25532119

Jin, Xinxin; Wang, Bin; Yan, Hongbo; Chen, Xi; Lai, Xiaowei; Zhang, Li; Zhang, Xiaohua; Li, Zhaoshen

2014-01-01

311

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

312

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

PubMed Central

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

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

2014-01-01

313

NDRG2 controls COX-2/PGE?-mediated breast cancer cell migration and invasion.  

PubMed

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

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

2014-10-31

314

The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain  

PubMed Central

Background and purpose: In adults, neurogenesis persists in the hippocampus and the subventricular zone (SVZ), and this is important for learning and memory. Inhibitors of COX-2 suppress ischaemia-induced neurogenesis in the hippocampus. Here, we have determined the effects of COX-2 inhibitors on neurogenesis throughout the normal adult mouse brain. Experimental approach: Young adult mice were treated with COX-2 inhibitors, and the proliferation of neural progenitor cells was measured in the SVZ and hippocampus. In addition, the local uptake of lentiviral vectors in the rostral migratory stream enabled the formation of new neurons in the olfactory bulb (OB) to be assessed. Key results: The COX-2 inhibitor meloxicam suppressed progenitor cell proliferation in the SVZ and hippocampus. A significant decrease in the appearance of new neurons in the OB was also observed. Similar effects on progenitor proliferation in the SVZ were seen with nimesulide. The absence of COX-2 expression in the proliferating progenitors in vivo, and the lack of effect of the COX-2 inhibitors on the growth rate of a cultured progenitor cell line, suggest that the effect is indirect. The specific expression of COX-2 in resting microglia that closely associate with the proliferating progenitor cells provides for a possible site of action. Conclusions and implications: Treatment with a COX-2 inhibitor results in a substantial inhibition of adult neurogenesis. Studies on human tissues are warranted in order to determine if this effect extends to humans, and whether inhibition of neurogenesis should be considered as an adverse effect of these drugs. PMID:20136845

Goncalves, Maria Beatriz; Williams, Emma-Jane; Yip, Ping; Yáñez-Muñoz, Rafael J; Williams, Gareth; Doherty, Patrick

2010-01-01

315

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

316

Quantitative structure-activity relationships for commercially available inhibitors of COX-2.  

PubMed

Quantitative structure activity relationship (QSAR) studies of selective COX-2 inhibitors of commercial interest (drugs in market and on clinical trials) were performed. The COX-2 inhibitory activity (pIC(50)=-logIC(50)) of these twelve compounds was correlated with nineteen descriptors including steric, electronic and constitutional parameters. pIC(50) activity showed high positive correlation with both volume and HOMO (Highest occupied molecular orbital). A Biparametric model was developed that included both these descriptors. The predictive capability (q(2)= 0.66) of this equation was satisfactory. So it can be used to design newer templates or modify existing templates. Volume is an important parameter for the selective COX-2 inhibitory activity, because the secondary pocket in the active site of this enzyme is bigger than the active site of COX-1 enzyme (by 17%). HOMO is a measure of the nucleophilicity of the molecule and a molecule with high HOMO energy is ready to donate its electrons and thus is more reactive than molecule with low values. Binding studies were performed between the COX-2 enzyme and these molecules. The inhibitory activity increased with decrease in binding energy (or interaction energy) between the compounds with the COX-2 enzyme (with a correlation coefficient = -0.65). Calculated Log BBB (Blood Brain barrier), Log P (octonol water partition) and HBD (hydrogen bond donor) values were in the acceptable range (i.e., BBB = -1 to 0.3; LogP= 0 to 5; HBD < 5). PMID:18336329

Sivakumar, P M; Doble, M

2008-03-01

317

[COX-2 inhibitor non-steroidal anti-inflammatory drugs, myth or reality?].  

PubMed

The discovery of two isoforms of cyclooxygenase, Cox-1 constitutive and Cox-2 inducible, has prompted the development of new molecules with high Cox-2 selectivity. These new NSAIDs belong to the coxib class and have theoretically a better digestive tolerability than classical NSAID have. In Belgium, rofecoxib ((Vioxx) and celecoxib (Celebrex) are commercialized. Rofecoxib is indicated in the symptomatic treatment of osteoarthritis (12.5 to 25 mg/d) and celecoxib is indicated in osteoarthritis (200 mg/d) and in rheumatoid arthritis (200 to 400 mg/d). Several studies have demonstrated their efficacy, similarly to classical NSAID as diclofenac (Voltaren), naproxen (Naprosyne), ibuprofen (Brufen) and their superiority compared to placebo. Their safety profile for gastrointestinal events is proven in patients without ulcer history compared to classical NSAID. However, the concomitant use of aspirin decreases the benefit as demonstrated for celecoxib at 400 mg/d but not investigated for rofecoxib. The selective inhibition of Cox-2 with no effect on Cox-1 favors cardiovascular events in patients at risk. Other side effects are similar to classical NSAID. Thus Cox-2 inhibitors NSAID are interesting molecules for their sparing gastrointestinal activity. They must be used with caution in patients with ulcer history, in the elderly and in patients requiring aspirin for cardiovascular prophylaxis. PMID:11680204

Peretz, A

2001-09-01

318

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

PubMed

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to ?(9)-tetrahydrocannabinol (?(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by ?(9)-THC is mediated via CB1 receptor-coupled G protein ?? subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated ?(9)-THC exposures. Ablation of COX-2 also eliminates ?(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing ?-amyloid plaques and neurodegeneration by ?(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

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

2013-11-21

319

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

PubMed Central

SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to ?9-tetrahydrocannabinol (?9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by ?9-THC is mediated via CB1 receptor-coupled G-protein ?? subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated ?9-THC exposures. Ablation of COX-2 also eliminates ?9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing ?-amyloid plaques and neurodegeneration by ?9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

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

2013-01-01

320

Design, synthesis, and biological evaluation of N-acetyl-2-carboxybenzenesulfonamides: a novel class of cyclooxygenase-2 (COX-2) inhibitors.  

PubMed

N-Acetyl-2-carboxybenzenesulfonamide (11), and a group of analogues possessing an appropriately substituted-phenyl substituent (4-F, 2,4-F(2), 4-SO(2)Me, 4-OCHMe(2)) attached to its C-4, or C-5 position, were synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 inhibition studies showed that 11 is a more potent inhibitor (COX-1 IC(50)=0.06microM; COX-2 IC(50)=0.25microM) than aspirin (COX-1 IC(50)=0.35microM; COX-2 IC(50)=2.4microM), and like aspirin [COX-2 selectivity index (S.I.)=0.14], 11 is a nonselective COX-2 inhibitor (COX-2 S.I.=0.23). Regioisomers having a 2,4-difluorophenyl substituent attached to the C-4 (COX-2 IC(50)=0.087microM; COX-2 S.I. >1149), or C-5 (COX-2 IC(50)=0.77microM, SI>130), position of 11 exhibited the most potent and selective COX-2 inhibitory activity relative to the reference drug celecoxib (COX-1 IC(50)=33.1microM; COX-2 IC(50)=0.07microM; COX-2 S.I.=472). N-Acetyl-2-carboxybenzenesulfonamide (11, ED(50)=49 mg/kg), and its C-4 2,4-difluorophenyl derivative (ED(50)=91 mg/kg), exhibited superior antiinflammatory activity (oral dosing) in a carrageenan-induced rat paw edema assay compared to aspirin (ED(50)=129 mg/kg). These latter compounds exhibited comparable analgesic activity to the reference drug diflunisal, and superior analgesic activity compared to aspirin, in a 4% NaCl-induced abdominal constriction assay. A molecular modeling (docking) study indicated that the SO(2)NHCOCH(3) substituent present in N-acetyl-2-carboxy-4-(2,4-fluorophenyl)benzenesulfonamide, like the acetoxy substituent in aspirin, is suitably positioned to acetylate the Ser(530) hydroxyl group in the COX-2 primary binding site. The results of this study indicate that the SO(2)NHCOCH(3) pharmacophore present in N-acetyl-2-carboxybenzenesulfonamides is a suitable bioisostere for the acetoxy (OCOMe) group in aspirin. PMID:15755648

Chen, Qiao-Hong; Rao, P N Praveen; Knaus, Edward E

2005-04-01

321

Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement.  

PubMed

Pain is among the major problems during orthodontic treatment. Recent studies have shown that central Cyclooxygenase2 (COX2) pathway was involved in several pain models. The present study investigated whether inducible COX2 within the trigeminal nucleus caudalis (Vc) contributed to experimental tooth movement pain in freely moving rats. Elastic rubber bands were inserted between the first and second maxillary molars bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. COX2 distribution in Vc was studied by immunohistochemistry and the changes of COX2 expression were detected by Western blot at different time point after rubber band insertion. Our results showed that tooth movement significantly increased COX2 expression in Vc and the time spent on mouth wiping, reaching a maximum at 1 day and then decreasing gradually. Furthermore, the rhythm change of COX2 expression in Vc and the mouth wiping behavior were much correlative with each other. All of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive. Importantly, the mouth wiping behavior could be attenuated by intracisternal injection of NS-398 (a selective COX2 inhibitor) but not by periodontal administration of NS-398. All these results suggested that increased COX2 in Vc was involved in tooth movement pain and thus may be a central target for orthodontic pain treatment. PMID:20091889

Gao, Yuan; Duan, Yin-Zhong

2010-03-01

322

Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy.  

PubMed

Isolated cytochrome c oxidase (COX) deficiency is a prevalent cause of mitochondrial disease and is mostly caused by nuclear-encoded mutations in assembly factors while rarely by mutations in structural subunits. We hereby report a case of isolated COX deficiency manifesting with encephalomyopathy, hydrocephalus and hypertropic cardiomyopathy due to a missense p.R20C mutation in the COX6B1 gene, which encodes an integral, nuclear-encoded COX subunit. This novel mutation was predicted to be severe in silico. In accord, enzymatic activity was undetectable in muscle and fibroblasts, was severely decreased in lymphocytes and the COX6B1 protein was barely detectable in patient's muscle mitochondria. Complementation with the wild-type cDNA by a lentiviral construct restored COX activity, and mitochondrial function was improved by 5-aminoimidazole-4-carboxamide ribonucleotide, resveratrol and ascorbate in the patient's fibroblasts. We suggest that genetic analysis of COX6B1should be included in the investigation of isolated COX deficiency, including patients with cardiac defects. Initial measurement of COX activity in lymphocytes may be useful as it might circumvent the need for invasive muscle biopsy. The evaluation of ascorbate supplementation to patients with mutated COX6B1 is warranted. PMID:24781756

Abdulhag, Ulla Najwa; Soiferman, Devorah; Schueler-Furman, Ora; Miller, Chaya; Shaag, Avraham; Elpeleg, Orly; Edvardson, Simon; Saada, Ann

2015-02-01

323

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

SciTech Connect

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

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

2013-04-15

324

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

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

325

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

PubMed Central

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

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

2013-01-01

326

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

PubMed

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

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

2014-09-01

327

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

PubMed Central

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

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

2014-01-01

328

Mss51p, a putative translational activator of cytochrome c oxidase subunit-1 ( COX1 ) mRNA, is required for synthesis of Cox1p in Saccharomyces cerevisiae  

Microsoft Academic Search

Mutants of Saccharomyces cerevisiae that lack a functional MSS51 gene are respiratory deficient due to the absence of cytochrome c oxidase subunit 1 (Cox1p). It has been previously suggested, but not formally proven, that Mss51p is required for translational\\u000a activation of COX1 mRNA, rather than being involved in a subsequent step in the synthesis of Cox1p or its assembly into

M. Siep; K. van Oosterum; H. Neufeglise; H. van der Spek; L. A. Grivell

2000-01-01

329

Regression-fuzzy approach to land valuation  

Microsoft Academic Search

In this paper, we demonstrate that the fuzzy pricing model can improve regression analysis in applications where non-smoothness\\u000a appears. Combining the fuzzy and regression approaches it is capable of modelling complex non-linearities. The application\\u000a of this approach describes an effort to design a regression-fuzzy system to estimate real estate market values, especially\\u000a for vacant urban plots. The results are compared

Marija Bogataj; Danijela Tuljak Suban; Samo Drobne

330

Outlier Detecting in Fuzzy Switching Regression Models  

Microsoft Academic Search

\\u000a Fuzzy switching regression models have been extensively used in economics and data mining research. We present a new algorithm\\u000a named FCWRM (Fuzzy C Weighted Regression Model) to detect the outliers in fuzzy switching regression models while preserving\\u000a the merits of FCRM algorithm proposed by Hathaway. The theoretic analysis shows that FCWRM can converge to a local minimum\\u000a of the object

Hong-bin Shen; Jie Yang; Shi-tong Wang

2004-01-01

331

Quantum Energy Regression using Scattering Transforms  

E-print Network

We present a novel approach to the regression of quantum mechanical energies based on a scattering transform of an intermediate electron density representation. A scattering transform is a deep convolution network computed with a cascade of multiscale wavelet transforms. It possesses appropriate invariant and stability properties for quantum energy regression. This new framework removes fundamental limitations of Coulomb matrix based energy regressions, and numerical experiments give state-of-the-art accuracy over planar molecules.

Hirn, Matthew; Mallat, Stephane

2015-01-01

332

Support Vector Regression Methods for Functional Data  

Microsoft Academic Search

Many regression tasks in practice dispose in low gear instance of digitized functions as predictor variables. This has motivated\\u000a the development of regression methods for functional data. In particular, Naradaya-Watson Kernel (NWK) and Radial Basis Function\\u000a (RBF) estimators have been recently extended to functional nonparametric regression models. However, these methods do not\\u000a allow for dimensionality reduction. For this purpose, we

Noslén Hernández-gonzález; Rolando J. Biscay; Isneri Talavera-bustamante

2007-01-01

333

Optimal spline regression utilizing steepest descent  

E-print Network

OPTIMAL SPLINE REGRESSION UTILIZING STEEPEST DESCENT A Thesis ERIC SHIRLEY FLORA Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree of MASTER OF SCIENCE May l975 Major Sub...]ect: Mathematics OPTIMAL SPLINE REGRESSION UTILIZING STEEPEST DESCENT A Thesis ERIC SHIRLEY FLORA Approved as to style and content by; (Chai an of Committee) (Head of Department) ~' (Member) (Member ) May 1975 ABSTRACT Optimal Spline Regression Utilizing...

Flora, Eric Shirley

1975-01-01

334

Insulin resistance: regression and clustering.  

PubMed

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

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

2014-01-01

335

Insulin Resistance: Regression and Clustering  

PubMed Central

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

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

2014-01-01

336

Diversity of sponge mitochondrial introns revealed by cox 1 sequences of Tetillidae  

PubMed Central

Background Animal mitochondrial introns are rare. In sponges and cnidarians they have been found in the cox 1 gene of some spirophorid and homosclerophorid sponges, as well as in the cox 1 and nad 5 genes of some Hexacorallia. Their sporadic distribution has raised a debate as to whether these mobile elements have been vertically or horizontally transmitted among their hosts. The first sponge found to possess a mitochondrial intron was a spirophorid sponge from the Tetillidae family. To better understand the mode of transmission of mitochondrial introns in sponges, we studied cox 1 intron distribution among representatives of this family. Results Seventeen tetillid cox 1 sequences were examined. Among these sequences only six were found to possess group I introns. Remarkably, three different forms of introns were found, named introns 714, 723 and 870 based on their different positions in the cox 1 alignment. These introns had distinct secondary structures and encoded LAGLIDADG ORFs belonging to three different lineages. Interestingly, sponges harboring the same intron form did not always form monophyletic groups, suggesting that their introns might have been transferred horizontally. To evaluate whether the introns were vertically or horizontally transmitted in sponges and cnidarians we used a host parasite approach. We tested for co-speciation between introns 723 (the introns with the highest number of sponge representatives) and their nesting cox 1 sequences. Reciprocal AU tests indicated that the intron and cox 1 tree are significantly different, while a likelihood ratio test was not significant. A global test of co-phylogeny had significant results; however, when cnidarian sequences were analyzed separately the results were not significant. Conclusions The co-speciation analyses thus suggest that a vertical transmission of introns in the ancestor of sponges and cnidarians, followed by numerous independent losses, cannot solely explain the current distribution of metazoan group I introns. An alternative scenario that includes horizontal gene transfer events appears to be more suitable to explain the incongruence between the intron 723 and the cox 1 topologies. In addition, our results suggest that three different intron forms independently colonized the cox 1 gene of tetillids. Among sponges, the Tetillidae family seems to be experiencing an unusual number of intron insertions. PMID:20849667

2010-01-01

337

Geodesic least squares regression on information manifolds  

NASA Astrophysics Data System (ADS)

We present a novel regression method targeted at situations with significant uncertainty on both the dependent and independent variables or with non-Gaussian distribution models. Unlike the classic regression model, the conditional distribution of the response variable suggested by the data need not be the same as the modeled distribution. Instead they are matched by minimizing the Rao geodesic distance between them. This yields a more flexible regression method that is less constrained by the assumptions imposed through the regression model. As an example, we demonstrate the improved resistance of our method against some flawed model assumptions and we apply this to scaling laws in magnetic confinement fusion.

Verdoolaege, Geert

2014-12-01

338

Synthesis of novel pyrazole–thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors.  

PubMed

A series of 1,3,4-trisubstituted pyrazole derivatives (3 a-f), (4 a-f), and (5 a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 ?M. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 ?M), with a significant selectivity index (SI > 60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents. PMID:25444084

Alegaon, S G; Hirpara, M B; Alagawadi, K R; Hullatti, K K; Kashniyal, K

2014-11-15

339

In -silico molecular docking analysis of prodigiosin and cycloprodigiosin as COX-2 inhibitors.  

PubMed

Prodigiosin and cycloprodigiosin are tripyrrole red pigmented compounds with medical importance for their anticancer property. In the present investigation, molecular docking studies were performed for both prodigiosin and cycloprodigiosins to evaluate the in- silico anti-inflammatory activity against Cycloxigenase-2 (COX-2) protein as model compound and the data compared with rofecoxib and celcoxid. Cycloprodigiosin showed higher initial potential, initial RMS gradient and potential energy values compared to prodigiosin. Analysis of COX-2 protein and ligand binding revealed that cyclprodigiosin interacted with COX-2 protein amino acid residues of Tyr(324), Phe(487) and Arg(89) while prodigiosin interaction was observed with two amino acids i.e. Leu(321) and Tyr(324). The computational ligand binding interaction suggested > 45% higher fitness score value for prodigiosin to that of cycloprodigiosin with COX-2 protein while the standard compounds rofecoxib and celecoxid revealed fitness score of 44 and 62, respectively. The prodigiosin ligand revealed the best fitness score compared with the standard drug rofecoxib suggesting the prodigiosin could be effective as the potential inhibitor compound against COX-2 protein and can be evaluated as anti-inflammatory drug molecule using clinical trials. PMID:23741639

Krishna, Pabba Shiva; Vani, Kompally; Prasad, Metuku Ram; Samatha, Burra; Bindu, Nidadavolu Shesha Venkata Sathya Siva Surya Laxmi Hima; Charya, Maringanti Alaha Singara; Reddy Shetty, Prakasham

2013-12-01

340

Antiinflammatory and neuroprotective actions of COX2 inhibitors in the injured brain  

PubMed Central

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

Strauss, Kenneth I.

2008-01-01

341

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

PubMed

Celecoxib plays antitumor roles via multiple mechanisms in a variety of human cancers. The aim of this study was to clarify the mechanism of action of celecoxib in canine mammary tumors. We examined the antitumor effects of celecoxib in AZACB canine mammary tumor cells expressing low levels of cyclooxygenase?2 (COX?2) to minimize the effect of COX?2 on its activity. Our data revealed that celecoxib inhibited cell proliferation mainly via COX?2?independent mechanisms. Specifically, celecoxib decreased the proportion of cells in S phase and increased G2/M arrest, which was associated with increased expression of the cyclin?dependent kinase inhibitors (CDKIs) p21 and p27. In addition, treatment with celecoxib downregulated COX?2 expression, and induced apoptosis via both the intrinsic and extrinsic pathways. These findings suggest that celecoxib might be a useful agent for the treatment of canine mammary tumors, regardless of COX?2 expression. In the future, it might be possible to use a combination of celecoxib and other antitumor agents to treat canine mammary tumors. PMID:25571853

Tamura, Dai; Saito, Teruyoshi; Murata, Kanae; Kawashima, Masafumi; Asano, Ryuji

2015-03-01

342

Inhibition of phorbol ester-induced COX-2 expression by some edible African plants.  

PubMed

Cancer bush (CB, Sutherlandia frutescens), Devil's claw (DEV, Harpagophytum procumbens), Rooibos tea (RT, Aspalathus linearis), and Bambara groundnut (BB, Vignea subterranean) have been used to treat some malignancies and inflammatory disorders in Africa. However, biochemical basis for chemopreventive effects of these medicinal plants remains unclear. An abnormally elevated expression of cyclooxygenase-2 (COX-2) has been implicated in pathogenesis and progression of carcinogenesis. In the present study, we found that the methanol extracts of CB, DEV, RT, and BB inhibited, to a different extent, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in human breast epithelial (MCF10A) cells and in mouse skin in vivo. To determine the molecular mechanism of COX-2 inhibition by the above medicinal plants, we examined their effects on activation of NF-kappaB which is one of the major transcription factors responsible for regulating COX-2 expression. Methanol extracts of both CB and BB inhibited the DNA binding of NF-kappaB activated by TPA in MCF10A cells in a dose-dependent manner. Based on above findings, CB and BB are likely to inhibit TPA-induced COX-2 expression through suppression of DNA binding of NF-kappaB, which may contribute to the chemopreventive or chemoprotective activity of these African plants. PMID:15630188

Na, Hye-Kyung; Mossanda, Kensese S; Lee, Ji-Yoon; Surh, Young-Joon

2004-01-01

343

COX2-derived primary and cyclopentenone prostaglandins are increased after asphyxial cardiac arrest  

PubMed Central

Background Cyclopentenone prostaglandins have been identified as potential neurotoxic agents in the setting of hypoxia-ischemia. Cyclooxygenase-2 (COX-2), the upstream enzyme responsible for prostaglandin production is upregulated following hypoxic-ischemic brain injury. However, the temporal production and concentration of cyclopentenone prostaglandins has not been described following global brain ischemia. Methods Global brain ischemia was induced in rats by asphyxial cardiac arrest (ACA) followed by resuscitation. Rats were sacrificed between 24 hours and 7 days following resuscitation and their brains removed. Western blot, immunohistochemistry, and mass spectroscopy were performed. A cohort of rats was pretreated with the COX-2 inhibitor SC58125. Results COX-2 is induced in hippocampus at 24 hours following ACA. Multiple prostaglandins, including cyclopentenone prostaglandin species, are increased in hippocampus as 24 hours following ACA. Prostaglandin and cyclopentenone prostaglandin concentrations are returned to baseline at 3 and 7 days post-ischemia. The COX-2 inhibitor SC58125 completely abrogates the post-ischemic increase in prostaglandins and cyclopentenone prostaglandins. Conclusions Prostaglandins, including cyclopentenone prostaglandins, are increased in ischemic brain, peak at 24 hours and can be attenuated by the COX-2 inhibitor SC58125. These data establish the presence of potentially neurotoxic cyclopentenone prostaglandins in post-ischemic brains, thus identifying a target and therapeutic window for neuroprotective therapies. PMID:23624225

Liu, Hao; Rose, Marie E.; Miller, Tricia M.; Li, Wenjin; Shinde, Sunita N.; Pickrell, Alicia M.; Poloyac, Samuel M.; Graham, Steven H.

2013-01-01

344

STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression.  

PubMed

Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.Oncogene advance online publication, 10 November 2014; doi:10.1038/onc.2014.366. PMID:25381814

Wang, J-Y; Sun, J; Huang, M-Y; Wang, Y-S; Hou, M-F; Sun, Y; He, H; Krishna, N; Chiu, S-J; Lin, S; Yang, S; Chang, W-C

2014-11-10

345

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

PubMed Central

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

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

2011-01-01

346

Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy.  

PubMed

Angiogenesis is required for multistage carcinogenesis. The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. COX-2 expression occurs in a wide range of preneoplastic and malignant conditions; and the enzyme has been localized to the neoplastic cells, endothelial cells, immune cells, and stromal fibroblasts within tumors. The proangiogenic effects of COX-2 are mediated primarily by three products of arachidonic metabolism: thromboxane A(2) (TXA(2)), prostaglandin E(2) (PGE(2)), and prostaglandin I(2) (PGI(2)). Downstream proangiogenic actions of these eicosanoid products include: (1) production of vascular endothelial growth factor; (2) promotion of vascular sprouting, migration, and tube formation; (3) enhanced endothelial cell survival via Bcl-2 expression and Akt signaling; (4) induction of matrix metalloproteinases; (5) activation of epidermal growth factor receptor-mediated angiogenesis; and (6) suppression of interleukin-12 production. Selective inhibition of COX-2 activity has been shown to suppress angiogenesis in vitro and in vivo. Because these agents are safe and well tolerated, selective COX-2 inhibitors could have clinical utility as antiangiogenic agents for cancer prevention, as well as for intervention in established disease alone or in combination with chemotherapy, radiation, and biological therapies. PMID:15179620

Gately, Stephen; Li, William W

2004-04-01

347

TGF-? Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells  

PubMed Central

Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor ? (TGF-?) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-? can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-?-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-?. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-?. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-?, suggesting that TGF-?–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-? rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-?. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-?. Conclusion The results of this study show that TGF-? down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells. PMID:25544576

Kang, Soyeong; Min, Ahrum; Im, Seock-Ah; Song, Sang-Hyun; Kim, Sang Gyun; Kim, Hyun-Ah; Kim, Hee-Jun; Oh, Do-Youn; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue

2015-01-01

348

The effect of COX2 specific inhibitors on blood pressure control in patients with osteoarthritis and hypertension  

Microsoft Academic Search

In treated hypertensive patients, NSAIDs may cause significant loss of blood pressure (BP) control, primarily systolic, through drug-drug\\/drug-disease interactions. It is not known whether COX-2 specific inhibitors, which spare renal COX-1, might have an effect on BP similar to that of conventional NSAIDs. To evaluate effects of COX-2 specific inhibitors on BP control in hypertensive OA patients at their most

Andrewm Whelton; William B. White; John G. Fort; Alfonso Bello

2002-01-01

349

BMP9 and COX-2 form an important regulatory loop in BMP9-induced osteogenic differentiation of mesenchymal stem cells.  

PubMed

Mesenchymal stem cells (MSCs) can self-renew and differentiate into osteogenic, chondrogenic, adipogenic and myogenic lineages. It's reported that bone morphogenetic protein 9 (BMP9) is one of the most potent osteogenic BMPs to initiate the commitment of MSCs to osteoblast lineage. Cyclooxygenase-2 (COX-2) is critical for bone fracture healing and osteogenic differentiation in MSCs. However, the relationship between COX-2 and BMP9 in osteogenesis remains unknown. Herein, we investigate the role of COX-2 in BMP9-induced osteogenesis in MSCs. We demonstrate that COX-2 is up-regulated as a target of BMP9 in MSCs. Both COX-2 inhibitor (NS-398) and COX-2 knockdown siRNAs can effectively decrease alkaline phosphatase (ALP) activities induced by BMP9 in MSCs. NS-398 also down-regulates BMP9-induced expression of osteopontin and osteocalcin, so does the matrix mineralization. The in vivo studies indicate that knockdown of COX-2 attenuates BMP9-induced ectopic bone formation. In perinatal limb culture assay, NS-398 is shown to reduce the hypertropic chondrocyte zone and ossification induced by BMP9. Mechanistically, knockdown of COX-2 significantly inhibits the BMP9 up-regulated expression of Runx2 and Dlx-5 in MSCs, which can be rescued by exogenous expression of COX-2. Furthermore, knockdown of COX-2 apparently reduces BMP9 induced BMPR-Smad reporter activity, the phosphorylation of Smad1/5/8, and the expression of Smad6 and Smad7 in MSCs. NS-398 blocks the expression of BMP9 mediated by BMP9 recombinant adenovirus. Taken together, our findings suggest that COX-2 plays an important role in BMP9 induced osteogenic differentiation in MSCs; BMP9 and COX-2 may form an important regulatory loop to orchestrate the osteogenic differentiation in MSCs. PMID:23981660

Wang, Jin-Hua; Liu, Ying-Zi; Yin, Liang-Jun; Chen, Liang; Huang, Jun; Liu, Yang; Zhang, Ran-Xi; Zhou, Long-Yang; Yang, Qiu-Jun; Luo, Jin-Yong; Zuo, Guo-wei; Deng, Zhong-Liang; He, Bai-Cheng

2013-11-01

350

Cyclooxygenase2 (COX2), Epidermal Growth Factor Receptor (EGFR), and Her2\\/neu Expression in Ovarian Cancer  

Microsoft Academic Search

Objectives. Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2\\/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigated by immunohistochemistry the expression of COX-2, EGFR, and Her-2\\/neu in

G. Ferrandina; F. O. Ranelletti; L. Lauriola; F. Fanfani; F. Legge; M. Mottolese; M. R. Nicotra; P. G. Natali; V. H. Zakut; G. Scambia

2002-01-01

351

COX2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer  

Microsoft Academic Search

BACKGROUND: Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. METHODS: Tumor COX-2, HER2 and estrogen receptor ? (ER) expression and phosphorylation of Akt, BAD,

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

2010-01-01

352

Synthesis, pharmacological characterization, and docking analysis of a novel family of diarylisoxazoles as highly selective cyclooxygenase-1 (COX-1) inhibitors.  

PubMed

3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a known selective cyclooxygenase-1 (COX-1) inhibitor, was used to design a new series of 3,4-diarylisoxazoles in order to improve its biochemical COX-1 selectivity and antiplatelet efficacy. Structure-activity relationships were studied using human whole blood assays for COX-1 and COX-2 inhibition in vitro, and results showed that the simultaneous presence of 5-methyl (or -CF3), 4-phenyl, and 5-chloro(-bromo or -methyl)furan-2-yl groups on the isoxazole core was essential for their selectivity toward COX-1. 3g, 3s, 3d were potent and selective COX-1 inhibitors that affected platelet aggregation in vitro through the inhibition of COX-1-dependent thromboxane (TX) A2. Moreover, we characterized their kinetics of COX-1 inhibition. 3g, 3s, and 3d were more potent inhibitors of platelet COX-1 and aggregation than P6 (named 6) for their tighter binding to the enzyme. The pharmacological results were supported by docking simulations. The oral administration of 3d to mice translated into preferential inhibition of platelet-derived TXA2 over protective vascular-derived prostacyclin (PGI2). PMID:23651359

Vitale, Paola; Tacconelli, Stefania; Perrone, Maria Grazia; Malerba, Paola; Simone, Laura; Scilimati, Antonio; Lavecchia, Antonio; Dovizio, Melania; Marcantoni, Emanuela; Bruno, Annalisa; Patrignani, Paola

2013-06-13

353

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

PubMed

A new group of regioisomeric 2,3-diaryl-1,3-benzdiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition studies identified 3-(p-fluorophenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinane-4-one (2b) as a potent and highly selective (IC(50) = 0.07 µM; selectivity index = 572.8) COX-2 inhibitor. PMID:22076641

Zarghi, Afshin; Zebardast, Tannaz; Hajighasemali, Fatemeh; Alipoor, Eskandar; Daraie, Bahram; Hedayati, Mehdi

2012-04-01

354

Test-retest bias, reliability, and regression equations for neuropsychological measures repeated over a 12-16-week period.  

PubMed

The interpretation of neurobehavioral change over time requires knowledge of the test-retest characteristics of the measures. Without this information it is not possible to distinguish a true change (i.e., one reflecting the occurrence or resolution of an intervening process) from that occurring on the basis of chance or systematic bias. We tested a group of 72 healthy young to middle aged adults twice over a 12-to-16-week interval in order to observe the change in scores over time when there was no known intervention. The test battery consisted of seven commonly used cognitive measures and the Profile of Mood States (POMS). Test-retest regression equations were calculated for each measure using initial performance, age, education, and a measure of general intellectual function (Wonderlic Personnel Test) as regressors. Test-retest correlations ranged from .39 (POMS Fatigue) to .89 (Digit Symbol). Cognitive measures generally yielded higher correlations than did the POMS. Univariate regressions based only on initial performance adequately predicted retest performance for the majority of measures. Age and education had a relatively minor influence. Practice effects and regression to the mean were common. These test-retest regression equations can be used to predict retest scores when there has been no known intervention. They can also be used to generate statistical statements regarding the significance of change in an individual's performance over a 12-to-16-week interval. PMID:11459111

Salinsky, M C; Storzbach, D; Dodrill, C B; Binder, L M

2001-07-01

355

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

PubMed

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

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

2014-07-01

356

The untranslated leader of nuclear COX4 gene of Saccharomyces cerevisiae contains an intron.  

PubMed Central

The nuclear gene for subunit IV of cytochrome oxidase (COX4) in Saccharomyces cerevisiae contains a 342 bp intron which is contained entirely within the 5' leader of the message. Splicing of the intron results in removal of several small open reading frames; subsequently, the COX4 AUG becomes the 5' proximal initiation codon. A strain with an rna2- mutation fails to splice mRNA efficiently at restrictive temperature and was used to map the intron splice junctions by RNase protection. Two major mRNA initiation sites were mapped by primer extension of synthetic oligodeoxynucleotides. The splice junctions and internal TACTAAC box conform to consensus sequences previously determined from other yeast introns. One gene for subunit V of cytochrome oxidase (COX5b) has also been shown to contain an intron. The significance of introns in two nuclear genes encoding subunits of cytochrome oxidase is discussed. Images PMID:3033605

Schneider, J C; Guarente, L

1987-01-01

357

Pyrazolobenzotriazinone derivatives as COX inhibitors: synthesis, biological activity, and molecular-modeling studies.  

PubMed

Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX-2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3-pyrazolyl-substituted benzotriazinones as anti-inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a-c and 18a-c have been prepared by reacting the opportune ethyl 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate or 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)-1-pyridin-2-yl-1H-pyrazole-4-carboxylate, a good COX-1/COX-2 selectivity. Molecular modeling studies confirmed the obtained biological results. PMID:21110338

Raffa, Demetrio; Migliara, Onofrio; Maggio, Benedetta; Plescia, Fabiana; Cascioferro, Stella; Cusimano, Maria Grazia; Tringali, Giuseppe; Cannizzaro, Carla; Plescia, Fulvio

2010-11-01

358

Identification and initial characterisation of a Plasmodium falciparum Cox17 copper metallochaperone.  

PubMed

Copper is an essential micronutrient for all living organisms as an important catalytic co-factor for key enzymes. In higher eukaryotes intracellular copper is distributed by copper metallochaperones. Copper chelators such as neocuproine and tetrathiomolybdate inhibit Plasmodium falciparum erythrocytic development, indicating a requirement for copper by the parasite. A screen of the P. falciparum genome database identified eight potential copper-requiring protein orthologs, including four candidate copper metallochaperones implicated in the delivery of copper to cytochrome-c oxidase. A P. falciparum Cox17 ortholog (PfCox17) was recombinantly expressed and the purified protein bound reduced copper in vitro. PfCox17 was localised to the parasite cytoplasm. Characterisation of plasmodial proteins involved in copper metabolism will help us understand the role of this essential microelement in plasmodial homeostasis. PMID:25447123

Choveaux, David L; Krause, Robert G E; Przyborski, Jude M; Goldring, J P Dean

2015-01-01

359

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

PubMed

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

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

2014-05-01

360

Fuzzy Factor in Switching Regression Models  

Microsoft Academic Search

Switching regression models is a kind of special mixture regression models, and the clustering method of it can be classified as hard partitioning and fuzzy partitioning. The former is simple in coding and fast in execution, but its partitioning is too pure since it overlooks the fuzziness; whereas the latter, taking the fuzziness into account, is more reasonable for partitioning,

Xiaobing Yang; Lingmin He; Jin Tan

2007-01-01

361

Similarities and distances in fuzzy regression modeling  

Microsoft Academic Search

Abstract We study the set of the solutions of a fuzzy regression model as a metric space. For each metric, we define a similarity ratio in order to compare,the spaces of solutions of a fuzzy regression model. We prove that the similarity ratios, that can be extracted from these different metrics, are all the same as in [4]. As an

Basil K. Papadopoulos; M. A. Sirpi

2004-01-01

362

Interval regression analysis by quadratic programming approach  

Microsoft Academic Search

When we use linear programming in possibilistic regression analysis, some coefficients tend to become crisp because of the characteristic of linear programming. On the other hand, a quadratic programming approach gives more diverse spread coefficients than a linear programming one. Therefore, to overcome the crisp characteristic of linear programming, we propose interval regression analysis based on a quadratic programming approach.

Hideo Tanaka; Haekwan Lee

1998-01-01

363

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

364

Suppression Situations in Multiple Linear Regression  

ERIC Educational Resources Information Center

This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

Shieh, Gwowen

2006-01-01

365

Risk Tuning with Generalized Linear Regression  

Microsoft Academic Search

A framework is set up in which linear regression, as a way of approximating a random variable by other random variables, can be carried out in a variety of ways, which moreover can be tuned to the needs of a particular model in flnance, or operations research more broadly. Although the idea of adapting the form of regression to the

R. Tyrrell Rockafellar; Stan Uryasev; Michael Zabarankin

2008-01-01

366

Interval regression analysis using support vector networks  

Microsoft Academic Search

Support vector machines (SVMs) have been very successful in pattern classification and function estimation problems for crisp data. In this paper, the v-support vector interval regression network (v-SVIRN) is proposed to evaluate interval linear and nonlinear regression models for crisp input and output data. As it is difficult to select an appropriate value of the insensitive tube width in ?-support

Pei-yi Hao

2009-01-01

367

Kernel Support Vector Regression with imprecise output  

E-print Network

Jan 27, 2008 ... ?-Support Vector Regression approach is given, where two hyperplanes need to ... the simplest version of possibilistic regression analysis, introduced by Tanaka et al. (see ... Function networks which identify the upper and lower sides of the output. ..... conditions must be satisfied (see Section 4.3 in [1]),.

2008-01-27

368

Accurate On-line Support Vector Regression  

Microsoft Academic Search

Batch implementations of support vector regression (SVR) are inefé cient when used in an on-line setting because they must be retrained from scratch every time the training set is modié ed. Following an incremen- tal support vector classié cation algorithm introduced by Cauwenberghs and Poggio (2001), we have developed an accurate on-line support vec- tor regression (AOSVR) that efé ciently

Junshui Ma; James Theiler; Simon Perkins

2003-01-01

369

A Regression-Based Linear Classification Procedure.  

ERIC Educational Resources Information Center

A linear regression function is developed for use in a classification procedure. The procedure is applied to faculty merit review data, resulting in an interpretable regression function and within-sample classifications as good as a four-funtion discriminant analysis. (Author/BW)

LaMotte, Lynn Roy; McWhorter, Archer, Jr.

1981-01-01

370

MLREG, stepwise multiple linear regression program  

Microsoft Academic Search

This program is written in FORTRAN for an IBM computer and performs multiple linear regressions according to a stepwise procedure. The program transforms and combines old variables into new variables, prints input and transformed data, sums, raw sums or squares, residual sum of squares, means and standard deviations, correlation coefficients, regression results at each step, ANOVA at each step, and

Carder

1981-01-01

371

Software Testing and Maintenance 1 Regression Testing  

E-print Network

1 Software Testing and Maintenance 1 Regression Testing Introduction Test Selection Test Minimization Test Prioritization Summary Software Testing and Maintenance 2 What is it? Regression testing refers to the portion of the test cycle in which a program is tested to ensure that changes do not affect

Lei, Jeff Yu

372

Time Series Regression with a Unit Root  

Microsoft Academic Search

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

P. C. B. Phillips

1987-01-01

373

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

374

Principles of Quantile Regression and an Application  

ERIC Educational Resources Information Center

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

Chen, Fang; Chalhoub-Deville, Micheline

2014-01-01

375

Regression Testing Ajax Applications: Coping with Dynamism  

Microsoft Academic Search

There is a growing trend to move desktop applications towards the web using advances made in web technologies such as Ajax. One common way to provide assurance about the correctness of such complex and evolving systems is through regression testing. Regression testing classical web applications has already been a notoriously daunting task because of the dynamism in web interfaces. Ajax

Danny Roest; Ali Mesbah; Arie van Deursen

2010-01-01

376

Parametric regression on cumulative incidence function  

Microsoft Academic Search

SUMMARY We propose parametric regression analysis of cumulative incidence function with competing risks data. A simple form of Gompertz distribution is used for the improper baseline subdistribution of the event of interest. Maximum likelihood inferences on regression parameters and associated cumulative incidence function are developed for parametric models, including a flexible generalized odds rate model. Estima- tion of the long-term

JONG-HYEON JEONG; JASON P. FINE

2007-01-01

377

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

PubMed Central

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

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

2014-01-01

378

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

PubMed Central

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

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

2014-01-01

379

Reduced COX-2 Expression in Aged Mice Is Associated With Impaired Fracture Healing  

E-print Network

ABSTRACT: The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E2 (PGE2) synthesis, is critical for normal bone repair. A femoral fracture repair model was used in mice at either 7–9 or 52–56 wk of age, and healing was evaluated by imaging, histology, and gene expression studies. Aging was associated with a decreased rate of chondrogenesis, decreased bone formation, reduced callus vascularization, delayed remodeling, and altered expression of genes involved in repair and remodeling. COX-2 expression in young mice peaked at 5 days, coinciding with the transition of mesenchymal progenitors to cartilage and the onset of expression of early cartilage markers. In situ hybridization and immunohistochemistry showed that COX-2 is expressed primarily in early cartilage precursors that co-express col-2. COX-2 expression was reduced by 75 % and 65 % in fractures from aged mice compared with young mice on days 5 and 7, respectively. Local administration of an EP4 agonist to the fracture repair site in aged mice enhanced the rate of chondrogenesis and bone formation to levels observed in young mice, suggesting that the expression of COX-2 during the early inflammatory phase of repair regulates critical subsequent events including chondrogenesis, bone formation, and remodeling. The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging. J Bone Miner Res 2009;24:251–264. Published online on October 13, 2008; doi: 10.1359/JBMR.081002 Key words: fracture, aging, cyclooxygenases, prostaglandin E2, endochondral ossification

Amish A Naik; Chao Xie; Michael J Zuscik; Paul Kingsley; Edward M Schwarz; Hani Awad; Robert Guldberg; Hicham Drissi; J Edward Puzas; Brendan Boyce; Xinping Zhang; Regis J O’keefe

380

Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a pharmacologist's perspective.  

PubMed

Two classes of antipyretic analgesics were developed about 100 years ago, namely the acidic aspirin-like drugs and non-acidic acetaminophen-phenazone-like compounds. Since then, research has aimed at improving the side-effect profile of the acidic anti-inflammatory aspirin-like drugs and improving the anti-inflammatory efficacy of the non-acidic acetaminophen-phenazone-like compounds. Both drug classes inhibit the cyclooxygenase (COX)-1 and -2 enzymes non-selectively. The aspirin-like drugs achieve particularly high concentrations in inflamed tissue, which is assumed to account for their superior anti-inflammatory potency. These acidic drugs also reach comparatively high concentrations in the stomach wall, kidney cortex and blood, resulting in the well-known side effects that occur with acidic compounds but not with acetaminophen and phenazone. Following the discovery of the two differentially distributed and regulated COXs, two non-acidic COX-2-selective compounds--celecoxib and rofecoxib--were introduced. They proved to be less toxic to the gastrointestinal tract compared with, for example, diclofenac or naproxen. These non-acidic drugs distribute homogeneously throughout the body--a cause for concern since COX-2 has been found to be present constitutively in many organ systems, including brain, bone and the genito-urinary tract. It appears desirable to combine the tissue-targeted distribution of the highly protein-bound acidic aspirin-type drugs with the selectivity of the COX-2 inhibitors, in order to achieve improved anti-inflammatory activity and at the same time reduce the risk of side effects. Such agents should be devoid of COX-1-related side effects in, for example, the inhibition of blood coagulation and should only weakly affect COX-2 related functions of the central nervous system, due to slow blood-brain barrier penetration. We therefore propose that a drug combining the pharmacokinetic characteristics of, for example, ibuprofen with the COX-2 selectivity of rofecoxib is likely to be a superior anti-inflammatory analgesic. PMID:11695253

Brune, K; Neubert, A

2001-01-01

381

Cox report and the US-China arms control technical exchange program  

SciTech Connect

The ACE program furthered the national security interests of the US by promoting technical approaches to the implementation and verification of arms control treaties that the international community embraces. The Cox Committee report suggests that uncontrolled interactions were taking place between US and Chinese nuclear weapons scientists in the course of the ACE program. On the contrary, elaborate controls were in place at the very beginning and remained in place to control the interactions and protect US national security information. The ACE program payoff to national security was just beginning and its suspension, resulting from the Cox reports allegations, is a setback to US-China progress on arms control.

Di Capua, M S

1999-09-01

382

Expected estimating equations via EM for proportional hazards regression with covariate misclassification.  

PubMed

In epidemiological and medical studies, covariate misclassification may occur when the observed categorical variables are not perfect measurements for an unobserved categorical latent predictor. It is well known that covariate measurement error in Cox regression may lead to biased estimation. Misclassification in covariates will cause bias, and adjustment for misclassification will be challenging when the gold standard variables are not available. In general, statistical modeling for misclassification is very different from that of the measurement error. In this paper, we investigate an approximate induced hazard estimator and propose an expected estimating equation estimator via an expectation-maximization algorithm to accommodate covariate misclassification when multiple surrogate variables are available. Finite sample performance is examined via simulation studies. The proposed method and other methods are applied to a human immunodeficiency virus clinical trial in which a few behavior variables from questionnaires are used as surrogates for a latent behavior variable. PMID:23178735

Wang, Ching-Yun; Song, Xiao

2013-04-01

383

Design and synthesis of acyclic triaryl (Z)-olefins: a novel class of cyclooxygenase-2 (COX-2) inhibitors.  

PubMed

A group of acyclic 2-alkyl-1,1-diphenyl-2-(4-methylsulfonylphenyl)ethenes was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition structure-activity studies identified 1,1-diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene as a highly potent (IC(50) = 0.014 microM), and an extremely selective [COX-2 selectivity index (SI) > 7142], COX-2 inhibitor that showed superior anti-inflammatory (AI) activity (ID(50) = 2.5 mg/kg) relative to celecoxib (ID(50) = 10.8 mg/kg). This initial study was extended to include the design of a structurally related group of acyclic triaryl (Z)-olefins possessing an acetoxy (OAc) substituent at the para-position of the C-1 phenyl ring that is cis to a C-2 4-methylsulfonylphenyl substituent. COX-1 and COX-2 inhibition studies showed that (Z)-1-(4-acetoxyphenyl)-1-phenyl-2-(4-methylsulfonylphenyl)but-1-ene [(Z)-13b] is a potent (COX-1 IC(50) = 2.4 microM; COX-2 IC(50) = 0.03 microM), and selective (COX-2 SI = 81), COX-2 inhibitor which is a potent AI agent (ID(50) = 4.1mg/kg) with equipotent analgesic activity to celecoxib. A molecular modeling (docking) study showed that the SO(2)Me substituent of (Z)-13b inserts deep inside the 2 degrees -pocket of the COX-2 active site, where one of the O-atoms of SO(2) group undergoes a H-bonding interaction with Phe(518). The p-OAc substituent on the C-1 phenyl ring is oriented in a hydrophobic pocket comprised of Met(522), Gly(526), Trp(387), Tyr(348), and Tyr(385), and the C-2 ethyl substituent is oriented towards the mouth of the COX-2 channel in the vicinity of amino acid residues Arg(120), Leu(531), and Val(349). Structure-activity data acquired indicate that a (Z)-olefin having cis C-1 4-acetoxyphenyl (phenyl) and C-2 4-methylsulfonylphenyl substituents, and a C-1 phenyl substituent in conjunction with either a C-2 hydrogen or short alkyl substituent provides a novel template to design acyclic olefinic COX-2 inhibitors that, like aspirin, have the potential to acetylate COX-2. PMID:15498669

Uddin, Md Jashim; Rao, P N Praveen; Knaus, Edward E

2004-11-15

384

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

SciTech Connect

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

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

2012-08-31

385

Obtaining the best subset in regression analysis  

E-print Network

Sequence Second Sequence . 26 27 44 LIST OF FIGURES Figure Page 3. 1 3. 2 3. 3 3. 4 3. 5 3. 6 3. 7 3. 8 Graph of Alphas Graph of Alphas Graph of Alphas Graph of Alphas Graph of Mallows C Graph of Mallows C Graph of Mallows C Graph... in the regression equation, are used to evaluate the regressions. Subsets for which C is much greater than k indicate that important variables have been omitted from the regression. C. Garside Method: Garside ( 4 ) has developed an efficient method of computing...

Leslie, Robert Norton

2012-06-07

386

Regression of altitude-produced cardiac hypertrophy.  

NASA Technical Reports Server (NTRS)

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

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

1973-01-01

387

Medicare reimbursement and regression to the mean  

PubMed Central

There is evidence that Medicare's payment formula for health maintenance organizations (HMO's) overpays or underpays HMO's in cases of biased selection. There is also evidence that costs of biased groups regress toward the population mean cost, so the incorrect payment is temporary. We found that reimbursement regressed toward the mean for cohorts biased on medical use but not for groups biased on demographic factors. In a simulation of HMO-favorable selection, Medicare lost money in the first 3 years, but, because of regression toward the mean, early losses were recouped by the seventh year. PMID:10312522

Beebe, James C.

1988-01-01

388

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

PubMed

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

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

2014-09-16

389

Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study.  

PubMed

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC?? value of 0.45 ?M and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. PMID:21570309

El-Sayed, Magda A-A; Abdel-Aziz, Naglaa I; Abdel-Aziz, Alaa A-M; El-Azab, Adel S; Asiri, Yousif A; Eltahir, Kamal E H

2011-06-01

390

Novel pyrazoline derivatives as bi-inhibitor of COX-2 and B-Raf in treating cervical carcinoma.  

PubMed

Twenty four pyrazoline derivatives modified from Celecoxib were designed and synthesized as bi-inhibitor of COX-2 and B-Raf. They were evaluated for their COX-1/COX-2/B-Raf inhibitory and anti-proliferation activities. Compound A3 displayed the most potent activity against COX-2 and HeLa cell line (IC??=0.008 ?M; GI??=19.86 ?M) and showed superb COX-1/COX-2 selectivity (>500), being more potent and selective than positive control Celecoxib or 5-fluorouracil. Compounds A5 and B5 were introduced best B-Raf inhibitory activities (IC??=0.15 ?M and 0.12 ?M, respectively). Compound A4 retained superb bioactivity against COX-2 and HeLa cell line (IC??=0.015 ?M; GI??=23.82 ?M) and displayed moderate B-Raf inhibitory activity (IC??=3.84 ?M). Docking simulation was conducted to give binding patterns. QSAR models were built using bioactivity data and optimized conformations to provide a future modification of COX-2/B-Raf inhibitors. PMID:24934992

Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan

2014-08-01

391

Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors.  

PubMed

A series of 3-heteroaryloxy4-phenyl-2-5H)-furanones were prepared and evaluated for their potency and selectivity as COX-2 inhibitors. This led to the identification of L-778,736 as a potent, orally active and selective inhibitor of the COX-2 enzyme. PMID:10576685

Lau, C K; Brideau, C; Chan, C C; Charleson, S; Cromlish, W A; Ethier, D; Gauthier, J Y; Gordon, R; Guay, J; Kargman, S; Li, C S; Prasit, P; Riendeau, D; Thérien, M; Visco, D M; Xu, L

1999-11-15

392

Ann Williamson, Deputy Director, Office of Environmental Assessment Mike Cox, Manager, Risk Assessment Unit, Office of Environmental Assessment  

E-print Network

Ann Williamson, Deputy Director, Office of Environmental Assessment Mike Cox, Manager, Risk Assessment Unit, Office of Environmental Assessment U.S. Environmental Protection Agency ­ Region 10 Greg, WA Ann Williamson and Mike Cox, EPA Region 10 Office of Environmental Assessment, will be presenting

393

Mammalian Copper Chaperone Cox17p Has an Essential Role in Activation of Cytochrome c Oxidase and Embryonic Development  

Microsoft Academic Search

Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO) and for delivery of copper ions to the mitochondrion for insertion into the enzyme in yeast. Although this small protein has already been cloned or purified from humans, mice, and pigs, the function of Cox17p in the mammalian system has not yet been elucidated. In vitro biochemical data

Yoshinori Takahashi; Koichiro Kako; Shin-ichi Kashiwabara; Akio Takehara; Y. Inada; Hidenori Arai; Kazuto Nakada; Hiroko Kodama; Jun-ichi Hayashi; Tadashi Baba; Eisuke Munekata

2002-01-01

394

Relative contribution of acetylated cyclooxygenase (COX)-2 and 5-lipooxygenase (LOX) in regulating gastric mucosal integrity and adaptation to aspirin  

Microsoft Academic Search

In addition to inhibiting formation of prothrombotic eicosanoids, aspirin causes the acetylation of cyclooxygenase (COX)-2. The acetylated COX-2 remains active, and upon cell activation, initiates the generation of 15R-HETE, a lipid substrate for 5-lipoxygenase (LOX) leading to the formation of 15-epi-LXA4 (also termed \\

Stefano Fiorucci; Eleonora Distrutti; Octavio Menezes de Lima; Mario Romano; Andrea Mencarelli; Miriam Barbanti; Ernesto Palazzini; Antonio Morelli; John L. Wallace

2003-01-01

395

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

ERIC Educational Resources Information Center

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

Albrecht, Doris

2007-01-01

396

Sulfonilamidothiopyrimidone and thiopyrimidone derivatives as selective COX-2 inhibitors: synthesis, biological evaluation, and docking studies.  

PubMed

Newly synthesized sulfonilamidothiopyrimidone derivatives and a subset of 14 sulfonilamidothiopyrimidones and thiopyrimidones selected by an MTT assays cell viability guided selection from an in house collection were evaluated to determine the inhibitory effect on the PGE(2) formation in human peripheral blood lymphocytes (PBLs) using commercial ELISA. The newly synthesized sulfonilamidothiopyrimidone derivatives showed interesting pharmacological activities. Preliminary in vitro assays showed that compounds 2-5 are endowed with very high activity. Compound 2 was the most active as hCOX-2 inhibitor. The observed effects were not due to an inhibition of cell proliferation as proved by the BrdU assay. Western blot of COX-2 confirmed the inhibition on the PGE(2) secretion. Further evidence on the inhibitory potential and selectivity as COX-2 inhibitors of the selected compounds came from the in vitro screening. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data. Compounds 2-5 were able to fit into the active site of COX-2 with highest scores and interaction energies. Furthermore, compound 2, which showed an inhibition of around 50% on PGE(2) production, was the best scored in all the docking calculations carried out. PMID:23047231

Basile, Livia; Alvarez, Susana; Blanco, Almudena; Santagati, Andrea; Granata, Giuseppe; Di Pietro, Patrizia; Guccione, Salvatore; Muñoz-Fernández, M Ángeles

2012-11-01

397

Ediacaran terrane accretion within the ArabianNubian Shield Grant M. Cox a,  

E-print Network

Ediacaran terrane accretion within the Arabian­Nubian Shield Grant M. Cox a, , Christopher J. Lewis 22 February 2011 Available online 5 March 2011 Keywords: Arabian Nubian Shield Ediacaran Saudi Arabia in the Arabian­Nubian Shield, but we suggest even younger sutures lie further east beneath the Phanerozoic cover

398

Generalized anxiety and panic disorders: Response to Cox, Cohen, Direnfeld, and Swinson (1996)  

Microsoft Academic Search

Contrary to the contention of Cox, Cohen, Direnfeld and Swinson (1996, Behaviour Research and Therapy, 34, 949–954) that the Beck Anxiety Inventory (BAI; Beck & Steer, 1993, Manual for the Beck Anxiety Inventory) measures primarily symptoms associated with panic attacks rather than anxiety in general, we propose that the higher level of anxiety found in patients with panic disorders not

Robert A. Steer; Aaron T. Beck

1996-01-01

399

Solvent Effects on the Barrier to Rotation in Christopher Cox and Thomas Lectka*  

E-print Network

Solvent Effects on the Barrier to Rotation in Carbamates Christopher Cox and Thomas Lectka and understand the barrier to rotation about the C-N bond in amides.1 Carbamates, which also exhibit amides and carbamates share common features, the additional oxygen of the carbamate functionality exerts

Lectka, Thomas

400

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

E-print Network

to a study of risk factors of nursing cow infertility F Bugnard C Ducrot D Calavas Centre d factors of nursing cow infertility. The risk factors resulting from the 2 models were the same. The Cox'Eco- pathologie Animale in order to highlight the risk factors of nursing cow infertility. MATERIALS AND METHODS

Paris-Sud XI, Université de

401

Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products.  

PubMed

Glycyrrhiza glabra and its phytoconstituents have been known to possess widespread pharmacological properties as an anti-inflammatory, anti-viral, antitumour and hepatoprotective drug. In this study, we examined the inhibitory potential of extract of G. glabra (GutGard™) root and its phytoconstituents (glabridin, glycyrrhizin, and isoliquiritigenin) on both cyclooxygenase (COX) and lipoxygenase (LOX) products in order to understand the mechanism of its anti-inflammatory action. Inhibitory effect of GutGard™ and its phytoconstituents on lipopolysaccharide (LPS) induced prostaglandin E(2) (PGE(2)), calcimycin (A23187) induced thromboxane (TXB(2)), and leukotriene (LTB(4)) release was studied using murine macrophages (J774A.1) and human neutrophil (HL-60) cells. Results revealed that, G. glabra and glabridin significantly inhibited PGE(2), TXB(2) (COX) and LTB(4) (LOX), while, isoliquiritigenin exerted inhibitory effect only against COX products but failed to suppress LOX product. However, glycyrrhizin at the tested concentrations failed to exhibit inhibitory effect on both COX and LOX products. Here, we report for the first time that G. glabra (almost devoid of glycyrrhizin) exhibits anti-inflammatory property likely through the inhibition of PGE(2), TXB(2) and LTB(4) in mammalian cell assay system, which could be influenced in part by glabridin and isoliquiritigenin. PMID:20864324

Chandrasekaran, C V; Deepak, H B; Thiyagarajan, P; Kathiresan, S; Sangli, Gopal Krishna; Deepak, M; Agarwal, Amit

2011-02-15

402

SpanDex: Secure Password Tracking for Android Landon P. Cox  

E-print Network

SpanDex: Secure Password Tracking for Android Landon P. Cox Duke University Peter Gilbert Duke only one attempt for all users. 1 Introduction Today's consumer mobile platforms such as Android and iOS manage large ecosystems of untrusted third-party applications called "apps." Apps are often integrated

Cox, Landon

403

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

SciTech Connect

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

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

2013-10-11

404

EtherFuse: An Ethernet Watchdog Khaled Elmeleegy, Alan L. Cox, T. S. Eugene Ng  

E-print Network

Ethernet to speed the reconfiguration of the spanning tree and prevent congestion due to packet duplicationEtherFuse: An Ethernet Watchdog Khaled Elmeleegy, Alan L. Cox, T. S. Eugene Ng Department of Computer Science Rice University Abstract Ethernet is pervasive. This is due in part to its ease of use

Ng, T. S. Eugene

405

Scalable Ethernet for Data Centers Brent Stephens , Alan Cox , Wes Felter , Colin Dixon , and  

E-print Network

PAST Scalable Ethernet for Data Centers Brent Stephens , Alan Cox , Wes Felter , Colin Dixon , and John Carter Rice University IBM Research February 11th, 2013 Brent Stephens PAST: Scalable Ethernet for Data Centers 1 / 38 #12;PAST . . . . . . is a large flat Ethernet network for using arbitrary

Mellor-Crummey, John

406

Phil Cox Takes on APPA Presidency with Energy, Experience, and Commitment.  

ERIC Educational Resources Information Center

Describes the background, experience, and goals of Philip L. Cox, the new president of APPA, the Association of Higher Education Facilities Officers, who currently serves as director of facilities management for Cornell University in Ithaca, New York. Explores his vision for APPA. (EV)

Thaler-Carter, Ruth E.

2002-01-01

407

Modeling Charitable Giving Using a Box-Cox Standard Tobit Model  

Microsoft Academic Search

There is a large literature investigating the determinants of charitable giving, in particular, price and income elasticities. We find that many of the most often reported results from this literature rely on a model specification that is inappropriate when applied to recent Federal Tax File data. We develop a standard Tobit model with a Box-Cox transformation parameter that nests a

R. Hamilton Lankford; James S. Wyckoff

1991-01-01

408

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

PubMed

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

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

2005-10-01

409

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

E-print Network

correlated with a high pollutant elimination. In the present paper, we demonstrate that biodegradationORIGINAL PAPER H. H. J. Cox á T. T. Nguyen á M. A. Deshusses Toluene degradation in the recycle. One assumption commonly made for biotrickling ®lter modeling pur- poses is that biodegradation takes

410

Helicobacter pylori attenuates the delay in ulcer healing induced by aspirin and selective COX2 inhibitor  

Microsoft Academic Search

Helicobacter pylori (H. pylori) and NSAIDs are recognized as major pathogenic factors in peptic ulcer disease. However, whether these two factors exert synergistic or antagonistic effects on ulcer healing has not yet been fully explained. In this study, the effects of aspirin (ASA) alone and rofecoxib, a specific prostaglandin cyclooxygenase (COX)-2 inhibitor, were compared with that of ASA and rofecoxib

Tomasz Brzozowski; Peter C. Konturek; Zbigniew Sliwowski; Stanislaw Konturek; Wladyslaw Bielanski; Robert Pajdo; Danuta Drozdowicz; Eckhart Hahn

2002-01-01

411

Is there an inhibitory effect of COX2 inhibitors on bone healing?  

Microsoft Academic Search

The use of the new selective cyclooxygenase-2 (COX-2) inhibitors (such as celecoxib and rofecoxib) for the treatment of pain and inflammation caused by fractures, cementless total joint replacements, soft tissue healing to bone, and spinal fusion surgeries has been controversial due to the convincing data collected from nonspecific NSAIDs such as indomethacin and naproxen regarding their inhibitory effects on bone

Andrew B Seidenberg; Yuehuei H An

2004-01-01

412

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

Microsoft Academic Search

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

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

2004-01-01

413

COX2 is necessary for venous ligation-mediated bone adaptation in mice  

Microsoft Academic Search

In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by

H. Y. Stevens; D. R. Meays; J. Yeh; L. M. Bjursten; J. A. Frangos

2006-01-01

414

Prion Disease: Exponential Growth Requires Membrane Binding Daniel L. Cox,*y  

E-print Network

Prion Disease: Exponential Growth Requires Membrane Binding Daniel L. Cox,*y Rajiv R. P. Sing A hallmark feature of prions, whether in mammals or yeast and fungi, is exponential growth associated that the membrane is necessary for exponential growth of prion aggregates; without it, the kinetics is simply

Yang, Sichun

415

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

EPA Science Inventory

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

416

Thresholding Multivariate Regression and Generalized Principal Components  

E-print Network

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

Sun, Ranye

2014-03-17

417

A new bivariate negative binomial regression model  

NASA Astrophysics Data System (ADS)

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

Faroughi, Pouya; Ismail, Noriszura

2014-12-01

418

Developmental Regression in Children with Down Syndrome  

E-print Network

or pervasive developmental disorders and only one received the diagnosis of stereotype movement disorder with loss. With the onset of regression, data also showed that there was an emergence of maladaptive behaviors among participants. The most common...

Bernad Ripoll, Susana

2011-05-18

419

Introducing Evolutionary Computing in Regression Analysis  

NSDL National Science Digital Library

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

Akman, Olcay

420

Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor.  

PubMed

New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2-((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1?µM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenan-induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2?µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors. PMID:25303727

Rathore, Ankita; Rahman, Mujeeb Ur; Siddiqui, Anees Ahamad; Ali, Abuzer; Shaharyar, Mohammad

2014-12-01

421

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

PubMed

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

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

2013-05-13

422

Relationship between 12/15-lipoxygenase and COX-2 in mesangial cells: potential role in diabetic nephropathy.  

PubMed

The 12/15-lipoxygenase (12/15-LO) and cyclooxygenase-2 (COX-2) pathways of arachidonate metabolism have been implicated in the pathogenesis of diabetic nephropathy (DN). In this study, we evaluated whether there is an interplay between 12/15-LO and COX-2 pathways in mesangial cells (MC). We utilized MC, microdissected glomeruli and renal cortical tissues. Transfections with cDNAs or short hairpin RNAs (shRNAs) were performed to overexpress or knockdown 12/15-LO and COX-2, respectively. Reverse transcription-polymerase chain reactions and Western blotting were used for evaluating mRNA and protein expression, respectively. We observed that the expression of both 12/15-LO and COX-2 were increased in high glucose stimulated rat MC relative to normal glucose, and also in cortical tissues from diabetic db/db and streptozotocin-injected mice relative to corresponding control mice. Treatment of rat MC with the 12/15-LO product, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), significantly increased COX-2 expression as well as levels of the COX-2 product, prostaglandin E(2) (PGE(2)). Interestingly, treatment of rat MC with PGE(2) led to a reciprocal increase in 12/15-LO expression as well as levels of 12(S)-HETE. The 12/15-LO shRNA could significantly attenuate COX-2 protein expression and vice versa. Furthermore, COX-2 expression levels were lower in MC and glomeruli from 12/15-LO knockout mice relative to control. Conversely, mouse MC stably overexpressing 12/15-LO had greater levels of COX-2 expression relative to mock-transfected cells. These new results indicate for the first time that 12/15-LO and COX-2 pathways can cross-talk and activate each other in MC. These novel interactions may amplify their effects on the progression of DN. PMID:16514433

Xu, Z-G; Li, S-L; Lanting, L; Kim, Y-S; Shanmugam, N; Reddy, M A; Natarajan, R

2006-02-01

423

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

SciTech Connect

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

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

2012-11-15

424

COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB)  

PubMed Central

Background COX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased COX-2 gene expression is believed to participate in carcinogenesis. Recent studies have shown that COX-2 up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. COX-2 products stimulate endothelial cell proliferation and their overexpression has been demonstrated to be involved in the mechanism of decreased resistance to apoptosis. Suppressed angiogenesis was found in experimental animal studies as a consequence of null mutation of COX-2 gene in mice. Despite the role of COX-2 expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear. Methods Twenty three (23) patients with cytological diagnosis of PTC were evaluated. After FNAB examination, the needle was washed out with a lysis buffer and the obtained material was used for COX-2 expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. ?-actin was used as endogenous control. Relative COX-2 expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ??CT method. Results COX-2 gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG). Conclusions The preliminary results may indicate COX-2 role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis. PMID:21214962

2011-01-01

425

The Geometry of Enhancement in Multiple Regression  

ERIC Educational Resources Information Center

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

Waller, Niels G.

2011-01-01

426

Fuzzy multiple linear regression: A computational approach  

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

427

Multiple functional regression—II. Rotation followed by classical regression technique  

NASA Astrophysics Data System (ADS)

A method and FORTRAN program is presented for calculating a multivariate functional regression, analogous to the reduced major axis regression for the bivariate situation. The method is based on rotating the coordinates of the experimental points with respect to the axes. The rotation is such that the direction of distances whose sums of squares are to be minimized now are parallel to the " Y" axis. A classical regression, using matrix expressions, then is performed following which the best-fit line is rotated back to give its equation in the original space. The rotation is performed to give a regression in a direction proportional to the square roots of the total variances of the parameters in the regression (which is the reduced major axis regression for the bivariate situation). Standard errors of the regression coefficients are estimated by a Monte-Carlo method. The program also can perform a classical regression, simply be omitting the rotation phase. The two examples used in Part 1 are repeated. In both examples the program gives the same result for classical regression as other methods including the function minimization method of Part 1. The first example is a bivariate example and the program gives the same answer as analytical expressions for the reduced major axis regression. In the second, the multivariate example, the program gives the same result as the function minimization method of Part 1.

Kirby, J. M.

428

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

PubMed

A new group of 3-alkyl-2-aryl-1,3-thiazinan-4-ones, possessing a methylsulfonyl 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-benzyl-2-(4-methylsulfonylphenyl)-1,3-thiazinan-4-one (11a) as a potent (IC(50)=0.06 microM) and selective (selectivity index >285) COX-2 inhibitor. PMID:19447036

Zebardast, Tannaz; Zarghi, Afshin; Daraie, Bahram; Hedayati, Mehdi; Dadrass, Orkideh G

2009-06-15

429

Univariate versus Bivariate analysis and synthesis of floods to assess the risk of overtopping a dam - a case study for Argentina  

NASA Astrophysics Data System (ADS)

Considering floods as multivariate events allows a better representation of the process generating them. In this work the relevance of multivariate analysis for designing or assessing the risk of overtopping a dam is discussed. Generally, peak flow and volume are two statistically dependent variables; therefore they are used to characterize the flood events. A bivariate statistical frequency analysis is carried out to find a suitable model that adequately represents the data set of flood peak flow and volume. The dependence between the variables is modeled with a copula. The copula model is used to generate 1000 random pairs of variables characterizing the flood, which are transformed into hydrographs. The shape of the floods is modeled using a Beta distribution function. The synthetic flood events are routed through a reservoir to assess its behavior. The maximum water levels and outflows are computed for all hydrograph and compared to estimations considering peak flow and volume separately. The analysis is carried out using flood peak and volume series observed in the river Agrio basin with a drainage area of 7300 km2, located in the province of Neuquén, Argentina. The results show that the maximum water levels and outflows obtained based on the bivariate approach are higher compared to the univariate case. If the risk of an existing dam is to be assessed, the bivariate approach would indicate a greater risk of overtopping the dam for a given dam height and spillway geometry. If a dam is to be designed considering the joint behavior of both variables would result in a smaller risk for the structure compared to the univariate case.

Callau Poduje, Ana Claudia; Haberlandt, Uwe

2013-04-01

430

Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.  

PubMed

Tight regulation of COX-2 expression is a key feature controlling eicosanoid production in atherosclerosis and other inflammatory syndromes. Adhesive interactions between platelets and monocytes occur in these conditions and deliver specific signals that trigger inflammatory gene expression. Using a cellular model of monocyte signaling induced by activated human platelets, we identified the central posttranscriptional mechanisms that regulate timing and magnitude of COX-2 expression. Tethering of monocytes to platelets and to purified P-selectin, a key adhesion molecule displayed by activated platelets, induces NF-kappaB activation and COX-2 promoter activity. Nevertheless, COX-2 mRNA is rapidly degraded, leading to aborted protein synthesis. Time-dependent signaling of monocytes induces a second phase of transcript accumulation accompanied by COX-2 enzyme synthesis and eicosanoid production. Here, generation of IL-1beta, a proinflammatory cytokine, promoted stabilization of COX-2 mRNA by silencing of the AU-rich mRNA decay element (ARE) in the 3'-untranslated region (3'UTR) of the mRNA. Consistent with observed mRNA stabilization, activated platelets or IL-1beta treatment induced cytoplasmic accumulation and enhanced ARE binding of the mRNA stability factor HuR in monocytes. These findings demonstrate that activated platelets induce COX-2 synthesis in monocytes by combinatorial signaling to transcriptional and posttranscriptional checkpoints. These checkpoints may be altered in disease and therefore useful as targets for antiinflammatory intervention. PMID:16998585

Dixon, Dan A; Tolley, Neal D; Bemis-Standoli, Kristi; Martinez, Mark L; Weyrich, Andrew S; Morrow, Jason D; Prescott, Stephen M; Zimmerman, Guy A

2006-10-01

431

Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.  

PubMed

COX inhibitors which selectively inhibits the inducible COX-2 is an oenzyme that causes inflammation. They are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicity. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular trombotic events such as myocardial infarction. Therefore, there is still a need to develop better therapeutic effect and tolerability COX-2 inhibitor. The majority of COX-2 inhibitors are diaryl heterocycles. For optimum COX-2 selectivity and inhibitory potency a -SO(3)CH(3) or a- SO(2)NH(2) substituent at the para-position of phenyl ring was essential. A wide variety of heterocycles can serve as central ring system of the diaryl heterocycles structures. We report the screening of various 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety, directly or indirectly bound to the ring system, using the Protein-Ligand ANT System (PLANTS) docking software against the COX-2 enzyme. Various molecular structures of ligands were docked and scored to identify structurally similar ligands to SC-558 (reference ligand) in binding interaction to COX-2 binding site. The results show that 2,3-disubstituted-4(3H)-quinazolinones possess pbenzenesulfonamide moiety at C-2, and phenyl moiety at N-3 binds directly or indirectly to the ring system with high binding affinity. The docked ligand has orientations similar to that observed with SC-558 satisfying Lipinski's rule of five. PMID:22125393

Hayun; Yanuar, Arry; Hanafi, Muhammad; Pws, Sumi Hudiyono

2011-01-01

432

Differential effect of DDT, DDE, and DDD on COX-2 expression in the human trophoblast derived HTR-8/SVneo cells.  

PubMed

The purpose of this study was to investigate the effect of 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) isomers on COX-2 expression in a human trophoblast-derived cell line. Cultured HTR-8/SVneo trophoblast cells were exposed to DDT isomers and its metabolites for 24 h, and COX-2 mRNA and protein expression were assessed by RT-PCR, Western blotting, and ELISA. Prostaglandin E? production was also measured by ELISA. Both COX-2 mRNA and protein were detected under control (unexposed) conditions in the HTR-8/SVneo cell line. COX-2 protein expression and prostaglandin E? production but not COX-2 mRNA levels increased only after DDE and DDD isomers exposure. It is concluded that DDE and DDD exposure induce the expression of COX-2 protein, leading to increased prostaglandin E2 production. Interestingly, the regulation of COX-2 by these organochlorines pesticides appears to be at the translational level. PMID:23132776

Dominguez-Lopez, Pablo; Diaz-Cueto, Laura; Olivares, Aleida; Ulloa-Aguirre, Alfredo; Arechavaleta-Velasco, Fabian

2012-11-01

433

Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and mononuclear cells by NSAIDs and Cox 2 inhibitors.  

PubMed

A range of NSAIDs and reported Cox 2 selective compounds were tested in human freshly isolated platelets and LPS-stimulated mononuclear cells to determine their potency and selectivity as inhibitors of constitutive (presumably Cox 1) and inducible (presumably Cox 2) cyclooxygenase respectively. All compounds tested were either equipotent at inhibiting constitutive and inducible cyclooxygenase or were selective for the inducible form. The most selective compound was Dup697 and the least selective, ketoprofen. Several compounds only produced a partial inhibition of constitutive cyclooxygenase as the maximum inhibitor concentration achievable in the assay was limited to 1 mM. With the exception of paracetamol, all compounds were able to produce full inhibition curves against the inducible form. Potency estimates against constitutive Cox compare closely with published data but most compounds were consistently more potent against the inducible isoform than in published data for human cloned, microsomal Cox 2. These data suggest that human mononuclear cells are either exquisitely sensitive to some NSAIDs or they may contain another Cox isoform as yet indistinguishable from Cox 2. PMID:7583521

Grossman, C J; Wiseman, J; Lucas, F S; Trevethick, M A; Birch, P J

1995-06-01

434

The MIF homologue D-dopachrome tautomerase promotes COX-2 expression through ?-catenin-dependent and -independent mechanisms.  

PubMed

The cytokine/growth factor, macrophage migration inhibitory factor (MIF), contributes to pathologies associated with immune, inflammatory, and neoplastic disease processes. Several studies have shown an important contributing role for MIF-dependent COX-2 expression in the progression of these disorders. We now report that the MIF homologue, D-dopachrome tautomerase (D-DT), is both sufficient and necessary for maximal COX-2 expression in colorectal adenocarcinoma cell lines. D-DT-dependent COX-2 transcription is mediated in part by ?-catenin protein stabilization and subsequent transcription. Also contributing to D-DTs regulation of COX-2 expression are the activities of both c-jun-N-terminal kinase and the MIF-interacting protein, Jab1/CSN5. Interestingly, D-DT-dependent ?-catenin stabilization is regulated by COX-2 expression, suggesting the existence of an amplification loop between COX-2- and ?-catenin-mediated transcription in these cells. Because both COX-2- and ?-catenin-mediated transcription are important contributors to colorectal cancer (CRC) disease maintenance and progression, these findings suggest a unique and novel regulatory role for MIF family members in CRC pathogenesis. PMID:21071513

Xin, Dan; Rendon, Beatriz E; Zhao, Ming; Winner, Millicent; McGhee Coleman, Arlixer; Mitchell, Robert A

2010-12-01

435

Cyclooxygenase-2 (COX-2) mediates arsenite inhibition of UVB-induced cellular apoptosis in mouse epidermal Cl41 cells.  

PubMed

Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 ?M) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a coinductive effect on COX-2 expression and nuclear factor-?B (NF?B) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NF?B pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NF?B-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis. PMID:22463588

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

2012-07-01

436

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

PubMed Central

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

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

2013-01-01

437

Proportional hazards regression in epidemiologic follow-up studies: an intuitive consideration of primary time scale.  

PubMed

In epidemiologic cohort studies of chronic diseases, such as heart disease or cancer, confounding by age can bias the estimated effects of risk factors under study. With Cox proportional-hazards regression modeling in such studies, it would generally be recommended that chronological age be handled nonparametrically as the primary time scale. However, studies involving baseline measurements of biomarkers or other factors frequently use follow-up time since measurement as the primary time scale, with no explicit justification. The effects of age are adjusted for by modeling age at entry as a parametric covariate. Parametric adjustment raises the question of model adequacy, in that it assumes a known functional relationship between age and disease, whereas using age as the primary time scale does not. We illustrate this graphically and show intuitively why the parametric approach to age adjustment using follow-up time as the primary time scale provides a poor approximation to age-specific incidence. Adequate parametric adjustment for age could require extensive modeling, which is wasteful, given the simplicity of using age as the primary time scale. Furthermore, the underlying hazard with follow-up time based on arbitrary timing of study initiation may have no inherent meaning in terms of risk. Given the potential for biased risk estimates, age should be considered as the preferred time scale for proportional-hazards regression with epidemiologic follow-up data when confounding by age is a concern. PMID:22517300

Cologne, John; Hsu, Wan-Ling; Abbott, Robert D; Ohishi, Waka; Grant, Eric J; Fujiwara, Saeko; Cullings, Harry M

2012-07-01

438

An empirical evaluation of spatial regression models  

NASA Astrophysics Data System (ADS)

Conventional statistical methods are often ineffective to evaluate spatial regression models. One reason is that spatial regression models usually have more parameters or smaller sample sizes than a simple model, so their degree of freedom is reduced. Thus, it is often unlikely to evaluate them based on traditional tests. Another reason, which is theoretically associated with statistical methods, is that statistical criteria are crucially dependent on such assumptions as normality, independence, and homogeneity. This may create problems because the assumptions are open for testing. In view of these problems, this paper proposes an alternative empirical evaluation method. To illustrate the idea, a few hedonic regression models for a house and land price data set are evaluated, including a simple, ordinary linear regression model and three spatial models. Their performance as to how well the price of the house and land can be predicted is examined. With a cross-validation technique, the prices at each sample point are predicted with a model estimated with the samples excluding the one being concerned. Then, empirical criteria are established whereby the predicted prices are compared with the real, observed prices. The proposed method provides an objective guidance for the selection of a suitable model specification for a data set. Moreover, the method is seen as an alternative way to test the significance of the spatial relationships being concerned in spatial regression models.

Gao, Xiaolu; Asami, Yasushi; Chung, Chang-Jo F.

2006-10-01

439

O-desmethylquinine as a cyclooxygenase-2 (COX-2) inhibitors using AutoDock Vina  

NASA Astrophysics Data System (ADS)

Computational approach was employed to evaluate the biological activity of novel cyclooxygenase-2 COX-2 inhibitor, O-desmethylquinine, in comparison to quinine as common inhibitor which can also be used an agent of antipyretic, antimalaria, analgesic and antiinflamation. The molecular models of the compound were constructed and optimized with the density function theory with at the B3LYP/6-31G (d,p) level using Gaussian 09 program. Molecular docking studies of the compounds were done to obtain the COX-2 complex structures and their binding energies were analyzed using the AutoDock Vina. The results of docking of the two ligands were comparable and cannot be differentiated from the energy scoring function with AutoDock Vina.

Damayanti, Sophi; Mahardhika, Andhika Bintang; Ibrahim, Slamet; Chong, Wei Lim; Lee, Vannajan Sanghiran; Tjahjono, Daryono Hadi

2014-10-01

440

Aerobic oxidation of hydroxymethylfurfural and furfural by using heterogeneous cox oy -n@c catalysts.  

PubMed

2,5-Furandicarboxylic acid (FDCA) is considered to be a promising replacement for terephthalic acid since they share similar structures and properties. In contrast to FDCA, 2,5-furandicarboxylic acid methyl (FDCAM) has properties that allow it to be easily purified. In this work, we reported an oxidative esterification of 5-hydroxymethylfurfural (HMF) and furfural to prepare corresponding esters over Cox Oy -N@C catalysts using O2 as benign oxidant. High yield and selectivity of FDCAM and methyl 2-furoate were obtained under optimized conditions. Factors which influenced the product distribution were examined thoroughly. The Cox Oy -N@C catalysts were recycled five times and no significant loss of activity was detected. Characterization of the catalysts could explain such phenomena. Using XPS and TGA, we made a thorough investigation of the effects of ligand and pyrolysis temperature on catalyst activity. PMID:25353711

Deng, Jin; Song, Hai-Jie; Cui, Min-Shu; Du, Yi-Ping; Fu, Yao

2014-12-01

441

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

PubMed

The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independ