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Adaptive regression splines in the Cox model.  


We develop a method for constructing adaptive regression spline models for the exploration of survival data. The method combines Cox's (1972, Journal of the Royal Statistical Society, Series B 34, 187-200) regression model with a weighted least-squares version of the multivariate adaptive regressi on spline (MARS) technique of Friedman (1991, Annals of Statistics 19, 1-141) to adaptively select the knots and covariates. The new technique can automatically fit models with terms that represent nonlinear effects and interactions among covariates. Applications based on simulated data and data from a clinical trial for myeloma are presented. Results from the myeloma application identified several important prognostic variables, including a possible nonmonotone relationship with survival in one laboratory variable. Results are compared to those from the adaptive hazard regression (HARE) method of Kooperberg, Stone, and Truong (1995, Journal of the American Statistical Association 90, 78-94). PMID:11318156

LeBlanc, M; Crowley, J



Misspecification of Cox regression models with composite endpoints  

PubMed Central

Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22736519

Wu, Longyang; Cook, Richard J



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 PMID:24516529

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



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

E-print Network

i n f o Available online 3 August 2011 Keywords: Popularity of online contents Survival analysis Cox the popularity of contents only with publicly available information. Thus, the goal of our proposed methodologyModeling and predicting the popularity of online contents with Cox proportional hazard regression

Moon, Sue B.


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


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


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

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



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

The aim of this paper is to compare the results of two statistical methods for landslide susceptibility analysis: 1) univariate probabilistic method based on landslide susceptibility index, 2) multivariate method (logistic regression). The study area is the Febbraro valley, located in the central Italian Alps, where different types of metamorphic rocks croup out. On the eastern part of the studied

M. Rossi; T. Apuani; F. Felletti



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

Microsoft Academic Search

Background  We investigated dynamic patterns and predictors of HPV vaccination initiation in Flanders (Belgium) by girls aged 12 to 18,\\u000a between 2007 and 2009, the period immediately after the introduction of the HPV vaccines on the Belgian market. During this\\u000a period the initiative for vaccination was taken by the girl, her family or the general practitioner\\/pediatrician\\/gynecologist.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We used a Cox regression

Eva Lefevere; Niel Hens; Frank De Smet; Pierre Van Damme



A new method to analyse the pace of child development: Cox regression validated by a bootstrap resampling procedure  

PubMed Central

Background Various perinatal factors influencing neuromotor development are known from cross sectional studies. Factors influencing the age at which distinct abilities are acquired are uncertain. We hypothesized that the Cox regression model might identify these factors. Methods Neonates treated at Aachen University Hospital in 2000/2001 were identified retrospectively (n = 796). Outcome data, based on a structured interview, were available from 466 children, as were perinatal data. Factors possibly related to outcome were identified by bootstrap selection and then included into a multivariate Cox regression model. To evaluate if the parental assessment might change with the time elapsed since birth we studied five age cohorts of 163 normally developed children. Results Birth weight, gestational age, congenital cardiac disease and periventricular leukomalacia were related to outcome in the multivariate analysis (p < 0.05). Analysis of the control cohorts revealed that the parents' assessment of the ability of bladder control is modified by the time elapsed since birth. Conclusions Combined application of the bootstrap resampling procedure and multivariate Cox regression analysis effectively identifies perinatal factors influencing the age at which distinct abilities are acquired. These were similar as known from previous cross sectional studies. Retrospective data acquistion may lead to a bias because the parental memories change with time. This recommends applying this statistical approach in larger prospective trials. PMID:20205739



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.



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


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 Published online 24 February 2004 PMID:15026798

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



Bootstrap-based methods for estimating standard errors in Cox's regression analyses of clustered event times.  


We propose two bootstrap-based methods to correct the standard errors (SEs) from Cox's model for within-cluster correlation of right-censored event times. The cluster-bootstrap method resamples, with replacement, only the clusters, whereas the two-step bootstrap method resamples (i) the clusters, and (ii) individuals within each selected cluster, with replacement. In simulations, we evaluate both methods and compare them with the existing robust variance estimator and the shared gamma frailty model, which are available in statistical software packages. We simulate clustered event time data, with latent cluster-level random effects, which are ignored in the conventional Cox's model. For cluster-level covariates, both proposed bootstrap methods yield accurate SEs, and type I error rates, and acceptable coverage rates, regardless of the true random effects distribution, and avoid serious variance under-estimation by conventional Cox-based standard errors. However, the two-step bootstrap method over-estimates the variance for individual-level covariates. We also apply the proposed bootstrap methods to obtain confidence bands around flexible estimates of time-dependent effects in a real-life analysis of cluster event times. PMID:20213705

Xiao, Yongling; Abrahamowicz, Michal



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


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

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



Univariate and Bivariate Data  

NSDL National Science Digital Library

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




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



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


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

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



COX-1 and COX-3 inhibitors.  


Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory action of aspirin requires a much higher dose. It is possible that inhibition of cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic and antipyretic effects, and inhibition of COX-2 is responsible for its anti-inflammatory action. We compared the analgesic effects of an aspirin-like drug (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse stretching test and confirmed that the analgesic action of the aspirin-like drug was peripheral. Two possible sites have been postulated for the antipyretic action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in endothelial cells of hypothalamic blood vessels or (b) inhibition of COX synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal afferents. The antipyretic action of aspirin may be mediated by inhibition of COX-3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to sensory receptors of peripheral vagal afferents. It is also possible that both enzymes are involved in the antipyretic action of aspirin. Whereas lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice, suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection. PMID:14592546

Botting, Regina



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

PubMed Central

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

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



HyperStat Online: Describing Univariate Data  

NSDL National Science Digital Library

This site from David Lane features the univariate data chapter of an online statistics text. Median, mean, and mode are discussed along with spreads, skews and different types of graphs. There are also exercises and links to other statistics sites.

Lane, David M.


Univariate input models for stochastic simulation  

Microsoft Academic Search

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

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



Manuals for Univariate and Multivariate Statistics  

NSDL National Science Digital Library

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

Wendorf, Craig A.



Lab 2--Investigating Univariate Data Introduction  

E-print Network

="Histogram of Text Messages Yesterday", xlab="text messages") Note that we initially read in the data file classdata to your WORD. stem(data1[,2]) HOMEWORK [5]: Open the data file marriage_ages.csv and produce histogramLab 2--Investigating Univariate Data Introduction: In this lab we will read in some quantitative

Steele, Brian


Cox Process Learning Gerard Biau  

E-print Network

, and if the jump size of N at time t is, with probability one, either 0 or 1. In more pedestrian terms, the process stochastic Poisson processes). In a word, we say that N is a Cox process with (random) intensity process process with intensity function . Thus, a Cox process is a generalization of a Poisson process where

Boyer, Edmond


Adams & Cox Simple Proofreading Circuit  

E-print Network

Adams & Cox Simple Proofreading Circuit Hebbian Proofreading ­ the J-I connection is Hebbian. This arrangement corresponds to that found biologically (e.g. Sherman and Guillery; Callaway). The layer 6 cell evidence. #12;Adams & Cox Push-Pull Proofreading Circuit Simple proofreading lowers the error rate

Adams, Paul R.


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

E-print Network

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

Goldstein, Larry


Quantile Regression with Censored Data  

ERIC Educational Resources Information Center

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

Lin, Guixian



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

PubMed Central

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763

Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza




EPA Science Inventory

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


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



COX-1 and COX-2 expression in osteoid osteomas.  


Osteoid osteoma is a benign bone forming neoplasm that is characterized by its small size (less than 2 cm), self-limited growth, and the tendency to cause extensive reactive changes in the adjacent tissue. The lesion classically presents with severe pain at night that is dramatically relieved by NSAIDs. The tumor has been shown to express very high levels of prostaglandins, particularly PGE2 and PGI2. The high local levels of these prostaglandins are presumed to be the cause of the intense pain seen in patients with this lesion. One generally accepted form of treatment is the prolonged use of NSAIDs. Since the cyclooxygenases are thought to be the source of these prostaglandins, and the central target of NSAIDs, we evaluated the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in osteoid osteoma tissues from patients following surgery. In the 12 specimens examined we found that the tumor osteoblasts had strong immunohistochemical staining for COX-2, while the staining in the surrounding host osteoblasts in the reactive bone was scant. Significant COX-1 staining was also detected in both tumor and host osteoblasts. For comparison we examined the COX expression in human fracture callus, fibrous dysplasia, osteoblastoma, osteofibrous dysplasia, and myositis ossificans. With the exception of fracture callus, very limited amounts of COX-2 could be detected in these tissues. Taken together, we conclude that the increased production of prostaglandins by osteoid osteomas implicates that COX-2 is one of the mediators of this condition. These findings suggest that the newly selective COX-2 inhibitors could be used to more safely treat osteoid osteomas. PMID:11853083

Mungo, David V; Zhang, Xinping; O'Keefe, Regis J; Rosier, Randy N; Puzas, J Edward; Schwarz, Edward M



High Dimensional Model Representation Supported by Products of Univariate Functions  

NASA Astrophysics Data System (ADS)

This work extends the High Dimensional Model Representation (HDMR) proposed by Sobol and many contributions to the development have been made by some other authors including Rabitz and his group and the author and his group. The additivity measurers developed and used by the author and his group enabled us to measure the truncation approximation quality of HDMR. Now it is very well known that the multiplicativity in the target function of HDMR prevents to truncate it at univariate or at most bivariate level. It requires all expansion. In HDMR an ascending multivariance structure is used. Hence the leading constant component is followed by the univariate, bivariate terms and so on. This work extends the representation by feeding univariate factors to support each such term in missing variables. The result is a new representation which is enable us to exactly have the target function at the first component even if it is purely multiplicative.

Demiralp, Metin



A univariate model for long-term streamflow forecasting  

NASA Astrophysics Data System (ADS)

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

Krstanovic, P. F.; Singh, V. P.



Univariate Modeling and Forecasting of Monthly Energy Demand Time Series  

E-print Network

Univariate Modeling and Forecasting of Monthly Energy Demand Time Series Using Abductive and Neural Networks R. E. Abdel-Aal Computer Engineering Department, King Fahd University of Petroleum and Minerals Neural networks have been widely used for short-term, and to a lesser degree medium and long term, demand

Abdel-Aal, Radwan E.


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.


Estimating Components of Univariate Gaussian Mixtures Using Prony's Method  

Microsoft Academic Search

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

Haluk Derin



HUMANITIES 1 Professor Stephen Cox  

E-print Network

HUMANITIES 1 Professor Stephen Cox Winter 2013 Books: The Bible (King James Version), American Bible Society or any other publisher of this version. It must say "King James" on the title page­not "New King James," etc. Homer, Odyssey (Fitzgerald translation), Farrar, Straus, Giroux Plato, Symposium

Blanco, Philip R.


HUMANITIES 1 Professor Stephen Cox  

E-print Network

HUMANITIES 1 Professor Stephen Cox Winter 2012 Books: The Bible (King James Version), American Bible Society or any other publisher of this version. It must say "King James" on the title page­not "New King James, etc. Homer, Odyssey (Fitzgerald translation), Farrar, Straus, Giroux Plato, Symposium

Russell, Lynn


Title stpower cox — Sample size, power, and effect size for the Cox proportional hazards model Syntax Menu Description Options Remarks and examples Stored results Methods and formulas References Also see Syntax  

E-print Network

Sample-size determination stpower cox [ coef] [ , options] Power determination stpower cox [ coef] , n(numlist) [ options] Effect-size determination stpower cox, n(numlist) { power(numlist) | beta(numlist) } [ options] where coef is the regression coefficient (effect size) of a covariate of interest, in a Cox proportional hazards model, desired to be detected by a test with a prespecified power. coef may be specified either as one number or as a list of values (see [U] 11.1.8 numlist) enclosed in parentheses. options

unknown authors


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



Incorporating published univariable associations in diagnostic and prognostic modeling  

PubMed Central

Background Diagnostic and prognostic literature is overwhelmed with studies reporting univariable predictor-outcome associations. Currently, methods to incorporate such information in the construction of a prediction model are underdeveloped and unfamiliar to many researchers. Methods This article aims to improve upon an adaptation method originally proposed by Greenland (1987) and Steyerberg (2000) to incorporate previously published univariable associations in the construction of a novel prediction model. The proposed method improves upon the variance estimation component by reconfiguring the adaptation process in established theory and making it more robust. Different variants of the proposed method were tested in a simulation study, where performance was measured by comparing estimated associations with their predefined values according to the Mean Squared Error and coverage of the 90% confidence intervals. Results Results demonstrate that performance of estimated multivariable associations considerably improves for small datasets where external evidence is included. Although the error of estimated associations decreases with increasing amount of individual participant data, it does not disappear completely, even in very large datasets. Conclusions The proposed method to aggregate previously published univariable associations with individual participant data in the construction of a novel prediction models outperforms established approaches and is especially worthwhile when relatively limited individual participant data are available. PMID:22883206



Evaluation of droplet size distributions using univariate and multivariate approaches.  


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



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



Detection of synchronization from univariate data using wavelet transform  

NASA Astrophysics Data System (ADS)

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

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



Cache Complexity and Multicore Implementation for Univariate Real Root Isolation  

NASA Astrophysics Data System (ADS)

We present parallel algorithms with optimal cache complexity for the kernel routine of many real root isolation algorithms, namely the Taylor shift by 1. We then report on multicore implementation for isolating the real roots of univariate polynomials with integer coefficients based on a classical algorithm due to Vincent, Collins and Akritas. For processing some well-known benchmark examples with sufficiently large size, our software tool reaches linear speedup on an 8-core machine. In addition, we show that our software is able to fully utilize the many cores and the memory space of a 32-core machine to tackle large problems that are out of reach for a desktop implementation.

Chen, Changbo; Moreno Maza, Marc; Xie, Yuzhen



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

Microsoft Academic Search

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

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



The Pathways for Intelligible Speech: Multivariate and Univariate Perspectives  

PubMed Central

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.; Mourao-Miranda, J.; Wise, R.J.S.; Scott, S.K.



Allan Cox 1926”1987  

NASA Astrophysics Data System (ADS)

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

Coe, Rob; Dalrymple, Brent


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

SciTech Connect

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

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



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



A proposal for variable selection in the Cox model Robert Tibshirani  

E-print Network

A proposal for variable selection in the Cox model Robert Tibshirani Department of Preventive. The method is a variation of the ``lasso'' proposal of Tibshirani (1994), designed for the linear regression, Tibshirani (1994) proposed minimization of the residual sum of squares, subject to a constraint of the form P

Tibshirani, Robeert


Autistic Regression  

ERIC Educational Resources Information Center

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

Matson, Johnny L.; Kozlowski, Alison M.



Survival analysis and regression models  

PubMed Central

Time-to-event outcomes are common in medical research as they offer more information than simply whether or not an event occurred. To handle these outcomes, as well as censored observations where the event was not observed during follow-up, survival analysis methods should be used. Kaplan-Meier estimation can be used to create graphs of the observed survival curves, while the log-rank test can be used to compare curves from different groups. If it is desired to test continuous predictors or to test multiple covariates at once, survival regression models such as the Cox model or the accelerated failure time model (AFT) should be used. The choice of model should depend on whether or not the assumption of the model (proportional hazards for the Cox model, a parametric distribution of the event times for the AFT model) is met. The goal of this paper is to review basic concepts of survival analysis. Discussions relating the Cox model and the AFT model will be provided. The use and interpretation of the survival methods model are illustrated using an artificially simulated dataset. PMID:24810431

George, Brandon; Seals, Samantha; Aban, Inmaculada



Collision prediction models using multivariate Poisson-lognormal regression  

Microsoft Academic Search

This paper advocates the use of multivariate Poisson-lognormal (MVPLN) regression to develop models for collision count data. The MVPLN approach presents an opportunity to incorporate the correlations across collision severity levels and their influence on safety analyses. The paper introduces a new multivariate hazardous location identification technique, which generalizes the univariate posterior probability of excess that has been commonly proposed

Karim El-Basyouny; Tarek Sayed



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



COX2 selective NSAID decreases bone ingrowth in vivo  

Microsoft Academic Search

Whether non-steroidal anti-inflammatory drug (NSAID)––induced suppression of bone ingrowth is due to cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, or through a yet unidentified pathway is unknown. In this study, the effects of a non-specific COX-1 and COX-2 inhibitor, versus a specific COX-2 inhibitor on bone ingrowth and tissue differentiation are examined in vivo. Harvest chambers were implanted unilaterally in the

Stuart Goodman; Ting Ma; Michael Trindade; Takashi Ikenoue; Ippe Matsuura; Neal Wong; Nora Fox; Mark Genovese; Don Regula



Finite-Sample Diagnostics for Multivariate Regressions with Applications to Linear Asset Pricing Models  

Microsoft Academic Search

In this paper, we propose several finite-sample specification tests for multivariate linear regressions (MLR) with applications to asset pricing models. We focus on departures from the assumption of i.i.d. errors assumption, at univariate and multivariate levels, with Gaussian and non-Gaussian (including Student t) errors. The univariate tests studied extend existing exact procedures by allowing for unspecified parameters in the error

Jean-Marie Dufour; Lynda Khalaf; Marie-Claude Beaulieu



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.


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 environments requires an understanding of the im- pacts on water quality and an understanding of the e#11;ectiveness of man- agement actions. Monitoring programs to assess water quality typically aim to assess

Smyth, Gordon K.


Estimating Transformations for Regression via Additivity and Variance Stabilization  

Microsoft Academic Search

I propose a method for the nonparametric estimation of transformations for regression. It is much more flexible than the familiar Box-Cox procedure, allowing general smooth transformations of the variables, and is similar to the ACE (alternating conditional expectation) algorithm of Breiman and Friedman (1985). The ACE procedure uses scatterplot smoothers in an iterative fashion to find the maximally correlated transformations

Robert Tibshirani



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

E-print Network

, Horn, Susse, Vollandt, & Weiss, 2005; Lage-Castellanos, Martinez-Mon- tes, Hernandez-Cabrera, & Galan, 2010; Maris & Oostenveld, 2007), mass univariate analyses do not yet enjoy the widespread application

Kutas, Marta



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.


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.



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



How to make R, PostGIS and QGis cooperate for statistical modelling duties: a case study on hedonic regressions  

E-print Network

­ LVMT Hedonic regressions used to model housing prices are a good example), pi the housing prices (or more generally Box- Cox transforms of these prices price databases. The location of each housing consists in a postal addresses

Paris-Sud XI, Université de


A simple method for estimating relative risk using logistic regression  

PubMed Central

Background Odds ratios (OR) significantly overestimate associations between risk factors and common outcomes. The estimation of relative risks (RR) or prevalence ratios (PR) has represented a statistical challenge in multivariate analysis and, furthermore, some researchers do not have access to the available methods. Objective: To propose and evaluate a new method for estimating RR and PR by logistic regression. Methods A provisional database was designed in which events were duplicated but identified as non-events. After, a logistic regression was performed and effect measures were calculated, which were considered RR estimations. This method was compared with binomial regression, Cox regression with robust variance and ordinary logistic regression in analyses with three outcomes of different frequencies. Results ORs estimated by ordinary logistic regression progressively overestimated RRs as the outcome frequency increased. RRs estimated by Cox regression and the method proposed in this article were similar to those estimated by binomial regression for every outcome. However, confidence intervals were wider with the proposed method. Conclusion This simple tool could be useful for calculating the effect of risk factors and the impact of health interventions in developing countries when other statistical strategies are not available. PMID:22335836



Electron Spectroscopy of COx Magnetron Sputtered Films  

NASA Astrophysics Data System (ADS)

COx films were deposited by magnetron sputtering of a graphite target within two different routes: (i) by sputtering in an Ar+O2 gas mixture or (ii) by sputtering in pure Ar followed by annealing at 300 °C in air. Surface composition and chemical bonding was studied by X-ray induced photoelectron and Auger electron spectroscopy (XPS/XAES), and electron energy loss spectroscopy (EELS) in a low energy loss region. Oxygen content reached ˜20 at. % in the COx layers, independent on the route used. The C 1s spectral line shapes indicate C-O and C=O bonding states, regardless dominating C-C and CHx bonds. Substantial differences were found in the XAES and reflection electron energy loss spectra (REELS) recorded from surface regions of the samples. The both spectra indicate dominating sp2 bonding of carbon atoms in an analyzed volume of COx films sputtered in Ar and oxidized in air at elevated temperature whereas for those deposited in an Ar+O2 mixture the sp3 bonding prevails over sp2.

Zemek, J.; Bohac, P.; Kulikovsky, V.



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


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

Frautschy, Sally A



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-



Representation of exposures in regression analysis and interpretation of regression coefficients: basic concepts and pitfalls.  


Regression models are being used to quantify the effect of an exposure on an outcome, while adjusting for potential confounders. While the type of regression model to be used is determined by the nature of the outcome variable, e.g. linear regression has to be applied for continuous outcome variables, all regression models can handle any kind of exposure variables. However, some fundamentals of representation of the exposure in a regression model and also some potential pitfalls have to be kept in mind in order to obtain meaningful interpretation of results. The objective of this educational paper was to illustrate these fundamentals and pitfalls, using various multiple regression models applied to data from a hypothetical cohort of 3000 patients with chronic kidney disease. In particular, we illustrate how to represent different types of exposure variables (binary, categorical with two or more categories and continuous), and how to interpret the regression coefficients in linear, logistic and Cox models. We also discuss the linearity assumption in these models, and show how wrongly assuming linearity may produce biased results and how flexible modelling using spline functions may provide better estimates. PMID:24366898

Leffondré, Karen; Jager, Kitty J; Boucquemont, Julie; Stel, Vianda S; Heinze, Georg



A convergent algorithm for a generalized multivariate isotonic regression problem  

Microsoft Academic Search

Sasabuchi et al. (Biometrika 70(2):465–472, 1983) introduces a multivariate version of the well-known univariate isotonic\\u000a regression which plays a key role in the field of statistical inference under order restrictions. His proposed algorithm for\\u000a computing the multivariate isotonic regression, however, is guaranteed to converge only under special conditions (Sasabuchi\\u000a et al., J Stat Comput Simul 73(9):619–641, 2003). In this paper, a more

Jürgen Hansohm; Xiaomi Hu



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


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

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



COX-2 oxidative metabolism of endocannabinoids augments hippocampal synaptic plasticity.  


Endocannabinoids (eCBs) are important endogenous lipid mediators in synaptic transmission and plasticity and are oxygenated by cyclooxygenase-2 (COX-2) to form new types of prostaglandins. However, little is known about whether COX-2 oxidative metabolism of eCBs and their metabolites alter synaptic signaling. Here we demonstrate that increased COX-2 expression significantly enhances basal synaptic transmission and augments long-term potentiation (LTP) in the mouse hippocampus. This augmentation was inhibited in the presence of a selective COX-2 inhibitor or with deletion of the COX-2 gene. The CB(1) receptor-mediated depolarization-induced suppression of inhibition (DSI) was diminished when COX-2 expression was increased either with lipopolysaccharide (LPS) stimulation or transgenic neuronal over-expression of COX-2. Conversely, DSI was potentiated when COX-2 activity was pharmacologically or genetically inhibited. Interestingly, COX-2 oxidative metabolites of eCBs elevated LTP, an effect opposite to that of their parent molecules 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA). In addition, the ERK/MAPK and IP(3) pathways were found to mediate PGE(2)-G-induced enhancement of LTP. Our results indicate that COX-2 oxidative metabolism of eCBs is an important signaling pathway in modulation of synaptic transmission and plasticity. PMID:18295507

Yang, Hongwei; Zhang, Jian; Andreasson, Katrin; Chen, Chu



Rule induction for forecasting method selection: Meta-learning the characteristics of univariate time series  

Microsoft Academic Search

For univariate forecasting, there are various statistical models and computational algorithms available. In real-world exercises, too many choices can create difficulties in selecting the most appropriate technique, especially for users lacking sufficient knowledge of forecasting. This paper provides evidence, in the form of an empirical study on forecasting accuracy, to show that there is no best single method that can

Xiaozhe Wang; Kate Amanda Smith-miles; Rob J. Hyndman



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, 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


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.



COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.  


The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition. PMID:19880317

Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael



Modeling and Predicting the Popularity of Online Contents with Cox Proportional Hazard Regression Model  

E-print Network

datasets crawled from two different discussion forums, and, which Dpreview (Myspace) by observing a thread during the first 56 days (24 hours, respectively) and the number

Paris-Sud XI, Université de


Unitary Response Regression Models  

ERIC Educational Resources Information Center

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

Lipovetsky, S.



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


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

Misra, Shashank; Sharma, Kulbhushan



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


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



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.



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



Two dimensions are not better than one: STREAK and the univariate signal detection model of remember\\/know performance  

Microsoft Academic Search

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 data showed that the univariate model provided a better

Jeffrey J. Starns; Roger Ratcliff



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.



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



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



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

Microsoft Academic Search

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

Mohab Safey El Din; Philippe Trebuchet



Short-term forecasting of halibut CPUE: Linear and non-linear univariate approaches  

Microsoft Academic Search

In the present paper, two univariate forecasting techniques were tested to evaluate the short-term CPUE capacity forecast for Pacific halibut, Hippoglossus stenolepis (Pleuronectidae). The first methodology, based on the Box–Jenkins approach (autoregressive integrated moving average models [ARIMA models]), assumes a linear relationship between the time series data. The second methodology, using artificial neural network models (ANNs), enables highly non-linear processes

Ivone Alejandra Czerwinski; Juan Carlos Gutiérrez-Estrada; José Antonio Hernando-Casal



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

SciTech Connect

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

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



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)



The Association of Four Common Polymorphisms from Four Candidate Genes (COX-1, COX-2, ITGA2B, ITGA2) with Aspirin Insensitivity: A Meta-Analysis  

PubMed Central

Objective Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis. Methods and Results In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44–2.41; <0.0005) and rs1126643 (2.37; 1.44–3.89; 0.001) with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42–20.83; 0.013 versus aspirin resistance: 1.96; 1.07–3.6; 0.03). Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P?=?0.034) and averaged platelet numbers (P?=?0.012) between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. Conclusion Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations. PMID:24244288

Weng, Zhiyuan; Li, Xiaobo; Li, Yuqiong; Lin, Jinxiu; Peng, Feng; Niu, Wenquan



COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma: relationship to disease relapse and long-term survival.  


COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence tumor invasion and apoptosis. The objective of the study was to assess the relationship between COX-1 and COX-2 expression in early-stage disease and subsequent disease relapse and long-term survival. Women with FIGO stage I and II cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were included. COX-1 and COX-2 expressions in the tumors were assessed by immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57% (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall survival compared to expressers (log-rank test, P= 0.09). There was no significant difference in the overall survival in COX-2 nonexpressers compared to expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2 expression was noted in six of eight tumors, and both were expressed in five of eight tumors. Our preliminary data suggest an adverse prognosis with COX-1 expression in early-stage cervical carcinoma and a trend toward COX-1 expression in disease relapse. The association between COX-2 expression and a worse prognosis was not proven in this study. PMID:16803521

Athavale, R; Clooney, K; O'Hagan, J; Shawki, H; Clark, A H; Green, J A



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; Burger, Jorg; Schwarzinger, Stephan; Meyer, Ortwin



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.



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; Rubel, Oliver; Bremer, Peer-Timo; Pascucci, Valerio; Whitaker, Ross T.




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



E-print Network

CURRICULUM VITAE L. Clarke Cox, Ph.D. Current Position: Chief of Audiology Department and Rehabilitation Sciences Boston University Former Positions: Chief of Audiology, University Hospital, Boston, MA (1988 ­ 1996) Assistant & Associate Professor of Audiology Cleveland State University, 1975

Guenther, Frank


COX Inhibitors and Overactive Bladder: The Potential for Future Therapy  

Microsoft Academic Search

Studies spanning four decades suggest that prostaglandins (PGs) are synthesized at high levels within the bladder by cyclooxygenase\\u000a (COX)-1 and COX-2 and that PG biosynthesis during bladder filling provides a non-neuronal vesicular volume signal. Evidence\\u000a is presented that interstitial cells of Cajal within the bladder seem to play a key role in PG biosynthesis, that bladder\\u000a PG concentration is a

Paul H. Ratz; John E. Speich; Adam P. Klausner



Understanding poisson regression.  


Nurse investigators often collect study data in the form of counts. Traditional methods of data analysis have historically approached analysis of count data either as if the count data were continuous and normally distributed or with dichotomization of the counts into the categories of occurred or did not occur. These outdated methods for analyzing count data have been replaced with more appropriate statistical methods that make use of the Poisson probability distribution, which is useful for analyzing count data. The purpose of this article is to provide an overview of the Poisson distribution and its use in Poisson regression. Assumption violations for the standard Poisson regression model are addressed with alternative approaches, including addition of an overdispersion parameter or negative binomial regression. An illustrative example is presented with an application from the ENSPIRE study, and regression modeling of comorbidity data is included for illustrative purposes. PMID:24654593

Hayat, Matthew J; Higgins, Melinda



Neuronal and nonneuronal COX-2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge.  


Treating acute brain injuries with COX-2 inhibitors can produce both neuroprotective and neurotoxic effects. This study investigated the role of COX-2 in modulating acute brain injury induced by excitotoxic neural damage. Intrastriatal injection of excitotoxin (RS)-(tetrazole-5yl) glycine elicited COX-2 expression in two distinct groups of cells. cortical neurons surrounding the lesion and vascular cells in the lesion core. The vascular COX-2 was expressed in two cell types, endothelial cells and monocytes. Selective deletion of COX-2 in vascular cells in Tie2Cre Cox-2(flox/flox) mice did not affect the induction of COX-2 in neurons after the excitotoxin injection but resulted in increased lesion volume, indicating a neuroprotective role for the COX-2 expressed in the vascular cells. Selective deletion of monocyte COX-2 in LysMCre Cox-2(flox/flox) mice did not reduce COX-2-dependent neuroprotection, suggesting that endothelial COX-2 is sufficient to confer neuroprotection. Pharmacological inhibition of COX-2 activity in Tie2Cre Cox-2(flox/flox) mice reduced lesion volume, indicating a neurotoxic role for the COX-2 expressed in neurons. Furthermore, COX-2-dependent neurotoxicity was mediated, at least in part, via the activation of the EP1 receptor. These results show that Cox-2 expression induced in different cell types can confer opposite effects. PMID:24375716

An, Ying; Belevych, Natalya; Wang, Yufen; Zhang, Hao; Herschman, Harvey; Chen, Qun; Quan, Ning



Epigenetic deregulation of the COX pathway in cancer.  


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

Cebola, Inês; Peinado, Miguel A



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.



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


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

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



Semiparametric Regression Pursuit.  


The semiparametric partially linear model allows flexible modeling of covariate effects on the response variable in regression. It combines the flexibility of nonparametric regression and parsimony of linear regression. The most important assumption in the existing methods for the estimation in this model is to assume a priori that it is known which covariates have a linear effect and which do not. However, in applied work, this is rarely known in advance. We consider the problem of estimation in the partially linear models without assuming a priori which covariates have linear effects. We propose a semiparametric regression pursuit method for identifying the covariates with a linear effect. Our proposed method is a penalized regression approach using a group minimax concave penalty. Under suitable conditions we show that the proposed approach is model-pursuit consistent, meaning that it can correctly determine which covariates have a linear effect and which do not with high probability. The performance of the proposed method is evaluated using simulation studies, which support our theoretical results. A real data example is used to illustrated the application of the proposed method. PMID:23559831

Huang, Jian; Wei, Fengrong; Ma, Shuangge



Semiparametric Regression Pursuit  

PubMed Central

The semiparametric partially linear model allows flexible modeling of covariate effects on the response variable in regression. It combines the flexibility of nonparametric regression and parsimony of linear regression. The most important assumption in the existing methods for the estimation in this model is to assume a priori that it is known which covariates have a linear effect and which do not. However, in applied work, this is rarely known in advance. We consider the problem of estimation in the partially linear models without assuming a priori which covariates have linear effects. We propose a semiparametric regression pursuit method for identifying the covariates with a linear effect. Our proposed method is a penalized regression approach using a group minimax concave penalty. Under suitable conditions we show that the proposed approach is model-pursuit consistent, meaning that it can correctly determine which covariates have a linear effect and which do not with high probability. The performance of the proposed method is evaluated using simulation studies, which support our theoretical results. A real data example is used to illustrated the application of the proposed method. PMID:23559831

Huang, Jian; Wei, Fengrong; Ma, Shuangge



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


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



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


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

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



A composite logistic regression approach for ordinal panel data regression  

Microsoft Academic Search

We propose in this article a Composite Logistic Regression (CLR) approach for ordinal panel data regression. The new method transforms the original ordinal regression problem into a number of binary ones. Thereafter, the method of conditional logistic regression (Chamberlain, 1984; Wooldridge, 2001; Hsiao, 2003) can be directly applied. As a result, the new method allows the unobserved subject effects to

Ronghua Luo; Hansheng Wang



Multiple linear regression analysis  

NASA Technical Reports Server (NTRS)

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

Edwards, T. R.



Modern Regression Discontinuity Analysis  

ERIC Educational Resources Information Center

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

Bloom, Howard S.



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



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



Bayesian ARTMAP for regression.  


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



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



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


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



Expression of Cyclooxygenase2 (COX2) in Human Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder1  

Microsoft Academic Search

Cyclooxygenase (COX)-inhibiting drugs have antitumor activity in ca- nine and rodent models of urinary bladder cancer. Two isoenzymes of COX have been identified, COX-1 and COX-2. The purpose of this study was to characterize COX-1 and COX-2 expression in human invasive transitional cell carcinoma of the urinary bladder by immunohistochem- istry and Western blot analysis. COX-2 was not expressed in

Sulma I. Mohammed; Deborah W. Knapp; David G. Bostwick; Richard S. Foster; Kanwar Nasir; M. Khan; Jaime L. Masferrer; Bryan M. Woerner; Paul W. Snyder; Alane T. Koki



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


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

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



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



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.



Unified univariate and multivariate random field theory Keith J. Worsley12  

E-print Network

-missile trauma patients are related to several verbal memory scores, to detect regions of changes in anatomical, age, gender, or disease state. The simplest approach is to use a multivariate multiple regression contrasts in explanatory variables, such as task, stimulus, performance measures, age, gender, or disease

Worsley, Keith


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


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



Programming gene expression with combinatorial Robert Sidney Cox III1  

E-print Network

Programming gene expression with combinatorial promoters Robert Sidney Cox III1 , Michael G Surette2 and Michael B Elowitz1,3 * 1 Division of Biology, California Institute of Technology, Pasadena, CA are predicted to generate robust oscillations (Hasty et al, 2002; Atkinson et al, 2003) or to create sign

Elowitz, Michael



Microsoft Academic Search

SUMMARY I propose a new method for variable selection and shrinkage in Cox's proportional hazards model. My proposal minimizes the log partial likelihood subject to the sum of the absolute values of the parameters being bounded by a constant. Because of the nature of this constraint, it shrinks coeƒcients and produces some coeƒcients that are exactly zero. As a result




On nonsingular potentials of Cox-Thompson inversion scheme  

NASA Astrophysics Data System (ADS)

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

Pálmai, Tamás; Apagyi, Barnabás



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

Microsoft Academic Search

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

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



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

PubMed Central

Fourier transform infrared (FTIR) chemical imaging can be used to investigate molecular chemical features of the adhesive/dentin interfaces. However, the information is not straightforward, and is not easily extracted. The objective of this study was to use multivariate analysis methods, principal component analysis and fuzzy c-means clustering, to analyze spectral data in comparison with univariate analysis. The spectral imaging data collected from both the adhesive/healthy dentin and adhesive/caries-affected dentin specimens were used and compared. The univariate statistical methods such as mapping of intensities of specific functional group do not always accurately identify functional group locations and concentrations due to more or less band overlapping in adhesive and dentin. Apart from the ease with which information can be extracted, multivariate methods highlight subtle and often important changes in the spectra that are difficult to observe using univariate methods. The results showed that the multivariate methods gave more satisfactory, interpretable results than univariate methods and were conclusive in showing that they can discriminate and classify differences between healthy dentin and caries-affected dentin within the interfacial regions. It is demonstrated that the multivariate FTIR imaging approaches can be used in the rapid characterization of heterogeneous, complex structure. PMID:18980198

Wang, Yong; Yao, Xiaomei; Parthasarathy, Ranganathan



On the Importance of Span of the Data in Univariate Estimation of the Persistence in Real Exchange Rates  

Microsoft Academic Search

This paper revisits the empirical evidence on real exchange rates' convergence to their purchasing power parity (PPP) levels. In their recent empirical study, Murray and Papell (2002) claim that the univariate approach provides no useful information on the size of the half-lives of real exchange rate deviations from PPP. However, we obtain finite confidence intervals for the half-life for a

Hyeongwoo Kim; Young-Kyu Moh



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; Keles, Sunduz



Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis.  


Overexpression of cyclooxygenase-2 (COX-2) is generally considered to promote tumorigenesis. To investigate a potential role of COX-2 in osteosarcoma, we overexpressed COX-2 in human osteosarcoma cells. Saos-2 cells deficient in COX-2 expression were retrovirally transduced or stably transfected with murine COX-2 cDNA. Functional expression of COX-2 was confirmed by Northern and Western analyses and prostaglandin production. Overexpression of COX-2 reduced cell numbers by 50% to 70% compared with controls. Decreased proliferation in COX-2-overexpressing cells was associated with cell cycle prolongation in G(2)-M. Apoptosis, measured by both Annexin V binding assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining, was increased in cells overexpressing COX-2, and the increase was not reversed by treatment with NS-398, indicating that the effects were not mediated by prostaglandins. Retroviral COX-2 overexpression in two other human osteosarcoma cell lines, U2OS and TE85, also decreased cell viability. However, in the human colon carcinoma HCT-116 cell line, which is deficient in COX-2, retroviral overexpression of COX-2, at similar efficiency as in Saos-2 cells, increased resistance to apoptosis. Reactive oxygen species (ROS), measured by flow cytometry, were increased by COX-2 overexpression in Saos-2 cells but not in HCT-116 cells. Inhibition of peroxidase activity, but not of COX activity, blocked the ROS increase. Antioxidants blocked the increase in ROS and the increase in apoptosis due to COX-2 overexpression in Saos-2 cells. Our results suggest that (a) COX-2 overexpression in osteosarcoma cells may increase resistance to tumorigenesis by increasing ROS to levels that decrease cell viability and (b) the effects of COX-2 overexpression are cell type/tissue dependent. PMID:16818639

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



Platelet responsiveness to in vitro aspirin is independent of COX1 and COX2 protein levels and polymorphisms  

Microsoft Academic Search

Aspirin's inhibitory effect on platelet function has been shown to be highly heterogeneous. However, due to the considerable individual variation in pharmacokinetics after aspirin intake, it has been difficult to investigate the mechanism of aspirin resistance empirically. Our objective was to examine whether platelet responsiveness to in vitro aspirin treatment could be affected by cyclooxygenase (COX)-1\\/2 protein levels in platelets

Shinichi Takahashi; Miho Ushida; Risa Komine; Aya Shimodaira; Toshihiro Uchida; Hiroaki Ishihara; Toshiro Shibano; Gentaro Watanabe; Yasuo Ikeda; Mitsuru Murata



Robust Minimax Probability Machine Regression Robust Minimax Probability Machine Regression  

E-print Network

show how to compute a direct estimate of this probability for any given margin > 0. Following the idea with a known mean and covariance matrix. In other words, we maximize the minimum probability of our regressionRobust Minimax Probability Machine Regression Robust Minimax Probability Machine Regression Thomas

Mulligan, Jane


Assessing the prediction accuracy of cure in the Cox proportional hazards cure model: an application to breast cancer data.  


A cure rate model is a survival model incorporating the cure rate with the assumption that the population contains both uncured and cured individuals. It is a powerful statistical tool for prognostic studies, especially in cancer. The cure rate is important for making treatment decisions in clinical practice. The proportional hazards (PH) cure model can predict the cure rate for each patient. This contains a logistic regression component for the cure rate and a Cox regression component to estimate the hazard for uncured patients. A measure for quantifying the predictive accuracy of the cure rate estimated by the Cox PH cure model is required, as there has been a lack of previous research in this area. We used the Cox PH cure model for the breast cancer data; however, the area under the receiver operating characteristic curve (AUC) could not be estimated because many patients were censored. In this study, we used imputation-based AUCs to assess the predictive accuracy of the cure rate from the PH cure model. We examined the precision of these AUCs using simulation studies. The results demonstrated that the imputation-based AUCs were estimable and their biases were negligibly small in many cases, although ordinary AUC could not be estimated. Additionally, we introduced the bias-correction method of imputation-based AUCs and found that the bias-corrected estimate successfully compensated the overestimation in the simulation studies. We also illustrated the estimation of the imputation-based AUCs using breast cancer data. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25044997

Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma



Steganalysis using logistic regression  

NASA Astrophysics Data System (ADS)

We advocate Logistic Regression (LR) as an alternative to the Support Vector Machine (SVM) classifiers commonly used in steganalysis. LR offers more information than traditional SVM methods - it estimates class probabilities as well as providing a simple classification - and can be adapted more easily and efficiently for multiclass problems. Like SVM, LR can be kernelised for nonlinear classification, and it shows comparable classification accuracy to SVM methods. This work is a case study, comparing accuracy and speed of SVM and LR classifiers in detection of LSB Matching and other related spatial-domain image steganography, through the state-of-art 686-dimensional SPAM feature set, in three image sets.

Lubenko, Ivans; Ker, Andrew D.



Univariate and multivariate methods for chemical mapping of cervical cancer cells  

NASA Astrophysics Data System (ADS)

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

Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei



Hierarchical Regression without Phantom Factors.  

ERIC Educational Resources Information Center

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

Bentler, Peter M.; Satorra, Albert



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



Shrinkage structure in biased regression  

Microsoft Academic Search

Biased regression is an alternative to ordinary least squares (OLS) regression, espe- cially when explanatory variables are highly correlated. In this paper, we examine the geometrical structure of the shrinkage factors of biased estimators. We show that, in most cases, shrinkage factors cannot belong to (0;1) in all directions. We also compare the shrinkage factors of ridge regression (RR), principal

Pierre Druilhet; Alain Mom



Design-adaptive Nonparametric Regression  

Microsoft Academic Search

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

Jianqing Fan



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

Microsoft Academic Search

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

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



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

PubMed Central

Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1?, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-?B, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue. PMID:21668942



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


It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP mRNA and peptide level, AVP plasma concentration, and AVP-regulated renal transport protein abundances were measured. In male COX-2(-/-), basal urine output and water intake were elevated while urine osmolality was decreased compared with WT. Water deprivation resulted in lower urine osmolality, higher plasma osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2(-/-) mice, but after WD plasma AVP was unchanged between COX-2(-/-) and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice. Medullary interstitial osmolality increased and did not differ between COX-2(-/-) and WT after WD. Aquaporin-2 (AQP2; cortex-outer medulla), AQP3 (all regions), and UT-A1 (inner medulla) protein abundances were elevated in COX-2(-/-) at baseline and further increased after WD. COX-2(-/-) mice had elevated plasma urea and creatinine and accumulation of small subcapsular glomeruli. In conclusion, hypothalamic COX-2 activity is not necessary for enhanced AVP expression and secretion in response to water deprivation. Renal medullary COX-2 activity negatively regulates AQP2 and -3. The urine concentrating defect in COX-2(-/-) is likely caused by developmental glomerular injury and not dysregulation of AVP or collecting duct aquaporins. PMID:21880835

Nørregaard, Rikke; Madsen, Kirsten; Hansen, Pernille B L; Bie, Peter; Thavalingam, Sugarna; Frøkiær, Jørgen; Jensen, Boye L



Simple aromatic compounds containing propenone moiety show considerable dual COX/5-LOX inhibitory activities.  


For the development of safer anti-inflammatory agents, simple aromatic compounds containing propenone moiety were prepared and evaluated for their dual COX/5-LOX inhibitory activities. Among the 17 prepared compounds, most of the compounds exhibited considerable COX/5-LOX inhibitory activities. Especially compound C(15) showed the most significant dual COX/5-LOX inhibitory activity. PMID:15109651

Jahng, Yurngdong; Zhao, Long-Xuan; Moon, Yoon-Soo; Basnet, Arjun; Kim, Eun-kyung; Chang, Hyeun Wook; Ju, Hye Kyung; Jeong, Tae Cheon; Lee, Eung-Seok



Upregulation of fibronectin expression by COX-2 is mediated by interaction with ELMO1  

PubMed Central

Engulfment and cell motility 1 (ELMO1), a bipartite guanine nucleotide exchange factor (GEF) for the small GTPase Rac 1, was identified as a susceptibility gene for glomerular disease. Here, we reported that ELMO1 interacted with COX-2 in human mesangial cells. Furthermore, we identified ELMO1 as a posttranslational regulator of COX-2 activity. We demonstrated that COX-2 cyclooxygenase activity increased fibronectin promoter activity. The protein-protein interaction between ELMO1 and COX-2 increased the cyclooxygenase activity of COX-2 and, correspondingly, fibronectin expression. We also found that ET625, the dominant negative form of ELMO1 lacking Rac1 activity, interacted with COX-2, increased cyclooxygenase activity of COX-2 and enhanced COX-2-mediated fibronectin upregulation. To further rule out Rac1 as an ELMO1-mediated regulator of COX-2 activity, we employed the constitutive active Rac1, Rac1Q63E, and demonstrated that Rac1 signaling has no effect on COX-2-mediated fibronectin promoter activity. These results suggest that ELMO1 contributes to the development of glomerular injury through serving as a regulator of COX-2 activity. The interaction of ELMO1 with COX-2 could play an important role in the development and progression of renal glomerular injury. PMID:20732417

Yang, Chen; Sorokin, Andrey



RESEARCH ARTICLE Open Access Multiple recent horizontal transfers of the cox1  

E-print Network

case of horizontal transfer in plants involves a group I intron in the mitochondrial gene cox1, which analysis of cox1 intron transfer in plants. Keywords: horizontal gene transfer, cox1 intron, Solanaceae is properly cited. #12;Background Horizontal gene transfer (HGT) is surprisingly common in plant mitochondrial

Olmstead, Richard


COX-2-dependent stabilization of survivin in non-small cell lung cancer.  


Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. The mechanism(s) by which COX-2 exerts its cytoprotective effects are not completely understood but may be due to an imbalance of pro- and anti-apoptotic gene expression. To analyze COX-2-dependent gene expression and apoptosis, we created cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations. Whereas COX-2 sense cells have significantly heightened resistance to radiation and drug-induced apoptosis, COX-2 antisense cells are highly sensitive to apoptosis induction. We found that the expression of the anti-apoptotic protein survivin correlated positively with COX-2 expression. A COX-2-dependent modulation of survivin ubiquitination led to its stabilization in COX-2 overexpressing cells, and this effect was replicated by exogenous PGE2 treatment of parental tumor cells. In contrast to previous studies in other cell types, in nonsmall cell lung cancer cells survivin was expressed in a cell cycle-independent manner. When established in SCID mice in vivo, COX-2 antisense-derived tumors had significantly decreased survivin levels while COX-2 sense-derived tumors demonstrated elevated levels compared with controls. In accord with these findings, survivin and COX-2 were frequently upregulated and co-expressed in human lung cancers in situ. PMID:14597555

Krysan, Kostyantyn; Merchant, Farrukh H; Zhu, Li; Dohadwala, Mariam; Luo, Jie; Lin, Ying; Heuze-Vourc'h, Nathalie; Põld, Mehis; Seligson, David; Chia, David; Goodglick, Lee; Wang, Hejing; Strieter, Robert; Sharma, Sherven; Dubinett, Steven



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.



Regression to the Mean  

NSDL National Science Digital Library

Created by David Lane of Rice University, this is a simulation illustrating the regression toward the mean phenomenon. The author has created a specific case study to explore, he states it as: "In this simulation, a group of students takes a test made up of 100 true/false questions. Each student knows the answers to a specific number of questions and guesses at the remaining. Students get one point for each question they answer correctly and lose one point for each question they answer incorrectly." After completing this study, students can then input their data into the interactive applet. Eleven exercise questions will then test the students knowledge and understanding of their findings.

Lane, David M.



Linear regression applet  

NSDL National Science Digital Library

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

Exner, Nicholas



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

Microsoft Academic Search

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

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



Sparse regression analysis of task-relevant information distribution in the brain  

NASA Astrophysics Data System (ADS)

One of key topics in fMRI analysis is discovery of task-related brain areas. We focus on predictive accuracy as a better relevance measure than traditional univariate voxel activations that miss important multivariate voxel interactions. We use sparse regression (more specifically, the Elastic Net1) to learn predictive models simultaneously with selection of predictive voxel subsets, and to explore transition from task-relevant to task-irrelevant areas. Exploring the space of sparse solutions reveals a much wider spread of task-relevant information in the brain than it is typically suggested by univariate correlations. This happens for several tasks we considered, and is most noticeable in case of complex tasks such as pain rating; however, for certain simpler tasks, a clear separation between a small subset of relevant voxels and the rest of the brain is observed even with multivariate approach to measuring relevance.

Rish, Irina; Cecchi, Guillermo A.; Heuton, Kyle; Baliki, Marwan N.; Apkarian, A. Vania



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



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


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



Bayesian Spatial Quantile Regression  

PubMed Central

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

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



Penalized Functional Regression.  


We develop fast fitting methods for generalized functional linear models. The functional predictor is projected onto a large number of smooth eigenvectors and the coefficient function is estimated using penalized spline regression; confidence intervals based on the mixed model framework are obtained. Our method can be applied to many functional data designs including functions measured with and without error, sparsely or densely sampled. The methods also extend to the case of multiple functional predictors or functional predictors with a natural multilevel structure. The approach can be implemented using standard mixed effects software and is computationally fast. The methodology is motivated by a study of white-matter demyelination via diffusion tensor imaging (DTI). The aim of this study is to analyze differences between various cerebral white-matter tract property measurements of multiple sclerosis (MS) patients and controls. While the statistical developments proposed here were motivated by the DTI study, the methodology is designed and presented in generality and is applicable to many other areas of scientific research. An online appendix provides R implementations of all simulations. PMID:22368438

Goldsmith, Jeff; Bobb, Jennifer; Crainiceanu, Ciprian M; Caffo, Brian; Reich, Daniel



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

Microsoft Academic Search

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

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



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


The annual disease incident worldwide is desirable to be predicted for taking appropriate policy to prevent disease outbreak. This chapter considers the performance of different forecasting method to predict the future number of disease incidence, especially for seasonal disease. Six forecasting methods, namely linear regression, moving average, decomposition, Holt-Winter's, ARIMA, and artificial neural network (ANN), were used for disease forecasting on tuberculosis monthly data. The model derived met the requirement of time series with seasonality pattern and downward trend. The forecasting performance was compared using similar error measure in the base of the last 5 years forecast result. The findings indicate that ARIMA model was the most appropriate model since it obtained the less relatively error than the other model. PMID:21431557

Permanasari, Adhistya Erna; Rambli, Dayang Rohaya Awang; Dominic, P Dhanapal Durai



Regression on Quantile Residual Life  

PubMed Central

Summary A time-specific log-linear regression method on quantile residual lifetime is proposed. Under the proposed regression model, any quantile of a time-to-event distribution among survivors beyond a certain time point is associated with selected covariates under right censoring. Consistency and asymptotic normality of the regression estimator are established. An asymptotic test statistic is proposed to evaluate the covariate effects on the quantile residual lifetimes at a specific time point. Evaluation of the test statistic does not require estimation of the variance-covariance matrix of the regression estimators, which involves the probability density function of the survival distribution with censoring. Simulation studies are performed to assess finite sample properties of the regression parameter estimator and test statistic. The new regression method is applied to a breast cancer data set with long-term follow-up to estimate the patients’ median residual lifetimes, adjusting for important prognostic factors. PMID:19432781

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



COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis  

PubMed Central

Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n?=?92), ampullary cancer (AC, n?=?62) and distal bile duct cancer (DBC, n?=?76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p?=?0.043 in PC, p?=?0.011 in AC, p?=?0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p?=?0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p?=?0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. PMID:24950702



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


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

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



Regression calibration method for correcting measurement-error bias in nutritional epidemiology.  


Regression calibration is a statistical method for adjusting point and interval estimates of effect obtained from regression models commonly used in epidemiology for bias due to measurement error in assessing nutrients or other variables. Previous work developed regression calibration for use in estimating odds ratios from logistic regression. We extend this here to estimating incidence rate ratios from Cox proportional hazards models and regression slopes from linear-regression models. Regression calibration is appropriate when a gold standard is available in a validation study and a linear measurement error with constant variance applies or when replicate measurements are available in a reliability study and linear random within-person error can be assumed. In this paper, the method is illustrated by correction of rate ratios describing the relations between the incidence of breast cancer and dietary intakes of vitamin A, alcohol, and total energy in the Nurses' Health Study. An example using linear regression is based on estimation of the relation between ultradistal radius bone density and dietary intakes of caffeine, calcium, and total energy in the Massachusetts Women's Health Study. Software implementing these methods uses SAS macros. PMID:9094918

Spiegelman, D; McDermott, A; Rosner, B



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



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


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

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



Symbolic regression in multicollinearity problems  

Microsoft Academic Search

In this paper the potential of GP-generated symbolic regression for alleviating multicollinearity problems in multiple regression is presented with a case study in an industrial setting. The main advantage of this approach is the potential to produce a simple and stable polynomial model in terms of the original variables.

Flor A. Castillo; Carlos M. Villa



Multiple Regression Assumptions. ERIC Digest.  

ERIC Educational Resources Information Center

This Digest presents a discussion of the assumptions of multiple regression that is tailored to the practicing researcher. The focus is on the assumptions of multiple regression that are not robust to violation, and that researchers can deal with if violated. Assumptions of normality, linearity, reliability of measurement, and homoscedasticity are…

Osborne, Jason W.; Waters, Elaine


Regression Testing as a Service  

Microsoft Academic Search

Selective regression testing involves retesting of software systems with a subset of the test suite to verify that modifications have not adversely impacted existing functions. Although this problem has been heavily researched, it has never been discussed in the context of SaaS (Software as a service). This paper presents the specific requirements, challenges and benefits in delivering regression test selection

Sheng Huang; Zhong Jie Li; Ying Liu; Jun Zhu



Multiple Use One-Sided Hypotheses Testing in Univariate Linear Calibration  

NASA Technical Reports Server (NTRS)

Consider a normally distributed response variable, related to an explanatory variable through the simple linear regression model. Data obtained on the response variable, corresponding to known values of the explanatory variable (i.e., calibration data), are to be used for testing hypotheses concerning unknown values of the explanatory variable. We consider the problem of testing an unlimited sequence of one sided hypotheses concerning the explanatory variable, using the corresponding sequence of values of the response variable and the same set of calibration data. This is the situation of multiple use of the calibration data. The tests derived in this context are characterized by two types of uncertainties: one uncertainty associated with the sequence of values of the response variable, and a second uncertainty associated with the calibration data. We derive tests based on a condition that incorporates both of these uncertainties. The solution has practical applications in the decision limit problem. We illustrate our results using an example dealing with the estimation of blood alcohol concentration based on breath estimates of the alcohol concentration. In the example, the problem is to test if the unknown blood alcohol concentration of an individual exceeds a threshold that is safe for driving.

Krishnamoorthy, K.; Kulkarni, Pandurang M.; Mathew, Thomas



The univariant curve liquid = forsterite + anorthite + diopside in the system CMAS at 1 bar: solid solutions and melt structure  

Microsoft Academic Search

One atmosphere liquid-present experiments were carried out in the CMAS system using an ordinary quench furnace apparatus. The runs, including reversal and duplicate experiments, describe the univariant curve l=fo+an+ di between the invariant points Q: l+fo+an=di+sp and F: l+fo=an+di+oen, located respectively at 1245±1° C and 1244±1° C. The thermal divide on this curve M3: l= fo+an+di is located at 1275±1°

Guy Libourel; Pierre Boivin; Gordon M. Biggar



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.



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

Microsoft Academic Search

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

Jane A. Mitchell; Timothy D. Warner



Effect of Specific and Non-Specific Inhibition of COX2 on Renal Oxygenation before and after Water Diuresis  

Microsoft Academic Search

Background\\/Aims: Water diuresis usually increases medullary oxygenation as a result of increased medullary synthesis of prostaglandins, but it is not clear whether this involves activation of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2). Methods: The effects of celecoxib, a selective inhibitor of COX-2, and of ibuprofen, a non-specific inhibitor of COX-1 and COX-2, upon renal oxygenation during water diuresis were studied in

Scott Gilbert; Chun Zuo; Franklin H. Epstein



COX2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin  

Microsoft Academic Search

Some previous studies have found worse prognosis among cyclooxygenase-2 (COX-2)-expressing breast cancers. Aspirin and NSAIDs\\u000a inhibit COX-2. Three studies, including ours, have reported a survival advantage among women with breast cancer who take either\\u000a aspirin or NSAIDs. Through this study we hypothesized that in the Nurses’ Health Study (NHS), COX-2 expression would be associated\\u000a with worse prognosis, and aspirin use

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


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


This paper presents some considerations about the use of adequate statistical techniques in the framework of the neuroelectromagnetic brain mapping. With the use of advanced EEG/MEG recording setup involving hundred of sensors, the issue of the protection against the type I errors that could occur during the execution of hundred of univariate statistical tests, has gained interest. In the present experiment, we investigated the EEG signals from a mannequin acting as an experimental subject. Data have been collected while performing a neuromarketing experiment and analyzed with state of the art computational tools adopted in specialized literature. Results showed that electric data from the mannequin's head presents statistical significant differences in power spectra during the visualization of a commercial advertising when compared to the power spectra gathered during a documentary, when no adjustments were made on the alpha level of the multiple univariate tests performed. The use of the Bonferroni or Bonferroni-Holm adjustments returned correctly no differences between the signals gathered from the mannequin in the two experimental conditions. An partial sample of recently published literature on different neuroscience journals suggested that at least the 30% of the papers do not use statistical protection for the type I errors. While the occurrence of type I errors could be easily managed with appropriate statistical techniques, the use of such techniques is still not so largely adopted in the literature. PMID:20637802

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



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



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

PubMed Central

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

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



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

SciTech Connect

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

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



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


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



Structural Threshold Regression Andros Kourtellos  

E-print Network

Structural Threshold Regression Andros Kourtellos University of Cyprus Thanasis Stengos University, and 23rd (EC)2 conference. Department of Economics, P.O. Box 537, CY 1678 Nicosia, Cyprus,email: andros

Nesterov, Yurii


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


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)



Regression analysis with longitudinal measurements  

E-print Network

. . . . . . . . . . . . . . . 21 3.4.Simulation study . . . . . . . . . . . . . . . . . . . . . . . 25 3.5.Childhood growth data analysis for adulthood BMI . . . . 28 IV NONPARAMETRIC REGRESSION ANALYSIS FOR BI- NARY RESPONSE WHEN COVARIATES ARE SUBJECT- SPECIFIC PARAMETERS IN A... with measurement error . . . . 34 4.4.Simulation study . . . . . . . . . . . . . . . . . . . . . . . 39 4.5.Childhood growth data analysis for adulthood obesity . . . 41 V BAYESIAN NONPARAMETRIC REGRESSION OF OUTCOME- DEPENDENT FOLLOW-UP TIMES...

Ryu, Duchwan



L1 penalized estimation in the Cox proportional hazards model.  


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



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



Box-Cox Mixed Logit Model for Travel Behavior Analysis  

NASA Astrophysics Data System (ADS)

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

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




E-print Network

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

Bai, Hyoungwoo



Pathophysiology of motility dysfunction in bowel obstruction: role of stretch-induced COX-2  

PubMed Central

In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction. PMID:21051526

Lin, You-Min; Powell, Don W.; Sarna, Sushil K.



Allelic variation in the canine Cox-2 promoter causes hypermethylation of the canine Cox-2 promoter in clinical cases of renal dysplasia  

PubMed Central

Background Novel allelic variants in the promoter of the canine cyclooxygenase-2 (Cox-2) gene are associated with renal dysplasia (RD). These variants consist of either deletions of putative SP1 transcription factor-binding sites or insertions of tandem repeats of SP1-binding sites located in the CpG island just upstream of the ATG translation initiation site. The canine Cox-2 gene was studied because Cox-2-deficient mice have renal abnormalities and a pathology that is strikingly similar to RD in dogs. Findings The allelic variants were associated with hypermethylation of the Cox-2 promoter only in clinical cases of RD. The wild-type allele was never methylated, even in clinical cases that were heterozygous for a mutant allele. In cases that were biopsy-negative, the promoter remained unmethylated, regardless of the genotype. Methylated DNA was found in DNA from various adult tissues of dogs with clinical RD. Conclusions The mechanism of action of the allelic variation in the canine Cox-2 promoter most likely involves variation in the extent of epigenetic downregulation of this gene. This epigenetic downregulation must have occurred early in development because methylated Cox-2 promoter DNA sequences are found in various adult tissues. PMID:24708682



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

Microsoft Academic Search

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

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



Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer  

PubMed Central

Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC. PMID:23401648

Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F.; Waldner, Maximilian J.



Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer.  


Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC. PMID:23401648

Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F; Waldner, Maximilian J



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



The Origins of Racism: The Critical Theory of Oliver C. Cox  

E-print Network

Oliver C. Cox's theory of race relations and its impending problems in connection with the rise of capitalism have not been applied or addressed to the same extent as that of his contemporaries. Why does the work of Oliver Cox continue to be largely...

Klarlund, Susan E.



Diagnostics for multiple regression problems  

SciTech Connect

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

Daly, J.C.



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



On identification in Bayesian disease mapping and ecological-spatial regression models.  


We discuss identification of structural characteristics of the underlying relative risks ensemble for posterior relative risks inference within Bayesian generalized linear mixed model framework for small-area disease mapping and ecological-spatial regression. We revisit conditionally specified and locally characterized Gaussian Markov random field risks ensemble priors in univariate disease mapping and communicate insight into Gaussian Markov random field variance-covariance characteristics for representing disease risks variability and spatial risks interactions and for structural identification with respect to risks ensemble prior choices. Illustrative examples of identification in Bayesian disease mapping and ecological-spatial regression models are presented for Bayesian hierarchical generalized linear mixed Poisson models and zero-inflated Poisson models. PMID:22573502

MacNab, Ying C



Improving Your Data Transformations: Applying the Box-Cox Transformation  

ERIC Educational Resources Information Center

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

Osborne, Jason W.



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


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



Regressive Evolution in Astyanax Cavefish  

PubMed Central

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

Jeffery, William R.



The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up  

Microsoft Academic Search

We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer (SCLC) patients included in a prospective multicenter study with a minimum 5-year follow-up. Pretreatment clinical and laboratory parameters were registered. Possible prognostic factors were evaluated by univariate analysis (log rank test) and by the Cox multivariate regression model. In the univariate analysis of all

Roy M Bremnes; Stein Sundstrom; Ulf Aasebø; Stein Kaasa; Reidulv Hatlevoll; Steinar Aamdal



Late postoperative hemorrhage in a patient with undiagnosed COX-1 deficiency after third molar extractions.  


Oral maxillofacial surgeons direct invasive procedures that often cause significant bleeding. Uncontrolled hemorrhage is a rare, yet serious, complication that can be seen in patients with thrombocytopathy. Platelets have 3 distinct roles in coagulation: initial adhesion, phospholipid externalization, and platelet aggregation.(1) Several types of platelet deficiencies, including defects of adhesion (Bernard-Soulier syndrome), defects of aggregation (Glanzmann thrombasthenia), and disorders of platelet secretion due to a deficiency of adenosine diphosphate (ADP) or cyclooxygenase-1 (COX-1).(2-4) COX has 2 isoforms: COX-1 and COX-2.(5,6) COX-1 is expressed constitutively in most tissues, and COX-2 is induced primarily by inflammatory mediators.(7,8) Although both isoforms are present in platelets, COX-1 is the major isoform that contributes to coagulation, because it is critically important in the formation of thromboxane A2 (TXA2) by way of the arachidonic acid (AA) pathway.(9) AA is a potent inducer of platelet aggregation.(1,3,4) When AA is exposed to an activating agent, such as ADP, it undergoes a series of enzymatic reactions that culminates in the production of TXA2.(10) TXA2 is the predominant product of the COX-1 pathway and is a major metabolite of AA in platelets. TXA2 is necessary for normal platelet function. Therefore, the inhibition of, or a deficiency in, COX-1 will compromise the AA pathway, thereby reducing platelet secretion and altering normal platelet aggregatory function.(1,3) COX-1 deficiencies are usually caused by drug interactions with the enzyme itself. In addition, studies have identified genetic mutations that can result in COX-1 deficiency.(2) We present the hospital course, management, and diagnosis of a patient with an undiagnosed COX-1 deficiency who had had third molars removed in a private office. To our knowledge, this is the first case of COX-1 deficiency diagnosed after exodontia documented in English studies. In addition, we reviewed the published data of this rare disorder that has significant clinical implications. PMID:24480756

Doscher, Jesse C; Volpe, Fedele N



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

E-print Network

Heme Biosynthetic Pathway, Causing Early-Onset Fatal Hypertrophic Cardiomyopathy Hana Antonicka,1 in fibroblasts from a patient with fatal, infantile hypertrophic cardiomyopathy. Mutation analysis of COX15, of fatal infantile, hypertrophic cardiomyopathy associated with isolated COX deficiency. Introduction

Shoubridge, Eric


Cactus: An Introduction to Regression  

ERIC Educational Resources Information Center

When the author first used "VisiCalc," the author thought it a very useful tool when he had the formulas. But how could he design a spreadsheet if there was no known formula for the quantities he was trying to predict? A few months later, the author relates he learned to use multiple linear regression software and suddenly it all clicked into…

Hyde, Hartley



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.



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.



Standards for Regression Discontinuity Designs  

ERIC Educational Resources Information Center

Regression discontinuity (RD) designs are increasingly used by researchers to obtain unbiased estimates of the effects of education-related interventions. These designs are applicable when a continuous "scoring" rule is used to assign the intervention to study units (for example, school districts, schools, or students). Under an RD design, the…

Schochet, P.; Cook, T.; Deke, J.; Imbens, G.; Lockwood, J. R.; Porter, J.; Smith, J.



Logistic Regression with Random Coefficients.  

ERIC Educational Resources Information Center

An approximation to the likelihood for the generalized linear models with random coefficients is derived and is the basis for an approximate Fisher scoring algorithm. The method is illustrated on the logistic regression model for one-way classification, but it has an extension to the class of generalized linear models and to more complex data…

Longford, Nicholas T.


Optimum Designs in Regression Problems  

Microsoft Academic Search

Although regression problems have been considered by workers in all sciences for many years, until recently relatively little attention has been paid to the optimum design of experiments in such problems. At what values of the independent variable should one take observations, and in what proportions? The purpose of this paper is to develop useful computational procedures for finding optimum

J. Kiefer; J. Wolfowitz



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.



Three Steps Toward Robust Regression  

ERIC Educational Resources Information Center

A new measure of correlation and a measure of scale are proposed which are substantially more robust than their least squares counterparts. Increased robustness may also be obtained by use of equal regression weights, or knowledge of the theoretical structure of the weights. (Author/HG)

Thissen, David; Wainer, Howard



Computational Reality XII Linear regression  

E-print Network

Computational Reality XII Linear regression Inverse analysis I B. Emek Abali @ LKM - TU Berlin have the loading (input) as well as the response (output) as a measurement data. What is the correct measurement points like input on abscissa and output on ordinate. We want to fit the data by a straight line f

Berlin,Technische Universität


Weighting Regressions by Propensity Scores  

Microsoft Academic Search

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 investigators have a good causal model, it seems

David A. Freedman; Richard A. Berk



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



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.



Model Selection for Cox Models with Time-Varying Coefficients  

PubMed Central

Summary Cox models with time-varying coefficients offer great flexibility in capturing the temporal dynamics of covariate effects on right censored failure times. Since not all covariate coefficients are time-varying, model selection for such models presents an additional challenge, which is to distinguish covariates with time-varying coefficient from those with time-independent coefficient. We propose an adaptive group lasso method that not only selects important variables but also selects between time-independent and time-varying specifications of their presence in the model. Each covariate effect is partitioned into a time-independent part and a time-varying part, the latter of which is characterized by a group of coefficients of basis splines without intercept. Model selection and estimation are carried out through a fast, iterative group shooting algorithm. Our approach is shown to have good properties in a simulation study that mimics realistic situations with up to 20 variables. A real example illustrates the utility of the method. PMID:22506825

Yan, Jun; Huang, Jian



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


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



Nimesulide, a COX2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis  

Microsoft Academic Search

BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2

M. L. Hull; A. Prentice; D. Y. Wang; R. P. Butt; S. C. Phillips; S. K. Smith; D. S. Charnock-Jones



Structure of nuclear-localized cox3 genes in Chlamydomonas reinhardtii and in its colorless close relative Polytomella sp  

Microsoft Academic Search

Several chlorophyte algae do not have the cox3 gene, encoding subunit III of cytochrome c oxidase, in their mitochondrial genomes. The cox3 gene is nuclear-encoded in the photosynthetic alga Chlamydomonas reinhardtii and in the colorless alga Polytomella sp. In this work, the genomic sequences of the cox3 genes of these two closely related algae are reported. The cox3 genes of

Xochitl Pérez-Martínez; Soledad Funes; Elena Tolkunova; Edgar Davidson; Michael P. King; Diego González-Halphen



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.



Carvacrol, a component of thyme oil, activates PPAR? and ? and suppresses COX-2 expression[S  

PubMed Central

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor superfamily and are involved in the control of COX-2 expression, and vice versa. Here, we show that COX-2 promoter activity was suppressed by essential oils derived from thyme, clove, rose, eucalyptus, fennel, and bergamot in cell-based transfection assays using bovine arterial endothelial cells. Moreover, from thyme oil, we identified carvacrol as a major component of the suppressor of COX-2 expression and an activator of PPAR? and ?. PPAR?-dependent suppression of COX-2 promoter activity was observed in response to carvacrol treatment. In human macrophage-like U937 cells, carvacrol suppressed lipopolysaccharide-induced COX-2 mRNA and protein expression, suggesting that carvacrol regulates COX-2 expression through its agonistic effect on PPAR?. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. PMID:19578162

Hotta, Mariko; Nakata, Rieko; Katsukawa, Michiko; Hori, Kazuyuki; Takahashi, Saori; Inoue, Hiroyasu



Citral, a component of lemongrass oil, activates PPAR? and ? and suppresses COX-2 expression.  


Lemongrass is a widely used herb as a food flavoring, as a perfume, and for its analgesic and anti-inflammatory purposes; however, the molecular mechanisms of these effects have not been elucidated. Previously, we identified carvacrol from the essential oil of thyme as a suppressor of cyclooxygenase (COX)-2, a key enzyme for prostaglandin synthesis, and also an activator of peroxisome proliferator-activated receptor (PPAR), a molecular target for "lifestyle-related" diseases. In this study, we evaluated the essential oil of lemongrass using our established assays for COX-2 and PPARs. We found that COX-2 promoter activity was suppressed by lemongrass oil in cell-based transfection assays, and we identified citral as a major component in the suppression of COX-2 expression and as an activator of PPAR? and ?. PPAR?-dependent suppression of COX-2 promoter activity was observed in response to citral treatment. In human macrophage-like U937 cells, citral suppressed both LPS-induced COX-2 mRNA and protein expression, dose-dependently. Moreover, citral induced the mRNA expression of the PPAR?-responsive carnitine palmitoyltransferase 1 gene and the PPAR?-responsive fatty acid binding protein 4 gene, suggesting that citral activates PPAR? and ?, and regulates COX-2 expression. These results are important for understanding the anti-inflammatory and anti-lifestyle-related disease properties of lemongrass. PMID:20656057

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



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



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


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-2(flox/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



Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors  

PubMed Central

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

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



Brain activity for chronic knee osteoarthritis: dissociating evoked from spontaneous pain and modulation by COX2inhibitor treatment  

E-print Network

and modulation by COX2inhibitor treatment PH 071 IASP 2010 Montreal Funded by NIH NINDS NS35115, Endo 06510 INTRODUCTION Osteoarthritis (OA) is the most common type of arthritis, and a leading threshold determinations. Treatments for OA have included COX2inhibitors (COX2i), but the effects

Apkarian, A. Vania


Survivin expression in in situ and invasive breast cancer relates to COX2 expression and DCIS recurrence  

Microsoft Academic Search

In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma

N Barnes; P Haywood; P Flint; W F Knox; N J Bundred



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


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

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



Outliers and Residual Distributions in Logistic Regression  

Microsoft Academic Search

Detection of outliers and other diagnostics based on residuals have gained widespread use in linear regression. Logistic regression has been both blessed and hindered by this development. Certainly logistic regression requires procedures to detect global and local model weaknesses. Thus the wealth of work done in linear regression provides guides and suggestions that may, with care and ingenuity, be applied

Dennis E. Jennings



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



Monotone Nonparametric Regression and Confidence Intervals  

Microsoft Academic Search

Several variations of monotone nonparametric regression have been developed over the past 30 years. One approach is to first apply nonparametric regression to data and then monotone smooth the initial estimates to “iron out” violations to the assumed order. Here, such estimators are considered, where local polynomial regression is first used, followed by either least squares isotonic regression or a

Matthew Strand; Yu Zhang; Bruce J. Swihart



Illustrated techniques for performing the Cox-Maze IV procedure through a right mini-thoracotomy  

PubMed Central

The Cox-Maze IV procedure has replaced the “cut-and-sew” technique of the original Cox-Maze operation with lines of ablation created using bipolar radiofrequency (RF) and cryothermal energy devices. In select patients, this procedure can be performed through a right mini-thoracotomy. This illustrated review is the first to detail the complete steps of the Cox-Maze IV procedure performed through a right mini-thoracotomy with careful attention paid to operative anatomy and advice. Pre- and post-operative management and outcomes are also discussed. This should be a practical guide for the practicing cardiac surgeon. PMID:24516807

Robertson, Jason O.; Saint, Lindsey L.; Leidenfrost, Jeremy E.



Spontaneous regression of intraspinal neuroblastoma.  


In two infants aged 5 days and 2 months paresis of the legs due to spinal cord compression by a dumbbell neuroblastoma suddenly appeared. Immediate surgical resection of only the paraspinal tumor mass was performed. Without any further treatment, prompt spontaneous regression of the intraspinal component occurred, and the paresis disappeared within 2 weeks in both infants. We advocate surgical excision of the paraspinal tumor mass as the sole treatment in infants with symptomatic dumbbell neuroblastoma. PMID:9099653

Kullendorff, C M; Strömblad, L G



Markov regression models for time series: a quasi-likelihood approach.  


This paper discusses a quasi-likelihood (QL) approach to regression analysis with time series data. We consider a class of Markov models, referred to by Cox (1981, Scandinavian Journal of Statistics 8, 93-115) as "observation-driven" models in which the conditional means and variances given the past are explicit functions of past outcomes. The class includes autoregressive and Markov chain models for continuous and categorical observations as well as models for counts (e.g., Poisson) and continuous outcomes with constant coefficient of variation (e.g., gamma). We focus on Poisson and gamma data for illustration. Analogous to QL for independent observations, large-sample properties of the regression coefficients depend only on correct specification of the first conditional moment. PMID:3148334

Zeger, S L; Qaqish, B



Celebration of the contributions of Art Cox to stellar pulsation interpretations  

SciTech Connect

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

Castor, J.I.



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



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

EPA Science Inventory

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


Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX2) inhibitors  

Microsoft Academic Search

BACKGROUND: Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were

Randall E Harris; Joanne Beebe-Donk; Galal A Alshafie



Macrophages induce COX-2 expression in breast cancer cells: role of IL-1? autoamplification.  


Tumor-associated macrophages and high levels of cyclooxygenase-2 (COX-2) are associated with poor prognosis in breast cancer patients, but their potential interdependence has not been evaluated. The objective of this study was to determine whether macrophages regulate COX-2 expression in breast cancer cells. For this purpose, THP-1 cells were cocultured with HCC1954 breast cancer cells. Coculture led to increased COX-2 expression in the HCC1954 cells and elevated prostaglandin E(2) levels in conditioned media. Similar results were observed when THP-1 cells were incubated with HCC1937 breast cancer cells or when human monocyte-derived macrophages were cocultured with HCC1954 cells. Coculture triggered production of reactive oxygen species (ROS) in HCC1954 cells. COX-2 induction was blocked in cells preincubated with an reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or by silencing p67PHOX, a subunit of NADPH oxidase. ROS production triggered activation of Src and mitogen-activated protein kinases (MAPKs). Blocking Src or MAPK activities or antagonizing the activator protein-1 (AP-1) transcription factor attenuated COX-2 induction in HCC1954 cells. Coculture caused rapid induction of interleukin-1? (IL-1?) in both breast cancer cells and macrophages. Increased IL-1? expression was blocked by an interleukin-1 receptor antagonist (IL-1Ra), suggesting autocrine and paracrine effects. Importantly, macrophage-induced COX-2 expression was blocked in HCC1954 cells preincubated with IL-1Ra or anti-IL-1? IgG. Together, these results indicate that macrophage-mediated induction of COX-2 in breast cancer cells is a consequence of IL-1?-mediated stimulation of ROS?Src?MAPK?AP-1 signaling. IL-1?-dependent induction of COX-2 in breast cancer cells provides a mechanism whereby macrophages contribute to tumor progression and potential therapeutic targets in breast cancer. PMID:21310944

Hou, Zhe; Falcone, Domenick J; Subbaramaiah, Kotha; Dannenberg, Andrew J



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



Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX2 transcription  

Microsoft Academic Search

CEBPB, one of the CEBP family members, is a crucial regulator of gene expression during innate immunity, inflammatory responses and adipogenesis. In this study, the EGF-induced increase of CEBPB mRNA is shown to be coincident with the decrease of COX-2 mRNA. We identified that all of the individual CEBPB isoforms, LAP1, LAP2 and LIP, attenuate EGF-induced COX-2 promoter activity. Although

Wen-Ling Wang; Yi-Chao Lee; Wen-Ming Yang; Wen-Chang Chang; Ju-Ming Wang



Single crystal growth and superconductivity of Ca(Fe1-xCox)2As2  

SciTech Connect

We report the single crystal growth of Ca(Fe1-xCox)2As2 (0 <= x <= 0.082) from Sn flux. The temperature-composition phase diagram is mapped out based on the magnetic susceptibility and electrical transport measurements. Phase diagram of Ca(Fe1-xCox)2As2 is qualitatively different from those of Sr and Ba, it could be due to both the charge doping and structural tuning effects associated with Co substitution.

Hu, Rongwei; Ran, Sheng; Budko, Serguei; Straszheim, Warren E.; Canfield, Paul C.



Effects of prodelphinidins isolated from Ribes nigrum on chondrocyte metabolism and COX activity.  


Articular diseases, such as osteoarthritis, is the clinical expression of the loss of cartilage function. COX inhibitors are widely used in the treatment of such pathologies for their beneficial effects on inflammation but often produce a negative activity on cartilage synthesis. In this study, we determined the effect of different prodelphinidins, the major compounds isolated from Ribes nigrum leaves, on the proteoglycans (PGs), type II collagen (coll. II) and prostaglandin E(2) (PGE(2)) production by differentiated human chondrocytes cultivated in long term (12 days) and in clusters as well as their inhibition potential on COX-1 and COX-2 in vitro. Gallocatechin trimer (GC-GC-GC) showed the higher stimulation of PGs and coll. II production (1 microg ml(-1)) and the synthesis of PGE(2) was significantly reduced by gallocatechin dimer (GC-GC), gallocatechin-epigallocatechin (GC-EGC) and GC-GC-GC at 10 and 100 microg ml(-1). The inhibition of PGE(2) synthesis was confirmed by the in vitro test on purified COX enzymes, showing the selectivity of prodelphinidins on COX-2. However, the prodelphinidins had no effects on COX activity in the whole blood assay. Our studies suggest that the prodelphinidins fractions from R. nigrum may be useful as an additive agent in the prevention of osteoarthritis. PMID:12070756

Garbacki, Nancy; Angenot, Luc; Bassleer, Corinne; Damas, Jacques; Tits, Monique



Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation  

PubMed Central

Augmentation of endogenous cannabinoid (eCB) signaling represents an emerging approach to the treatment of affective disorders. Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid to form prostaglandins, but also inactivates eCBs in vitro. However, the viability of COX-2 as a therapeutic target for in vivo eCB augmentation has not been explored. Here we utilized medicinal chemistry and in vivo analytical and behavioral pharmacological approaches to demonstrate a key role for COX-2 in the regulation of endocannabinoid (eCB) levels in vivo. A novel pharmacological strategy involving “substrate-selective” inhibition of COX-2 was used to augment eCB signaling without affecting related non-eCB lipids or prostaglandin synthesis. Behaviorally, substrate-selective inhibition of COX-2reducedanxiety-like behaviors in mice via increasede CB signaling. These data elucidate a key role for COX-2 in the regulation of eCB signaling and suggest substrate-selective pharmacology represents a viable approach for eCB augmentation with broad therapeutic potential. PMID:23912944

Hermanson, Daniel J.; Hartley, Nolan D.; Gamble-George, Joyonna; Brown, Naoko; Shonesy, Brian C.; Kingsley, Phillip J.; Colbran, Roger J.; Reese, Jeffrey



Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity  

PubMed Central

Aims Inducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. Chamomile has long been used in traditional medicine for the treatment of inflammatory diseases. In this study we aimed to investigate whether chamomile interferes with the COX-2 pathway. Main Methods We used lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as an in vitro model for our studies. Key Findings Chamomile treatment inhibited the release of LPS-induced prostaglandin E(2) in RAW 264.7 macrophages. This effect was found to be due to inhibition of COX-2 enzyme activity by chamomile. In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. The non-steroidal anti-inflammatory drug, sulindac and a specific COX-2 inhibitor, NS398, were shown to act similarly in LPS-activated RAW 264.7 cells. Our data suggest that chamomile works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs. Significance These findings add a novel aspect to the biological profile of chamomile which might be important for understanding the usefulness of aqueous chamomile extract in the form of tea in preventing inflammation and cancer. PMID:19788894

Srivastava, Janmejai K; Pandey, Mitali; Gupta, Sanjay



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

PubMed Central

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

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



Intracellular gene transfer in action: Dual transcription and multiple silencings of nuclear and mitochondrial cox2 genes in legumes  

PubMed Central

The respiratory gene cox2, normally present in the mitochondrion, was previously shown to have been functionally transferred to the nucleus during flowering plant evolution, possibly during the diversification of legumes. To search for novel intermediate stages in the process of intracellular gene transfer and to assess the evolutionary timing and frequency of cox2 transfer, activation, and inactivation, we examined nuclear and mitochondrial (mt) cox2 presence and expression in over 25 legume genera and mt cox2 presence in 392 genera. Transfer and activation of cox2 appear to have occurred during recent legume evolution, more recently than previously inferred. Many intermediate stages of the gene transfer process are represented by cox2 genes in the studied legumes. Nine legumes contain intact copies of both nuclear and mt cox2, although transcripts could not be detected for some of these genes. Both cox2 genes are transcribed in seven legumes that are phylogenetically interspersed with species displaying only nuclear or mt cox2 expression. Inactivation of cox2 in each genome has taken place multiple times and in a variety of ways, including loss of detectable transcripts or transcript editing and partial to complete gene loss. Phylogenetic evidence shows about the same number (3–5) of separate inactivations of nuclear and mt cox2, suggesting that there is no selective advantage for a mt vs. nuclear location of cox2 in plants. The current distribution of cox2 presence and expression between the nucleus and mitochondrion in the studied legumes is probably the result of chance mutations silencing either cox2 gene. PMID:10570164

Adams, Keith L.; Song, Keming; Roessler, Philip G.; Nugent, Jacqueline M.; Doyle, Jane L.; Doyle, Jeff J.; Palmer, Jeffrey D.



Ipomotaosides A-D, resin glycosides from the aerial parts of Ipomoea batatas and their inhibitory activity against COX-1 and COX-2.  


Four new resin glycosides, namely, ipomotaosides A-D (1-4), were isolated from the dried aerial parts of Ipomoea batatas. The structures of 1-4 were elucidated by analysis of their spectroscopic data and by chemical derivatization and were tested for their anti-inflammatory activity against cyclooxygenase (COX)-1 and -2. PMID:20961090

Yoshikawa, Kazuko; Yagi, Chiho; Hama, Hiroshi; Tanaka, Masami; Arihara, Shigenobu; Hashimoto, Toshihiro



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


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



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

PubMed Central

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

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



Semiparametric regression during 2003-2007*  

PubMed Central

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

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



Genetics Home Reference: Caudal regression syndrome  


... blood flow causes the abnormal mesoderm development. Many scientists think that the cause of caudal regression syndrome is a combination of abnormal mesoderm development and decreased blood flow to the caudal areas of the fetus. How do people inherit caudal regression syndrome? Caudal regression ...


Graphical Methods for Assessing Logistic Regression Models  

Microsoft Academic Search

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

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



Partial least-squares regression: a tutorial  

Microsoft Academic Search

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




Developmental Regression in Autism Spectrum Disorders  

ERIC Educational Resources Information Center

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

Rogers, Sally J.



Structural Logistic Regression for Link Analysis  

Microsoft Academic Search

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

Alexandrin Popescul; Lyle H. Ungar



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.



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: [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)



Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel disease  

PubMed Central

BACKGROUND—Inflammatory bowel disease (IBD) is associated with changes in colonic motility which may contribute to the pain and diarrhoea associated with exacerbations of this disease. These changes may be mediated by prostaglandins which are increased in this condition. Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) has been found in active IBD although its cellular distribution remains uncertain.?AIMS—To evaluate the cellular distribution of COX-2 in active IBD.?PATIENTS AND METHODS—Using reverse transcription-polymerase chain reaction, in situ hybridisation, and immunohistochemistry, COX-2 expression was evaluated in 12 colectomy specimens from patients with active ulcerative colitis (UC), and six specimens from patients with Crohn's colitis that had failed medical therapy. Histologically normal colon was obtained from 12 patients having resection for colorectal neoplasia and evaluated as above, acting as control specimens.?RESULTS—All specimens expressed COX-2 mRNA, with some 6-8-fold increase in inflamed tissues on densitometric analysis (both UC and Crohn's) compared with controls. In situ hybridisation localised this mRNA to myenteric neural cells, surrounding smooth muscle cells, and inflammatory cells of the lamina propria in the IBD specimens, with some weaker labelling seen in the epithelium. No COX-2 labelling was seen in normal tissues. Immunohistochemistry confirmed these sites of COX-2 expression in all inflamed specimens, with absence of immunoreactivity in control tissues.?CONCLUSIONS—These findings provide the first evidence of COX-2 expression in neural cells of the myenteric plexus in active IBD which, via increased prostaglandin synthesis at this site, may contribute to the dysmotilty seen in this condition.???Keywords: inducible cyclo-oxygenase; prostaglandins; myenteric plexus; inflammatory bowel disease PMID:11247889

Roberts, P; Morgan, K; Miller, R; Hunter, J; Middleton, S



Quantification of Burkholderia coxL Genes in Hawaiian Volcanic Deposits?  

PubMed Central

Isolation of multiple carbon monoxide (CO)-oxidizing Burkholderia strains and detection by culture-independent approaches suggest that Burkholderia may be an important component of CO-oxidizing communities in Hawaiian volcanic deposits. The absolute and relative abundance of the bacteria in these communities remains unknown, however. In this study, a quantitative PCR (Q-PCR) approach has been developed to enumerate Burkholderia coxL genes (large subunit of carbon monoxide dehydrogenase). This represents the first attempt to enumerate coxL genes from CO oxidizers in environmental samples. coxL copy numbers have been determined for samples from three sites representing a vegetation gradient on a 1959 volcanic deposit that included unvegetated cinders (bare), edges of vegetated sites (edge), and sites within tree stands (canopy). Q-PCR has also been used to estimate copy numbers of Betaproteobacteria 16S rRNA gene copy numbers and total Bacteria 16S rRNA. coxL genes could not be detected in the bare site (detection limit, ?4.7 × 103 copies per reaction) but average 1.0 × 108 ± 2.4 × 107 and 8.6 × 108 ± 7.6 ×107 copies g?1 (dry weight) in edge and canopy sites, respectively, which differ statistically (P = 0.0007). Average Burkholderia coxL gene copy numbers, expressed as a percentage of total Bacteria 16S rRNA gene copy numbers, are 6.2 and 0.7% for the edge and canopy sites, respectively. Although the percentage of Burkholderia coxL is lower in the canopy site, significantly greater gene copy numbers demonstrate that absolute abundance of coxL increases in vegetated sites and contributes to the expansion of CO oxidizer communities during biological succession on volcanic deposits. PMID:20139318

Weber, C. F.; King, G. M.



Pathophysiology of regression of synovial cysts of the lumbar spine: the 'anti-inflammatory hypothesis'.  


The term 'synovial cysts' of the lumbar spine refers to cysts that arise from the zygapophyseal joint capsule of the lumbar spine. Although several cases of regression of lumbar spine synovial cysts after oral anti-inflammatory therapy as well as local steroid injection have already been reported in the literature, no study up to now has addressed the role of 'inflammation suppression' in the regression of such lesions. In fact most of the previous studies have regarded 'spontaneous rupture' as well as 'instability resolution' as the most probable explanations for such phenomenon. In this article the authors review the current experimental data about the role of cytokines and inflammation in the development of synovial cysts of the lumbar spine. Additionally with basis on both our clinical experience of regression of a synovial cyst after conservative treatment with a non-steroidal anti-inflammatory drug (Cox-2 inhibitor) as well as on the experimental data supporting the multi-factorial effects of such drugs on the lumbar facet joints, the authors hypothesize that inhibition of inflammation might play a significant role in the pathophysiology of lumbar spine synovial cysts' regression. PMID:23021571

Mattei, Tobias A; Goulart, Carlos R; McCall, Todd D



In-vitro test system for the evaluation of cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) inhibitors based on a single HPLC run with UV detection using bovine aortic coronary endothelial cells (BAECs)  

Microsoft Academic Search

Objective and Design: The aim of this study was to develop a new, whole-cell test system which is easy to handle and requires a standard equipment for the parallel screening of COX-1 and COX-2 inhibitors.¶ Materials: Bovine aortic endothelial cells (BAECs).¶ Treatment and methods: Unstimulated bovine aortic coronary endothelial cells (BAECs) were used as a source of COX-1 and BAECs

G. Dannhardt; H. Ulbrich



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



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

NASA Astrophysics Data System (ADS)

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

Larrinaga, Asier R.



The Characterization And Role of Zinc Binding in Yeast Cox4  

SciTech Connect

Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two {beta} sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

Coyne, H.J., III; Ciofi-Baffoni, S.; Banci, L.; Bertini, I.; Zhang, L.; George, G.N.; Winge, D.R.; /Utah U. /Florence U. /Saskatchewan U.



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.



Virtual screening of compounds from the patchouli oil of Pogostemon herba for COX-1 inhibition  

PubMed Central

Our interest is to identify compounds from the patchouli oil of Pogostemon herba to inhibit the cyclooxygenase-1 (COX-1) enzyme activity. The data for the major compounds (alpha-patchouli alcohol isomer (CD521903, CD442384, and/or CD6432585), alphabulnusene, seychellene and alpha-guaiene) of patchouli oil were explored from the PubChem database. The compounds to COX-1 interactions were studied using the molecular docking tools Hex 6.12 and LeadIT2 Bisolve. The interactions were further visualized using the Chimera 1.7s viewer software tool. The analysis of the major compounds of patchouli oil showed that alpha-Patchouli alcohol (CD521903) binds to COX-1 at many active sites including: Leu223B, Asp228B, Leu237B, Arg332B, Trp138A, Glu139A, Ser142A, and Asn143A. Further analysis revealed that these binding sites are maintained by hydrogen bonds with Ser142A, Glu139A, and Asp228B. The interaction energy between COX-1 and alpha-patchouli alcohol (CD521903) is -6 kJ/mol (without solvent) and -15 kJ/ mol (with solvent DMSO). These theoretical data suggests alpha-patchouli alcohol as a potential inhibitor of the COX-1 enzyme. However, these observations should be investigated and confirmed using experimental evidence. PMID:23559751

Raharjo, Sentot Joko; Fatchiyah, Fatchiyah



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


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



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


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

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



Pifithrin-?, an Inhibitor of p53 Transactivation, Up-Regulates COX2 Expression through an MAPK-Dependent Pathway  

Microsoft Academic Search

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-?, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by

Sangmin Kim; Jeonghun Han; Se Kyung Lee; Sung Mo Hur; Minyoung Koo; Dong Hui Cho; Soo Youn Bae; Min-Young Choi; Incheol Shin; Jung-Hyun Yang; Seok Jin Nam; Jeong Eon Lee



Cross Talk between PKC and CREB in the Induction of COX-2 by PGF2? in Human Amnion Fibroblasts  

PubMed Central

Compelling evidence indicates a crucial role of prostaglandin F2? (PGF2?) in parturition. Both the maternal and fetal sides of the fetal membranes synthesize PGF2?, which exerts effects via the prostaglandin F2? receptor (FP) that is coupled to the activation of protein kinase C (PKC). Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of the inducible synthesis of prostaglandin. Although activation of PKC is known to induce COX-2 expression, it is not clear whether PGF2? can induce COX-2 via FP receptor-coupled PKC activation. COX-2 promoter carries a cAMP-response element (CRE) and phosphorylation of CRE binding protein 1 (CREB1) is associated with COX-2 expression in human amnion fibroblasts. We demonstrated that human amnion fibroblasts produced PGF2? and expressed FP receptor. PGF2? increased COX-2 expression and CREB1 phosphorylation, which could be blocked by either the FP receptor antagonist AL8810 or PKC inhibitor Ro31-7549. The PKC activator, phorbol-12-myristate-13-acetate (PMA), could mimic the induction of COX-2 and CREB1 phosphorylation. The induction of COX-2 by PGF2? and PMA could be attenuated by the small interfering RNA-mediated knockdown of CREB1 expression or overexpressing dominant-negative CREB1. A chromatin immunoprecipitation assay showed that the binding of CREB1 to the COX-2 promoter was increased by PGF2? and PMA in amnion fibroblasts. In conclusion, we provide evidence that PGF2? induces COX-2 expression via the FP receptor and phosphorylates CREB1 by PKC, thus increasing CREB1 binding to the COX-2 promoter and the expression of COX-2 in human amnion fibroblasts. This feed-forward loop may be crucial for the production of prostaglandins in the fetal membranes prior to the onset of labor. PMID:22919060

Guo, C. M.; Kasaraneni, N.



Postpartum mammary gland involution drives DCIS progression through collagen and COX-2  

PubMed Central

Prognosis of young women’s breast cancer is influenced by reproductive history. Women diagnosed within five years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors characterized by abundant fibrillar collagen, high COX-2 expression, and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high-risk for postpartum breast cancer would benefit from treatment with NSAIDs during postpartum involution. PMID:21822285

Lyons, Traci R; O’Brien, Jenean; Borges, Virginia; Conklin, Matthew W; Keely, Patricia J; Eliceiri, Kevin W; Marusyk, Andriy; Tan, Aik-Choon; Schedin, Pepper



Is Australia's national medicines policy failing? The case of COX-2 inhibitors.  


Australia has a National Medicines Policy with aims that include quality use of medicines, but policy stakeholders failed to protect Australia from the COX-2 (cyclo-oxygenase-2) inhibitor disaster. Drug regulators did not warn prescribers appropriately about potential cardiovascular risks. The Pharmaceutical Benefits Scheme did not limit unjustified drug expenditures on COX-2 inhibitors. Drug companies ran intense and misleading promotional campaigns on COX-2 inhibitors without adequate controls. Independent drug information was insufficient to counter the effects of the millions of dollars spent on advertising. Core elements of the National Medicines Policy--in particular the drug approval process, the post-marketing surveillance system, the control of drug promotion, and the quality of independent drug information--require major reappraisal if we want to avoid similar disasters in the future. PMID:18072318

Vitry, Agnes; Lexchin, Joel; Mansfield, Peter R



Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts.  


Periodontitis is an infectious disease caused by microorganisms present in dental bacterial plaque. Lipoteichoic acid (LTA) is a component of the external membrane of Gram-positive bacteria. It causes septic shock. Ingested flavonoids have been reported to directly affect the regulation of cyclooxygenase-2 (COX-2) expression induced by bacterial toxins. In this study, we examined the effects of four flavonoids (luteolin, fisetin, morin and myricetin) on the activation of ERK1/2, p38 and AKT, and on the synthesis of COX-2 in human gingival fibroblasts treated with LTA from Streptococcus sanguinis. We found that luteolin and myricetin blocked AKT and p38 activation and that myricetin blocked LTA-induced COX-2 expression. The results of our study are important for elucidating the mechanism of action of flavonoid regulation of inflammatory responses. PMID:24569980

Gutiérrez-Venegas, Gloria; Luna, Oscar Alonso; Arreguín-Cano, Juan Antonio; Hernández-Bermúdez, Cristina



COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models.  


Antiangiogenic agents that block vascular endothelial growth factor (VEGF) signaling are important components of current cancer treatment modalities but are limited by alternative ill-defined angiogenesis mechanisms that allow persistent tumor vascularization in the face of continued VEGF pathway blockade. We identified prostaglandin E2 (PGE2) as a soluble tumor-derived angiogenic factor associated with VEGF-independent angiogenesis. PGE2 production in preclinical breast and colon cancer models was tightly controlled by cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition augmented VEGF pathway blockade to suppress angiogenesis and tumor growth, prevent metastasis, and increase overall survival. These results demonstrate the importance of the COX-2/PGE2 pathway in mediating resistance to VEGF pathway blockade and could aid in the rapid development of more efficacious anticancer therapies. PMID:24964992

Xu, Lihong; Stevens, Janine; Hilton, Mary Beth; Seaman, Steven; Conrads, Thomas P; Veenstra, Timothy D; Logsdon, Daniel; Morris, Holly; Swing, Deborah A; Patel, Nimit L; Kalen, Joseph; Haines, Diana C; Zudaire, Enrique; St Croix, Brad



Spin alignment of surface oxidized CoxNi1-x/Cu(001)  

NASA Astrophysics Data System (ADS)

We investigated the ferromagnetic (FM)/antiferromagnetic (AF) spin alignment of a 13 monolayer oxidized CoxNi1-x/Cu(001) (x = 0 or 0.05) surface by X-ray magnetic circular dichroism and X-ray magnetic linear dichroism photoemission electron microscopy (XMCD-PEEM and XMLD-PEEM). Surface NiO and the underlying Ni (CoxNi1-x) were found to be AF and FM by analyzing the gray scale of XMLD-PEEM and XMCD-PEEM images; this indicates the spin orientation with respect to the polarization of the incident X-ray. We found both collinear and perpendicular alignment of the FM and AF spins. This suggests that the AF NiO is magnetically random, resulting in coercivity enhancement without exchange bias in the surface-oxidized CoxNi1-x/Cu(001) films.

Shih, Ying-Ta; Tsai, Chung-Wei; Su, Chien-Yu; Pan, Wei; Wei, Der-Hsin; Chan, Yuet-Loy; Chang, Hui-Ching



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

PubMed Central

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

Lin, Chen-Yen; Halabi, Susan



Discovery of potential and selective COX-1 inhibitory leads using pharmacophore modelling, in silico screening and in vitro evaluation.  


Cyclooxygenase -1 (COX-1) selective inhibitors are anticipated to be potential therapeutic agents for thrombosis, tumorigenesis, atherosclerosis, neuroprotection, and oxidative stress. In this study, a 3D-QSAR pharmacophore model was developed for potent and selective COX-1 inhibition based on 44 compounds from four different scaffolds using Phase, Schrödinger. One (hydrogen-bond) acceptor, one hydrophobic, and two aromatic sites (AHRR) contribute to COX-1 inhibitory activity. Test and decoy sets were used to corroborate the best hypothesis and the validated hypothesis was used to screen the SPECS database. The resultant hits were filtered by standard precision (SP) and extra precision (XP) modes of docking using Glide, Schrödinger which yielded five hits. Free energy calculations were carried out to quantify the affinity differences of the hits towards COX enzymes. These five hits were subjected to in vitro COX (ovine) inhibitory activity studies. The hits displayed potent COX-1 inhibitory activity and good selectivity versus COX-2 enzyme. The compounds also protected the nitric oxide (NO) induced cell death mediated by COX-1 in mouse macrophages cell line. Hence, we hypothesize that these compounds could be promising leads for the design of superior COX-1 inhibitors and insights gained from further exploration of the same could provide pertinent clues for the treatment of the conditions mentioned above. PMID:25203777

Balaji, Bhaskar; Hariharan, Sivaram; Shah, Darshit B; Ramanathan, Muthiah



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


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



Association between COX-2 rs 6681231 Genotype and Interleukin-6 in Periodontal Connective Tissue. A Pilot Study  

PubMed Central

Objectives The aim of this pilot study was to investigate associations between IL-6 and COX-2 expression in gingival biopsies and both clinical diagnosis and genotypes in the IL-6 and COX-2 genes. Design A case-control study included 41 gingival biopsies obtained from Caucasian patients grouped according to clinical diagnosis of gingival health (n?=?10), gingivitis (n?=?15) or chronic periodontitis (n?=?16). Immunohistochemistry analyses were performed to determine COX-2 expression in lamina propria, IL-6 expression in lamina propria and gingival epithelium and level of inflammatory cell infiltrate. Individual DNA was extracted and genotyped by real-time PCR for IL6 SNPs rs 2069827 and rs 2069825 and for COX-2 rs 6681231. Results The percentage of cellular COX-2 expression was associated with the extent of periodontal disease (Arbes index p?=?0.026) and inflammatory infiltrate (p<0.0001). No association was observed between IL6 haplotypes and cells positive to IL-6 or COX-2 in gingival tissues. The COX-2 rs 6681231 was associated with cells positive to IL-6 in the connective tissue (p?=?0.032). Conclusions COX-2 expression in gingival tissues may be a marker of periodontal disease severity. COX-2 rs 6681231 may be associated with IL-6 local production in gingival tissues. PMID:24551049

Mesa, Francisco; O'Valle, Francisco; Rizzo, Manfredi; Cappello, Francesco; Donos, Nikos; Parkar, Mohamed; Chaudhary, Navidah; Carini, Francesco; Munoz, Ricardo; Nibali, Luigi



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

PubMed Central

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

Liu, Sophia Z.



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


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

Trappe, Todd A; Liu, Sophia Z



NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure  

PubMed Central

The nuclear factor of activated T cells (NFAT) transcription factors are regulated by calcium/calcineurin signals and play important roles in T cells, muscle, bone, and neural tissue. NFAT is expressed in the epidermis, and although recent data suggest that NFAT is involved in the skin’s responses to ultraviolet radiation (UVR), the wavelengths of radiation that activate NFAT and the biological function of UV-activated NFAT remain undefined. We demonstrate that NFAT transcriptional activity is preferentially induced by UVB wavelengths in keratinocytes. The derived action spectrum for NFAT activation indicates that NFAT transcriptional activity is inversely associated with wavelength. UVR also evoked NFAT2 nuclear translocation in a parallel wavelength-dependent fashion and both transcriptional activation and nuclear translocation were inhibited by the calcineurin inhibitor cyclosporin A. UVR also evoked NFAT2 nuclear translocation in three-dimensional skin equivalents. Evidence suggests that COX-2 contributes to UV-induced carcinogenesis. Inhibiting UV-induced NFAT activation in keratinocytes, reduced COX-2 protein induction, and increased UV-induced apoptosis. COX-2 luciferase reporters lacking functional NFAT binding sites were less responsive to UVR, highlighting that NFAT is required for UV-induced COX-2 induction. Taken together, these data suggest that the proinflammatory, antiapoptotic, and procarcinogenic functions of UV-activated COX-2 may be mediated, in part, by upstream NFAT signaling. Flockhart, R. J., Diffey, B. L., Farr, P. M., Lloyd, J., Reynolds, N. J. NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure. PMID:18708588

Flockhart, R. J.; Diffey, B. L.; Farr, P. M.; Lloyd, J.; Reynolds, N. J.



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

PubMed Central

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

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



Harmonic regression and scale stability.  


Monitoring a very frequently administered educational test with a relatively short history of stable operation imposes a number of challenges. Test scores usually vary by season, and the frequency of administration of such educational tests is also seasonal. Although it is important to react to unreasonable changes in the distributions of test scores in a timely fashion, it is not a simple matter to ascertain what sort of distribution is really unusual. Many commonly used approaches for seasonal adjustment are designed for time series with evenly spaced observations that span many years and, therefore, are inappropriate for data from such educational tests. Harmonic regression, a seasonal-adjustment method, can be useful in monitoring scale stability when the number of years available is limited and when the observations are unevenly spaced. Additional forms of adjustments can be included to account for variability in test scores due to different sources of population variations. To illustrate, real data are considered from an international language assessment. PMID:24092490

Lee, Yi-Hsuan; Haberman, Shelby J



Estimating equivalence with quantile regression.  


Equivalence testing and corresponding confidence interval estimates are used to provide more enlightened statistical statements about parameter estimates by relating them to intervals of effect sizes deemed to be of scientific or practical importance rather than just to an effect size of zero. Equivalence tests and confidence interval estimates are based on a null hypothesis that a parameter estimate is either outside (inequivalence hypothesis) or inside (equivalence hypothesis) an equivalence region, depending on the question of interest and assignment of risk. The former approach, often referred to as bioequivalence testing, is often used in regulatory settings because it reverses the burden of proof compared to a standard test of significance, following a precautionary principle for environmental protection. Unfortunately, many applications of equivalence testing focus on establishing average equivalence by estimating differences in means of distributions that do not have homogeneous variances. I discuss how to compare equivalence across quantiles of distributions using confidence intervals on quantile regression estimates that detect differences in heterogeneous distributions missed by focusing on means. I used one-tailed confidence intervals based on inequivalence hypotheses in a two-group treatment-control design for estimating bioequivalence of arsenic concentrations in soils at an old ammunition testing site and bioequivalence of vegetation biomass at a reclaimed mining site. Two-tailed confidence intervals based both on inequivalence and equivalence hypotheses were used to examine quantile equivalence for negligible trends over time for a continuous exponential model of amphibian abundance. PMID:21516905

Cade, Brian S



Functional Regression for Quasar Spectra  

E-print Network

The Lyman-alpha forest is a portion of the observed light spectrum of distant galactic nuclei which allows us to probe remote regions of the Universe that are otherwise inaccessible. The observed Lyman-alpha forest of a quasar light spectrum can be modeled as a noisy realization of a smooth curve that is affected by a `damping effect' which occurs whenever the light emitted by the quasar travels through regions of the Universe with higher matter concentration. To decode the information conveyed by the Lyman-alpha forest about the matter distribution, we must be able to separate the smooth `continuum' from the noise and the contribution of the damping effect in the quasar light spectra. To predict the continuum in the Lyman-alpha forest, we use a nonparametric functional regression model in which both the response and the predictor variable (the smooth part of the damping-free portion of the spectrum) are function-valued random variables. We demonstrate that the proposed method accurately predicts the unobserv...

Ciollaro, Mattia; Freeman, Peter; Genovese, Christopher; Lei, Jing; O'Connell, Ross; Wasserman, Larry



Ordinal regression with continuous pairwise preferences  

Microsoft Academic Search

We investigate the problem of data-driven ordinal regression—the problem of learning to rank order new data items based on\\u000a information inherent in existing data items. Ordinal regression shares common features with multi-category classification\\u000a and metric regression. However, it requires new, tailor-made methodologies to reduce prediction error. The approach has application\\u000a in various domains, including information retrieval, collaborative filtering and social

Maria Dobrska; Hui Wang; William Blackburn


Large-Scale Sparse Logistic Regression  

Microsoft Academic Search

Logistic Regression is a well-known classification method that has been used widely in many applications of data mining, machine learning, computer vision, and bioinformatics. Sparse logistic regression embeds feature selection in the classification framework using the l1-norm regularization, and is attractive in many applications involving high-dimensional data. In this paper, we propose Lassplore for solving large-scale sparse logistic regression. Specifically,

Jun Liu; Jianhui Chen; Jieping Ye



Regression models for estimating coseismic landslide displacement  

Microsoft Academic Search

Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived

Randall W. Jibson



Principles of MIR, multivariate image regression  

Microsoft Academic Search

We present an introduction to Multivariate Image Regression (MIR) with a selection of illustrative application studies. Generalisation from two-way multivariate calibration to the three-way regimen leads to—at least—three alternative image regression cases depending on the nature of the available Y-data: IPLS-Ydiscrim; IPLS-Ygrid; IPLS-Ytotal. A systematic image regression typology is briefly introduced.We here present the core of the principles of applied

Thorbjørn T Lied; Kim H Esbensen



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

PubMed Central

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

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



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

SciTech Connect

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

Sun, Lixin; Zhang, Shuang; Jiang, Zhenzhou; Huang, Xin; Wang, Tao; Huang, Xiao; Li, Han [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)] [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Zhang, Luyong, E-mail: [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)] [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)



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: [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)



Quantile regression applied to spectral distance decay  

USGS Publications Warehouse

Remotely sensed imagery has long been recognized as a powerful support for characterizing and estimating biodiversity. Spectral distance among sites has proven to be a powerful approach for detecting species composition variability. Regression analysis of species similarity versus spectral distance allows us to quantitatively estimate the amount of turnover in species composition with respect to spectral and ecological variability. In classical regression analysis, the residual sum of squares is minimized for the mean of the dependent variable distribution. However, many ecological data sets are characterized by a high number of zeroes that add noise to the regression model. Quantile regressions can be used to evaluate trend in the upper quantiles rather than a mean trend across the whole distribution of the dependent variable. In this letter, we used ordinary least squares (OLS) and quantile regressions to estimate the decay of species similarity versus spectral distance. The achieved decay rates were statistically nonzero (p < 0.01), considering both OLS and quantile regressions. Nonetheless, the OLS regression estimate of the mean decay rate was only half the decay rate indicated by the upper quantiles. Moreover, the intercept value, representing the similarity reached when the spectral distance approaches zero, was very low compared with the intercepts of the upper quantiles, which detected high species similarity when habitats are more similar. In this letter, we demonstrated the power of using quantile regressions applied to spectral distance decay to reveal species diversity patterns otherwise lost or underestimated by OLS regression. ?? 2008 IEEE.

Rocchini, D.; Cade, B.S.



Larry Cox,, (505) 665-7344 Monte Carlo mini-App --  

E-print Network

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


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


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



Functional Role of Two Interhelical Disulfide Bonds in Human Cox17 Protein from a Structural Perspective*  

PubMed Central

Human Cox17 is the mitochondrial copper chaperone responsible for supplying copper ions, through the assistance of Sco1, Sco2, and Cox11, to cytochrome c oxidase, the terminal enzyme of the mitochondrial energy-transducing respiratory chain. It consists of a coiled coil-helix-coiled coil-helix domain stabilized by two disulfide bonds and binds one copper(I) ion through a Cys–Cys motif. Here, the structures and the backbone mobilities of two Cox17 mutated forms with only one interhelical disulfide bond have been analyzed. It appears that the inner disulfide bond (formed by Cys-36 and Cys-45) stabilizes interhelical hydrophobic interactions, providing a structure with essentially the same structural dynamic properties of the mature Cox17 state. On the contrary, the external disulfide bond (formed by Cys-26 and Cys-55) generates a conformationally flexible ?-helical protein, indicating that it is not able to stabilize interhelical packing contacts, but is important for structurally organizing the copper-binding site region. PMID:21816817

Banci, Lucia; Bertini, Ivano; Cefaro, Chiara; Ciofi-Baffoni, Simone; Gallo, Angelo



Redesign of CDBS S. Lubow, C. Cox, L. Hurt, B. Simon  

E-print Network

Redesign of CDBS S. Lubow, C. Cox, L. Hurt, B. Simon Space Telescope Science Institute Baltimore redesign are described in "Report on CDBS Review" by Lubow and we do not repeat them all here. The design and DADS. CDBS automatically updates its database when response les are received. Extended Bestref

Sirianni, Marco


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


Robyn M. Cox, PhD Professor ofAudiology, University ofMemphis, Memphis, TN  

E-print Network

Robyn M. Cox, PhD Professor ofAudiology, University ofMemphis, Memphis, TN ABSTRACT: Hearing Aids and the Loudness problem Perhaps the lnost ubiquitous problem encountered in hearing aid fitting .is a lack of satisfaction with loudness continues to be a significant and substantial problem for hearing aid wearers

Dasgupta, Dipankar


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: [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: [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)



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



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



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

Microsoft Academic Search

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

Gavin Birch; Made Siaka; Christopher Owens



Simultaneous Targeting of COX-2 and AKT Using Selenocoxib-1-GSH to Inhibit Melanoma  

PubMed Central

Melanoma is a highly metastatic and deadly disease. An agent simultaneously targeting COX-2, PI3K/Akt and MAPK signaling pathways that are deregulated in up to 70% of sporadic melanoma might be an effective treatment but no agent of this type exists. To develop a single drug inhibiting COX-2 and PI3K/Akt signaling (and increasing MAPK pathway activity to inhibitory levels as a result of Akt inhibition), a selenium-containing glutathione (GSH) analog of celecoxib, called selenocoxib-1-GSH was synthesized. It killed melanoma cells with an average IC50 of 7.66 µmol/L compared to control celecoxib at 55.6 µmol/L. The IC50 range for normal cells was 36.3–41.2 µmol/L compared to 7.66 µmol/L for cancer cells. Selenocoxib-1-GSH reduced xenografted tumor development by ~70% with negligible toxicity by targeting COX-2, like celecoxib, and having new inhibitory properties acting as a PI3K/Akt inhibitor (and MAPK pathway activator to inhibitory levels due to Akt inhibition). The consequence of this inhibitory activity was an ~80% decrease in cultured cell proliferation and a ~200% increase in apoptosis following 24 hours treatment with 15.5 µmol/L of drug. Thus, this study details development of selenocoxib-1-GSH, which is a non-toxic agent that targets the COX-2 and PI3K/Akt signaling pathways in melanomas to inhibit tumor development. PMID:23112250

Gowda, Raghavendra; Madhunapantula, SubbaRao V.; Desai, Dhimant; Amin, Shantu; Robertson, Gavin P.



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

Microsoft Academic Search

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

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



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


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



Pimarane Cyclooxygenase 2 (COX-2) Inhibitor and its StructureActivity Relationship  

E-print Network

activities, although the inhibitory potency was not satisfactory. Our docking study9 revealed that the COX-2. *Corresponding author. Tel.: +82-02-880-7875; fax: +82-02-888- 0649; e-mail: #12

Suh, Young-Ger


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

E-print Network

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

Edinburgh, University of


Characterization of Novel Radicals from COX-Catalyzed Arachidonic Acid Peroxidation  

PubMed Central

The peroxidation of arachidonic acid (AA) catalyzed by cyclooxygenase (COX) is a well known free radical-mediated process that forms many bioactive products. Due to a lack of appropriate methodologies, however, no comprehensive structural evidence has been found previously for the formation of COX-mediated and AA-derived free radicals. Here we have used a combination of LC/ESR and LC/MS with a spin trap, ?-[4-pyridyl-1-oxide]-N-tert-butyl nitrone (POBN), to characterize the carbon-centered radicals formed from COX-catalyzed AA peroxidation in vitro, including cellular peroxidation in human prostate cancer cells (PC-3). Three types of radicals with numerous isomers were trapped by POBN as ESR-active peaks and MS-active ions of m/z 296, m/z 448, and m/z 548, all stemming from PGF2-type alkoxyl radicals. One of these was a novel radical centered on the carbon-carbon double bond nearest the PGF ring, caused by an unusual ?-scission of PGF2-type alkoxyl radicals. The complementary non-radical product was 1-hexanol, another novel ?-scission product, instead of the more common aldehyde. The characterization of these novel products formed from in vitro peroxidation provides a new mechanistic insight into COX-catalyzed AA peroxidation in cancer biology. PMID:19482075

Yu, Qingfeng; Purwaha, Preeti; Ni, Kunyi; Sun, Chengwen; Mallik, Sanku; Qian, Steven Y.



Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account  

E-print Network

and hypertrophic cardiomyopathy, have so far only been associated with mutations in SURF1 or SCO2 and COX15 infantile hypertrophic cardiomyopathy. A partial rescue was also obtained following microcell Canadian form of Leigh syndrome, fatal infantile hypertrophic cardiomyopathy and myopathy, fatal infantile

Shoubridge, Eric


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.



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



Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs  

PubMed Central

Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs. PMID:21346820

Whiteley, Mary H.; Bell, Jerold S.; Rothman, Debby A.



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



Program Slicing-Based Regression Testing Techniques  

Microsoft Academic Search

After changes are made to a previously tested program, a goal of regression testing is to perform retesting based on the modifications while maintaining the same testing coverage as completely retesting the program. We p resent a novel approach to data flow based regression testing that uses slicing algorithms to explicitly detect definition-use associations that are affected by a program

Rajiv Gupta; Mary Jean Harrold; Mary Lou Soffa



COBRA: A Collective Regression Grard Biau  

E-print Network

COBRA: A Collective Regression Strategy Gérard Biau Université Pierre et Marie Curie1 & Ecole to declare which might be the best basic estimator for the given data set. A companion R package called COBRA (stand- ing for COmBined Regression Alternative) is presented (downloadable on

Biau, Gérard


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


Stationary Markov chains with linear regressions  

Microsoft Academic Search

In Bryc (Ann. Probab., (1998), to appear), we determined one-dimensional distributions of a stationary field with linear regressions (1) and quadratic conditional variances (2) under a linear constraint (7) on the coefficients of the quadratic expression (3). In this paper, we show that for stationary Markov chains with linear regressions and quadratic conditional variances the coefficients of the quadratic expression

Wlodzimierz Bryc



WINKS Statistics Software - Simple Linear Regression  

NSDL National Science Digital Library

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



Performing Exact Logistic Regression with the SAS  

Microsoft Academic Search

Exact logistic regression has become an important analytical technique, especially in the pharmaceuti- cal industry, since the usual asymptotic methods for analyzing small, skewed, or sparse data sets are un- reliable. Inference based on enumerating the ex- act distributions of sufficient statistics for parameters of interest in a logistic regression model, conditional on the remaining parameters, is computationally in- feasible

Robert E. Derr


Efficient L1 Regularized Logistic Regression  

Microsoft Academic Search

L1 regularized logistic regression is now a workhorse of machine learning: it is widely used for many classifica- tion problems, particularly ones with many features. L1 regularized logistic regression requires solving a convex optimization problem. However, standard algorithms for solving convex optimization problems do not scale well enough to handle the large datasets encountered in many practical settings. In this

Su-in Lee; Honglak Lee; Pieter Abbeel; Andrew Y. Ng



Combining Estimates in Regression and Classification  

Microsoft Academic Search

We consider the problem of how to combine a collection of generalregression fit vectors in order to obtain a better predictive model. Theindividual fits may be from subset linear regression, ridge regression, orsomething more complex like a neural network. We develop a generalframework for this problem and examine a recent cross-validation-basedproposal called "stacking" in this context. Combination methods basedon the

Michael Leblanc; Robert Tibshirani



Regression Analysis and the Sociological Imagination  

ERIC Educational Resources Information Center

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

De Maio, Fernando



Proportional Mean Regression Models for Censored Data  

Microsoft Academic Search

A novel semiparametric regression model for censored data is proposed as an alternative to the widely used proportional hazards survival model. The proposed regression model for censored data turns out to be flexible and practically meaningful. Features include physical interpretation of the re- gression coefficients through the mean response time instead of the hazard functions, and a rigorous proof of

Sujit K. Ghosh; Subhashis Ghosal


Hyaluronic acid is radioprotective in the intestine through a TLR4 and COX-2-mediated mechanism  

PubMed Central

The intestinal epithelium is sensitive to radiation injury. Damage to the intestinal epithelium is dose limiting in radiation therapy of abdominal cancers. There is a need for agents that can be given before radiation therapy to protect the intestinal epithelium. C57BL6 mice were subjected to 12 Gy of total body radiation. Some mice received intraperitoneal hyaluronic acid (HA) before radiation. Mice were killed 6 h after radiation to assess radiation-induced apoptosis in the intestine; other mice were killed at 84 h to assess crypt survival. Total body radiation (12 Gy) resulted in increased expression of HA synthases and HA in the intestine and increased plasma HA (5-fold). Intraperitoneal injection of HA (30 mg/kg) before radiation resulted in a 1.8-fold increase in intestinal crypt survival and a decrease in radiation-induced apoptosis. The radioprotective effects of HA were not seen in Toll-like receptor 4 (TLR4)- or cyclooxygenase-2 (COX-2)-deficient mice. Intraperitoneal injection of HA induced a 1.5-fold increase in intestinal COX-2 expression, a 1.5-fold increase in intestinal PGE2, and the migration of COX-2-expressing mesenchymal stem cells from the lamina propria in the villi to the lamina propria near the crypt. We conclude that 1) radiation induces increased HA expression through inducing HA synthases, 2) intraperitoneal HA given before radiation reduces radiation-induced apoptosis and increases crypt survival, and 3) these radioprotective effects are mediated through TLR4, COX-2, and the migration of COX-2-expressing mesenchymal stem cells. PMID:22038822

Riehl, Terrence E.; Foster, Lynne



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


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



Regression of Environmental Noise in LIGO data  

NASA Astrophysics Data System (ADS)

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

Tiwari, Vaibhav; Klimenko, Sergei



Partial least squares regression as a powerful tool for investigating large combinatorial polymer libraries  

PubMed Central

Partial Least Squares (PLS) regression is an established analytical tool in surface science, particularly for relating multivariate ToF-SIMS data to a univariate surface property. Herein we construct a PLS model using ToF-SIMS and surface energy data from a 496 copolymer micro-patterned library. Using this 496 copolymer library we investigate how changing the number of samples used to construct the PLS model affects the identity of the most influential ions identified in the regression vector. The regression coefficients vary in magnitude, but the general relationship between ion structure and surface energy is maintained. As expected, if copolymers containing monomers with unique chemistries are removed from the training set, secondary ions specific to these copolymers are not present in the regression vector. The use of PLS to obtain quantitative predictions has not been actively explored in the surface analytical field. We investigate whether the PLS model obtained can be used to predict the surface energies of polymers within and outside of the training set. The model systematically underestimated the surface energy of a group of acrylate copolymers synthesised using monomers common to the training set, but in different compositions. The predictions for a group of acrylate copolymers that were synthesised from monomers not used in the training set were very poor. When the model was used to obtain predictions for six commercially available polymers the values obtained were all close to the mean surface energy of the training set. This exercise suggests that PLS may be able to predict the surface energy of polymers synthesised from monomers common to the training set, confirming the importance that the training set reflects the chemistry of the samples to be predicted.

Taylor, Michael; Urquhart, Andrew J.; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.; Alexander, Morgan R.



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: [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)




E-print Network

PARAMETRIC REGRESSION OF 3D MEDICAL IMAGES THROUGH THE EXPLORATION OF NON-PARAMETRIC REGRESSION. As predictors, the regres- sion model uses patient-specific metadata (e.g. age, weight, body mass index, etc at the greater trochanter. (b) End point between condyles. (c) CCD angle. Currently in medical image regression

Paris-Sud XI, Université de


Methods for stratification of person-time and events - a prerequisite for Poisson regression and SIR estimation  

PubMed Central

Introduction Many epidemiological methods for analysing follow-up studies require the calculation of rates based on accumulating person-time and events, stratified by various factors. Managing this stratification and accumulation is often the most difficult aspect of this type of analysis. Tutorial We provide a tutorial on accumulating person-time and events, stratified by various factors i.e. creating event-time tables. We show how to efficiently generate event-time tables for many different outcomes simultaneously. We also provide a new vocabulary to characterise and differentiate time-varying factors. The tutorial is focused on using a SAS macro to perform most of the common tasks in the creation of event-time tables. All the most common types of time-varying covariates can be generated and categorised by the macro. It can also provide output suitable for other types of survival analysis (e.g. Cox regression). The aim of our methodology is to support the creation of bug-free, readable, efficient, capable and easily modified programs for making event-time tables. We briefly compare analyses based on event-time tables with Cox regression and nested case-control studies for the analysis of follow-up data. Conclusion Anyone working with time-varying covariates, particularly from large detailed person-time data sets, would gain from having these methods in their programming toolkit. PMID:19014582

Rostgaard, Klaus



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.



Sparse Multivariate Regression With Covariance Estimation  

PubMed Central

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

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



Semiparametric Regression in Size-Biased Sampling  

PubMed Central

Summary Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of the covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that the regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses. PMID:19432792

Chen, Ying Qing



Exocrine Pancreatic Insufficiency, Dyserythropoeitic Anemia, and Calvarial Hyperostosis Are Caused by a Mutation in the COX4I2 Gene  

PubMed Central

Steatorrhea and malabsorption of lipid-soluble vitamins due to exocrine pancreatic insufficiency are common in patients with cystic fibrosis and are predominant in Shwachman-Bodian-Diamond, Pearson, and Johanson-Blizzard syndromes. In four patients who suffered from congenital exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis, we excluded these disorders and identified, by using homozygosity mapping, a mutation in the COX4I2 gene. The COX4 protein is an essential structural subunit of cytochrome c oxidase complex and has two isoforms, encoded by two different genes. We show that the ratio of COX4I2 to COX4I1 mRNA is relatively high in human acinar cells. The mutation is associated with marked reduction of COX4I2 expression and with striking attenuation of the physiologic COX4I2 response to hypoxia. Mutation analysis of COX4I2 is warranted in patients with malabsorption due to exocrine pancreatic insufficiency and in patients with dyserythropoeitic anemia. PMID:19268275

Shteyer, Eyal; Saada, Ann; Shaag, Avraham; Al-Hijawi, Fida' Aziz; Kidess, Rojette; Revel-Vilk, Shoshanah; Elpeleg, Orly



The Spatiotemporal Role of COX-2 in Osteogenic and Chondrogenic Differentiation of Periosteum-Derived Mesenchymal Progenitors in Fracture Repair  

PubMed Central

Periosteum provides a major source of mesenchymal progenitor cells for bone fracture repair. Combining cell-specific targeted Cox-2 gene deletion approaches with in vitro analyses of the differentiation of periosteum-derived mesenchymal progenitor cells (PDMPCs), here we demonstrate a spatial and temporal role for Cox-2 function in the modulation of osteogenic and chondrogenic differentiation of periosteal progenitors in fracture repair. Prx1Cre-targeted Cox-2 gene deletion in mesenchyme resulted in marked reduction of intramembraneous and endochondral bone repair, leading to accumulation of poorly differentiated mesenchyme and immature cartilage in periosteal callus. In contrast, Col2Cre-targeted Cox-2 gene deletion in cartilage resulted in a deficiency primarily in cartilage conversion into bone. Further cell culture analyses using Cox-2 deficient PDMPCs demonstrated reduced osteogenic differentiation in monolayer cultures, blocked chondrocyte differentiation and hypertrophy in high density micromass cultures. Gene expression microarray analyses demonstrated downregulation of a key set of genes associated with bone/cartilage formation and remodeling, namely Sox9, Runx2, Osx, MMP9, VDR and RANKL. Pathway analyses demonstrated dysregulation of the HIF-1, PI3K-AKT and Wnt pathways in Cox-2 deficient cells. Collectively, our data highlight a crucial role for Cox-2 from cells of mesenchymal lineages in modulating key pathways that control periosteal progenitor cell growth, differentiation, and angiogenesis in fracture repair. PMID:24988184

Huang, Chunlan; Xue, Ming; Chen, Hongli; Jiao, Jing; Herschman, Harvey R.; O'Keefe, Regis J.; Zhang, Xinping



Butein downregulates phorbol 12-myristate 13-acetate-induced COX2 transcriptional activity in cancerous and non-cancerous breast cells  

Microsoft Academic Search

Butein is a flavonoid isolated from the bark of Rhus verniciflua Stokes and the flowers of Butea monosperma, and is known to be a potential therapeutic drug for treating inflammation and cancer. Cyclooxygenase (COX) converts arachidonic acid to prostanoids, and increased expression of its isoform COX-2 has been observed in breast cancer tissues. It has been suggested that COX inhibitors

Grace Tak Yi Lau; Hui Huang; Shu-mei Lin; Lai K. Leung



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


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

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



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.



Rescue of Impaired Fracture Healing in COX-2?/? Mice via Activation of Prostaglandin E2 Receptor Subtype 4  

PubMed Central

Although the essential role of cyclooxygenase (COX)-2 in fracture healing is known, the targeted genes and molecular pathways remain unclear. Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture healing. In a fracture-healing model, COX-2?/? mice showed delayed initiation and impaired endochondral bone repair, accompanied by a severe angiogenesis deficiency. The EP4 agonist markedly improved the impaired healing in COX-2?/? mice, as evidenced by restoration of bony callus formation on day 14, a near complete reversal of bone formation, and an approximately 70% improvement of angiogenesis in the COX-2?/? callus. In comparison, the EP2 agonist only marginally enhanced bone formation in COX-2?/? mice. To determine the differential roles of EP2 and EP4 receptors on COX-2-mediated fracture repair, the effects of selective EP agonists on chondrogenesis were examined in E11.5 long-term limb bud micromass cultures. Only the EP4 agonist significantly increased cartilage nodule formation similar to that observed during prostaglandin E2 treatment. The prostaglandin E2/EP4 agonist also stimulated MMP-9 expression in bone marrow stromal cell cultures. The EP4 agonist further restored the reduction of MMP-9 expression in the COX-2?/? fracture callus. Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2?/? mice. PMID:19628768

Xie, Chao; Liang, Bojian; Xue, Ming; Lin, Angela S.P.; Loiselle, Alayna; Schwarz, Edward M.; Guldberg, Robert E.; O'Keefe, Regis J.; Zhang, Xinping



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


Sparse Regression Using Mixed Norms Matthieu Kowalski  

E-print Network

Sparse Regression Using Mixed Norms Matthieu Kowalski LATP, CMI, Universit´e de Provence, 39, rue F: Phone: +33-(0)491054743 Fax: +33-(0)491054742 (Matthieu Kowalski). Preprint

Paris-Sud XI, Université de


Weighted L Isotonic Regression Quentin F. Stout  

E-print Network

- negative, and f, the values, is arbitrary. Given weighted data (f, w) on G, an Lp isotonic regression of tumors being treated by radiation and chemotherapy, it might be assumed that at any given radiation level

Stout, Quentin F.


Predictive capability of proportional hazards regression.  

PubMed Central

A measure of the predictive capability of a proportional hazards regression is derived. The measure is based on the residuals appropriate to proportional hazards regression. A population version is presented and can be seen not to depend on the censoring mechanism under the provision that any such censoring be independent or conditionally independent of the failure mechanism given the covariate. For the special case of a Weibull regression model, for which the covariate distribution follows binary, uniform, normal, or exponential laws, we derive analytic results. These alone give credence to the measure which can be seen to reflect strength of regression effect, as quantified by the parameter estimate, although on a scale between 0 and 1, independently of the intercept or shape parameter of the particular Weibull law and only weakly dependent on the covariate distribution. Extensions to partial and multiple measures of predictive ability are straightforward. An example is provided. PMID:8134393

O'Quigley, J; Flandre, P



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

PubMed Central

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

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



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


The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:25060703

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



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



Multivariate Locally Weighted Least Squares Regression  

Microsoft Academic Search

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

D. Ruppert; M. P. Wand



Regression-Discontinuity with Nonparametric Bootstrap  

Microsoft Academic Search

The regression-discontinuity design (RD) is a powerful methodological alternative to the quasi- experimental design when conducting evaluations. RD designs involve testing post-test mean treatment differences between the experimental and comparison group regression lines at the centered cutoff point for statistical significance. This study simulated a RD treatment effect of 7 points in simulated normal and non-normal data distributions. The bootstrap

Randall E. Schumacker; E. Mount



Logistic Regression Models for Categorical Outcome Variables  

Microsoft Academic Search

\\u000a Analysis of crime and criminal justice data often requires the researcher to deal with a categorical outcome variable that\\u000a may be ordered or unordered. Our focus in this chapter is a discussion on the type of logistic regression model best suited\\u000a to an analysis of categorical outcome variables. We review binary logistic regression models for situations where the dependent\\u000a variable

Chester L. Britt; David Weisburd


Obtaining Environmental Favourability Functions from Logistic Regression  

Microsoft Academic Search

Logistic regression is a statistical tool widely used for predicting species’ potential distributions starting from presence\\/absence\\u000a data and a set of independent variables. However, logistic regression equations compute probability values based not only\\u000a on the values of the predictor variables but also on the relative proportion of presences and absences in the dataset, which\\u000a does not adequately describe the environmental

Raimundo Real; A. Márcia Barbosa; J. Mario Vargas



Long-horizon regressions: theoretical results andapplications  

Microsoft Academic Search

I use asymptotic arguments to show that the t-statistics in long-horizon regressions do not converge to well-defined distributions. In some cases, moreover, the ordinary least squares estimator is not consistent andthe R2 is an inadequate measure of the goodness of fit. These findings can partially explain the tendency of long-horizon regressions to find ''significant'' results where previous short-term approaches findnone.

Rossen Valkanov



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

PubMed Central

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



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

PubMed Central

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

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



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


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

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



Enhanced contractility of rat aorta in DOCA-salt hypertension involves COX2 activation  

Microsoft Academic Search

Responsiveness to many contractile agonists increase in deoxycorticosterone acetate (DOCA)-salt induced hypertension We tested the hypothesis that enhanced contractility of rat aorta to norepinephrine (NE) in DOCA-salt hypertension is causally related to increased expression and activity of COX-2. Thoracic aortic rings were obtained from uninephrectomized rats fed for 3 weeks on either normal (control), or 8% sodium+potassium (experimental) diets. The

Ayotunde S. Adeagbo; Xiaodong Zhang; Yang Wang; Mabayoje A. Oriowo



Hands-free approach for the left atrial appendage in Cox maze IV.  


Surgical excision of the left atrial appendage is an essential key in the Cox maze IV procedure. Management of very thin, friable, and delicate tissue in the base of the left atrial appendage can be difficult. We have designed a simple method to expose adequately without handling the base of the left atrial appendage. With this technique, the risk of bleeding due to excessive traction or manipulation of the heart is dramatically reduced. PMID:24585281

Garcia-Villarreal, Ovidio A



Outcome trials of COX2 selective inhibitors: global safety evaluation does not promise benefits  

Microsoft Academic Search

Background. Gastrointestinal toxicity is the most frequent adverse effect associated with nonsteroidal anti-inflammatory drug use. The most clinically relevant side effects of this toxicity are ulcer complications, including perforation, obstruction, or bleeding. Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed as a safer alternative to traditional, nonsteroidal anti-inflammatory drugs and they are currently widely used in clinical practice. The aim

Jorge Gomez Cerezo; Rubin Lubomirov Hristov; Antonio J. Carcas Sansuán; Juan J. Vázquez Rodríguez



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


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

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



Acetaminophen: Antipyretic or hypothermic in mice? In either case, PGHS-1b (COX3) is irrelevant  

Microsoft Academic Search

Acetaminophen (AC) reduces the core temperatures (Tc) of febrile and non-febrile mice alike. Evidence has been adduced that the selectively AC-sensitive PGHS isoform, PGHS-1b (COX-3), mediates these effects. PGHS-1b, however, has no catalytic potency in mice. To resolve this contradiction, AC was injected intravenously (i.v.) into conscious PGHS-1 gene-sufficient (wild-type (WT)) and -deficient (PGHS-1?\\/?) mice 60min before or after pyrogen-free

Shuxin Li; Wenkai Dou; Ying Tang; Sarita Goorha; Leslie R. Ballou; Clark M. Blatteis



Coordinated Upregulation of COX2 and NF-?B Is a Steady Feature of Laryngeal Carcinogenesis  

Microsoft Academic Search

Background\\/Aims: Laryngeal cancer is the endpoint of a multistage process involving hyperplastic and dysplastic lesions, not adequately defined in their molecular aspect. Our objective was to evaluate the expression of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) and the chief transcription factor nuclear factor-?B (NF-?B) in laryngeal carcinomas and their precursors, as well as to explore any association between the two molecules.

Konstantinos Kourelis; Georgia Sotiropoulou-Bonikou; Gerasimos Vandoros; Maria Repanti; Ioannis Varakis; Panagiotis Goumas



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

NASA Technical Reports Server (NTRS)

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

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



Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src kinase activity  

PubMed Central

Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma skin cancer, and UVB in particular promotes tumor growth through various signaling pathways. Kaempferol, a flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-carcinogenesis. Here, we examined the effect of kaempferol on UVB-induced skin inflammation. We found that kaempferol suppressed UVB-induced cyclooxygenase-2 (COX-2) protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and activator protein-1 (AP-1). Kaempferol attenuated the UVB-induced phosphorylation of several mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo kinase assays demonstrated that kaempferol suppressed Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that kaempferol suppresses UVB-induced COX-2 expression by blocking Src kinase activity. A pull-down assay revealed that kaempferol competes with ATP for direct binding to Src. Docking data suggest that kaempferol docks easily into the ATP-binding site of Src, which is located between the N and C lobes of the kinase domain. Taken together, these results suggest that kaempferol is a potent chemopreventive agent against skin cancer through its inhibitory interaction with Src. PMID:20599768

Lee, Kyung Mi; Lee, Ki Won; Jung, Sung Keun; Lee, Eun Jung; Heo, Yong-Seok; Bode, Ann M.; Lubet, Ronald A.; Lee, Hyong Joo; Dong, Zigang



Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.  


Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development. PMID:16760271

Rocco, A; Caruso, R; Toracchio, S; Rigoli, L; Verginelli, F; Catalano, T; Neri, M; Curia, M C; Ottini, L; Agnese, V; Bazan, V; Russo, A; Pantuso, G; Colucci, G; Mariani-Costantini, R; Nardone, G



A Note Comparing Component-Slope, Scheffé, and Cox Parameterizations of the Linear Mixture Experiment Model  

SciTech Connect

A mixture experiment involves combining two or more components in various proportions and collecting data on one or more responses. A linear mixture model may adequately represent the relationship between a response and mixture component proportions and be useful in screening the mixture components. The Scheffé and Cox parameterizations of the linear mixture model are commonly used for analyzing mixture experiment data. With the Scheffé parameterization, the fitted coefficient for a component is the predicted response at that pure component (i.e., single-component mixture). With the Cox parameterization, the fitted coefficient for a mixture component is the predicted difference in response at that pure component and at a pre-specified reference composition. This paper presents a new component-slope parameterization, in which the fitted coefficient for a mixture component is the predicted slope of the linear response surface along the direction determined by that pure component and at a pre-specified reference composition. The component-slope, Scheffé, and Cox parameterizations of the linear mixture model are compared and their advantages and disadvantages are discussed.

Piepel, Gregory F.



Low-level laser therapy improves skeletal muscle performance, decreases skeletal muscle damage and modulates mRNA expression of COX-1 and COX-2 in a dose-dependent manner.  


We tested if modulation in mRNA expression of cyclooxygenase isoforms (COX-1 and COX-2) can be related to protective effects of phototherapy in skeletal muscle. Thirty male Wistar rats were divided into five groups receiving either one of four laser doses (0.1, 0.3, 1.0 and 3.0 J) or a no-treatment control group. Laser irradiation (904 nm, 15 mW average power) was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions. Immediately after sixth contraction, blood samples were collected to evaluate creatine kinase activity and muscles were dissected and frozen in liquid nitrogen to evaluate mRNA expression of COX-1 and COX-2. The 1.0 and 3.0 J groups showed significant enhancement (P < 0.01) in total work performed in six tetanic contractions compared with control group. All laser groups, except the 3.0 J group, presented significantly lower post-exercise CK activity than control group. Additionally, 1.0 J group showed increased COX-1 and decreased COX-2 mRNA expression compared with control group and 0.1, 0.3 and 3.0 J laser groups (P < 0.01). We conclude that pre-exercise infrared laser irradiation with dose of 1.0 J enhances skeletal muscle performance and decreases post-exercise skeletal muscle damage and inflammation. PMID:21749398

de Almeida, Patrícia; Lopes-Martins, Rodrigo Álvaro Brandão; Tomazoni, Shaiane Silva; Silva, José Antônio; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal Junior, Ernesto Cesar Pinto



A complex of Cox4 and mitochondrial Hsp70 plays an important role in the assembly of the cytochrome c oxidase  

PubMed Central

The formation of the mature cytochrome c oxidase (complex IV) involves the association of nuclear- and mitochondria-encoded subunits. The assembly of nuclear-encoded subunits like cytochrome c oxidase subunit 4 (Cox4) into the mature complex is poorly understood. Cox4 is crucial for the stability of complex IV. To find specific biogenesis factors, we analyze interaction partners of Cox4 by affinity purification and mass spectroscopy. Surprisingly, we identify a complex of Cox4, the mitochondrial Hsp70 (mtHsp70), and its nucleotide-exchange factor mitochondrial GrpE (Mge1). We generate a yeast mutant of mtHsp70 specifically impaired in the formation of this novel mtHsp70-Mge1-Cox4 complex. Strikingly, the assembly of Cox4 is strongly decreased in these mutant mitochondria. Because Cox4 is a key factor for the biogenesis of complex IV, we conclude that the mtHsp70-Mge1-Cox4 complex plays an important role in the formation of cytochrome c oxidase. Cox4 arrests at this chaperone complex in the absence of mature complex IV. Thus the mtHsp70-Cox4 complex likely serves as a novel delivery system to channel Cox4 into the assembly line when needed. PMID:23864706

Bottinger, Lena; Guiard, Bernard; Oeljeklaus, Silke; Kulawiak, Bogusz; Zufall, Nicole; Wiedemann, Nils; Warscheid, Bettina; van der Laan, Martin; Becker, Thomas



Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX2) inhibitors  

Microsoft Academic Search

BACKGROUND: Epidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A

Randall E Harris; Joanne Beebe-Donk; Galal A Alshafie



Gi-coupled prostanoid receptors are the likely targets for COX1-generated prostanoids in rat pheochromocytoma (PC12) cells  

Microsoft Academic Search

Cyclooxygenase-1 (COX-1) behaves as a delayed response gene in rat pheochromocytoma (PC12) cells exposed to nerve growth factor (NGF). To investigate the possible targets for COX-1 generated prostanoids in the early stages of neuronal differentiation, we have examined the expression of prostanoid receptors by PC12 cells using functional assays. Prostanoid receptor-specific agonists failed to activate adenylyl cyclase in undifferentiated and

H. S. Yung; Kevin B. S. Chow; K. H. Lai; H. Wise



Selective cyclooxygenase (COX) inhibition causes damage to portal hypertensive gastric mucosa: roles of nitric oxide and NF-kappaB.  


Portal hypertension (PHT) is associated with increased susceptibility of the gastric mucosa to injury by a variety of factors, including nonsteroidal anti-inflammatory drugs (NSAIDs) that nonselectively inhibit both isoforms of cyclooxygenase (COX-1 and -2). PHT gastric mucosa also has excessive nitric oxide (NO) production that contributes to the general increased susceptibility to injury. Using a rat model of PHT, we studied whether selective COX inhibition, which does not damage normal (normotensive) gastric mucosa, is sufficient to cause PHT gastric damage and, if so, whether and how excessive NO is involved. Indomethacin, a nonselective NSAID, caused 2.4-fold more gastric injury to PHT vs. normotensive sham-operated (SO) control rats. Neither NS-398 nor celecoxib, selective COX-2 inhibitors, caused gastric damage in either SO or PHT rats. SC-560, a selective COX-1 inhibitor, did not cause gastric damage in SO rats but dose-dependently caused gastric damage in PHT rats. There was a compensatory increase in COX-2 expression and activity in SC-560-treated SO rats but not SC-560-treated PHT rats. Partial inhibition of NO production restored gastric COX-2 expression and activity levels in SC-560-treated PHT rats to those of SC-560-treated SO rats, by a mechanism consistent with induction of NF-kappaB, and significantly reduced gastric damage. These studies indicate that, in contrast to normotensive gastric mucosa, inhibition of COX-1 alone is sufficient to cause PHT gastric damage as a result of excessive NO that prevents the induction of NF-kappaB and the compensatory increase in COX-2. PMID:15845610

Akahoshi, Tomohiko; Tanigawa, Tetsuya; Sarfeh, I James; Chiou, Shiun-Kwei; Hashizume, Makoto; Maehara, Yoshihiko; Jones, Michael K



Moraxella catarrhalis induces ERK and NF B-dependent COX2 and prostaglandin E2 in lung epithelium  

Microsoft Academic Search

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. Cyclooxygenase (COX)-derived prostaglandins, such as prostaglandin E2 (PGE2), are considered to be important regulators of lung function. The present authors tested the hypothesis that M. catarrhalis induces COX-2-dependent PGE2 production in pulmonary epithelial cells. In the present study, the authors demonstrate that M. catarrhalis specifically induces

P. D. N'Guessan; B. Temmesfeld-Wollbruck; J. Zahlten; J. Eitel; S. Zabel; B. Schmeck; B. Opitz; S. Hippenstiel; N. Suttorp; H. Slevogt



Deletion Diagnostics for Alternating Logistic Regressions  

PubMed Central

Deletion diagnostics are introduced for the regression analysis of clustered binary outcomes estimated with alternating logistic regressions, an implementation of generalized estimating equations (GEE) that estimates regression coefficients in a marginal mean model and in a model for the intracluster association given by the log odds ratio. The diagnostics are developed within an estimating equations framework that recasts the estimating functions for association parameters based upon conditional residuals into equivalent functions based upon marginal residuals. Extensions of earlier work on GEE diagnostics follow directly, including computational formulae for one-step deletion diagnostics that measure the influence of a cluster of observations on the estimated regression parameters and on the overall marginal mean or association model fit. The diagnostic formulae are evaluated with simulations studies and with an application concerning an assessment of factors associated with health maintenance visits in primary care medical practices. The application and the simulations demonstrate that the proposed cluster-deletion diagnostics for alternating logistic regressions are good approximations of their exact fully iterated counterparts. PMID:22777960

Preisser, John S.; By, Kunthel; Perin, Jamie; Qaqish, Bahjat F.



On regression adjustment for the propensity score.  


Propensity scores are widely adopted in observational research because they enable adjustment for high-dimensional confounders without requiring models for their association with the outcome of interest. The results of statistical analyses based on stratification, matching or inverse weighting by the propensity score are therefore less susceptible to model extrapolation than those based solely on outcome regression models. This is attractive because extrapolation in outcome regression models may be alarming, yet difficult to diagnose, when the exposed and unexposed individuals have very different covariate distributions. Standard regression adjustment for the propensity score forms an alternative to the aforementioned propensity score methods, but the benefits of this are less clear because it still involves modelling the outcome in addition to the propensity score. In this article, we develop novel insights into the properties of this adjustment method. We demonstrate that standard tests of the null hypothesis of no exposure effect (based on robust variance estimators), as well as particular standardised effects obtained from such adjusted regression models, are robust against misspecification of the outcome model when a propensity score model is correctly specified; they are thus not vulnerable to the aforementioned problem of extrapolation. We moreover propose efficient estimators for these standardised effects, which retain a useful causal interpretation even when the propensity score model is misspecified, provided the outcome regression model is correctly specified. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24825821

Vansteelandt, S; Daniel, R M



Symbolic Regression of Conditional Target Expressions  

NASA Astrophysics Data System (ADS)

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

Korns, Michael F.


Regression models for estimating coseismic landslide displacement  

USGS Publications Warehouse

Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived from a collection of 2270 strong-motion records from 30 worldwide earthquakes. The regression equations predict Newmark displacement in terms of (1) critical acceleration ratio, (2) critical acceleration ratio and earthquake magnitude, (3) Arias intensity and critical acceleration, and (4) Arias intensity and critical acceleration ratio. These equations are well constrained and fit the data well (71% < R2 < 88%), but they have standard deviations of about 0.5 log units, such that the range defined by the mean ?? one standard deviation spans about an order of magnitude. These regression models, therefore, are not recommended for use in site-specific design, but rather for regional-scale seismic landslide hazard mapping or for rapid preliminary screening of sites. ?? 2007 Elsevier B.V. All rights reserved.

Jibson, R. W.



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.



Logistic regression for longitudinal case-control Thierry Duchesne1  

E-print Network

supported by NSERC and FQRNT #12;Outline Introduction GEE GEE for conditional logistic regression Application Conclusion Outline 1 Introduction Conditional logistic regression Problem: What if several matched GEE for conditional logistic regression Conditional mean and variance Working correlation structures

Duchesne, Thierry


Arsenic reduces the antipyretic activity of paracetamol in rats: modulation of brain COX-2 activity and CB? receptor expression.  


We examined whether subacute arsenic exposure can reduce paracetamol-mediated antipyretic activity by affecting COX pathway and cannabinoid CB1 receptor regulation. Rats were preexposed to elemental arsenic (4 ppm) as sodium arsenite through drinking water for 28 days. Next day pyrexia was induced with lipopolysaccharide and paracetamol's (200 mg/kg, oral) antipyretic activity was assessed. The activities of COX-1 and COX-2, the levels of PGE?, TNF-? and IL-1? and expression of CB? receptors were assessed in brain. Arsenic inhibited paracetamol-mediated antipyretic activity. COX-1 activity was not affected by any treatments. Paracetamol decreased COX-2 activity, levels of PGE?, TNF-? and IL-1? and caused up-regulation of CB1 receptors. Arsenic caused opposite effects on these parameters. In the arsenic-preexposed rats, paracetamol-mediated effects were attenuated, while CB? receptor up-regulation was reversed to down-regulation. Results suggest that elevated COX-2 activity and reduced CB? expression could be involved in the arsenic-mediated attenuation of the antipyretic activity of paracetamol. PMID:24448467

Vijayakaran, Karunakaran; Kannan, Kandasamy; Kesavan, Manickam; Suresh, Subramaniyam; Sankar, Palanisamy; Tandan, Surendra Kumar; Sarkar, Souvendra Nath



Quantitative Assessment of the Association of COX-2 (Cyclooxygenase-2) Immunoexpression with Prognosis in Human Osteosarcoma: A Meta-Analysis  

PubMed Central

Background Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2) immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. Methods We accordingly conducted a meta-analysis of 9 studies (442 patients) that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death). Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using the random-effects or fixed-effects model. Results Meta–analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10–3.74; P=0.009) and disease-free survival rate (RR=1.63; 95% CI: 1.17–2.28; P=0.004) at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. Conclusions COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma. PMID:24358237

Xiao, Zengming; Wu, Hao; Wu, Yang



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


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

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



AML1-ETO mediates hematopoietic self-renewal and leukemogenesis through a COX/?-catenin signaling pathway.  


Developing novel therapies that suppress self-renewal of leukemia stem cells may reduce the likelihood of relapses and extend long-term survival of patients with acute myelogenous leukemia (AML). AML1-ETO (AE) is an oncogene that plays an important role in inducing self-renewal of hematopoietic stem/progenitor cells (HSPCs), leading to the development of leukemia stem cells. Previously, using a zebrafish model of AE and a whole-organism chemical suppressor screen, we have discovered that AE induces specific hematopoietic phenotypes in embryonic zebrafish through a cyclooxygenase (COX)-2 and ?-catenin-dependent pathway. Here, we show that AE also induces expression of the Cox-2 gene and activates ?-catenin in mouse bone marrow cells. Inhibition of COX suppresses ?-catenin activation and serial replating of AE(+) mouse HSPCs. Genetic knockdown of ?-catenin also abrogates the clonogenic growth of AE(+) mouse HSPCs and human leukemia cells. In addition, treatment with nimesulide, a COX-2 selective inhibitor, dramatically suppresses xenograft tumor formation and inhibits in vivo progression of human leukemia cells. In summary, our data indicate an important role of a COX/?-catenin-dependent signaling pathway in tumor initiation, growth, and self-renewal, and in providing the rationale for testing potential benefits from common COX inhibitors as a part of AML treatments. PMID:23645839

Zhang, Yiyun; Wang, Jianfeng; Wheat, Justin; Chen, Xi; Jin, Shan; Sadrzadeh, Hossein; Fathi, Amir T; Peterson, Randall T; Kung, Andrew L; Sweetser, David A; Yeh, Jing-Ruey Joanna



A comparison of stratified versus regression estimators  

NASA Technical Reports Server (NTRS)

LANDSAT data acquired over an agricultural area along with ground enumeration of the same area are used to obtain crop acreage estimates which are better (as measured in terms of bias and variance) than can be obtained from either data source alone. Two basic approaches considered within the AgRISTARS program are a stratified crop acreage estimator and a regression estimator. A statement of the problem was mathematically formulated and some theorems were proved which relate to the variance of the two estimators. For a particular set of data, the regression and stratified estimators are compared in terms of certain easily computed parameters.

Takacs, H. C.



Topics in route-regression analysis  

USGS Publications Warehouse

The route-regression method has been used in recent years to analyze data from roadside surveys. With this method, a population trend is estimated for each route in a region, then regional trends are estimated as a weighted mean of the individual route trends. This method can accurately incorporate data that is unbalanced by changes in years surveyed and observer differences. We suggest that route-regression methodology is most efficient in the estimation of long-term (>5 year) trends, and tends to provide conservative results for low-density species.

Geissler, P.H.; Sauer, J.R.



Bootstrap methods for comparing independent regression slopes.  


In this study, we explore the effects of non-normality and heteroscedasticity when testing the hypothesis that the regression lines associated with multiple independent groups have the same slopes. The conventional approach involving the F-test and the t-test (F/t approach) is examined. In addition, we introduce two robust methods which allow simultaneous testing of regression slopes. Our results suggest that the F/t approach is extremely sensitive to violations of assumptions and tends to yield misleading conclusions. The new robust alternatives are recommended for general use. PMID:21827447

Ng, Marie; Wilcox, Rand R



Modelling Area Market Demand: A Case Study using Multiple Regression and Multivariate Adaptive Regression Splines  

Microsoft Academic Search

Statistical models help marketers explore the nature of marketing phenomena for effective targeting of customers within local areas. However, conventional multiple regression (MR) models can only reveal patterns in a simple way by forcing data into linear relationships, whereas it may be advantageous to tease out more complex relationships within the data. Multivariate adaptive regression splines (MARS) is applied to

Hongwei Lu; Mark D. Uncles; Gary D. Gregory; Lihua Zhao



E-print Network

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


Different impacts of saturated and unsaturated free fatty acids on COX-2 expression in C(2)C(12) myotubes.  


In skeletal muscle, saturated free fatty acids (FFAs) act as proinflammatory stimuli, and cyclooxygenase-2 (COX-2) is a pro/anti-inflammatory enzyme induced at sites of inflammation, which contributes to prostaglandin production. However, little is known about the regulation of COX-2 expression and its responses to FFAs in skeletal muscle. Herein, we examined the effects of saturated and unsaturated FFAs, including a recently identified lipokine (lipid hormone derived from adipocytes), palmitoleate, on COX-2 expression in C(2)C(12) myotubes as a skeletal muscle model. Exposure of myotubes to saturated FFAs [palmitate (16:0) and stearate (18:0)], but not to unsaturated FFAs [palmitoleate (16:1), oleate (18:1), and linoleate (18:2)], led to a slow-onset induction of COX-2 expression and subsequent prostaglandin E(2) production via mechanisms involving the p38 MAPK and NF-kappaB but not the PKC signaling cascades. Pharmacological modulation of mitochondrial oxidative function failed to interfere with COX-2 expression, suggesting the mitochondrial overload/excessive beta-oxidation contribution to this event to be minimal. On the contrary, unsaturated FFAs appeared to effectively antagonize palmitate-induced COX-2 expression with markedly different potencies (linoleate > oleate > palmitoleate), being highly associated with the suppressive profile of each unsaturated FFA toward palmitate-evoked intracellular signals, including p38, JNK, ERK1/2 MAPKs, and PKCtheta, as well as IkappaB degradation. In addition, our data suggest little involvement of PPAR in the protective actions of unsaturated FFAs against palmitate-induced COX-2 expression. No direct contribution of the increased COX-2 activity in generating palmitate-induced insulin resistance was detected, at least in terms of insulin-responsive Akt phosphorylation and GLUT4 translocation. Taken together, our data provide a novel insight into the molecular mechanisms responsible for the FFA-induced COX-2 expression in skeletal muscle and raise the possibility that, in skeletal myocytes, COX-2 and its product prostaglandins may play an important role in the complex inflammation responses caused by elevated FFAs, for example, in the diabetic state. PMID:19755671

Kadotani, Akito; Tsuchiya, Yo; Hatakeyama, Hiroyasu; Katagiri, Hideki; Kanzaki, Makoto



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

PubMed Central

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



Multiple recent horizontal transfers of the cox1 intron in Solanaceae and extended co-conversion of flanking exons  

PubMed Central

Background The most frequent case of horizontal transfer in plants involves a group I intron in the mitochondrial gene cox1, which has been acquired via some 80 separate plant-to-plant transfer events among 833 diverse angiosperms examined. This homing intron encodes an endonuclease thought to promote the intron's promiscuous behavior. A promising experimental approach to study endonuclease activity and intron transmission involves somatic cell hybridization, which in plants leads to mitochondrial fusion and genome recombination. However, the cox1 intron has not yet been found in the ideal group for plant somatic genetics - the Solanaceae. We therefore undertook an extensive survey of this family to find members with the intron and to learn more about the evolutionary history of this exceptionally mobile genetic element. Results Although 409 of the 426 species of Solanaceae examined lack the cox1 intron, it is uniformly present in three phylogenetically disjunct clades. Despite strong overall incongruence of cox1 intron phylogeny with angiosperm phylogeny, two of these clades possess nearly identical intron sequences and are monophyletic in intron phylogeny. These two clades, and possibly the third also, contain a co-conversion tract (CCT) downstream of the intron that is extended relative to all previously recognized CCTs in angiosperm cox1. Re-examination of all published cox1 genes uncovered additional cases of extended co-conversion and identified a rare case of putative intron loss, accompanied by full retention of the CCT. Conclusions We infer that the cox1 intron was separately and recently acquired by at least three different lineages of Solanaceae. The striking identity of the intron and CCT from two of these lineages suggests that one of these three intron captures may have occurred by a within-family transfer event. This is consistent with previous evidence that horizontal transfer in plants is biased towards phylogenetically local events. The discovery of extended co-conversion suggests that other cox1 conversions may be longer than realized but obscured by the exceptional conservation of plant mitochondrial sequences. Our findings provide further support for the rampant-transfer model of cox1 intron evolution and recommend the Solanaceae as a model system for the experimental analysis of cox1 intron transfer in plants. PMID:21943226



Differential expression of biphenyl synthase gene family members in fire-blight-infected apple 'Holsteiner Cox'.  


Fire blight, caused by the bacterium Erwinia amylovora, is a devastating disease of apple (Malus × domestica). The phytoalexins of apple are biphenyls and dibenzofurans, whose carbon skeleton is formed by biphenyl synthase (BIS), a type III polyketide synthase. In the recently published genome sequence of apple 'Golden Delicious', nine BIS genes and four BIS gene fragments were detected. The nine genes fall into four subfamilies, referred to as MdBIS1 to MdBIS4. In a phylogenetic tree, the BIS amino acid sequences from apple and Sorbus aucuparia formed an individual cluster within the clade of the functionally diverse type III polyketide synthases. cDNAs encoding MdBIS1 to MdBIS4 were cloned from fire-blight-infected shoots of apple 'Holsteiner Cox,' heterologously expressed in Escherichia coli, and functionally analyzed. Benzoyl-coenzyme A and salicoyl-coenzyme A were the preferred starter substrates. In response to inoculation with E. amylovora, the BIS3 gene was expressed in stems of cv Holsteiner Cox, with highest transcript levels in the transition zone between necrotic and healthy tissues. The transition zone was the accumulation site of biphenyl and dibenzofuran phytoalexins. Leaves contained transcripts for BIS2 but failed to form immunodetectable amounts of BIS protein. In cell cultures of apple 'Cox Orange,' expression of the BIS1 to BIS3 genes was observed after the addition of an autoclaved E. amylovora suspension. Using immunofluorescence localization under a confocal laser-scanning microscope, the BIS3 protein in the transition zone of stems was detected in the parenchyma of the bark. Dot-shaped immunofluorescence was confined to the junctions between neighboring cortical parenchyma cells. PMID:22158676

Chizzali, Cornelia; Gaid, Mariam M; Belkheir, Asma K; Hänsch, Robert; Richter, Klaus; Flachowsky, Henryk; Peil, Andreas; Hanke, Magda-Viola; Liu, Benye; Beerhues, Ludger



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

PubMed Central

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

Vidergar, Nina; Toplak, Nataša; Kuntner, Matjaž



Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm  

PubMed Central

We investigated the prostaglandin (PG)E2 pathway in human abdominal aortic aneurysm (AAA) and its relationship with hypervascularization. We analyzed samples from patients undergoing AAA repair in comparison with those from healthy multiorgan donors. Patients were stratified according to maximum aortic diameter: low diameter (LD) (<55 mm), moderate diameter (MD) (55–69.9 mm), and high diameter (HD) (?70 mm). AAA was characterized by abundant microvessels in the media and adventitia with perivascular infiltration of CD45-positive cells. Like endothelial cell markers, cyclooxygenase (COX)-2 and the microsomal isoform of prostaglandin E synthase (mPGES-1) transcripts were increased in AAA (4.4- and 1.4-fold, respectively). Both enzymes were localized in vascular cells and leukocytes, with maximal expression in the LD group, whereas leukocyte markers display a maximum in the MD group, suggesting that the upregulation of COX-2/mPGES-1 precedes maximal leukocyte infiltration. Plasma and in vitro tissue secreted levels of PGE2 metabolites were higher in AAA than in controls (plasma-controls, 19.9 ± 2.2; plasma-AAA, 38.8 ± 5.5 pg/ml; secretion-normal aorta, 16.5 ± 6.4; secretion-AAA, 72.9 ± 6.4 pg/mg; mean ± SEM). E-prostanoid receptor (EP)-2 and EP-4 were overexpressed in AAA, EP-4 being the only EP substantially expressed and colocalized with mPGES-1 in the microvasculature. Additionally, EP-4 mediated PGE2-induced angiogenesis in vitro. We provide new data concerning mPGES-1 expression in human AAA. Our findings suggest the potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated hypervascularization. PMID:24133193

Camacho, Mercedes; Dilmé, Jaume; Solà-Villà, David; Rodríguez, Cristina; Bellmunt, Sergi; Siguero, Laura; Alcolea, Sonia; Romero, José-María; Escudero, José-Román; Martínez-González, José; Vila, Luis



KRAS, EGFR, PDGFR-?, KIT and COX-2 status in carcinoma showing thymus-like elements (CASTLE)  

PubMed Central

Background CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid. Methods We retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-? and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets. Results Diagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-? gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene. Conclusions All tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-? gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined. Virtual Slides The virtual slide(s) for this article can be found here: PMID:24934485




E-print Network

HIGH�DIMENSIONAL INSTRUMENTAL VARIABLES REGRESSION AND CONFIDENCE SETS ERIC GAUTIER AND ALEXANDRE B for partial identification. Our procedure, called STIV (Self Tuning Instrumental Variables) estimator, is realized as a solution of a conic program. The joint confidence sets can be obtained by solving K convex

Paris-Sud XI, Université de


Using Regression Analysis: A Guided Tour.  

ERIC Educational Resources Information Center

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

Shelton, Fred Ames



Robust Locally Weighted Regression and Smoothing Scatterplots  

Microsoft Academic Search

The visual information on a scatterplot can be greatly enhanced, with little additional cost, by computing and plotting smoothed points. Robust locally weighted regression is a method for smoothing a scatterplot, (xi, yi), i = 1, …, n, in which the fitted value at zk is the value of a polynomial fit to the data using weighted least squares, where

William S. Cleveland



Ordinal logistic regression for affective product design  

Microsoft Academic Search

Affective product design, which focuses on customers¿ affective responses and aspirations, is arousing attention increasingly. This paper draws on ordinal logistic regression to deal with affective product design, mapping from designer domain to customer domain. It takes a designer¿s perspective and facilitates the handling of affective information and assists the designers to make trade-off decisions. Specifically, ten generic affective dimensions

F. Zhou; D. Wu; X. Yang; J. Jiao



Robust Regression: Asymptotics, Conjectures and Monte Carlo  

Microsoft Academic Search

Maximum likelihood type robust estimates of regression are defined and their asymptotic properties are investigated both theoretically and empirically. Perhaps the most important new feature is that the number $p$ of parameters is allowed to increase with the number $n$ of observations. The initial terms of a formal power series expansion (essentially in powers of $p\\/n$) show an excellent agreement

Peter J. Huber



Regression Models and Life-Tables  

Microsoft Academic Search

The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age-specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to

D. R. Cox



Research Journal (Multivariate Regression) Aleksandra Orlova  

E-print Network

/22 · What was done this week: Figured out the unanswered questions from the last week (correlation analysis on Multivariate Regression. · Questions and difficulties: Questions about the project draft: * formulation-squared distribution to estimate coefficients). · What needs to be done next: Meet with Dr. Lin to figure out questions

Mohlenkamp, Martin J.


A Spline Regression Model for Latent Variables  

ERIC Educational Resources Information Center

Spline (or piecewise) regression models have been used in the past to account for patterns in observed data that exhibit distinct phases. The changepoint or knot marking the shift from one phase to the other, in many applications, is an unknown parameter to be estimated. As an extension of this framework, this research considers modeling the…

Harring, Jeffrey R.



Invariant Ordering of Item-Total Regressions  

ERIC Educational Resources Information Center

A new observable consequence of the property of invariant item ordering is presented, which holds under Mokken's double monotonicity model for dichotomous data. The observable consequence is an invariant ordering of the item-total regressions. Kendall's measure of concordance "W" and a weighted version of this measure are proposed as measures for…

Tijmstra, Jesper; Hessen, David J.; van der Heijden, Peter G. M.; Sijtsma, Klaas



Bayesian isotonic regression and trend analysis.  


In many applications, the mean of a response variable can be assumed to be a nondecreasing function of a continuous predictor, controlling for covariates. In such cases, interest often focuses on estimating the regression function, while also assessing evidence of an association. This article proposes a new framework for Bayesian isotonic regression and order-restricted inference. Approximating the regression function with a high-dimensional piecewise linear model, the nondecreasing constraint is incorporated through a prior distribution for the slopes consisting of a product mixture of point masses (accounting for flat regions) and truncated normal densities. To borrow information across the intervals and smooth the curve, the prior is formulated as a latent autoregressive normal process. This structure facilitates efficient posterior computation, since the full conditional distributions of the parameters have simple conjugate forms. Point and interval estimates of the regression function and posterior probabilities of an association for different regions of the predictor can be estimated from a single MCMC run. Generalizations to categorical outcomes and multiple predictors are described, and the approach is applied to an epidemiology application. PMID:15180665

Neelon, Brian; Dunson, David B



A Skew-Normal Mixture Regression Model  

ERIC Educational Resources Information Center

A challenge associated with traditional mixture regression models (MRMs), which rest on the assumption of normally distributed errors, is determining the number of unobserved groups. Specifically, even slight deviations from normality can lead to the detection of spurious classes. The current work aims to (a) examine how sensitive the commonly…

Liu, Min; Lin, Tsung-I



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

ERIC Educational Resources Information Center

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

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



A Constrained Linear Estimator for Multiple Regression  

ERIC Educational Resources Information Center

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

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



Confidence Intervals for Bisquare Regression Estimates  

Microsoft Academic Search

This paper describes the results from a Monte Carlo study of robust regression confidence-interval estimation in the model y = a + bx + ?. Bisquare estimators were studied on samples of 11 and 21 with five design matrices. Four estimators of scale were used to form confidence intervals. Samples were generated from two distributions: normal and slash. For many

Alan M. Gross



Partitioned logistic regression for spam filtering  

Microsoft Academic Search

Naive Bayes and logistic regression perform well in different regimes. While the former is a very simple generative model which is ef- cient to train and performs well empirically in many applications, the latter is a discriminative model which often achieves better ac- curacy and can be shown to outperform naive Bayes asymptotically. In this paper, we propose a novel

Ming-wei Chang; Wen-tau Yih; Christopher Meek



Logistic regression with incompletely observed binary  

Microsoft Academic Search

Logistic regression is one of the most important tools in the analysis of epidemiological and clinical data. Such data often contain missing values for one or more variables. Common practice is to eliminate all individuals for whom any information is missing. This deletion approach does not make efficient use of available information and often introduces bias.^ Two methods were developed

Hai-An Hsu



Conditional logistic regression with missing data  

Microsoft Academic Search

Methods for parameter estimation in conditional logistic regression analysis with missing data are compared in a simulation study. The data consist of a matching variable and two covariates, one of which has missing values. Sample size, percent of data missing, and the relationships between the variables are varied. Four methods are compared when the covariates are continuous: 1) Analysis based

Laura E Gibbons; David W Hosmer JR



Commonality Analysis for the Regression Case.  

ERIC Educational Resources Information Center

Commonality analysis is a procedure for decomposing the coefficient of determination (R superscript 2) in multiple regression analyses into the percent of variance in the dependent variable associated with each independent variable uniquely, and the proportion of explained variance associated with the common effects of predictors in various…

Murthy, Kavita


Verification-Aided Regression Testing Fabrizio Pastore,  

E-print Network

of behavioral properties specific to the upgrade, by (i) automatically producing properties that are proved to hold for the base version of a program, (ii) automatically identifying and checking on the upgraded to detect such regression faults early Permission to make digital or hard copies of all or part of this work

Milano-Bicocca, Università


Semantics Guided Regression Test Cost Reduction  

Microsoft Academic Search

Software maintainers are faced with the task of regression testing: retesting a modified program on an often large num- ber of test cases. The cost of re gression testing can be reduced if the size of the program that must be retested is reduced and if old test cases and old test results can be reused. Tw o complimentary algorithms

David Binkley



Bayesian nonparametric regression with varying residual density  

PubMed Central

We consider the problem of robust Bayesian inference on the mean regression function allowing the residual density to change flexibly with predictors. The proposed class of models is based on a Gaussian process prior for the mean regression function and mixtures of Gaussians for the collection of residual densities indexed by predictors. Initially considering the homoscedastic case, we propose priors for the residual density based on probit stick-breaking (PSB) scale mixtures and symmetrized PSB (sPSB) location-scale mixtures. Both priors restrict the residual density to be symmetric about zero, with the sPSB prior more flexible in allowing multimodal densities. We provide sufficient conditions to ensure strong posterior consistency in estimating the regression function under the sPSB prior, generalizing existing theory focused on parametric residual distributions. The PSB and sPSB priors are generalized to allow residual densities to change nonparametrically with predictors through incorporating Gaussian processes in the stick-breaking components. This leads to a robust Bayesian regression procedure that automatically down-weights outliers and influential observations in a locally-adaptive manner. Posterior computation relies on an efficient data augmentation exact block Gibbs sampler. The methods are illustrated using simulated and real data applications. PMID:24465053

Pati, Debdeep; Dunson, David B.



Regression with Missing X's: A Review  

Microsoft Academic Search

The literature of regression analysis with missing values of the independent variables is reviewed. Six classes of procedures are distinguished: complete case analysis, available case methods, least squares on imputed data, maximum likelihood, Bayesian methods, and multiple imputation. Methods are compared and illustrated when missing data are confined to one independent variable, and extensions to more general patterns are indicated.

Roderick J. A. Little



Misspecification in Linear Spatial Regression Models  

Microsoft Academic Search

Spatial effects are endemic in models based on spatially referenced data. The increased awareness of the relevance of spatial interactions, spatial externalities and networking effects among actors, evoked the area of spatial econometrics. Spatial econometrics focuses on the specification and estimation of regression models explicitly incorporating such spatial effects. The multidimensionality of spatial effects calls for misspecification tests and estimators

Raymond J. G. M. Florax; Peter Nijkamp



A Logistic Regression Model for Personnel Selection.  

ERIC Educational Resources Information Center

A two-parameter logistic regression model for personnel selection is proposed. The model was tested with a database of 84,808 military enlistees. The probability of job success was related directly to trait levels, addressing such topics as selection, validity generalization, employee classification, selection bias, and utility-based fair…

Raju, Nambury S.; And Others



EXAFS study of LaMn1-xCoxO3 compounds  

NASA Astrophysics Data System (ADS)

A systematic study of cobalt environment in the LaMn1-xCoxO3 perovskite series by means of X-ray absorption spectroscopy in the EXAFS range is reported. The spectra were measured at the K edge of Co on powder samples at room temperature and analysed using multiple scattering paths calculated with the FEFF8 computer program. The next neighbor oxygen shell of cobalt shows a decrease of the distance from the central ion with increasing Co doping. This corresponds to an increased oxidation level of 3d ions. An information on the distortion of the oxygen octahedra and the Debye-Waller factor is discussed.

Procházka, V.; Kapusta, Cz.; Sikora, M.; Zajaç, D.; Knížek, K.; Jirák, Z.; Št?pánková, H.


NMR study of LaMn1-xCoxO3 perovskites  

NASA Astrophysics Data System (ADS)

The perovskite compounds of LaMn1-xCoxO3 (0.2?x?0.5) have been studied by means of NMR spectroscopy in powder samples prepared by the solid state reaction and sol-gel methods. The NMR signals were observed in the frequency range 250-650 MHz at 4.2 K in zero external magnetic field. A relatively narrow spectral line assigned to 55Mn in Mn is situated around 270-320 MHz in all spectra. Additional spectral lines are observed at higher frequencies. Line intensities and forms are dependent on the cobalt concentration and preparation techniques.

Procházka, V.; Št?pánková, H.; Sedlák, B.; Kapusta, Cz.; Knížek, K.; Jirák, Z.; Englich, J.; ?ezní?ek, R.


A Modified Golgi-Cox Procedure for use in Undergraduate Courses  

PubMed Central

The Golgi staining method has a long history in the field of neuroscience, and remains an important teaching tool in undergraduate laboratory settings. The ability to visualize a cell with all the processes makes the method useful when teaching introductory neuroscience courses. However, the amount of time required for post-stain tissue processing makes it a difficult procedure to use when teaching laboratory classes. We detail a modified Golgi-Cox method with a short incubation period and minimal post-stain processing that produces well differentiated cells, making it ideal for use in an undergraduate laboratory. PMID:23626498

Wright, Katharine A; Zimmerman, Eliana L; Harrington, Mary E



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


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 activation of COX1 mRNA, rather than being involved in a subsequent step in the synthesis of Cox1p or its assembly into cytochrome c oxidase. Pulse-chase labelling experiments now show that the absence of detectable levels of Cox1p in mss51-null strains is indeed due to the lack of synthesis of Cox1p, and is not caused by reduced stability of the protein. To gain more insight into the exact function of Mss51p, we determined the subcellular localization of the protein. We were able to show that an epitope-tagged version of Mss51p (Mss51HA) complements the mutation and can be localized in mitochondria, where it is firmly associated with the mitochondrial inner membrane. In addition, we characterized the previously identified mutant allele mss51-3. Sequence analysis revealed the presence of a short open reading frame upstream of MSS51 resulting from the creation of an extra ATG start-codon. PMID:10803883

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



Interpreting regression toward the mean in developmental research  

Microsoft Academic Search

Explicates the fundamental nature of regression toward the mean, which is frequently misunderstood by developmental researchers. While errors of measurement are commonly assumed to be the sole source of regression effects, the latter also are obtained with errorless measures. The conditions under which regression phenomena can appear are first clearly defined. Next, an explanation of regression effects is presented which

Lita Furby



Analyzing Historical Count Data: Poisson and Negative Binomial Regression Models.  

ERIC Educational Resources Information Center

Asserts that traditional approaches to multivariate analysis, including standard linear regression techniques, ignore the special character of count data. Explicates three suitable alternatives to standard regression techniques, a simple Poisson regression, a modified Poisson regression, and a negative binomial model. (MJP)

Beck, E. M.; Tolnay, Stewart E.



CS535D Project: Bayesian Logistic Regression through Auxiliary Variables  

Microsoft Academic Search

This project deals with the estimation of Logistic Regression parameters. We first review the binary logistic regression model and the multinomial extension, including standard MAP parameter estimation with a Gaussian prior. We then turn to the case of Bayesian Logistic Regression under this same prior. We review the cannonical approach of performing Bayesian Probit Regression through auxiliary variables, and extensions

Mark Schmidt


The Regression Trunk Approach to Discover Treatment Covariate Interaction  

ERIC Educational Resources Information Center

The regression trunk approach (RTA) is an integration of regression trees and multiple linear regression analysis. In this paper RTA is used to discover treatment covariate interactions, in the regression of one continuous variable on a treatment variable with "multiple" covariates. The performance of RTA is compared to the classical method of…

Dusseldorp, Elise; Meulman, Jacqueline J.



Multivariate versus Univariate Decision Trees  

Microsoft Academic Search

In this paper we present a new multivariate decision tree algorithm LMDT,which combines linear machines with decision trees. LMDT constructs eachtest in a decision tree by training a linear machine and then eliminating irrelevantand noisy variables in a controlled manner. To examine LMDT's abilityto find good generalizations we present results for a variety of domains. Wecompare LMDT empirically to a

Carla E. Brodley; Paul E. Utgoff



In Vivo Evidence for Platelet-Induced Physiological Angiogenesis by a COX Driven Mechanism  

PubMed Central

We sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C?F) of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longitudinal splitting by chronic hyperaemia. Platelet depletion was achieved by anti-GPIb? antibody treatment. Sprouting induced a significant increase in C?F (1.42±0.02 vs. contralateral 1.29±0.02, P<0.001) that was abolished by platelet depletion, while the significant C?F increase caused by splitting (1.40±0.03 vs. control 1.28±0.03, P<0.01) was unaffected. Granulocyte/monocyte depletion showed this response was not immune-regulated. VEGF overexpression failed to rescue angiogenesis following platelet depletion, suggesting the mechanism is not simply reliant on growth factor release. Sprouting occurred normally following antibody-induced GPVI shedding, suggesting platelet activation via collagen is not involved. BrdU pulse-labelling showed no change in the proliferative potential of cells associated with capillaries after platelet depletion. Inhibition of platelet activation by acetylsalicylic acid abolished sprouting, but not splitting angiogenesis, paralleling the response to platelet depletion. We conclude that platelets differentially regulate mechanisms of angiogenesis in vivo, likely via COX signalling. Since endothelial proliferation is not impaired, we propose a link between COX1 and induction of endothelial migration. PMID:25238071

Packham, Ian M.; Watson, Steve P.; Bicknell, Roy; Egginton, Stuart



Post-Exposure Therapeutic Efficacy of COX-2 Inhibition against Burkholderia pseudomallei  

PubMed Central

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens. PMID:23675544

Asakrah, Saja; Nieves, Wildaliz; Mahdi, Zaid; Agard, Mallory; Zea, Arnold H.; Roy, Chad J.; Morici, Lisa A.



Magnetostriction and thermal expansion of HoFe11-xCoxTi intermetallic compounds  

NASA Astrophysics Data System (ADS)

The thermal expansion and magnetostriction of the HoFe11-xCoxTi (0?x?11) alloys have been investigated, using the strain gauge technique in the temperature range 77-600 K. Both thermal expansion and thermal expansion coefficient exhibit an anomalous behaviour and Invar effect below Curie temperature (TC=516 K) in sample with x=0. The increase of x in HoFe11-xCoxTi system leads to disappearing of the Invar effect and increasing of the average thermal expansion coefficient from 6.370×10-6 K-1 in x=0 to 10.735×10-6 K-1 in x=11 below room temperature. In addition, the spontaneous volume magnetostriction decreases with Co content. The magnetostriction compensation point is observed in the anisotropic magnetostriction curve of all samples. The maximum value of anisotropic magnetostriction (???50×10-6) at room temperature is observed in sample with x=9. The saturation behaviour only appears in samples with x=5, 7 and 9. In samples with x=3, 5 and 7, a noticeable volume magnetostriction (?V/V) is observed in low temperature due to first-order magnetisation process. Moreover, ?V/V exhibits a large anomaly about 45×10-6 and 20×10-6 around room temperature related to spin reorientation transition in samples with x=9 and 11, respectively. The results are discussed based on the local magnetic moment model and irreducible magnetoelastic coupling modes.

Sanavi Khoshnoud, D.; Tajabor, N.; Motevalizadeh, L.; Fruchart, D.



Four cases of Taenia saginata infection with an analysis of COX1 gene.  


Human taeniases had been not uncommon in the Republic of Korea (=Korea) until the 1980s. The prevalence decreased and a national survey in 2004 revealed no Taenia egg positive cases. However, a subsequent national survey in 2012 showed 0.04% (10 cases) prevalence of Taenia spp. eggs suggesting its resurgence in Korea. We recently encountered 4 cases of Taenia saginata infection who had symptoms of taeniasis that included discharge of proglottids. We obtained several proglottids from each case. Because the morphological features of T. saginata are almost indistinguishable from those of Taenia asiatica, molecular analyses using the PCR-RFLP and DNA sequencing of the cytochrome c oxidase subunit 1 (cox1) were performed to identify the species. The PCR-RFLP patterns of all of the 4 specimens were consistent with T. saginata, and the cox1 gene sequence showed 99.8-100% identity with that of T. saginata reported previously from Korea, Japan, China, and Cambodia. All of the 4 patients had the history of travel abroad but its relation with contracting taeniasis was unclear. Our findings may suggest resurgence of T. saginata infection among people in Korea. PMID:24623887

Cho, Jaeeun; Jung, Bong-Kwang; Lim, Hyemi; Kim, Min-Jae; Yooyen, Thanapon; Lee, Dongmin; Eom, Keeseon S; Shin, Eun-Hee; Chai, Jong-Yil



Effect of cyclooxygenase (COX)-2 inhibition on mouse renal interstitial fibrosis.  


Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. In this study, we investigated the effects of a COX-2 inhibitor, meloxicam, on UUO-induced renal interstitial fibrosis in mice. Serum creatinine, blood urea nitrogen and urinary glucose were significantly increased by UUO. However, all of these changes were attenuated by meloxicam (1mg/kg/day). Masson?s trichrome staining showed that interstitial fibrosis was significantly increased by UUO, but that meloxicam also significantly diminished the area of UUO-induced fibrosis. Heat shock protein (HSP) 47 protein, a collagen-specific molecular chaperone essential for the biosynthesis of collagen molecules, and type IV collagen mRNA were increased in kidneys of UUO mice. Meloxicam reduced the expression of both HSP47 protein and type IV collagen mRNA. The phosphorylation of extracellular regulated kinase (ERK) and c-jun-N-terminal kinase (JNK) was increased by UUO, but these changes were inhibited by meloxicam. Collectively, these results suggest that COX-2 may be involved in the expression of HSP47 and type IV collagen through the phosphorylation of ERK and JNK, accelerating renal interstitial fibrosis. PMID:24975097

Honma, Shigeyoshi; Shinohara, Masahiro; Takahashi, Naho; Nakamura, Kazuki; Hamano, Shohei; Mitazaki, Satoru; Abe, Sumiko; Yoshida, Makoto



Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE2 synthesis and COX-2 expression.  


Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) can potentially affect most of the events in cancer development, including promotion of proliferation, resistance to apoptosis, angiogenesis, immune suppression and invasion. However, worldwide attention has predominantly centered on the cardiovascular toxicity of selective COX-2 inhibitors. Paeonol is a major active extract from the root bark of Paeonia suffruticosa Andrews with anti?inflammatory, anti-oxidant, anti-allergic, anti-oxidation and antitumor effects. In the present study, we investigated the underlying mechanisms of paeonol in inducing apoptosis and aimed to ascertain whether its antitumor effect is associated with a reduction in COX-2 expression and a decrease in the levels of PGE2 in colorectal cancer cells. We observed that paeonol inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner in colorectal cancer cells, which was associated with a reduction in COX-2 expression and PGE2 synthesis. Treatment with the selective COX-2 inhibitor, celecoxib, or transient transfection of colorectal cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Western blot analysis showed that paeonol inhibited the activation of NF-?B, an upstream regulator of COX-2, and its translocation to the nucleus. Treatment with increasing doses of paeonol led to increased expression of pro-apoptotic factor Bax and decreased expression of anti-apoptotic factor Bcl-2. Caspase-3 and caspase-9 were activated, and paeonol induced loss of mitochondrial membrane potential, suggesting that the apoptosis induced by paeonol was mediated by mitochondrial pathways. In addition, paeonol significantly suppressed tumor growth in a xenograft tumor mouse model in a dose-dependent manner. Our findings indicate that paeonol exerts an antitumor effect on human colorectal cancer cells by inhibiting PGE2 production and COX-2 expression. We expect that paeonol may replace selective COX-2 inhibitors due to their toxic effects, and may offer a new strategy for the therapy of colorectal cancer. PMID:25322760

Li, Ming; Tan, Shi-Yun; Wang, Xiao-Fan



Human cyclooxygenase-1 activity and its responses to COX inhibitors are allosterically regulated by nonsubstrate fatty acids  

PubMed Central

Recombinant human prostaglandin endoperoxide H synthase-1 (huPGHS-1) was characterized. huPGHS-1 has a single high-affinity heme binding site per dimer and exhibits maximal cyclooxygenase (COX) activity with one heme per dimer. Thus, huPGHS-1 functions as a conformational heterodimer having a catalytic monomer (Ecat) with a bound heme and an allosteric monomer (Eallo) lacking heme. The enzyme is modestly inhibited by common FAs including palmitic, stearic, and oleic acids that are not COX substrates. Studies of arachidonic acid (AA) substrate turnover at high enzyme-to-substrate ratios indicate that nonsubstrate FAs bind the COX site of Eallo to modulate the properties of Ecat. Nonsubstrate FAs slightly inhibit huPGHS-1 but stimulate huPGHS-2, thereby augmenting AA oxygenation by PGHS-2 relative to PGHS-1. Nonsubstrate FAs potentiate the inhibition of huPGHS-1 activity by time-dependent COX inhibitors, including aspirin, all of which bind Ecat. Surprisingly, preincubating huPGHS-1 with nonsubstrate FAs in combination with ibuprofen, which by itself is a time-independent inhibitor, causes a short-lived, time-dependent inhibition of huPGHS-1. Thus, in general, having a FA bound to Eallo stabilizes time-dependently inhibited conformations of Ecat. We speculate that having an FA bound to Eallo also stabilizes Ecat conformers during catalysis, enabling half of sites of COX activity. PMID:22547204

Zou, Hechang; Yuan, Chong; Dong, Liang; Sidhu, Ranjinder S.; Hong, Yu H.; Kuklev, Dmitry V.; Smith, William L.



Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents  

PubMed Central

Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC. PMID:22272378

Hashimoto, Naoki



An Investigation of Sleep Characteristics, EEG Abnormalities and Epilepsy in Developmentally Regressed and Non-Regressed Children with Autism  

ERIC Educational Resources Information Center

This study investigated sleep of children with autism and developmental regression and the possible relationship with epilepsy and epileptiform abnormalities. Participants were 104 children with autism (70 non-regressed, 34 regressed) and 162 typically developing children (TD). Results suggested that the regressed group had higher incidence of…

Giannotti, Flavia; Cortesi, Flavia; Cerquiglini, Antonella; Miraglia, Daniela; Vagnoni, Cristina; Sebastiani, Teresa; Bernabei, Paola



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

NASA Astrophysics Data System (ADS)

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

Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang



Divisive gaussian processes for nonstationary regression.  


Standard Gaussian process regression (GPR) assumes constant noise power throughout the input space and stationarity when combined with the squared exponential covariance function. This can be unrealistic and too restrictive for many real-world problems. Nonstationarity can be achieved by specific covariance functions, though prior knowledge about this nonstationarity can be difficult to obtain. On the other hand, the homoscedastic assumption is needed to allow GPR inference to be tractable. In this paper, we present a divisive GPR model which performs nonstationary regression under heteroscedastic noise using the pointwise division of two nonparametric latent functions. As the inference on the model is not analytically tractable, we propose a variational posterior approximation using expectation propagation (EP) which allows for accurate inference at reduced cost. We have also made a Markov chain Monte Carlo implementation with elliptical slice sampling to assess the quality of the EP approximation. Experiments support the usefulness of the proposed approach. PMID:25330423

Munoz-Gonzalez, Luis; Lazaro-Gredilla, Miguel; Figueiras-Vidal, Anibal R



Confidence bands for inverse regression models  

NASA Astrophysics Data System (ADS)

We construct uniform confidence bands for the regression function in inverse, homoscedastic regression models with convolution-type operators. Here, the convolution is between two non-periodic functions on the whole real line rather than between two periodic functions on a compact interval, since the former situation arguably arises more often in applications. First, following Bickel and Rosenblatt (1973 Ann. Stat. 1 1071-95) we construct asymptotic confidence bands which are based on strong approximations and on a limit theorem for the supremum of a stationary Gaussian process. Further, we propose bootstrap confidence bands based on the residual bootstrap and prove consistency of the bootstrap procedure. A simulation study shows that the bootstrap confidence bands perform reasonably well for moderate sample sizes. Finally, we apply our method to data from a gel electrophoresis experiment with genetically engineered neuronal receptor subunits incubated with rat brain extract.

Birke, Melanie; Bissantz, Nicolai; Holzmann, Hajo



Correlation-Based Feature Selection and Regression  

Microsoft Academic Search

\\u000a Music video is a well-known medium in music entertainment which contains rich affective information and has been widely accepted\\u000a as emotion expressions. Affective analysis plays an important role in the content-based indexing and retrieval of music video.\\u000a This paper proposes a general scheme for music video affective estimation using correlation-based feature selection followed\\u000a by regression. Arousal score and valence score

Yue Cui; Jesse S. Jin; Shiliang Zhang; Suhuai Luo; Qi Tian



Beta Regression: Practical Issues in Estimation  

Microsoft Academic Search

This document supplements the paper by Smithson and Verkuilen (2005) on beta regression, and focuses on maximum likelihood estimation procedures in several statistical packages. Maximizing the likelihood function can be achieved using a Newton-Raphson or a quasi-Newton method. Ferrari and Cribari-Neto (2004) use Fisher scoring. Buckley (2002) has used MCMC estimation in winBUGS, which provides a Bayesian posterior density. Buckley

Michael Smithson; Jay Verkuilen



Making Good Probability Estimates for Regression  

Microsoft Academic Search

In this paper, we show that the optimisation of density forecasting models for regression in machine learning can be formulated\\u000a as a multi-objective problem. We describe the two objectives of sharpness and calibration and suggest suitable scoring metrics for both. We use the popular negative log-likelihood as a measure of sharpness and the\\u000a probability integral transform as a measure of

Michael Carney; Padraig Cunningham



Regression Modelling Analysis on Compositional Data  

Microsoft Academic Search

\\u000a In data analysis of social, economic and technical fields, compositional data is widely used in problems of proportions to\\u000a the whole. This paper develops regression modelling methods of compositional data, discussing the relationships of one compositional\\u000a data to one or more than one compositional data and the interrelationship of multiple compositional data. By combining centered\\u000a logratio transformation proposed by Aitchison

Huiwen Wang; Jie Meng; Michel Tenenhaus



E-print Network

IV - REGRESSION LINEAIRE J-P. Croisille Universit´e de Lorraine UEL - Ann´ee 2012/2013 Jean-Pierre CROISILLE - Laboratoire LMAM [UEL: L'influence des math´ematiques sur la soci´et´e #12;1- DEPENDANCE-Pierre CROISILLE - Laboratoire LMAM [UEL: L'influence des math´ematiques sur la soci´et´e #12;EXEMPLE DE DEPENDANCE

Croisille, Jean-Pierre


Sparse regression as a sparse eigenvalue problem  

Microsoft Academic Search

We extend the lo-norm “subspectral” algorithms developed for sparse-LDA [5] and sparse-PCA [6] to more general quadratic costs such as MSE in linear (or kernel) regression. The resulting “Sparse Least Squares” (SLS) problem is also NP-hard, by way of its equivalence to a rank-1 sparse eigenvalue problem. Specifically, for minimizing general quadratic cost functions we use a highly-efficient method for

Baback Moghaddam; Amit Gruber; Yair Weiss; Shai Avidan



A permutation test for quantile regression  

Microsoft Academic Search

A drop in dispersion, F-ratio like, permutation test (D) for linear quantile regression estimates (0???1) had relative power ?1 compared to quantile rank score tests (T) for hypotheses on parameters other than the intercept. Power was compared for combinations of sample sizes (n=20?300) and quantiles (?=0.50?0.99) where both tests maintained valid Type I error rates in simulations with p=2 and

Brian S. Cade; Jon D. Richards



Chronic Nephropathies: Individual Risk for Progression to End-Stage Renal Failure as Predicted by an Integrated Probabilistic Model  

Microsoft Academic Search

Background\\/Aims: To predict risk of end-stage renal disease (ESRD) in individual patients with chronic nephropathy. Methods: Sequential use of univariate analyses and Cox regression to identify risk factors, artificial neural network to quantify their relative importance and Bayesian analysis to address uncertainty of relationships and incorporate ESRD prevalence information in 344 patients with chronic nephropathy enrolled in the Ramipril Efficacy

Borislav D. Dimitrov; Piero Ruggenenti; Rumen Stefanov; Annalisa Perna; Giuseppe Remuzzi



Satellite rainfall retrieval by logistic regression  

NASA Technical Reports Server (NTRS)

The potential use of logistic regression in rainfall estimation from satellite measurements is investigated. Satellite measurements provide covariate information in terms of radiances from different remote sensors.The logistic regression technique can effectively accommodate many covariates and test their significance in the estimation. The outcome from the logistical model is the probability that the rainrate of a satellite pixel is above a certain threshold. By varying the thresholds, a rainrate histogram can be obtained, from which the mean and the variant can be estimated. A logistical model is developed and applied to rainfall data collected during GATE, using as covariates the fractional rain area and a radiance measurement which is deduced from a microwave temperature-rainrate relation. It is demonstrated that the fractional rain area is an important covariate in the model, consistent with the use of the so-called Area Time Integral in estimating total rain volume in other studies. To calibrate the logistical model, simulated rain fields generated by rainfield models with prescribed parameters are needed. A stringent test of the logistical model is its ability to recover the prescribed parameters of simulated rain fields. A rain field simulation model which preserves the fractional rain area and lognormality of rainrates as found in GATE is developed. A stochastic regression model of branching and immigration whose solutions are lognormally distributed in some asymptotic limits has also been developed.

Chiu, Long S.



Lognormal and Gamma Mixed Negative Binomial Regression  

PubMed Central

In regression analysis of counts, a lack of simple and efficient algorithms for posterior computation has made Bayesian approaches appear unattractive and thus underdeveloped. We propose a lognormal and gamma mixed negative binomial (NB) regression model for counts, and present efficient closed-form Bayesian inference; unlike conventional Poisson models, the proposed approach has two free parameters to include two different kinds of random effects, and allows the incorporation of prior information, such as sparsity in the regression coefficients. By placing a gamma distribution prior on the NB dispersion parameter r, and connecting a lognormal distribution prior with the logit of the NB probability parameter p, efficient Gibbs sampling and variational Bayes inference are both developed. The closed-form updates are obtained by exploiting conditional conjugacy via both a compound Poisson representation and a Polya-Gamma distribution based data augmentation approach. The proposed Bayesian inference can be implemented routinely, while being easily generalizable to more complex settings involving multivariate dependence structures. The algorithms are illustrated using real examples.

Zhou, Mingyuan; Li, Lingbo; Dunson, David; Carin, Lawrence



Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent  

PubMed Central

The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-?B. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced I?B phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-?B signal transduction inhibitor independent of Sirt1. PMID:22523472

Annabi, Borhane; Lord-Dufour, Simon; Vézina, Amélie; Béliveau, Richard



Mechano-transcription of COX-2 is a common response to lumen dilation of the rat gastrointestinal tract  

PubMed Central

Background In obstructive bowel disorders (OBDs) such as achalasia, pyloric stenosis, and bowel obstruction, the lumen of the affected segments is markedly dilated and the motility function is significantly impaired. We tested the hypothesis that mechanical stress in lumen dilation leads to induction of cyclo-oxygenase-2 (COX-2) in smooth muscle throughout the gastrointestinal (GI) tract, contributing to motility dysfunction. Methods Lumen dilation was induced in vivo with obstruction bands (12 × 3 mm) applied over the lower esophageal sphincter (LES), the pyloric sphincter, and the ileum in rats for 48 hr. Mechanical stretch in vivo was also emulated by balloon distension of the distal colon. Direct stretch of muscle strips from the esophagus, gastric fundus, and ileum was mimicked in an in vitro tissue culture system. Key Results Partial obstruction in the LES, pylorus, and ileum significantly increased expression of COX-2 mRNA and protein in the muscularis externae of the dilated segment oral to the occlusions, but not in the aboral segment. Direct stretch of the lumen in vivo or of muscle strips in vitro markedly induced COX-2 expression. The smooth muscle contractility was significantly suppressed in the balloon distended segments. However, treatment with COX-2 inhibitor NS-398 restored the contractility. Furthermore, in vivo administration of NS-398 in gastric outlet obstruction significantly improved gastric emptying. Conclusions & Inferences Mechanical dilation of the gut lumen by occlusion or direct distension induces gene expression of COX-2 throughout the GI tract. Mechanical stress-induced COX-2 contributes to motility dysfunction in conditions with lumen dilation. PMID:22489918

Lin, You-Min; Li, Feng; Shi, Xuan-Zheng



Peripheral administration of morphine attenuates postincisional pain by regulating macrophage polarization through COX-2-dependent pathway  

PubMed Central

Background Macrophage infiltration to inflammatory sites promotes wound repair and may be involved in pain hypersensitivity after surgical incision. We recently reported that the development of hyperalgesia during chronic inflammation is regulated by macrophage polarity, often referred to as proinflammatory (M1) or anti-inflammatory (M2) macrophages. Although opioids such as morphine are known to alter the inflammatory milieu of incisional wounds through interactions with immunocytes, the macrophage-mediated effects of morphine on the development of postincisional pain have not been well investigated. In this study, we examined how morphine alters pain hypersensitivity through phenotypic shifts in local macrophages during the course of incision-induced inflammation. Results Local administration of morphine in the early phase, but not in the late phase alleviated mechanical hyperalgesia, and this effect was reversed by clodronate-induced peripheral depletion of local macrophages. At the morphine-injected incisional sites, the number of pro-inflammatory F4/80+iNOS+M1 macrophages was decreased during the course of pain development whereas increased infiltration of wound healing F4/80+CD206+M2 macrophages was observed during the early phase. Morphine increased the gene expression of endogenous opioid, proenkephalin, and decreased the pronociceptive cytokine, interleukin-1?. Heme oxygenase (HO)-1 promotes the differentiation of macrophages to the M2 phenotype. An inhibitor of HO-1, tin protoporphyrin reversed morphine-induced analgesic effects and the changes in macrophage phenotype. However, local expression levels of HO-1 were not altered by morphine. Conversely, cyclooxygenase (COX)-2, primarily produced from peripheral macrophages in acute inflammation states, was up-regulated in the early phase at morphine-injected sites. In addition, the analgesic effects and a phenotype switching of infiltrated macrophages by morphine was reversed by local administration of a COX inhibitor, indomethacin. Conclusions Local administration of morphine alleviated the development of postincisional pain, possibly by altering macrophage polarity at the incisional sites. A morphine-induced shift in macrophage phenotype may be mediated by a COX-2-dependent mechanism. Therefore, ?-opioid receptor signaling in macrophages may be a potential therapeutic target during the early phase of postincisional pain development. PMID:24928142



Self-organisation of size-selected CoxPt1-x clusters on graphite.  


Sub-monolayer thin film morphologies obtained by deposition of size-selected CoxPt1-x clusters on graphite have been analyzed for different values of x. In all cases, the preformed clusters can easily diffuse on the surface and gather to form islands of clusters. By changing the cluster stoichiometry, very different morphologies can be obtained, going from large ramified islands to "bunches" of non-contacting incident clusters. We put into evidence that the introduction of platinum atoms in the incident particles drastically changes the interaction between clusters and offers the opportunity to control the coalescence process between them. In this way, by modifying the cluster reactivity, a local self-organization of size-selected magnetic nanoparticles can be achieved. PMID:25387904

Bardotti, L; Tournus, F; Albin, C; Boisron, O; Dupuis, V



COX-2 inhibitors and the heart: are all coxibs the same?  

PubMed Central

The selective COX?2 inhibitors (coxibs) were originally developed to minimise the adverse effects of conventional non?steroidal anti?inflammatory drugs (NSAIDs) while maintaining the same analgesic and anti?inflammatory properties. Many large studies confirmed the improved gastric side effect profile of coxibs compared with non?selective NSAIDs; however, reports of increased cardiovascular morbidity and mortality followed, and the manufacturer Merck was forced to withdraw rofecoxib (Vioxx) from the market. Other coxibs have also either perished or had restrictions placed on their use. However, there seem to be significant differences between coxibs regarding their cardiovascular profiles, and the evidence for a class effect is dubious. In this paper, the current body of knowledge regarding the cardiovascular toxicities of coxibs is reviewed. The take home message for prescribing NSAIDs and those coxibs still on the market seems to be one of caution rather than contraindication, except in patients with significant cardiovascular risk factors. PMID:16597810