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Sample records for development cox regression

  1. Simultaneous confidence bands for Cox regression from semiparametric random censorship.

    PubMed

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

    Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined. PMID:25691289

  2. Partial least squares Cox regression for genome-wide data.

    PubMed

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

    2008-06-01

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

  3. Diagnostic Measures for the Cox Regression Model with Missing Covariates

    PubMed Central

    Zhu, Hongtu; Ibrahim, Joseph G.; Chen, Ming-Hui

    2015-01-01

    Summary This paper investigates diagnostic measures for assessing the influence of observations and model misspecification in the presence of missing covariate data for the Cox regression model. Our diagnostics include case-deletion measures, conditional martingale residuals, and score residuals. The Q-distance is proposed to examine the effects of deleting individual observations on the estimates of finite-dimensional and infinite-dimensional parameters. Conditional martingale residuals are used to construct goodness of fit statistics for testing possible misspecification of the model assumptions. A resampling method is developed to approximate the p-values of the goodness of fit statistics. Simulation studies are conducted to evaluate our methods, and a real data set is analyzed to illustrate their use. PMID:26903666

  4. Cox Regression Models with Functional Covariates for Survival Data

    PubMed Central

    Gellar, Jonathan E.; Colantuoni, Elizabeth; Needham, Dale M.; Crainiceanu, Ciprian M.

    2015-01-01

    We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge and daily measures of disease severity collected in the intensive care unit, among survivors of acute respiratory distress syndrome. PMID:26441487

  5. Survival analysis of cervical cancer using stratified Cox regression

    NASA Astrophysics Data System (ADS)

    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

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

    ERIC Educational Resources Information Center

    Chen, Chau-Kuang

    2005-01-01

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

  7. Factors Associated with Methadone Treatment Duration: A Cox Regression Analysis

    PubMed Central

    Peng, Ching-Yi; Chao, En; Lee, Tony Szu-Hsien

    2015-01-01

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

  8. Mortality Prediction in ICUs Using A Novel Time-Slicing Cox Regression Method

    PubMed Central

    Wang, Yuan; Chen, Wenlin; Heard, Kevin; Kollef, Marin H.; Bailey, Thomas C.; Cui, Zhicheng; He, Yujie; Lu, Chenyang; Chen, Yixin

    2015-01-01

    Over the last few decades, machine learning and data mining have been increasingly used for clinical prediction in ICUs. However, there is still a huge gap in making full use of the time-series data generated from ICUs. Aiming at filling this gap, we propose a novel approach entitled Time Slicing Cox regression (TS-Cox), which extends the classical Cox regression into a classification method on multi-dimensional time-series. Unlike traditional classifiers such as logistic regression and support vector machines, our model not only incorporates the discriminative features derived from the time-series, but also naturally exploits the temporal orders of these features based on a Cox-like function. Empirical evaluation on MIMIC-II database demonstrates the efficacy of the TS-Cox model. Our TS-Cox model outperforms all other baseline models by a good margin in terms of AUC_PR, sensitivity and PPV, which indicates that TS-Cox may be a promising tool for mortality prediction in ICUs. PMID:26958269

  9. COX-2 gene dosage-dependent defects in kidney development.

    PubMed

    Slattery, Patrick; Frölich, Stefanie; Schreiber, Yannik; Nüsing, Rolf M

    2016-05-15

    Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4-8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2(+/+), COX-2(+/-), and COX-2(-/-) mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg(-1)·day(-1)) and high (10 mg·kg(-1)·day(-1)) doses of the selective COX-2 inhibitor SC-236. COX-2(+/-) mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2(-/-) mice, only marginal cortical thinning. Moreover, in COX-2(+/-) and COX-2(-/-) kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2(+/-) kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity compared with COX-2(+/+) kidneys. The renal defects in COX-2(-/-) and COX-2(+/-) kidneys could be mimicked by high and low doses of SC-236, respectively. In aged COX-2(+/-) kidneys, glomerulosclerosis was observed; however, in contrast to COX-2(-/-) kidneys, periglomerular fibrosis was absent. COX-2(+/-) mice showed signs of kidney insufficiency, demonstrated by enhanced serum creatinine levels, quite similar to COX-2(-/-) mice, but, in contrast, serum urea remained at the control level. In summary, function of both COX-2 gene alleles is absolutely necessary to ensure physiological development of the mouse kidney. Loss of one copy of the COX-2 gene or partial COX-2 inhibition is associated with distinct renal damage and reduced kidney function. PMID:26984955

  10. Cancer Markers Selection Using Network-Based Cox Regression: A Methodological and Computational Practice

    PubMed Central

    Iuliano, Antonella; Occhipinti, Annalisa; Angelini, Claudia; De Feis, Italia; Lió, Pietro

    2016-01-01

    International initiatives such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) are collecting multiple datasets at different genome-scales with the aim of identifying novel cancer biomarkers and predicting survival of patients. To analyze such data, several statistical methods have been applied, among them Cox regression models. Although these models provide a good statistical framework to analyze omic data, there is still a lack of studies that illustrate advantages and drawbacks in integrating biological information and selecting groups of biomarkers. In fact, classical Cox regression algorithms focus on the selection of a single biomarker, without taking into account the strong correlation between genes. Even though network-based Cox regression algorithms overcome such drawbacks, such network-based approaches are less widely used within the life science community. In this article, we aim to provide a clear methodological framework on the use of such approaches in order to turn cancer research results into clinical applications. Therefore, we first discuss the rationale and the practical usage of three recently proposed network-based Cox regression algorithms (i.e., Net-Cox, AdaLnet, and fastcox). Then, we show how to combine existing biological knowledge and available data with such algorithms to identify networks of cancer biomarkers and to estimate survival of patients. Finally, we describe in detail a new permutation-based approach to better validate the significance of the selection in terms of cancer gene signatures and pathway/networks identification. We illustrate the proposed methodology by means of both simulations and real case studies. Overall, the aim of our work is two-fold. Firstly, to show how network-based Cox regression models can be used to integrate biological knowledge (e.g., multi-omics data) for the analysis of survival data. Secondly, to provide a clear methodological and computational approach for

  11. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER’S DISEASE*

    PubMed Central

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-01-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer’s disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM. PMID:26900412

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-12-01

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

  14. Box–Cox Transformation and Random Regression Models for Fecal egg Count Data

    PubMed Central

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

    2012-01-01

    Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box–Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box–Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated. PMID:22303406

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Devarajan, Karthik; Ebrahimi, Nader

    2010-01-01

    The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike’s Information Criterion is developed. We illustrate the applicability of our approach using real-life data. PMID:21076652

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

    PubMed

    Devarajan, Karthik; Ebrahimi, Nader

    2011-01-01

    The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike's Information Criterion is developed. We illustrate the applicability of our approach using real-life data. PMID:21076652

  18. The Effect of Ignoring Statistical Interactions in Regression Analyses Conducted in Epidemiologic Studies: An Example with Survival Analysis Using Cox Proportional Hazards Regression Model

    PubMed Central

    Vatcheva, KP; Lee, M; McCormick, JB; Rahbar, MH

    2016-01-01

    Objective To demonstrate the adverse impact of ignoring statistical interactions in regression models used in epidemiologic studies. Study design and setting Based on different scenarios that involved known values for coefficient of the interaction term in Cox regression models we generated 1000 samples of size 600 each. The simulated samples and a real life data set from the Cameron County Hispanic Cohort were used to evaluate the effect of ignoring statistical interactions in these models. Results Compared to correctly specified Cox regression models with interaction terms, misspecified models without interaction terms resulted in up to 8.95 fold bias in estimated regression coefficients. Whereas when data were generated from a perfect additive Cox proportional hazards regression model the inclusion of the interaction between the two covariates resulted in only 2% estimated bias in main effect regression coefficients estimates, but did not alter the main findings of no significant interactions. Conclusions When the effects are synergic, the failure to account for an interaction effect could lead to bias and misinterpretation of the results, and in some instances to incorrect policy decisions. Best practices in regression analysis must include identification of interactions, including for analysis of data from epidemiologic studies.

  19. [Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices].

    PubMed

    Nie, Z Q; Ou, Y Q; Zhuang, J; Qu, Y J; Mai, J Z; Chen, J M; Liu, X Q

    2016-05-10

    Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study, but Cox proportional hazard model is often used in survival data analysis. Most literature only refer to main effect model, however, generalized linear model differs from general linear model, and the interaction was composed of multiplicative interaction and additive interaction. The former is only statistical significant, but the latter has biological significance. In this paper, macros was written by using SAS 9.4 and the contrast ratio, attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions, and the confidence intervals of Wald, delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions. PMID:27188374

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    PubMed

    Fröhlich, Holger

    2014-03-01

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

  2. Empirical extensions of the lasso penalty to reduce the false discovery rate in high-dimensional Cox regression models.

    PubMed

    Ternès, Nils; Rotolo, Federico; Michiels, Stefan

    2016-07-10

    Correct selection of prognostic biomarkers among multiple candidates is becoming increasingly challenging as the dimensionality of biological data becomes higher. Therefore, minimizing the false discovery rate (FDR) is of primary importance, while a low false negative rate (FNR) is a complementary measure. The lasso is a popular selection method in Cox regression, but its results depend heavily on the penalty parameter λ. Usually, λ is chosen using maximum cross-validated log-likelihood (max-cvl). However, this method has often a very high FDR. We review methods for a more conservative choice of λ. We propose an empirical extension of the cvl by adding a penalization term, which trades off between the goodness-of-fit and the parsimony of the model, leading to the selection of fewer biomarkers and, as we show, to the reduction of the FDR without large increase in FNR. We conducted a simulation study considering null and moderately sparse alternative scenarios and compared our approach with the standard lasso and 10 other competitors: Akaike information criterion (AIC), corrected AIC, Bayesian information criterion (BIC), extended BIC, Hannan and Quinn information criterion (HQIC), risk information criterion (RIC), one-standard-error rule, adaptive lasso, stability selection, and percentile lasso. Our extension achieved the best compromise across all the scenarios between a reduction of the FDR and a limited raise of the FNR, followed by the AIC, the RIC, and the adaptive lasso, which performed well in some settings. We illustrate the methods using gene expression data of 523 breast cancer patients. In conclusion, we propose to apply our extension to the lasso whenever a stringent FDR with a limited FNR is targeted. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26970107

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Involvement of COX2-Thromboxane Pathway in TCDD-Induced Precardiac Edema in Developing Zebrafish

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-01

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

  7. Multilevel modelling of clustered grouped survival data using Cox regression model: an application to ART dental restorations.

    PubMed

    Wong, May C M; Lam, K F; Lo, Edward C M

    2006-02-15

    In some controlled clinical trials in dental research, multiple failure time data from the same patient are frequently observed that result in clustered multiple failure time. Moreover, the treatments are often delivered by more than one operator and thus the multiple failure times are clustered according to a multilevel structure when the operator effects are assumed to be random. In practice, it is often too expensive or even impossible to monitor the study subjects continuously, but they are examined periodically at some regular pre-scheduled visits. Hence, discrete or grouped clustered failure time data are collected. The aim of this paper is to illustrate the use of the Monte Carlo Markov chain (MCMC) approach and non-informative prior in a Bayesian framework to mimic the maximum likelihood (ML) estimation in a frequentist approach in multilevel modelling of clustered grouped survival data. A three-level model with additive variance components model for the random effects is considered in this paper. Both the grouped proportional hazards model and the dynamic logistic regression model are used. The approximate intra-cluster correlation of the log failure times can be estimated when the grouped proportional hazards model is used. The statistical package WinBUGS is adopted to estimate the parameter of interest based on the MCMC method. The models and method are applied to a data set obtained from a prospective clinical study on a cohort of Chinese school children that atraumatic restorative treatment (ART) restorations were placed on permanent teeth with carious lesions. Altogether 284 ART restorations were placed by five dentists and clinical status of the ART restorations was evaluated annually for 6 years after placement, thus clustered grouped failure times of the restorations were recorded. Results based on the grouped proportional hazards model revealed that clustering effect among the log failure times of the different restorations from the same child was

  8. Examining Non-Linear Associations between Accelerometer-Measured Physical Activity, Sedentary Behavior, and All-Cause Mortality Using Segmented Cox Regression

    PubMed Central

    Lee, Paul H.

    2016-01-01

    Healthy adults are advised to perform at least 150 min of moderate-intensity physical activity weekly, but this advice is based on studies using self-reports of questionable validity. This study examined the dose-response relationship of accelerometer-measured physical activity and sedentary behaviors on all-cause mortality using segmented Cox regression to empirically determine the break-points of the dose-response relationship. Data from 7006 adult participants aged 18 or above in the National Health and Nutrition Examination Survey waves 2003–2004 and 2005–2006 were included in the analysis and linked with death certificate data using a probabilistic matching approach in the National Death Index through December 31, 2011. Physical activity and sedentary behavior were measured using ActiGraph model 7164 accelerometer over the right hip for 7 consecutive days. Each minute with accelerometer count <100; 1952–5724; and ≥5725 were classified as sedentary, moderate-intensity physical activity, and vigorous-intensity physical activity, respectively. Segmented Cox regression was used to estimate the hazard ratio (HR) of time spent in sedentary behaviors, moderate-intensity physical activity, and vigorous-intensity physical activity and all-cause mortality, adjusted for demographic characteristics, health behaviors, and health conditions. Data were analyzed in 2016. During 47,119 person-year of follow-up, 608 deaths occurred. Each additional hour per day of sedentary behaviors was associated with a HR of 1.15 (95% CI 1.01, 1.31) among participants who spend at least 10.9 h per day on sedentary behaviors, and each additional minute per day spent on moderate-intensity physical activity was associated with a HR of 0.94 (95% CI 0.91, 0.96) among participants with daily moderate-intensity physical activity ≤14.1 min. Associations of moderate physical activity and sedentary behaviors on all-cause mortality were independent of each other. To conclude, evidence from

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

    PubMed Central

    2014-01-01

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

  10. TEMPERATURE SCENARIO DEVELOPMENT USING REGRESSION METHODS

    EPA Science Inventory

    A method of developing scenarios of future temperature conditions resulting from climatic change is presented. he method is straightforward and can be used to provide information about daily temperature variations and diurnal ranges, monthly average high, and low temperatures, an...

  11. Selective COX-2 inhibition and cardiovascular effects: a review of the rofecoxib development program.

    PubMed

    Weir, Matthew R; Sperling, Rhoda S; Reicin, Alise; Gertz, Barry J

    2003-10-01

    See related Editorials on pages 561 and 563. Cyclo-oxygenase-2 (COX-2) inhibitors appear to alter the balance of vasoactive eicosanoids (prostacyclin and thromboxane) and to suppress the inflammatory mediators implicated in the progression of atherogenesis and ischemic myocardial injury. Neutral, harmful, and beneficial cardiovascular (CV) effects have all been postulated to result from these changes. Investigations conducted with rofecoxib, a selective COX-2 inhibitor, have substantially contributed to our understanding of this scientific area. Rofecoxib had little or no effect on platelet aggregation or platelet-derived thromboxane synthesis but reduced systemic prostacyclin synthesis by 50% to 60%. These findings prompted extensive analyses of CV thrombotic events within the rofecoxib development program. Among 5435 osteoarthritis trial participants, similar rates of CV thrombotic events were reported with rofecoxib, placebo, and comparator, nonselective NSAIDs (ibuprofen, diclofenac, and nabumetone). In the VIGOR gastrointestinal outcomes trial of >8000 patients, naproxen (an NSAID with aspirin-like sustained antiplatelet effects throughout its dosing interval) was associated with a significantly lower risk of CV events than was rofecoxib. A subsequent pooled analysis from 23 studies (including VIGOR) encompassing multiple disease states and including more than 14,000 patient-years at risk also demonstrated that rofecoxib was not associated with excess CV thrombotic events compared with either placebo or nonnaproxen NSAIDs. Again, naproxen appeared to be the outlier, suggesting a cardioprotective benefit of naproxen. Finally, among the predominantly elderly, male population participating in Alzheimer trials, both rofecoxib- and placebo-treated patients had similar rates of CV thrombotic events. The totality of data is not consistent with an increased CV risk among patients taking rofecoxib. PMID:14564311

  12. The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

    PubMed Central

    Tsutsumimoto, Takahiro; Williams, Paul; Yoneda, Toshiyuki

    2014-01-01

    Neuroblastoma (NB), which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2). In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB. PMID:26909300

  13. Evaluation of a two-part regression calibration to adjust for dietary exposure measurement error in the Cox proportional hazards model: A simulation study.

    PubMed

    Agogo, George O; van der Voet, Hilko; Van't Veer, Pieter; van Eeuwijk, Fred A; Boshuizen, Hendriek C

    2016-07-01

    Dietary questionnaires are prone to measurement error, which bias the perceived association between dietary intake and risk of disease. Short-term measurements are required to adjust for the bias in the association. For foods that are not consumed daily, the short-term measurements are often characterized by excess zeroes. Via a simulation study, the performance of a two-part calibration model that was developed for a single-replicate study design was assessed by mimicking leafy vegetable intake reports from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. In part I of the fitted two-part calibration model, a logistic distribution was assumed; in part II, a gamma distribution was assumed. The model was assessed with respect to the magnitude of the correlation between the consumption probability and the consumed amount (hereafter, cross-part correlation), the number and form of covariates in the calibration model, the percentage of zero response values, and the magnitude of the measurement error in the dietary intake. From the simulation study results, transforming the dietary variable in the regression calibration to an appropriate scale was found to be the most important factor for the model performance. Reducing the number of covariates in the model could be beneficial, but was not critical in large-sample studies. The performance was remarkably robust when fitting a one-part rather than a two-part model. The model performance was minimally affected by the cross-part correlation. PMID:27003183

  14. A Comparison of Seven Cox Regression-Based Models to Account for Heterogeneity Across Multiple HIV Treatment Cohorts in Latin America and the Caribbean

    PubMed Central

    Giganti, Mark J.; Luz, Paula M.; Caro-Vega, Yanink; Cesar, Carina; Padgett, Denis; Koenig, Serena; Echevarria, Juan; McGowan, Catherine C.; Shepherd, Bryan E.

    2015-01-01

    Abstract Many studies of HIV/AIDS aggregate data from multiple cohorts to improve power and generalizability. There are several analysis approaches to account for cross-cohort heterogeneity; we assessed how different approaches can impact results from an HIV/AIDS study investigating predictors of mortality. Using data from 13,658 HIV-infected patients starting antiretroviral therapy from seven Latin American and Caribbean cohorts, we illustrate the assumptions of seven readily implementable approaches to account for across cohort heterogeneity with Cox proportional hazards models, and we compare hazard ratio estimates across approaches. As a sensitivity analysis, we modify cohort membership to generate specific heterogeneity conditions. Hazard ratio estimates varied slightly between the seven analysis approaches, but differences were not clinically meaningful. Adjusted hazard ratio estimates for the association between AIDS at treatment initiation and death varied from 2.00 to 2.20 across approaches that accounted for heterogeneity; the adjusted hazard ratio was estimated as 1.73 in analyses that ignored across cohort heterogeneity. In sensitivity analyses with more extreme heterogeneity, we noted a slightly greater distinction between approaches. Despite substantial heterogeneity between cohorts, the impact of the specific approach to account for heterogeneity was minimal in our case study. Our results suggest that it is important to account for across cohort heterogeneity in analyses, but that the specific technique for addressing heterogeneity may be less important. Because of their flexibility in accounting for cohort heterogeneity, we prefer stratification or meta-analysis methods, but we encourage investigators to consider their specific study conditions and objectives. PMID:25647087

  15. A Comparison of Seven Cox Regression-Based Models to Account for Heterogeneity Across Multiple HIV Treatment Cohorts in Latin America and the Caribbean.

    PubMed

    Giganti, Mark J; Luz, Paula M; Caro-Vega, Yanink; Cesar, Carina; Padgett, Denis; Koenig, Serena; Echevarria, Juan; McGowan, Catherine C; Shepherd, Bryan E

    2015-05-01

    Many studies of HIV/AIDS aggregate data from multiple cohorts to improve power and generalizability. There are several analysis approaches to account for cross-cohort heterogeneity; we assessed how different approaches can impact results from an HIV/AIDS study investigating predictors of mortality. Using data from 13,658 HIV-infected patients starting antiretroviral therapy from seven Latin American and Caribbean cohorts, we illustrate the assumptions of seven readily implementable approaches to account for across cohort heterogeneity with Cox proportional hazards models, and we compare hazard ratio estimates across approaches. As a sensitivity analysis, we modify cohort membership to generate specific heterogeneity conditions. Hazard ratio estimates varied slightly between the seven analysis approaches, but differences were not clinically meaningful. Adjusted hazard ratio estimates for the association between AIDS at treatment initiation and death varied from 2.00 to 2.20 across approaches that accounted for heterogeneity; the adjusted hazard ratio was estimated as 1.73 in analyses that ignored across cohort heterogeneity. In sensitivity analyses with more extreme heterogeneity, we noted a slightly greater distinction between approaches. Despite substantial heterogeneity between cohorts, the impact of the specific approach to account for heterogeneity was minimal in our case study. Our results suggest that it is important to account for across cohort heterogeneity in analyses, but that the specific technique for addressing heterogeneity may be less important. Because of their flexibility in accounting for cohort heterogeneity, we prefer stratification or meta-analysis methods, but we encourage investigators to consider their specific study conditions and objectives. PMID:25647087

  16. Comparing Methodologies for Developing an Early Warning System: Classification and Regression Tree Model versus Logistic Regression. REL 2015-077

    ERIC Educational Resources Information Center

    Koon, Sharon; Petscher, Yaacov

    2015-01-01

    The purpose of this report was to explicate the use of logistic regression and classification and regression tree (CART) analysis in the development of early warning systems. It was motivated by state education leaders' interest in maintaining high classification accuracy while simultaneously improving practitioner understanding of the rules…

  17. Development and Application of Nonlinear Land-Use Regression Models

    NASA Astrophysics Data System (ADS)

    Champendal, Alexandre; Kanevski, Mikhail; Huguenot, Pierre-Emmanuel

    2014-05-01

    The problem of air pollution modelling in urban zones is of great importance both from scientific and applied points of view. At present there are several fundamental approaches either based on science-based modelling (air pollution dispersion) or on the application of space-time geostatistical methods (e.g. family of kriging models or conditional stochastic simulations). Recently, there were important developments in so-called Land Use Regression (LUR) models. These models take into account geospatial information (e.g. traffic network, sources of pollution, average traffic, population census, land use, etc.) at different scales, for example, using buffering operations. Usually the dimension of the input space (number of independent variables) is within the range of (10-100). It was shown that LUR models have some potential to model complex and highly variable patterns of air pollution in urban zones. Most of LUR models currently used are linear models. In the present research the nonlinear LUR models are developed and applied for Geneva city. Mainly two nonlinear data-driven models were elaborated: multilayer perceptron and random forest. An important part of the research deals also with a comprehensive exploratory data analysis using statistical, geostatistical and time series tools. Unsupervised self-organizing maps were applied to better understand space-time patterns of the pollution. The real data case study deals with spatial-temporal air pollution data of Geneva (2002-2011). Nitrogen dioxide (NO2) has caught our attention. It has effects on human health and on plants; NO2 contributes to the phenomenon of acid rain. The negative effects of nitrogen dioxides on plants are the reduction of the growth, production and pesticide resistance. And finally, the effects on materials: nitrogen dioxide increases the corrosion. The data used for this study consist of a set of 106 NO2 passive sensors. 80 were used to build the models and the remaining 36 have constituted

  18. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    SciTech Connect

    Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia R.; Woodin, Bruce; Stegeman, John J.

    2012-12-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC{sub 50} values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells. -- Highlights: ► PCB126 caused cellular changes in the developing swim bladder. ► Swim bladder inflation was not related to expression of CYP1 or cox

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

    PubMed

    Sneeringer, Stacy

    2010-04-01

    While a recent paper by Cox in this journal uses as its motivating factor the benefits of quantitative risk assessment, its content is entirely devoted to critiquing Sneeringer's article in the American Journal of Agricultural Economics. Cox's two main critiques of Sneeringer are fundamentally flawed and misrepresent the original article. Cox posits that Sneeringer did A and B, and then argues why A and B are incorrect. However, Sneeringer in fact did C and D; thus critiques of A and B are not applicable to Sneeringer's analysis. PMID:20345577

  20. Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

    PubMed Central

    Laube, Markus; Kniess, Torsten; Pietzsch, Jens

    2016-01-01

    Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents. PMID:27104573

  1. Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy-A Hypothesis-Driven Review.

    PubMed

    Laube, Markus; Kniess, Torsten; Pietzsch, Jens

    2016-01-01

    Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents. PMID:27104573

  2. Development of Ni1-xCoxO as the cathode/interconnect contact for solid oxide fuel cells

    SciTech Connect

    Lu, Zigui; Xia, Guanguang; Templeton, Joshua D.; Li, Xiaohong S.; Nie, Zimin; Yang, Zhenguo; Stevenson, Jeffry W.

    2011-06-01

    A new type of material, Ni1-xCoxO, was developed for solid oxide fuel cell (SOFC) cathode/interconnect contact applications. The phase structure, coefficient of thermal expansion, sintering behavior, electrical property, and mechanical bonding strength of these materials were evaluated against the requirements of the SOFC cathode/interconnect contact. A dense cathode/interconnect contact layer was developed through reaction sintering from Ni and Co metal powders. An area specific resistance (ASR) as low as 5.5 mohm.cm2 was observed after 1000 h exposure in air at 800 °C for the LSM/Ni0.33Co0.67O/AISI441 assembly. Average mechanical strengths of 6.8 and 5.0 MPa were obtained for the cathode/contact/cathode and interconnect/contact/interconnect structures, respectively. The significantly low ASR was probably due to the dense structure and therefore improved electrical conductivity of the Ni0.33Co0.67O contact and the good bonding of the interfaces between the contact and the cathode, and between the contact and the interconnect.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  5. External validation of a Cox prognostic model: principles and methods

    PubMed Central

    2013-01-01

    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

  6. Gene-Based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions.

    PubMed

    Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y; Chen, Wei

    2016-02-01

    Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. PMID:26782979

  7. Development of a User Interface for a Regression Analysis Software Tool

    NASA Technical Reports Server (NTRS)

    Ulbrich, Norbert Manfred; Volden, Thomas R.

    2010-01-01

    An easy-to -use user interface was implemented in a highly automated regression analysis tool. The user interface was developed from the start to run on computers that use the Windows, Macintosh, Linux, or UNIX operating system. Many user interface features were specifically designed such that a novice or inexperienced user can apply the regression analysis tool with confidence. Therefore, the user interface s design minimizes interactive input from the user. In addition, reasonable default combinations are assigned to those analysis settings that influence the outcome of the regression analysis. These default combinations will lead to a successful regression analysis result for most experimental data sets. The user interface comes in two versions. The text user interface version is used for the ongoing development of the regression analysis tool. The official release of the regression analysis tool, on the other hand, has a graphical user interface that is more efficient to use. This graphical user interface displays all input file names, output file names, and analysis settings for a specific software application mode on a single screen which makes it easier to generate reliable analysis results and to perform input parameter studies. An object-oriented approach was used for the development of the graphical user interface. This choice keeps future software maintenance costs to a reasonable limit. Examples of both the text user interface and graphical user interface are discussed in order to illustrate the user interface s overall design approach.

  8. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

    PubMed Central

    Smith, Francine G.; Wade, Andrew W.; Lewis, Megan L.; Qi, Wei

    2012-01-01

    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function. PMID:24281306

  9. Development and validation of a reversed-phase liquid chromatographic method for separation and simultaneous determination of COX-2 inhibitors in pharmaceuticals and its application to biological fluids.

    PubMed

    Rao, R Nageswara; Meena, S; Nagaraju, D; Rao, A Raghu Ram

    2005-06-01

    An isocratic reversed-phase high-performance liquid chromatographic method has been developed for separation and simultaneous determination of COX-2 inhibitors, viz., celecoxib, rofecoxib, valdecoxib, nimesulide and nabumetone, using 4-chloro-2-nitroaniline as internal standard. Good chromatographic separation was achieved using a reversed-phase Inertsil C(18) column with mobile phase consisting of methanol and 0.05% aqueous glacial acetic acid (68:32 v/v) using photodiode array (PDA) detector at 230 nm. It was validated with respect to accuracy, precision, linearity, limit of detection and quantification. The linearity range was found to be 1.0--20 microg/mL and the percentage recoveries were between 97.55 and 100.14. The method is suitable not only for the estimation of active ingredients in pharmaceutical dosage forms but also in vitro estimations in human plasma. It is simple, rapid, selective and capable of detecting and determining COX-2 inhibitors with a detection limit of 0.127--1.040 microg/mL simultaneously. PMID:15627281

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

    PubMed Central

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

    2015-01-01

    The present study aimed to explore the importance of P53 and Cox-2 protein expression in esophageal cancer and assess their influence on prognosis. The expression of P53 and Cox-2 was assessed in esophageal cancer samples from 195 patients subjected to radical surgery at Changzhou First People's Hospital (Changzhou, China) between May 2010 and December 2011. Expression of P53 and Cox-2 proteins were detected in 60.5% (118/195) and 69.7% (136/195) of the samples, respectively, and were co-expressed in 43.1% (84/195) of the samples. A correlation was identified between P53 expression and overall survival (OS) (P=0.0351) as well as disease-free survival (DFS) (P=0.0307). In addition, the co-expression of P53 and Cox-2 also correlated with OS (P=0.0040) and DFS (P=0.0042). P53 expression (P=0.023), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.009) were identified as independent factors affecting OS in patients with esophageal cancer via a Cox multivariate regression model analysis. A similar analysis also identified P53 expression (P=0.020), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.008) as independent prognostic factors influencing DFS in these patients. Binary logistic regression analysis demonstrated a correlation between P53 expression (P=0.012), TNM staging (P<0.001), tumor differentiation level (P=0.023) and P53/Cox-2 co-expression (P=0.021), and local recurrence or distant esophageal cancer metastasis. The results of the present study indicate that P53 and Cox-2 proteins may act synergistically in the development of esophageal cancer, and the assessment of P53/Cox-2 co-expression status in esophageal cancer biopsies may become an important diagnostic criterion to evaluate the prognosis of patients with esophageal cancer. PMID:26622818

  11. The Development and Demonstration of Multiple Regression Models for Operant Conditioning Questions.

    ERIC Educational Resources Information Center

    Fanning, Fred; Newman, Isadore

    Based on the assumption that inferential statistics can make the operant conditioner more sensitive to possible significant relationships, regressions models were developed to test the statistical significance between slopes and Y intercepts of the experimental and control group subjects. These results were then compared to the traditional operant…

  12. Development and Application of Watershed Regressions for Pesticides (WARP) for Estimating Atrazine Concentration Distributions in Streams

    USGS Publications Warehouse

    Larson, Steven J.; Crawford, Charles G.; Gilliom, Robert J.

    2004-01-01

    Regression models were developed for predicting atrazine concentration distributions in rivers and streams, using the Watershed Regressions for Pesticides (WARP) methodology. Separate regression equations were derived for each of nine percentiles of the annual distribution of atrazine concentrations and for the annual time-weighted mean atrazine concentration. In addition, seasonal models were developed for two specific periods of the year--the high season, when the highest atrazine concentrations are expected in streams, and the low season, when concentrations are expected to be low or undetectable. Various nationally available watershed parameters were used as explanatory variables, including atrazine use intensity, soil characteristics, hydrologic parameters, climate and weather variables, land use, and agricultural management practices. Concentration data from 112 river and stream stations sampled as part of the U.S. Geological Survey's National Water-Quality Assessment and National Stream Quality Accounting Network Programs were used for computing the concentration percentiles and mean concentrations used as the response variables in regression models. Tobit regression methods, using maximum likelihood estimation, were used for developing the models because some of the concentration values used for the response variables were censored (reported as less than a detection threshold). Data from 26 stations not used for model development were used for model validation. The annual models accounted for 62 to 77 percent of the variability in concentrations among the 112 model development stations. Atrazine use intensity (the amount of atrazine used in the watershed divided by watershed area) was the most important explanatory variable in all models, but additional watershed parameters significantly increased the amount of variability explained by the models. Predicted concentrations from all 10 models were within a factor of 10 of the observed concentrations at most

  13. Oil and gas pipeline construction cost analysis and developing regression models for cost estimation

    NASA Astrophysics Data System (ADS)

    Thaduri, Ravi Kiran

    In this study, cost data for 180 pipelines and 136 compressor stations have been analyzed. On the basis of the distribution analysis, regression models have been developed. Material, Labor, ROW and miscellaneous costs make up the total cost of a pipeline construction. The pipelines are analyzed based on different pipeline lengths, diameter, location, pipeline volume and year of completion. In a pipeline construction, labor costs dominate the total costs with a share of about 40%. Multiple non-linear regression models are developed to estimate the component costs of pipelines for various cross-sectional areas, lengths and locations. The Compressor stations are analyzed based on the capacity, year of completion and location. Unlike the pipeline costs, material costs dominate the total costs in the construction of compressor station, with an average share of about 50.6%. Land costs have very little influence on the total costs. Similar regression models are developed to estimate the component costs of compressor station for various capacities and locations.

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

    PubMed

    Wu, Yichao

    2012-01-01

    For least squares regression, Efron et al. (2004) proposed an efficient solution path algorithm, the least angle regression (LAR). They showed that a slight modification of the LAR leads to the whole LASSO solution path. Both the LAR and LASSO solution paths are piecewise linear. Recently Wu (2011) extended the LAR to generalized linear models and the quasi-likelihood method. In this work we extend the LAR further to handle Cox's proportional hazards model. The goal is to develop a solution path algorithm for the elastic net penalty (Zou and Hastie (2005)) in Cox's proportional hazards model. This goal is achieved in two steps. First we extend the LAR to optimizing the log partial likelihood plus a fixed small ridge term. Then we define a path modification, which leads to the solution path of the elastic net regularized log partial likelihood. Our solution path is exact and piecewise determined by ordinary differential equation systems. PMID:23226932

  15. Gelatinases, endonuclease and Vascular Endothelial Growth Factor during development and regression of swine luteal tissue

    PubMed Central

    Ribeiro, Luciana Andrea; Turba, Maria Elena; Zannoni, Augusta; Bacci, Maria Laura; Forni, Monica

    2006-01-01

    Background The development and regression of corpus luteum (CL) is characterized by an intense angiogenesis and angioregression accompanied by luteal tissue and extracellular matrix (ECM) remodelling. Vascular Endothelial Growth Factor (VEGF) is the main regulator of angiogenesis, promoting endothelial cell mitosis and differentiation. After the formation of neovascular tubes, the remodelling of ECM is essential for the correct development of CL, particularly by the action of specific class of proteolytic enzymes known as matrix metalloproteinases (MMPs). During luteal regression, characterized by an apoptotic process and successively by an intense ECM and luteal degradation, the activation of Ca++/Mg++-dependent endonucleases and MMPs activity are required. The levels of expression and activity of VEGF, MMP-2 and -9, and Ca++/Mg++-dependent endonucleases throughout the oestrous cycle and at pregnancy were analyzed. Results Different patterns of VEGF, MMPs and Ca++/Mg++-dependent endonuclease were observed in swine CL during different luteal phases and at pregnancy. Immediately after ovulation, the highest levels of VEGF mRNA/protein and MMP-9 activity were detected. On days 5–14 after ovulation, VEGF expression and MMP-2 and -9 activities are at basal levels, while Ca++/Mg++-dependent endonuclease levels increased significantly in relation to day 1. Only at luteolysis (day 17), Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly. At pregnancy, high levels of MMP-9 and VEGF were observed. Conclusion Our findings, obtained from a precisely controlled in vivo model of CL development and regression, allow us to determine relationships among VEGF, MMPs and endonucleases during angiogenesis and angioregression. Thus, CL provides a very interesting model for studying factors involved in vascular remodelling. PMID:17137503

  16. Relationship of pressure regressions to secondary porosity development: exploration model for secondary porosity development in deep Wilcox of south Texas

    SciTech Connect

    Painter, J.

    1989-03-01

    In the deep Wilcox, as well as other deep Gulf Coast Tertiary formations, secondary porosity development is very important to reservoir quality. four major Wilcox fields and several abandoned wells were studied with respect to shale pore-pressure gradients to show the relationship between secondary porosity and shale pore-pressure regression. Secondary porosity is the result of chemical leaching and alteration of framework grains and clays in a rock by organic acids, fresh water, and other fluids or gases reacting with the rock constituents. These chemicals, water, and gases are formed in shales adjoining the sandstone reservoir rock and migrate into the adjoining aquifer sandstone, which is then leached. This release of fluids from the shale forms a pore-pressure regression which can be plotted using electric logs. The presence or absence of a pore-pressure regression gives indications of secondary porosity development in the adjoining reservoir rocks. If a regression is documented, the risk of inadequate reservoir porosity of a prospect can be lowered.

  17. Development and comparison of regression models for the uptake of metals into various field crops.

    PubMed

    Novotná, Markéta; Mikeš, Ondřej; Komprdová, Klára

    2015-12-01

    Field crops represent one of the highest contributions to dietary metal exposure. The aim of this study was to develop specific regression models for the uptake of metals into various field crops and to compare the usability of other available models. We analysed samples of potato, hop, maize, barley, wheat, rape seed, and grass from 66 agricultural sites. The influence of measured soil concentrations and soil factors (pH, organic carbon, content of silt and clay) on the plant concentrations of Cd, Cr, Cu, Mo, Ni, Pb and Zn was evaluated. Bioconcentration factors (BCF) and plant-specific metal models (PSMM) developed from multivariate regressions were calculated. The explained variability of the models was from 19 to 64% and correlations between measured and predicted concentrations were between 0.43 and 0.90. The developed hop and rapeseed models are new in this field. Available models from literature showed inaccurate results, except for Cd; the modelling efficiency was mostly around zero. The use of interaction terms between parameters can significantly improve plant-specific models. PMID:26448504

  18. The Moxie of Kathy Cox

    ERIC Educational Resources Information Center

    Johns, Stephanie

    2010-01-01

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

  19. Development of Refractive Error in Individual Children With Regressed Retinopathy of Prematurity

    PubMed Central

    Wang, Jingyun; Ren, Xiaowei; Shen, Li; Yanni, Susan E.; Leffler, Joel N.; Birch, Eileen E.

    2013-01-01

    Purpose. We investigated longitudinally the refraction development in children with regressed retinopathy of prematurity (ROP), including those with and those without a history of peripheral retinal laser photocoagulation. Methods. Longitudinal (0–7 years) cycloplegic refraction data were collected prospectively for two groups of preterm children: severe ROP group included those with regressed ROP following bilateral panretinal laser photocoagulation (n = 37; median gestational age [GA] = 25.2; range, 22.7–27.9 weeks) and mild/no ROP group included those with spontaneously regressed ROP or no ROP (n = 27; median GA = 27.1; range, 23.1–32.0 weeks). Analyses were based on spherical equivalent (SEQ), anisometropia, astigmatism, and age (corrected for gestation). Results. The prevalence, magnitude, and rate of myopic progression all were significantly higher in the severe ROP group than in the mild/no ROP group. Longitudinal SEQ in the severe ROP group were best fit with a bilinear model. Before 1.3 years old, the rate of myopic shift was −4.7 diopters (D)/y; after 1.3 years, the rate slowed to −0.15 D/y. Longitudinal SEQ in the mild/no ROP group was best fit with a linear model, with a rate of −0.004 D/y. Anisometropia in the severe ROP group increased approximately three times faster than in the mild/no ROP group. In the severe ROP group, with-the-rule astigmatism increased significantly with age. Conclusions. The severe ROP group progressed rapidly toward myopia, particularly during the first 1.3 years; anisometropia and astigmatism also increased with age. The mild/no ROP group showed little change in refraction. Infants treated with laser photocoagulation for severe ROP should be monitored with periodic cycloplegic refractions and provided with early optical correction. PMID:23920368

  20. COX2 Inhibition Reduces Aortic Valve Calcification In Vivo

    PubMed Central

    Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E.

    2016-01-01

    Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432

  1. Kernel Continuum Regression.

    PubMed

    Lee, Myung Hee; Liu, Yufeng

    2013-12-01

    The continuum regression technique provides an appealing regression framework connecting ordinary least squares, partial least squares and principal component regression in one family. It offers some insight on the underlying regression model for a given application. Moreover, it helps to provide deep understanding of various regression techniques. Despite the useful framework, however, the current development on continuum regression is only for linear regression. In many applications, nonlinear regression is necessary. The extension of continuum regression from linear models to nonlinear models using kernel learning is considered. The proposed kernel continuum regression technique is quite general and can handle very flexible regression model estimation. An efficient algorithm is developed for fast implementation. Numerical examples have demonstrated the usefulness of the proposed technique. PMID:24058224

  2. Quantile Regression with Censored Data

    ERIC Educational Resources Information Center

    Lin, Guixian

    2009-01-01

    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…

  3. Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.

    PubMed

    Park, Sun Ah; Chevallier, Nathalie; Tejwani, Karishma; Hung, Mary M; Maruyama, Hiroko; Golde, Todd E; Koo, Edward H

    2016-09-01

    Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Our studies showed that loss of either COX-1 or COX-2 gene did not alter amyloid burden in brains of the APP transgenic mice. However, one marker of microglial activation (CD45) was decreased in brains of COX-1 deficient/APP animals and showed a strong trend in reduction in COX-2 deficient/APP animals. These results suggest that COX activity and amyloid deposition in brain are likely independent processes. Further, if NSAIDs do causally reduce the risks of AD, then our findings indicate that the mechanisms are likely not due primarily to their inhibition on COX or γ-secretase modulation activity, the latter reported recently after acute dosing of ibuprofen in humans and nonhuman primates. PMID:27425247

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

    PubMed Central

    Herschman, Harvey

    2014-01-01

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

  5. JOINT STRUCTURE SELECTION AND ESTIMATION IN THE TIME-VARYING COEFFICIENT COX MODEL

    PubMed Central

    Xiao, Wei; Lu, Wenbin; Zhang, Hao Helen

    2016-01-01

    Time-varying coefficient Cox model has been widely studied and popularly used in survival data analysis due to its flexibility for modeling covariate effects. It is of great practical interest to accurately identify the structure of covariate effects in a time-varying coefficient Cox model, i.e. covariates with null effect, constant effect and truly time-varying effect, and estimate the corresponding regression coefficients. Combining the ideas of local polynomial smoothing and group nonnegative garrote, we develop a new penalization approach to achieve such goals. Our method is able to identify the underlying true model structure with probability tending to one and simultaneously estimate the time-varying coefficients consistently. The asymptotic normalities of the resulting estimators are also established. We demonstrate the performance of our method using simulations and an application to the primary biliary cirrhosis data. PMID:27540275

  6. Robust Regression.

    PubMed

    Huang, Dong; Cabral, Ricardo; De la Torre, Fernando

    2016-02-01

    Discriminative methods (e.g., kernel regression, SVM) have been extensively used to solve problems such as object recognition, image alignment and pose estimation from images. These methods typically map image features ( X) to continuous (e.g., pose) or discrete (e.g., object category) values. A major drawback of existing discriminative methods is that samples are directly projected onto a subspace and hence fail to account for outliers common in realistic training sets due to occlusion, specular reflections or noise. It is important to notice that existing discriminative approaches assume the input variables X to be noise free. Thus, discriminative methods experience significant performance degradation when gross outliers are present. Despite its obvious importance, the problem of robust discriminative learning has been relatively unexplored in computer vision. This paper develops the theory of robust regression (RR) and presents an effective convex approach that uses recent advances on rank minimization. The framework applies to a variety of problems in computer vision including robust linear discriminant analysis, regression with missing data, and multi-label classification. Several synthetic and real examples with applications to head pose estimation from images, image and video classification and facial attribute classification with missing data are used to illustrate the benefits of RR. PMID:26761740

  7. Regression methods for developing QSAR and QSPR models to predict compounds of specific pharmacodynamic, pharmacokinetic and toxicological properties.

    PubMed

    Yap, C W; Li, H; Ji, Z L; Chen, Y Z

    2007-11-01

    Quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) models have been extensively used for predicting compounds of specific pharmacodynamic, pharmacokinetic, or toxicological property from structure-derived physicochemical and structural features. These models can be developed by using various regression methods including conventional approaches (multiple linear regression and partial least squares) and more recently explored genetic (genetic function approximation) and machine learning (k-nearest neighbour, neural networks, and support vector regression) approaches. This article describes the algorithms of these methods, evaluates their advantages and disadvantages, and discusses the application potential of the recently explored methods. Freely available online and commercial software for these regression methods and the areas of their applications are also presented. PMID:18045213

  8. Spatial variations and development of land use regression models of levoglucosan in four European study areas

    NASA Astrophysics Data System (ADS)

    Jedynska, A.; Hoek, G.; Wang, M.; Eeftens, M.; Cyrys, J.; Beelen, R.; Cirach, M.; De Nazelle, A.; Nystad, W.; Makarem Akhlaghi, H.; Meliefste, K.; Nieuwenhuijsen, M.; de Hoogh, K.; Brunekreef, B.; Kooter, I. M.

    2014-05-01

    Relatively little is known about long term effects of wood smoke on population health. A wood burning marker - levoglucosan - was measured using a highly standardized sampling and measurement method in four study areas across Europe (Oslo, the Netherlands, Munich/Augsburg, Catalonia) to assess within and between study area spatial variation. Levoglucosan was analyzed in addition to other components: PM2.5, PM2.5 absorbance, PM10, polycyclic aromatic hydrocarbons (PAH), nitrogen oxides (NOx), elemental and organic carbon (EC / OC), hopanes, steranes and elemental composition. Measurements were conducted at street, urban and regional background sites. Three two-week samples were taken per site and the annual average concentrations of pollutants were calculated using continuous measurements at one background site as a eference. Land use regression (LUR) models were developed to explain the spatial variation of levoglucosan using standardized procedures. Much larger within than between study area contrast in levoglucosan concentration was found. Spatial variation patterns differed substantially from other measured pollutants including PM2.5, NOx and EC. Levoglucosan had the highest spatial correlation with ΣPAH (r = 0.65) and the lowest with traffic markers - NOx, Σhopanes/steranes (r = -0.22). The correlation of levoglucosan with potassium (K), which is also used as a wood burning marker, was moderate to low (median r = 0.33). Levoglucosan concentrations in the cold (heating) period were between 3 and 20 times higher compared to the warm period. The contribution of wood-smoke calculated based on levoglucosan measurements and previous European emission data to OC and PM2.5 mass were 13 to 28% and 3 to 9% respectively in the full year. Larger contributions were calculated for the cold period. The median model R2 of the LUR models was 60%. In Catalonia the model R2 was the highest (71%). The LUR models included population and natural land related variables but no

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

    PubMed Central

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

    2013-01-01

    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

  10. Development of regression models to estimate flow duration statistics at ungaged streams in Oklahoma using a regional approach

    USGS Publications Warehouse

    Esralew, R.A.

    2009-01-01

    Multiple-regression analysis was used to develop equations for estimating annual and seasonal flow-duration statistics at ungaged streams in and near Oklahoma that are not substantially affected by human alteration. Ordinary least-squares and left-censored (Tobit) multiple-regression techniques were used to develop equations that relate these statistics, from continuous streamflow data at gaged locations with 10 or more years of record, to physical and climatic basin characteristics. Separate equations were developed to estimate these statistics for stations within similar hydrologic and geologic regions. Use of separate regressions by region substantially improved the accuracy of the estimate for streams in eastern and central Oklahoma when compared with estimating equations developed for the entire State, especially for regressions estimating lower flow duration values. For all regions, the equations were more reliable for estimating higher flow duration values. The accuracy of regressions for estimating flow duration statistics in western Oklahoma was very poor, especially for lower flow duration values. ?? 2009 ASCE.

  11. Development of regression models to estimate flow duration statistics at ungaged streams in Oklahoma using a regional approach

    USGS Publications Warehouse

    Esralew, Rachel A.

    2009-01-01

    Multiple-regression analysis was used to develop equations for estimating annual and seasonal flow-duration statistics at ungaged streams in and near Oklahoma that are not substantially affected by human alteration. Ordinary least-squares and left-censored (Tobit) multiple-regression techniques were used to develop equations that relate these statistics, from continuous streamflow data at gaged locations with 10 or more years of record, to physical and climatic basin characteristics. Separate equations were developed to estimate these statistics for stations within similar hydrologic and geologic regions. Use of separate regressions by region substantially improved the accuracy of the estimate for streams in eastern and central Oklahoma when compared with estimating equations developed for the entire State, especially for regressions estimating lower flow duration values. For all regions, the equations were more reliable for estimating higher flow duration values. The accuracy of regressions for estimating flow duration statistics in western Oklahoma was very poor, especially for lower flow duration values.

  12. Development of the barrier system at Ferry Beach, Maine--Evidence of transgressive and regressive phases

    SciTech Connect

    Van Heteren, S.; Fitzgerald, D.M. . Dept. of Geology); Fink, L.K. Jr. . Dept. of Geological Sciences)

    1993-03-01

    Ferry Beach is part of a barrier system that borders the southern end of the Saco Embayment. This portion of the coast is characterized by mesotidal conditions and low wave energy. The beaches in this area are fronted by a low gradient sandy offshore and backed by a continuous foredune ridge. The backbarrier consists of fresh water ponds at Ferry Beach, in the central part, and salt marshes adjacent to Saco River and Goosefare Brook. New ground-penetrating radar and vibracore data, supplemented with topographic profiles, have enabled the delineation and interpretation of the major stratigraphic units present at Ferry Beach. The internal structure of the barrier lithosome and backbarrier sedimentary unit shows evidence of three phases in the late Holocene development of the study area. The first, transgressive phase is identified in the unconformity between glaciomarine clays of the Presumpscot Formation and overlying backbarrier, barrier, and shoreface units. The second, transitional phase is recognized as a distinctly outlined sandy unit with landward and southward dipping layers on top of backbarrier and shoreface deposits. The unit is inferred to be either a recurved spit deposit or part of a new barrier incompletely welded to the older beach ridges. The third, regressive phase has resulted in the present-day beach ridge system. The barrier lithosome associated with this phase is characterized by 150 m of offshore dipping layers. The evolutionary style of the Ferry Beach barrier system is likely linked to variations in rates of relative sea-level rise and sediment supply. Rapid rise of relative sea level was the determining factor during Phase 1, while offshore and longshore (notably from the Saco River) sediment supply during the Holocene sediment maximum caused the barrier expansion during Phases 2 and 3.

  13. Development of very high Jc in Ba(Fe1-xCox)2As2 thin films grown on CaF2

    DOE PAGESBeta

    Tarantini, C.; Kametani, F.; Lee, S.; Jiang, J.; Weiss, J. D.; Jaroszynski, J.; Hellstrom, E. E.; Eom, C. B.; Larbalestier, D. C.

    2014-12-03

    Ba(Fe1-xCox)2As2 is the most tunable of the Fe-based superconductors (FBS) in terms of acceptance of high densities of self-assembled and artificially introduced pinning centres which are effective in significantly increasing the critical current density, Jc. Moreover, FBS are very sensitive to strain, which induces an important enhancement in critical temperature,Tc, of the material. In this study we demonstrate that strain induced by the substrate can further improve Jc of both single and multilayer films by more than that expected simply due to the increase in Tc. The multilayer deposition of Ba(Fe1-xCox)2As2 on CaF2 increases the pinning force density (Fp=Jc xmore » μ₀H) by more than 60% compared to a single layer film, reaching a maximum of 84 GN/m3 at 22.5 T and 4.2 K, the highest value ever reported in any 122 phase.« less

  14. Development of very high Jc in Ba(Fe1-xCox)2As2 thin films grown on CaF2

    PubMed Central

    Tarantini, C.; Kametani, F.; Lee, S.; Jiang, J.; Weiss, J. D.; Jaroszynski, J.; Hellstrom, E. E.; Eom, C. B.; Larbalestier, D. C.

    2014-01-01

    Ba(Fe1-xCox)2As2 is the most tunable of the Fe-based superconductors (FBS) in terms of acceptance of high densities of self-assembled and artificially introduced pinning centres which are effective in significantly increasing the critical current density, Jc. Moreover, FBS are very sensitive to strain, which induces an important enhancement in critical temperature, Tc, of the material. In this paper we demonstrate that strain induced by the substrate can further improve Jc of both single and multilayer films by more than that expected simply due to the increase in Tc. The multilayer deposition of Ba(Fe1-xCox)2As2 on CaF2 increases the pinning force density (Fp = Jc × µ0H) by more than 60% compared to a single layer film, reaching a maximum of 84 GN/m3 at 22.5 T and 4.2 K, the highest value ever reported in any 122 phase. PMID:25467177

  15. Development of LACIE CCEA-1 weather/wheat yield models. [regression analysis

    NASA Technical Reports Server (NTRS)

    Strommen, N. D.; Sakamoto, C. M.; Leduc, S. K.; Umberger, D. E. (Principal Investigator)

    1979-01-01

    The advantages and disadvantages of the casual (phenological, dynamic, physiological), statistical regression, and analog approaches to modeling for grain yield are examined. Given LACIE's primary goal of estimating wheat production for the large areas of eight major wheat-growing regions, the statistical regression approach of correlating historical yield and climate data offered the Center for Climatic and Environmental Assessment the greatest potential return within the constraints of time and data sources. The basic equation for the first generation wheat-yield model is given. Topics discussed include truncation, trend variable, selection of weather variables, episodic events, strata selection, operational data flow, weighting, and model results.

  16. Development and Evaluation of Land-Use Regression Models Using Modeled Air Quality Concentrations

    EPA Science Inventory

    Abstract Land-use regression (LUR) models have emerged as a preferred methodology for estimating individual exposure to ambient air pollution in epidemiologic studies in absence of subject-specific measurements. Although there is a growing literature focused on LUR evaluation, fu...

  17. Using particle swarms for the development of QSAR models based on K-nearest neighbor and kernel regression.

    PubMed

    Cedeño, Walter; Agrafiotis, Dimitris K

    2003-01-01

    We describe the application of particle swarms for the development of quantitative structure-activity relationship (QSAR) models based on k-nearest neighbor and kernel regression. Particle swarms is a population-based stochastic search method based on the principles of social interaction. Each individual explores the feature space guided by its previous success and that of its neighbors. Success is measured using leave-one-out (LOO) cross validation on the resulting model as determined by k-nearest neighbor kernel regression. The technique is shown to compare favorably to simulated annealing using three classical data sets from the QSAR literature. PMID:13677491

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

    Yang, Chen; Sorokin, Andrey

    2011-01-01

    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, Rac1(Q63E), 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

  20. Regression versus No Regression in the Autistic Disorder: Developmental Trajectories

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  1. Applicability of Monte Carlo cross validation technique for model development and validation using generalised least squares regression

    NASA Astrophysics Data System (ADS)

    Haddad, Khaled; Rahman, Ataur; A Zaman, Mohammad; Shrestha, Surendra

    2013-03-01

    SummaryIn regional hydrologic regression analysis, model selection and validation are regarded as important steps. Here, the model selection is usually based on some measurements of goodness-of-fit between the model prediction and observed data. In Regional Flood Frequency Analysis (RFFA), leave-one-out (LOO) validation or a fixed percentage leave out validation (e.g., 10%) is commonly adopted to assess the predictive ability of regression-based prediction equations. This paper develops a Monte Carlo Cross Validation (MCCV) technique (which has widely been adopted in Chemometrics and Econometrics) in RFFA using Generalised Least Squares Regression (GLSR) and compares it with the most commonly adopted LOO validation approach. The study uses simulated and regional flood data from the state of New South Wales in Australia. It is found that when developing hydrologic regression models, application of the MCCV is likely to result in a more parsimonious model than the LOO. It has also been found that the MCCV can provide a more realistic estimate of a model's predictive ability when compared with the LOO.

  2. Development of a land-use regression model for ultrafine particles in Toronto, Canada

    NASA Astrophysics Data System (ADS)

    Sabaliauskas, Kelly; Jeong, Cheol-Heon; Yao, Xiaohong; Reali, Christopher; Sun, Tim; Evans, Greg J.

    2015-06-01

    This study applies land-use regression (LUR) to characterize the spatial distribution of ultrafine particles (UFP) in a large city. Particle number (PN) concentrations were measured in residential areas around Toronto, Canada, between June and August 2008. A combination of fixed and mobile monitoring was used to assess spatial gradients between and within communities. The fixed monitoring locations included a central site, two downtown sites, and four residential sites located 6-15 km from the downtown core. The mobile data included average PN concentrations collected on 112 road segments from 10 study routes that were repeated on three separate days. The mobile data was used to create the land-use regression model while the fixed sites were used for validation purposes. The predictor variables that best described the spatial variation of PN concentration (R2 = 0.72, validated R2 = 0.68) included population density within 300 m, total resource and industrial area within 1000 m, total residential area within 3000 m, and major roadway and highway length within 3000 m. The LUR model successfully predicted the afternoon peak PN concentration (slope = 0.96, R2 = 0.86) but over-predicted the 24-h average PN concentration (slope = 1.28, R2 = 0.72) measured at seven fixed monitoring sites.

  3. Development of regression equations to estimate flow durations and low-flow-frequency statistics in New Hampshire streams

    USGS Publications Warehouse

    Flynn, Robert H.

    2003-01-01

    Regression equations and basin-characteristic digital datasets were developed to help water-resource managers estimate surface-water resources during periods of low flow in New Hampshire. The regression equations were developed to estimate statistics for the seasonal and annual low-flow-frequency and seasonal period-of-record and period-of-record flow durations. Because streamflow is maintained by ground-water discharge during periods of low flow, these equations also will aid in the assessment of ground-water availability. Ultimately, the equations and datasets developed herein can be combined with data on water withdrawals, discharges, and interbasin transfers in a geographic information system (GIS) to allow assessments of water use and water availability in any drainage basin in the State of New Hampshire. Regression equations developed in this study provide estimates of the seasonal (spring, summer, fall, and winter) and annual 7-day 2-year (7Q2) and 7-day 10-year (7Q10) low-flow-frequency values, as well as seasonal period-of-record and period-of-record flow durations (60-, 70-, 80-, 90-, 95-, and 98-percent exceedences) for ungaged reaches of unregulated New Hampshire streams. Regression equations were developed using seasonal and annual low-flow statistics from 58 to 60 continuous-record stream-gaging stations in New Hampshire and nearby areas in neighboring states, and measurements of various characteristics of the drainage basins that contribute flow to those stations. The estimating equations for the seasonal and annual 7Q2 and 7Q10 values were developed using generalized-least-squares (GLS) regression analyses. The GLS equations developed for these flow statistics gave average prediction errors that ranged from 11 to 61 percent. The estimating equations for flow-duration exceedence frequency values were developed using ordinary-least-squares (OLS) regression analysis. The OLS equations developed for these flow statistics gave average prediction errors

  4. Logistic Regression

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

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

  5. Development of flood regressions and climate change scenarios to explore estimates of future peak flows

    USGS Publications Warehouse

    Burns, Douglas A.; Smith, Martyn J.; Freehafer, Douglas A.

    2015-01-01

    The application uses predictions of future annual precipitation from five climate models and two future greenhouse gas emissions scenarios and provides results that are averaged over three future periods—2025 to 2049, 2050 to 2074, and 2075 to 2099. Results are presented in ensemble form as the mean, median, maximum, and minimum values among the five climate models for each greenhouse gas emissions scenario and period. These predictions of future annual precipitation are substituted into either the precipitation variable or a water balance equation for runoff to calculate potential future peak flows. This application is intended to be used only as an exploratory tool because (1) the regression equations on which the application is based have not been adequately tested outside the range of the current climate and (2) forecasting future precipitation with climate models and downscaling these results to a fine spatial resolution have a high degree of uncertainty. This report includes a discussion of the assumptions, uncertainties, and appropriate use of this exploratory application.

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

    PubMed Central

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

    2013-01-01

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

  7. Allan Cox 1926”1987

    NASA Astrophysics Data System (ADS)

    Coe, Rob; Dalrymple, Brent

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

  8. Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia.

    PubMed

    Fosslien, E

    2000-10-01

    Several types of human tumors overexpress cyclooxygenase (COX) -2 but not COX-1, and gene knockout transfection experiments demonstrate a central role of COX-2 in experimental tumorigenesis. COX-2 produces prostaglandins that inhibit apoptosis and stimulate angiogenesis and invasiveness. Selective COX-2 inhibitors reduce prostaglandin synthesis, restore apoptosis, and inhibit cancer cell proliferation. In animal studies they limit carcinogen-induced tumorigenesis. In contrast, aspirin-like nonselective NSAIDs such as sulindac and indomethacin inhibit not only the enzymatic action of the highly inducible, proinflammatory COX-2 but the constitutively expressed, cytoprotective COX-1 as well. Consequently, nonselective NSAIDs can cause platelet dysfunction, gastrointestinal ulceration, and kidney damage. For that reason, selective inhibition of COX-2 to treat neoplastic proliferation is preferable to nonselective inhibition. Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1. For instance, meloxicam inhibits the growth of cultured colon cancer cells (HCA-7 and Moser-S) that express COX-2 but has no effect on HCT-116 tumor cells that do not express COX-2. NS-398 induces apoptosis in COX-2 expressing LNCaP prostate cancer cells and, surprisingly, in colon cancer S/KS cells that does not express COX-2. This effect may due to induction of apoptosis through uncoupling of oxidative phosphorylation and down-regulation of Bcl-2, as has been demonstrated for some nonselective NSAIDs, for instance, flurbiprofen. COX-2 mRNA and COX-2 protein is constitutively expressed in the kidney, brain, spinal cord, and ductus deferens, and in the uterus during implantation. In addition, COX-2 is constitutively and dominantly expressed in the pancreatic islet cells. These findings might somewhat limit the use of presently available selective COX-2 inhibitors

  9. Mass balance-based regression modeling of PAHs accumulation in urban soils, role of urban development.

    PubMed

    Peng, Chi; Wang, Meie; Chen, Weiping; Chang, Andrew C

    2015-02-01

    We investigated the polycyclic aromatic hydrocarbons (PAHs) contents in 68 soils samples collected at housing developments that represent different length of development periods across Beijing. Based on the data, we derived a mass balanced mathematical model to simulate the dynamics of PAH accumulations in urban soils as affected by the urban developments. The key parameters were estimated by fitting the modified mass balance model to the data of PAH concentrations vs. building age of the sampling green area. The total PAH concentrations would increase from the baseline of 267 ng g(-1) to 3631 ng g(-1) during the period of 1978-2048. It showed that the dynamic changes in the rates of accumulations of light and heavy PAH species were related to the shifting of sources of fuels, combustion efficiencies, and amounts of energy consumed during the course of development. PMID:25489746

  10. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement

    PubMed Central

    Acquaah, Frank; Robson Brown, Katharine A.; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L.

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior–superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant “sculpting” of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  11. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement.

    PubMed

    Acquaah, Frank; Robson Brown, Katharine A; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior-superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant "sculpting" of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  12. COX-2 inhibitor as a radiation enhancer: new strategies for the treatment of lung cancer.

    PubMed

    Saha, Debabrata; Pyo, Hongryull; Choy, Hak

    2003-08-01

    Lung cancer is one of the most common causes of cancer-related mortality throughout the world, and the incidence continues to increase. Smoking is the number one cause of lung cancer. Emerging data have implicated cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of lung carcinoma. In invasive lung tumors, COX-2 upregulation has been reported in up to 90% of cases. COX-2 upregulation is an early event in the development of non-small-cell lung cancer and may be integral to the development of new blood vessels and production of specific proteases that are critical to growth and spread of lung malignancies. COX-2 inhibitors are known to enhance the chemosensitivity in COX-2 overexpressing lung cancer cell lines. Recently, we have demonstrated that selective COX-2 inhibitors also enhance the effect of radiation in COX-2 overexpressed cells. Therefore, inhibitors of COX-2 in combination with chemoradiation therapy may be an alternative strategy that can be tested in clinical trials. The combination of COX-2 inhibitors and radiation suggest a complementary strategy to target angiogenesis while potentially minimizing the impact on quality of life. Currently, several groups are conducting clinical trials in cervix cancer, lung cancer, and brain tumors, using inhibitors of COX-2 in combination with chemotherapy and radiation therapy. These clinical trials will help to elucidate the role of this interesting class. PMID:12902860

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

    PubMed Central

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

    2015-01-01

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

  14. The cytochrome c oxidase biogenesis factor AtCOX17 modulates stress responses in Arabidopsis.

    PubMed

    Garcia, Lucila; Welchen, Elina; Gey, Uta; Arce, Agustín L; Steinebrunner, Iris; Gonzalez, Daniel H

    2016-03-01

    COX17 is a soluble protein from the mitochondrial intermembrane space that participates in the transfer of copper for cytochrome c oxidase (COX) assembly in eukaryotic organisms. In this work, we studied the function of both Arabidopsis thaliana AtCOX17 genes using plants with altered expression levels of these genes. Silencing of AtCOX17-1 in a cox17-2 knockout background generates plants with smaller rosettes and decreased expression of genes involved in the response of plants to different stress conditions, including several genes that are induced by mitochondrial dysfunctions. Silencing of either of the AtCOX17 genes does not affect plant development or COX activity but causes a decrease in the response of genes to salt stress. In addition, these plants contain higher reactive oxygen and lipid peroxidation levels after irrigation with high NaCl concentrations and are less sensitive to abscisic acid. In agreement with a role of AtCOX17 in stress and abscisic acid responses, both AtCOX17 genes are induced by several stress conditions, abscisic acid and mutation of the transcription factor ABI4. The results indicate that AtCOX17 is required for optimal expression of a group of stress-responsive genes, probably as a component of signalling pathways that link stress conditions to gene expression responses. PMID:26436309

  15. Development and evaluation of a regression equation of prediction for fat-free soft tissue in heterogenous populations of cattle.

    PubMed

    Jenkins, T G; Leymaster, K A; MacNeil, M D

    1995-12-01

    Regression equations to predict kilograms of fat-free soft tissue (the sum of water and protein from chemical analyses) were developed from data collected on 526 steers and heifers. Straightbred animals representing Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Pinzgauer, Red Poll, and Simmental breeds of cattle contributed to the data set. Cattle ranged in slaughter weight and age from approximately 350 to 575 kg and from 13 to 23 mo, respectively. Diets (100% ground alfalfa, 67% ground alfalfa and 33% ground corn or 33% ground alfalfa and 67% ground corn) were cross-classified with breed and sex. Estimative traits included in the equation were warm carcass weight, fat depth at the 12th rib, and body impedance. Carcass soft-tissue samples were taken for determination of chemical constituents. The prediction equation accounted for 94% of the variation in fat-free soft tissue of the carcass. Adjusting for breed-sex-diet contemporary groups increased the R2 value by 2% units. The prediction model was evaluated using data collected on 65 steers sired by Charolais or by Hereford bulls at the Ft Keogh Livestock and Range Research Laboratory (Miles City, MT). Postweaning feeding strategies and slaughter ages varied among these animals. Carcass weight, back fat depth, and resistive impedance measures were recorded. Carcass soft-tissue samples were taken for determination of chemical constituents. Values of estimator variables recorded at Ft. Keogh were used in the regression equation to predict fat-free soft tissue for each animal. The values for kilogram of fat-free soft tissue determined from chemical analysis were regressed on predicted fat-free soft tissue. the results indicate that fat-free soft tissue of carcasses can be accurately predicted using estimative traits that do not diminish carcass value. PMID:8655437

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

    PubMed Central

    Zarghi, Afshin; Arfaei, Sara

    2011-01-01

    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

  17. Changes in the content of sex steroid hormone receptors in the growing and regressing ovaries of Gallus domesticus during development.

    PubMed

    González-Morán, María Genoveva; González-Arenas, Aliesha; Germán-Castelán, Liliana; Camacho-Arroyo, Ignacio

    2013-08-01

    Sex steroids participate in the regulation of reproduction in female chickens. In this work, we determined the content of androgen receptor (AR), intracellular progesterone receptor isoforms (PR-A and PR-B), membrane progesterone receptor γ (mPRγ) and estrogen receptor α (ER-α) in the left growing and right regressing ovaries of Gallus domesticus from 13-day-old chicken embryos to 1-month-old chickens by western blot analysis. A marked difference in the morphological characteristics of the left and the right ovaries during development was observed. Results show a higher content of AR in the left ovary than in the right one in all ages. In the left ovary, the highest content of AR was observed on day 13 of embryonic development, and diminished with age. In the right ovary, AR was expressed from day 13 of embryonic development to 1-day-old, and became undetectable at 1-week and 1-month-old. In the left ovary, PR isoforms were not detected on day 13 of embryonic development, but they presented a marked expression after hatching. In the right ovary, the highest expression of both PR isoforms was found on 1-day-old, and significantly decreased with age. PR-B was the predominant isoform on 1-day and 1-month old in the left ovary, whereas PR-A was the predominant one on day 13 of embryonic development in the right ovary. Interestingly, mPRγ was detected at 1-week and 1-month-old in the left ovary meanwhile in the right ovary, it was detected from day 13 of embryonic development to 1-day-old. ER-α was only detected in the left ovary from day 13 to 1-week-old, while in 1-month-old chickens, it was expressed in both ovaries. In the left ovary, ER-α content was lower from 1-day to 1-month-old as compared with day 13 of embryonic development. Our results demonstrate a differential expression of sex steroid hormone receptors between the left growing and the right regressing ovary, and throughout chickens' age; and this is the first report about mPR expression in birds

  18. Developing logistic regression models using purchase attributes and demographics to predict the probability of purchases of regular and specialty eggs.

    PubMed

    Bejaei, M; Wiseman, K; Cheng, K M

    2015-01-01

    Consumers' interest in specialty eggs appears to be growing in Europe and North America. The objective of this research was to develop logistic regression models that utilise purchaser attributes and demographics to predict the probability of a consumer purchasing a specific type of table egg including regular (white and brown), non-caged (free-run, free-range and organic) or nutrient-enhanced eggs. These purchase prediction models, together with the purchasers' attributes, can be used to assess market opportunities of different egg types specifically in British Columbia (BC). An online survey was used to gather data for the models. A total of 702 completed questionnaires were submitted by BC residents. Selected independent variables included in the logistic regression to develop models for different egg types to predict the probability of a consumer purchasing a specific type of table egg. The variables used in the model accounted for 54% and 49% of variances in the purchase of regular and non-caged eggs, respectively. Research results indicate that consumers of different egg types exhibit a set of unique and statistically significant characteristics and/or demographics. For example, consumers of regular eggs were less educated, older, price sensitive, major chain store buyers, and store flyer users, and had lower awareness about different types of eggs and less concern regarding animal welfare issues. However, most of the non-caged egg consumers were less concerned about price, had higher awareness about different types of table eggs, purchased their eggs from local/organic grocery stores, farm gates or farmers markets, and they were more concerned about care and feeding of hens compared to consumers of other eggs types. PMID:26103791

  19. The effects of the Cox maze procedure on atrial function

    PubMed Central

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

    2010-01-01

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

  20. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

    PubMed

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-Sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-Quan; Hüttemann, Maik; Grossman, Lawrence I

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  1. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy

    PubMed Central

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P.; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-quan; Hüttemann, Maik; Grossman, Lawrence I.

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  2. Development of a modified factor analysis/multiple regression model to apportion suspended particulate matter in a complex urban airshed

    NASA Astrophysics Data System (ADS)

    Morandi, Maria T.; Daisey, Joan M.; Lioy, Paul J.

    A modified factor analysis/multiple regression (FA/MR) receptor-oriented source apportionment model has been developed which permits application of FA/MR statistical methods when some of the tracers are not unique to an individual source type. The new method uses factor and regression analyses to apportion non-unique tracer ambient concentrations in situations where there are unique tracers for all sources contributing to the non-unique tracer except one, and ascribes the residual concentration to that source. This value is then used as the source tracer in the final FA/MR apportionment model for ambient paniculate matter. In addition, factor analyses results are complemented with examination of regression residuals in order to optimize the number of identifiable sources. The new method has been applied to identify and apportion the sources of inhalable particulate matter (IPM; D5015 μm), Pb and Fe at a site in Newark, NJ. The model indicated that sulfate/secondary aerosol contributed an average of 25.8 μ -3 (48%) to IPM concentrations, followed by soil resuspension (8.2 μ -3 or 15%), paint spraying/paint pigment (6.7/gmm -3or 13%), fuel oil burning/space heating (4.3 μ -3 or 8 %), industrial emissions (3.6 μm -3 or 7 %) and motor vehicle exhaust (2.7 μ -3 or 15 %). Contributions to ambient Pb concentrations were: motor vehicle exhaust (0.16μm -3or 36%), soil resuspension (0.10μm -3 or 24%), fuel oil burning/space heating (0.08μm -3or 18%), industrial emissions (0.07 μ -3 or 17 %), paint spraying/paint pigment (0.036 μm -3or 9 %) and zinc related sources (0.022 μ -3 or 5 %). Contributions to ambient Fe concentrations were: soil resuspension (0.43μ -3or 51%), paint spraying/paint pigment (0.28 μm -3or 33 %) and industrial emissions (0.15 μ -3or 18 %). The models were validated by comparing partial source profiles calculated from modeling results with the corresponding published source emissions composition.

  3. Development and Application of Regression Models for Estimating Nutrient Concentrations in Streams of the Conterminous United States, 1992-2001

    USGS Publications Warehouse

    Spahr, Norman E.; Mueller, David K.; Wolock, David M.; Hitt, Kerie J.; Gronberg, JoAnn M.

    2010-01-01

    Data collected for the U.S. Geological Survey National Water-Quality Assessment program from 1992-2001 were used to investigate the relations between nutrient concentrations and nutrient sources, hydrology, and basin characteristics. Regression models were developed to estimate annual flow-weighted concentrations of total nitrogen and total phosphorus using explanatory variables derived from currently available national ancillary data. Different total-nitrogen regression models were used for agricultural (25 percent or more of basin area classified as agricultural land use) and nonagricultural basins. Atmospheric, fertilizer, and manure inputs of nitrogen, percent sand in soil, subsurface drainage, overland flow, mean annual precipitation, and percent undeveloped area were significant variables in the agricultural basin total nitrogen model. Significant explanatory variables in the nonagricultural total nitrogen model were total nonpoint-source nitrogen input (sum of nitrogen from manure, fertilizer, and atmospheric deposition), population density, mean annual runoff, and percent base flow. The concentrations of nutrients derived from regression (CONDOR) models were applied to drainage basins associated with the U.S. Environmental Protection Agency (USEPA) River Reach File (RF1) to predict flow-weighted mean annual total nitrogen concentrations for the conterminous United States. The majority of stream miles in the Nation have predicted concentrations less than 5 milligrams per liter. Concentrations greater than 5 milligrams per liter were predicted for a broad area extending from Ohio to eastern Nebraska, areas spatially associated with greater application of fertilizer and manure. Probabilities that mean annual total-nitrogen concentrations exceed the USEPA regional nutrient criteria were determined by incorporating model prediction uncertainty. In all nutrient regions where criteria have been established, there is at least a 50 percent probability of exceeding

  4. Tomato powder impedes the development of azoxymethane-induced colorectal cancer in rats through suppression of COX-2 expression via NF-κB and regulating Nrf2/HO-1 pathway.

    PubMed

    Tuzcu, Mehmet; Aslan, Abdullah; Tuzcu, Zeynep; Yabas, Mehmet; Bahcecioglu, Ibrahim Halil; Ozercan, Ibrahim Hanifi; Kucuk, Omer; Sahin, Kazim

    2012-09-01

    Cancer is one of the leading causes of death worldwide. Since dietary factors have been connected to a reduced risk of a diversity of human cancers, in this study we investigated the effects of tomato powder (TP) on the development of azoxymethane (AOM)-induced colorectal cancer in Wistar rats, and possible mechanism(s) by which TP shows its chemopreventive activity. Here we show that TP added to feed at 5% rate decreases the rate of aberrant crypt foci (ACF) and reduces the development of adenocarcinoma and growth of AOM-induced colorectal cancer in rats. In addition, we demonstrate that TP supplementation shows its chemopreventive activities through inhibition of cyclooxygenase-2 (COX-2) expression via NF-κB pathway and promotion of apoptosis, as well as regulating Nrf2/HO-1 signaling pathway in colorectal tissue of AOM-treated rats. Our findings identify an intimate connection between dietary supplementation of TP and the decreased risk of colorectal cancer in rats, and suggest that consumption of TP would be a natural candidate for the prevention of colorectal cancer in men. PMID:22859375

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

    SciTech Connect

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

    2005-11-01

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

  6. Development and application of generalized-least-squares regression models to estimate low-flow duration discharges in Massachusetts

    USGS Publications Warehouse

    Ries, Kernell G., III

    1994-01-01

    Physically based mathematical models were developed by use of generalized-least-squares regression analyses to estimate long-term 95-, 98-, and 99-percent duration discharges for ungaged streams in Massachusetts. Duration discharges for 61 sites were used in the recession analyses; 37 sites were streamflow-gaging stations and 24 sites were low-flow partial-record stations. The duration discharges were related to basin chacteristics measured from digital data bases, by use of geographic information systems computer software. Significant chacterisfics used in the models were drainage area, area underlain by stratified-drift deposits per unit of stream length in the basin, and a surrogate for the effective head on the aquifer in the stratified-drift deposits, computed by subtracting the minimum basin elevation from the mean basin elevation. Standard errors of prediction were 57.5, 85.6, and 98.5 percent for models for the 95-, 98-, and 99-percent duration discharges, respectively. Model error variances were about 10 times the sampling error variances, indicating that the precision of future models are likely to be improved more by obtaining better measurements of basin characteristics or by adding new sites to the analyses than by collecting more streamflow data at the sites presently used in the analyses. The models were used to predict duration discharges for 35 selected sites in the Concord River, Noah Coastal, South Coastal, Narragansett and Tenmile River Basins. Ninety-perrcent prediction intervals were computed for the estimates at each of the sites, except at sites where values of the independent variables were outside the ranges of those for the sites used in the regression analyses.

  7. Development and evaluation of a regression-based model to predict cesium-137 concentration ratios for saltwater fish.

    PubMed

    Pinder, John E; Rowan, David J; Smith, Jim T

    2016-02-01

    Data from published studies and World Wide Web sources were combined to develop a regression model to predict (137)Cs concentration ratios for saltwater fish. Predictions were developed from 1) numeric trophic levels computed primarily from random resampling of known food items and 2) K concentrations in the saltwater for 65 samplings from 41 different species from both the Atlantic and Pacific Oceans. A number of different models were initially developed and evaluated for accuracy which was assessed as the ratios of independently measured concentration ratios to those predicted by the model. In contrast to freshwater systems, were K concentrations are highly variable and are an important factor in affecting fish concentration ratios, the less variable K concentrations in saltwater were relatively unimportant in affecting concentration ratios. As a result, the simplest model, which used only trophic level as a predictor, had comparable accuracies to more complex models that also included K concentrations. A test of model accuracy involving comparisons of 56 published concentration ratios from 51 species of marine fish to those predicted by the model indicated that 52 of the predicted concentration ratios were within a factor of 2 of the observed concentration ratios. PMID:26675543

  8. Changes in the cellular localization of estrogen receptor alpha in the growing and regressing ovaries of Gallus domesticus during development.

    PubMed

    González-Morán, María Genoveva

    2014-04-25

    In this work, the presence of estrogen receptor alpha (ER-α) was determined in different cell subpopulations in the left growing and right regressing ovaries of Gallus domesticus from 13-day-old chicken embryos to one-month-old chickens by immunohistochemistry. Results revealed positive ER-α immunostaining in both ovaries during development, but the percentage, staining intensity, and cellular distribution of ER-α immunostaining changes according to whether it is the left or right ovary and with the animal's age. In the left ovary, the ER-α was localized in the nuclei of the germinal epithelium and in germ cells of the ovarian cortex, as well as in the interstitial cells, undifferentiated cells, and epithelial cells of the lacunar channels of the ovarian medulla in all ages. In contrast, in the right ovary from 13-day-old chicken embryos to one-week-old chickens, only the epithelial cells of lacunar channels were ER-α immunoreactive, but in the right ovary of one-month-old chickens both the epithelial cells of lacunar channels and the interstitial cells presented ER-α. These results demonstrate differential expression of ER-α in both chicken ovaries during development in a cell type-specific distribution, suggesting that these differences may be regarded as an important cause in the process of asymmetric ovarian development in the chicken. PMID:24704443

  9. Development of a clusterwise-linear-regression-based forecasting system for characterizing DNAPL dissolution behaviors in porous media.

    PubMed

    Wang, S; Huang, G H; He, L

    2012-09-01

    Groundwater contamination by dense non-aqueous phase liquids (DNAPLs) has become an issue of great concern in many industrialized countries due to their serious threat to human health. Dissolution and transport of DNAPLs in porous media are complicated, multidimensional and multiphase processes, which pose formidable challenges for investigation of their behaviors and implementation of effective remediation technologies. Numerical simulation models could help gain in-depth insight into complex mechanisms of DNAPLs dissolution and transport processes in the subsurface; however, they were computationally expensive, especially when a large number of runs were required, which was considered as a major obstacle for conducting further analysis. Therefore, proxy models that mimic key characteristics of a full simulation model were desired to save many orders of magnitude of computational cost. In this study, a clusterwise-linear-regression (CLR)-based forecasting system was developed for establishing a statistical relationship between DNAPL dissolution behaviors and system conditions under discrete and nonlinear complexities. The results indicated that the developed CLR-based forecasting system was capable not only of predicting DNAPL concentrations with acceptable error levels, but also of providing a significance level in each cutting/merging step such that the accuracies of the developed forecasting trees could be controlled. This study was a first attempt to apply the CLR model to characterize DNAPL dissolution and transport processes. PMID:22789814

  10. Decomposition of Variance for Spatial Cox Processes

    PubMed Central

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2012-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees. PMID:23599558

  11. Observational Studies: Matching or Regression?

    PubMed

    Brazauskas, Ruta; Logan, Brent R

    2016-03-01

    In observational studies with an aim of assessing treatment effect or comparing groups of patients, several approaches could be used. Often, baseline characteristics of patients may be imbalanced between groups, and adjustments are needed to account for this. It can be accomplished either via appropriate regression modeling or, alternatively, by conducting a matched pairs study. The latter is often chosen because it makes groups appear to be comparable. In this article we considered these 2 options in terms of their ability to detect a treatment effect in time-to-event studies. Our investigation shows that a Cox regression model applied to the entire cohort is often a more powerful tool in detecting treatment effect as compared with a matched study. Real data from a hematopoietic cell transplantation study is used as an example. PMID:26712591

  12. Development of synthetic velocity - depth damage curves using a Weighted Monte Carlo method and Logistic Regression analysis

    NASA Astrophysics Data System (ADS)

    Vozinaki, Anthi Eirini K.; Karatzas, George P.; Sibetheros, Ioannis A.; Varouchakis, Emmanouil A.

    2014-05-01

    Damage curves are the most significant component of the flood loss estimation models. Their development is quite complex. Two types of damage curves exist, historical and synthetic curves. Historical curves are developed from historical loss data from actual flood events. However, due to the scarcity of historical data, synthetic damage curves can be alternatively developed. Synthetic curves rely on the analysis of expected damage under certain hypothetical flooding conditions. A synthetic approach was developed and presented in this work for the development of damage curves, which are subsequently used as the basic input to a flood loss estimation model. A questionnaire-based survey took place among practicing and research agronomists, in order to generate rural loss data based on the responders' loss estimates, for several flood condition scenarios. In addition, a similar questionnaire-based survey took place among building experts, i.e. civil engineers and architects, in order to generate loss data for the urban sector. By answering the questionnaire, the experts were in essence expressing their opinion on how damage to various crop types or building types is related to a range of values of flood inundation parameters, such as floodwater depth and velocity. However, the loss data compiled from the completed questionnaires were not sufficient for the construction of workable damage curves; to overcome this problem, a Weighted Monte Carlo method was implemented, in order to generate extra synthetic datasets with statistical properties identical to those of the questionnaire-based data. The data generated by the Weighted Monte Carlo method were processed via Logistic Regression techniques in order to develop accurate logistic damage curves for the rural and the urban sectors. A Python-based code was developed, which combines the Weighted Monte Carlo method and the Logistic Regression analysis into a single code (WMCLR Python code). Each WMCLR code execution

  13. Developing synergy regression models with space-borne ALOS PALSAR and Landsat TM sensors for retrieving tropical forest biomass

    NASA Astrophysics Data System (ADS)

    Sinha, Suman; Jeganathan, C.; Sharma, L. K.; Nathawat, M. S.; Das, Anup K.; Mohan, Shiv

    2016-06-01

    Forest stand biomass serves as an effective indicator for monitoring REDD (reducing emissions from deforestation and forest degradation). Optical remote sensing data have been widely used to derive forest biophysical parameters inspite of their poor sensitivity towards the forest properties. Microwave remote sensing provides a better alternative owing to its inherent ability to penetrate the forest vegetation. This study aims at developing optimal regression models for retrieving forest above-ground bole biomass (AGBB) utilising optical data from Landsat TM and microwave data from L-band of ALOS PALSAR data over Indian subcontinental tropical deciduous mixed forests located in Munger (Bihar, India). Spatial biomass models were developed. The results using Landsat TM showed poor correlation (R 2 = 0.295 and RMSE = 35 t/ha) when compared to HH polarized L-band SAR (R 2 = 0.868 and RMSE = 16.06 t/ha). However, the prediction model performed even better when both the optical and SAR were used simultaneously (R 2 = 0.892 and RMSE = 14.08 t/ha). The addition of TM metrics has positively contributed in improving PALSAR estimates of forest biomass. Hence, the study recommends the combined use of both optical and SAR sensors for better assessment of stand biomass with significant contribution towards operational forestry.

  14. Study of heat-stress levels in naturally ventilated sheep barns during heat waves: development and assessment of regression models

    NASA Astrophysics Data System (ADS)

    Papanastasiou, D. K.; Bartzanas, T.; Panagakis, P.; Zhang, G.; Kittas, C.

    2016-03-01

    It is well documented that heat-stress burdens sheep welfare and productivity. Peak heat-stress levels are observed when high temperatures prevail, i.e. during heat waves; however, continuous measurements inside livestock buildings are not usually available for long periods so as to study the variation of summer heat-stress levels for several years, especially during extreme hot weather. Α methodology to develop a long time series of summer temperature and relative humidity inside naturally ventilated sheep barns is proposed. The accuracy and the transferability of the developed linear regression models were verified. Temperature Humidity Index (THI) was used to assess sheep's potential heat-stress. Τhe variation of THI inside a barn during heat wave and non-heat wave days was examined, and the results were comparatively assessed. The analysis showed that sheep were exposed to moderate, severe, and extreme severe heat-stress in 10, 21 and 66 % of hours, respectively, during heat wave days, while the corresponding values during non-heat wave days were 14, 33 and 43 %, respectively. The heat load on sheep was much higher during heat wave events than during non-heat wave periods. Additionally, based on the averaged diurnal variation of THI, it was concluded that extreme severe heat-stress conditions were prevailing between 1000 and 2400 hours local time during heat wave days. Cool off night periods were never and extremely rarely detected during heat wave and non-heat wave days, respectively.

  15. Developing synergy regression models with space-borne ALOS PALSAR and Landsat TM sensors for retrieving tropical forest biomass

    NASA Astrophysics Data System (ADS)

    Sinha, Suman; Jeganathan, C.; Sharma, L. K.; Nathawat, M. S.; Das, Anup K.; Mohan, Shiv

    2016-06-01

    Forest stand biomass serves as an effective indicator for monitoring REDD (reducing emissions from deforestation and forest degradation). Optical remote sensing data have been widely used to derive forest biophysical parameters inspite of their poor sensitivity towards the forest properties. Microwave remote sensing provides a better alternative owing to its inherent ability to penetrate the forest vegetation. This study aims at developing optimal regression models for retrieving forest above-ground bole biomass (AGBB) utilising optical data from Landsat TM and microwave data from L-band of ALOS PALSAR data over Indian subcontinental tropical deciduous mixed forests located in Munger (Bihar, India). Spatial biomass models were developed. The results using Landsat TM showed poor correlation ( R 2 = 0.295 and RMSE = 35 t/ha) when compared to HH polarized L-band SAR ( R 2 = 0.868 and RMSE = 16.06 t/ha). However, the prediction model performed even better when both the optical and SAR were used simultaneously ( R 2 = 0.892 and RMSE = 14.08 t/ha). The addition of TM metrics has positively contributed in improving PALSAR estimates of forest biomass. Hence, the study recommends the combined use of both optical and SAR sensors for better assessment of stand biomass with significant contribution towards operational forestry.

  16. Development of land-use regression models for metals associated with airborne particulate matter in a North American city

    NASA Astrophysics Data System (ADS)

    Zhang, Joyce J. Y.; Sun, Liu; Barrett, Olesya; Bertazzon, Stefania; Underwood, Fox E.; Johnson, Markey

    2015-04-01

    Airborne particulate matter has been associated with cardiovascular and respiratory morbidity and mortality, and there is evidence that metals may contribute to these adverse health effects. However, there are few tools for assessing exposure to airborne metals. Land-use regression modeling has been widely used to estimate exposure to gaseous pollutants. This study developed seasonal land-use regression (LUR) models to characterize the spatial distribution of trace metals and other elements associated with airborne particulate matter in Calgary, Alberta. Two-week integrated measurements of particulate matter with <1.0 μm in aerodynamic diameter (PM1.0) were collected in the City of Calgary at 25 sites in August 2010 and 29 sites in January 2011. PM1.0 filters were analyzed using inductively-coupled plasma mass spectrometry. Industrial sources were obtained through the National Pollutant Release Inventory and their locations verified using Google Maps. Traffic volume data were obtained from the City of Calgary and zoning data were obtained from Desktop Mapping Technologies Incorporated. Seasonal wind direction was incorporated using wind rose shapes produced by Wind Rose PRO3, and predictor variables were generated using ArcMap-10.1. Summer and winter LUR models for 30 PM1.0 components were developed using SAS 9.2. We observed significant intra-urban gradients for metals associated with airborne particulate matter in Calgary, Alberta. LUR models explained a high proportion of the spatial variability in those PM1.0 components. Summer models performed slightly better than winter models. However, 24 of the 30 PM1.0 related elements had models that were either good (R2 > 0.70) or acceptable (R2 > 0.50) in both seasons. Industrial point-sources were the most influential predictor for the majority of PM1.0 components. Industrial and commercial zoning were also significant predictors, while traffic indicators and population density had a modest but significant

  17. Development of a Likelihood of Survival Scoring System for Hospitalized Equine Neonates Using Generalized Boosted Regression Modeling

    PubMed Central

    Dembek, Katarzyna A.; Hurcombe, Samuel D.; Frazer, Michele L.; Morresey, Peter R.; Toribio, Ramiro E.

    2014-01-01

    Background Medical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission. Methods and Results Data from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively. Conclusions The survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed. PMID:25295600

  18. Multivariate Regression with Calibration*

    PubMed Central

    Liu, Han; Wang, Lie; Zhao, Tuo

    2014-01-01

    We propose a new method named calibrated multivariate regression (CMR) for fitting high dimensional multivariate regression models. Compared to existing methods, CMR calibrates the regularization for each regression task with respect to its noise level so that it is simultaneously tuning insensitive and achieves an improved finite-sample performance. Computationally, we develop an efficient smoothed proximal gradient algorithm which has a worst-case iteration complexity O(1/ε), where ε is a pre-specified numerical accuracy. Theoretically, we prove that CMR achieves the optimal rate of convergence in parameter estimation. We illustrate the usefulness of CMR by thorough numerical simulations and show that CMR consistently outperforms other high dimensional multivariate regression methods. We also apply CMR on a brain activity prediction problem and find that CMR is as competitive as the handcrafted model created by human experts. PMID:25620861

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

  1. Time windows matter in ADHD-related developing neuropsychological basic deficits: A comprehensive review and meta-regression analysis.

    PubMed

    Pauli-Pott, Ursula; Becker, Katja

    2015-08-01

    Normative development of neuropsychological functions that are assumed to underlie attention deficit/hyperactivity disorder (ADHD) may show transition periods, i.e., periods of heightened developmental discontinuity and reduced differential continuity. During such periods differences between ADHD cases and controls in these functions might be obscured because assessments probably not only reflect individual differences in the ADHD-related deviation but also individual differences in speed/onset of the transition. Our review focuses on executive inhibitory control (IC) and delay aversion/discounting (DA) because normative developmental processes of these characteristics are relatively well described. For complex IC performance a transition period can be assumed in preschool years, for DA around puberty. Published meta-analyses on neuropsychological IC tasks and a meta-regression analysis of 23 case-control comparisons in DA tasks comprising 1395 individuals with ADHD and 1195 controls confirmed our assumption. Effect sizes of case-control comparisons were significantly larger outside transition periods, i.e., in age-periods of relative developmental continuity. An increasingly precise identification of such time windows could contribute to the understanding of the etiological pathways of ADHD. PMID:25956255

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

    PubMed Central

    Krawczyk, Michal; Emerson, Beverly M

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Development and transferability of a nitrogen dioxide land use regression model within the Veneto region of Italy

    NASA Astrophysics Data System (ADS)

    Marcon, Alessandro; de Hoogh, Kees; Gulliver, John; Beelen, Rob; Hansell, Anna L.

    2015-12-01

    When measurements or other exposure models are unavailable, air pollution concentrations could be estimated by transferring land-use regression (LUR) models from other areas. No studies have looked at transferability of LUR models from regions to cities. We investigated model transferability issues. We developed a LUR model for 2010 using annual average nitrogen dioxide (NO2) concentrations retrieved from 47 regulatory stations of the Veneto region, Northern Italy. We applied this model to 40 independent sites in Verona, a city inside the region, where NO2 had been monitored in the European Study of Cohorts for Air Pollution Effects (ESCAPE) during 2010. We also used this model to estimate average NO2 concentrations at the regulatory network in 2008, 2009 and 2011. Of 33 predictor variables offered, five were retained in the LUR model (R2 = 0.75). The number of buildings in 5000 m buffers, industry surface area in 1000 m buffers and altitude, mainly representing large-scale air pollution dispersion patterns, explained most of the spatial variability in NO2 concentrations (R2 = 0.68), while two local traffic proxy indicators explained little of the variability (R2 = 0.07). The performance of this model transferred to urban sites was poor overall (R2 = 0.18), but it improved when only predicting inner-city background concentrations (R2 = 0.52). Recalibration of LUR coefficients improved model performance when predicting NO2 concentrations at the regulatory sites in 2008, 2009 and 2011 (R2 between 0.67 and 0.80). Models developed for a region using NO2 regulatory data are unable to capture small-scale variability in NO2 concentrations in urban traffic areas. Our study documents limitations in transferring a regional model to a city, even if it is nested within that region.

  5. Development of fuzzy system and nonlinear regression models for ozone and PM2.5 air quality forecasts

    NASA Astrophysics Data System (ADS)

    Lin, Yiqiu

    2007-12-01

    Ozone forecast models using nonlinear regression (NLR) have been successfully applied to daily ozone forecast for seven metro areas in Kentucky, including Ashland, Bowling Green, Covington, Lexington, Louisville, Owensboro, and Paducah. In this study, the updated 2005 NLR ozone forecast models for these metro areas were evaluated on both the calibration data sets and independent data sets. These NLR ozone forecast models explained at least 72% of the variance of the daily peak ozone. Using the models to predict the ozone concentrations during the 2005 ozone season, the metro area mean absolute errors (MAEs) of the model hindcasts ranged from 5.90 ppb to 7.20 ppb. For the model raw forecasts, the metro area MAEs ranged from 7.90 ppb to 9.80 ppb. Based on previously developed NLR ozone forecast models for those areas, Takagi-Sugeno fuzzy system models were developed for the seven metro areas. The fuzzy "c-means" clustering technique coupled with an optimal output predefuzzification approach (least square method) was used to train the Takagi-Sugeno fuzzy system. Two types of fuzzy models, basic fuzzy and NLR-fuzzy system models, were developed. The basic fuzzy and NLR-fuzzy models exhibited essentially equivalent performance to the existing NLR models on 2004 ozone season hindcasts and forecasts. Both types of fuzzy models had, on average, slightly lower metro area averaged MAEs than the NLR models. Among the seven Kentucky metro areas Ashland, Covington, and Louisville are currently designated nonattainment areas for both ground level O 3 and PM2.5. In this study, summer PM2.5 forecast models were developed for providing daily average PM2.5 forecasts for the seven metro areas. The performance of the PM2.5 forecast models was generally not as good as that of the ozone forecast models. For the summer 2004 model hindcasts, the metro-area average MAE was 5.33 mug/m 3. Exploratory research was conducted to find the relationship between the winter PM2.5 concentrations and

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

    PubMed

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

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer. PMID:26193871

  7. Interaction of the renin angiotensin and cox systems in the kidney.

    PubMed

    Quadri, Syed S; Culver, Silas A; Li, Caixia; Siragy, Helmy M

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in mediating actions of the renin-angiotensin system (RAS). This review sheds light on the recent developments regarding the complex interactions between components of RAS and COX-2; and their implications on renal function and disease. COX-2 is believed to counter regulate the effects of RAS activation and therefore counter balance the vasoconstriction effect of Ang II. In kidney, under normal conditions, these systems are essential for maintaining a balance between vasodilation and vasoconstriction. However, recent studies suggested a pivotal role for this interplay in pathology. COX-2 increases the renin release and Ang II formation leading to increase in blood pressure. COX-2 is also associated with diabetic nephropathy, where its upregulation in the kidney contributes to glomerular injury and albuminuria. Selective inhibition of COX-2 retards the progression of renal injury. COX-2 also mediates the pathologic effects of the (Pro)renin receptor (PRR) in the kidney. In summary, this review discusses the interaction between the RAS and COX-2 in health and disease. PMID:27100703

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

    PubMed

    Spiegelman, D; McDermott, A; Rosner, B

    1997-04-01

    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

  9. Developing a Referral Protocol for Community-Based Occupational Therapy Services in Taiwan: A Logistic Regression Analysis

    PubMed Central

    Chang, Ling-Hui; Tsai, Athena Yi-Jung; Huang, Wen-Ni

    2016-01-01

    Because resources for long-term care services are limited, timely and appropriate referral for rehabilitation services is critical for optimizing clients’ functions and successfully integrating them into the community. We investigated which client characteristics are most relevant in predicting Taiwan’s community-based occupational therapy (OT) service referral based on experts’ beliefs. Data were collected in face-to-face interviews using the Multidimensional Assessment Instrument (MDAI). Community-dwelling participants (n = 221) ≥ 18 years old who reported disabilities in the previous National Survey of Long-term Care Needs in Taiwan were enrolled. The standard for referral was the judgment and agreement of two experienced occupational therapists who reviewed the results of the MDAI. Logistic regressions and Generalized Additive Models were used for analysis. Two predictive models were proposed, one using basic activities of daily living (BADLs) and one using instrumental ADLs (IADLs). Dementia, psychiatric disorders, cognitive impairment, joint range-of-motion limitations, fear of falling, behavioral or emotional problems, expressive deficits (in the BADL-based model), and limitations in IADLs or BADLs were significantly correlated with the need for referral. Both models showed high area under the curve (AUC) values on receiver operating curve testing (AUC = 0.977 and 0.972, respectively). The probability of being referred for community OT services was calculated using the referral algorithm. The referral protocol facilitated communication between healthcare professionals to make appropriate decisions for OT referrals. The methods and findings should be useful for developing referral protocols for other long-term care services. PMID:26863544

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

    PubMed Central

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

    2013-01-01

    Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are reported to suppress carcinogenesis by targeting COX-2. A major question was accordingly raised: why has the lifelong use of phytochemicals that likely inhibit COX-2 presumably not been associated with adverse cardiovascular side effects. To answer this question, we selected a library of dietary-derived phytochemicals and evaluated their potential cardiovascular toxicity in human umbilical vein endothelial cells. Our data indicated that the possibility of cardiovascular toxicity of these dietary phytochemicals was low. Further mechanistic studies revealed that the actions of these phytochemicals were similar to aspirin in that they mainly inhibited COX-1 rather than COX-2, especially at low doses. PMID:24098505

  11. Regression: A Bibliography.

    ERIC Educational Resources Information Center

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

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

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

    PubMed

    Huang, Jian; Zhang, Di; Xie, Fuqiang; Lin, Degui

    2015-01-01

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

  13. The Contribution of Schooling to the Cognitive Development of Secondary Education Students in Cyprus: An Application of Regression Discontinuity with Multiple Cut-Off Points

    ERIC Educational Resources Information Center

    Kyriakides, Leonidas; Luyten, Hans

    2009-01-01

    This article reports the results of a study in which the basic regression-discontinuity approach to assess the effect of 1 year of schooling is extended. The data analysis covers the 6 grades of secondary education in Cyprus and thus assesses the contribution of secondary education to the cognitive development of 12- to 18-year-old students. A…

  14. Suppression mechanisms of COX assembly defects in yeast and human: Insights into the COX assembly process

    PubMed Central

    Barrientos, Antoni; Gouget, Karine; Horn, Darryl; Soto, Ileana C.; Fontanesi, Flavia

    2008-01-01

    Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin whose assembly is intricate and highly regulated. In addition to the structural subunits, a large number of accessory factors are required to build the holoenzyme. The function of these factors is required in all stages of the assembly process. They are relevant to human health because devastating human disorders have been associated with mutations in nuclear genes encoding conserved COX assembly factors. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to attain the current state of knowledge, even if still fragmentary, of the COX assembly process. After the identification of the genes involved, the isolation and characterization of genetic and metabolic suppressors of COX assembly defects, reviewed here, have become a profitable strategy to gain insight into their functions and the pathways in which they operate. Additionally, they have the potential to provide useful information for devising therapeutic approaches to combat human disorders associated with COX deficiency. PMID:18522805

  15. Oxidative switches in functioning of mammalian copper chaperone Cox17

    PubMed Central

    Voronova, Anastassia; Meyer-Klaucke, Wolfram; Meyer, Thomas; Rompel, Annette; Krebs, Bernt; Kazantseva, Jekaterina; Sillard, Rannar; Palumaa, Peep

    2007-01-01

    Cox17, a copper chaperone for cytochrome-c oxidase, is an essential and highly conserved protein in eukaryotic organisms. Yeast and mammalian Cox17 share six conserved cysteine residues, which are involved in complex redox reactions as well as in metal binding and transfer. Mammalian Cox17 exists in three oxidative states, each characterized by distinct metal-binding properties: fully reduced mammalian Cox170S–S binds co-operatively to four Cu+; Cox172S–S, with two disulfide bridges, binds to one of either Cu+ or Zn2+; and Cox173S–S, with three disulfide bridges, does not bind to any metal ions. The Em (midpoint redox potential) values for two redox couples of Cox17, Cox173S–S↔Cox172S–S (Em1) and Cox172S–S↔Cox170S–S (Em2), were determined to be −197 mV and −340 mV respectively. The data indicate that an equilibrium exists in the cytosol between Cox170S-S and Cox172S–S, which is slightly shifted towards Cox170S-S. In the IMS (mitochondrial intermembrane space), the equilibrium is shifted towards Cox172S–S, enabling retention of Cox172S–S in the IMS and leading to the formation of a biologically competent form of the Cox17 protein, Cox172S–S, capable of copper transfer to the copper chaperone Sco1. XAS (X-ray absorption spectroscopy) determined that Cu4Cox17 contains a Cu4S6-type copper–thiolate cluster, which may provide safe storage of an excess of copper ions. PMID:17672825

  16. Partial covariate adjusted regression

    PubMed Central

    Şentürk, Damla; Nguyen, Danh V.

    2008-01-01

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

  17. A new statistical modeling and optimization framework for establishing high-resolution PM10 emission inventory - I. Stepwise regression model development and application

    NASA Astrophysics Data System (ADS)

    Cheng, Shuiyuan; Zhou, Ying; Li, Jianbing; Lang, Jianlei; Wang, Haiyan

    2012-12-01

    A new stepwise regression method was proposed in this study to develop a high-resolution emission inventory. Utilizing PM10 emission inventory as an example, a group of regression models for various industrial and non-industrial sectors were developed based on an emission case study of Handan region in northern China. The main data requirements of the regression models for industrial sectors were coal consumption, electricity consumption, other solid fuel consumption, and annual operating cost of exhaust gas control devices. The data requirements for non-industrial sector emission estimations were the area of construction sites, the length of transportation routes, the vehicle population, and the cultivated land area. The models were then applied to Tangshan region in northern China, and the results revealed that the developed regression models had relatively satisfactory performance. Modeling error at the regional level and county level was 17.0% and 30.4%, respectively. The regression models were also applied to other regions in northern China. The results indicated that the new method could generate emission estimations with significantly lower error than found in previous emission inventory studies. The modeling uncertainty due to the allocation of modeling input parameter value, from regional level to county level, was also discussed in this study. It was concluded that the new statistical method presented is a promising technique for the development and updating of high-resolution emission inventories based on easily obtained statistical data. It can be performed with data available from the current statistical reporting system in China. It does not require a detailed data investigation and survey, as is necessary by conventional “bottom-up” emission inventory investigation approach.

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2010-12-01

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

  1. Linear regression in astronomy. II

    NASA Technical Reports Server (NTRS)

    Feigelson, Eric D.; Babu, Gutti J.

    1992-01-01

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

  2. Quantile regression for climate data

    NASA Astrophysics Data System (ADS)

    Marasinghe, Dilhani Shalika

    Quantile regression is a developing statistical tool which is used to explain the relationship between response and predictor variables. This thesis describes two examples of climatology using quantile regression.Our main goal is to estimate derivatives of a conditional mean and/or conditional quantile function. We introduce a method to handle autocorrelation in the framework of quantile regression and used it with the temperature data. Also we explain some properties of the tornado data which is non-normally distributed. Even though quantile regression provides a more comprehensive view, when talking about residuals with the normality and the constant variance assumption, we would prefer least square regression for our temperature analysis. When dealing with the non-normality and non constant variance assumption, quantile regression is a better candidate for the estimation of the derivative.

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

    SciTech Connect

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

    1982-09-01

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

  4. Precision Efficacy Analysis for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.

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

  5. Golgi-Cox Staining Step by Step

    PubMed Central

    Zaqout, Sami; Kaindl, Angela M.

    2016-01-01

    Golgi staining remains a key method to study neuronal morphology in vivo. Since most protocols delineating modifications of the original staining method lack details on critical steps, establishing this method in a laboratory can be time-consuming and frustrating. Here, we describe the Golgi-Cox staining in such detail that should turn the staining into an easily feasible method for all scientists working in the neuroscience field. PMID:27065817

  6. Ridge Regression Signal Processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

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

  7. Fast Censored Linear Regression

    PubMed Central

    HUANG, YIJIAN

    2013-01-01

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

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

    PubMed

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

    2015-11-01

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

  9. Splines for Diffeomorphic Image Regression

    PubMed Central

    Singh, Nikhil; Niethammer, Marc

    2016-01-01

    This paper develops a method for splines on diffeomorphisms for image regression. In contrast to previously proposed methods to capture image changes over time, such as geodesic regression, the method can capture more complex spatio-temporal deformations. In particular, it is a first step towards capturing periodic motions for example of the heart or the lung. Starting from a variational formulation of splines the proposed approach allows for the use of temporal control points to control spline behavior. This necessitates the development of a shooting formulation for splines. Experimental results are shown for synthetic and real data. The performance of the method is compared to geodesic regression. PMID:25485370

  10. Fungible weights in logistic regression.

    PubMed

    Jones, Jeff A; Waller, Niels G

    2016-06-01

    In this article we develop methods for assessing parameter sensitivity in logistic regression models. To set the stage for this work, we first review Waller's (2008) equations for computing fungible weights in linear regression. Next, we describe 2 methods for computing fungible weights in logistic regression. To demonstrate the utility of these methods, we compute fungible logistic regression weights using data from the Centers for Disease Control and Prevention's (2010) Youth Risk Behavior Surveillance Survey, and we illustrate how these alternate weights can be used to evaluate parameter sensitivity. To make our work accessible to the research community, we provide R code (R Core Team, 2015) that will generate both kinds of fungible logistic regression weights. (PsycINFO Database Record PMID:26651981

  11. Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.

    PubMed

    Rossmeisl, J H; Robertson, J L; Zimmerman, K L; Higgins, M A; Geiger, D A

    2009-09-01

    Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis. PMID:19691646

  12. Validation of a heteroscedastic hazards regression model.

    PubMed

    Wu, Hong-Dar Isaac; Hsieh, Fushing; Chen, Chen-Hsin

    2002-03-01

    A Cox-type regression model accommodating heteroscedasticity, with a power factor of the baseline cumulative hazard, is investigated for analyzing data with crossing hazards behavior. Since the approach of partial likelihood cannot eliminate the baseline hazard, an overidentified estimating equation (OEE) approach is introduced in the estimation procedure. It by-product, a model checking statistic, is presented to test for the overall adequacy of the heteroscedastic model. Further, under the heteroscedastic model setting, we propose two statistics to test the proportional hazards assumption. Implementation of this model is illustrated in a data analysis of a cancer clinical trial. PMID:11878222

  13. Development of a regression model to predict copper toxicity to Daphnia magna and site-specific copper criteria across multiple surface-water drainages in an arid landscape.

    PubMed

    Fulton, Barry A; Meyer, Joseph S

    2014-08-01

    The water effect ratio (WER) procedure developed by the US Environmental Protection Agency is commonly used to derive site-specific criteria for point-source metal discharges into perennial waters. However, experience is limited with this method in the ephemeral and intermittent systems typical of arid climates. The present study presents a regression model to develop WER-based site-specific criteria for a network of ephemeral and intermittent streams influenced by nonpoint sources of Cu in the southwestern United States. Acute (48-h) Cu toxicity tests were performed concurrently with Daphnia magna in site water samples and hardness-matched laboratory waters. Median effect concentrations (EC50s) for Cu in site water samples (n=17) varied by more than 12-fold, and the range of calculated WER values was similar. Statistically significant (α=0.05) univariate predictors of site-specific Cu toxicity included (in sequence of decreasing significance) dissolved organic carbon (DOC), hardness/alkalinity ratio, alkalinity, K, and total dissolved solids. A multiple-regression model developed from a combination of DOC and alkalinity explained 85% of the toxicity variability in site water samples, providing a strong predictive tool that can be used in the WER framework when site-specific criteria values are derived. The biotic ligand model (BLM) underpredicted toxicity in site waters by more than 2-fold. Adjustments to the default BLM parameters improved the model's performance but did not provide a better predictive tool compared with the regression model developed from DOC and alkalinity. PMID:24796294

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    SciTech Connect

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

    2006-09-10

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

  17. Multiple linear regression.

    PubMed

    Eberly, Lynn E

    2007-01-01

    This chapter describes multiple linear regression, a statistical approach used to describe the simultaneous associations of several variables with one continuous outcome. Important steps in using this approach include estimation and inference, variable selection in model building, and assessing model fit. The special cases of regression with interactions among the variables, polynomial regression, regressions with categorical (grouping) variables, and separate slopes models are also covered. Examples in microbiology are used throughout. PMID:18450050

  18. Incremental hierarchical discriminant regression.

    PubMed

    Weng, Juyang; Hwang, Wey-Shiuan

    2007-03-01

    This paper presents incremental hierarchical discriminant regression (IHDR) which incrementally builds a decision tree or regression tree for very high-dimensional regression or decision spaces by an online, real-time learning system. Biologically motivated, it is an approximate computational model for automatic development of associative cortex, with both bottom-up sensory inputs and top-down motor projections. At each internal node of the IHDR tree, information in the output space is used to automatically derive the local subspace spanned by the most discriminating features. Embedded in the tree is a hierarchical probability distribution model used to prune very unlikely cases during the search. The number of parameters in the coarse-to-fine approximation is dynamic and data-driven, enabling the IHDR tree to automatically fit data with unknown distribution shapes (thus, it is difficult to select the number of parameters up front). The IHDR tree dynamically assigns long-term memory to avoid the loss-of-memory problem typical with a global-fitting learning algorithm for neural networks. A major challenge for an incrementally built tree is that the number of samples varies arbitrarily during the construction process. An incrementally updated probability model, called sample-size-dependent negative-log-likelihood (SDNLL) metric is used to deal with large sample-size cases, small sample-size cases, and unbalanced sample-size cases, measured among different internal nodes of the IHDR tree. We report experimental results for four types of data: synthetic data to visualize the behavior of the algorithms, large face image data, continuous video stream from robot navigation, and publicly available data sets that use human defined features. PMID:17385628

  19. Development and implementation of a regression model for predicting recreational water quality in the Cuyahoga River, Cuyahoga Valley National Park, Ohio 2009-11

    USGS Publications Warehouse

    Brady, Amie M.G.; Plona, Meg B.

    2012-01-01

    The Cuyahoga River within Cuyahoga Valley National Park (CVNP) is at times impaired for recreational use due to elevated concentrations of Escherichia coli (E. coli), a fecal-indicator bacterium. During the recreational seasons of mid-May through September during 2009–11, samples were collected 4 days per week and analyzed for E. coli concentrations at two sites within CVNP. Other water-quality and environ-mental data, including turbidity, rainfall, and streamflow, were measured and (or) tabulated for analysis. Regression models developed to predict recreational water quality in the river were implemented during the recreational seasons of 2009–11 for one site within CVNP–Jaite. For the 2009 and 2010 seasons, the regression models were better at predicting exceedances of Ohio's single-sample standard for primary-contact recreation compared to the traditional method of using the previous day's E. coli concentration. During 2009, the regression model was based on data collected during 2005 through 2008, excluding available 2004 data. The resulting model for 2009 did not perform as well as expected (based on the calibration data set) and tended to overestimate concentrations (correct responses at 69 percent). During 2010, the regression model was based on data collected during 2004 through 2009, including all of the available data. The 2010 model performed well, correctly predicting 89 percent of the samples above or below the single-sample standard, even though the predictions tended to be lower than actual sample concentrations. During 2011, the regression model was based on data collected during 2004 through 2010 and tended to overestimate concentrations. The 2011 model did not perform as well as the traditional method or as expected, based on the calibration dataset (correct responses at 56 percent). At a second site—Lock 29, approximately 5 river miles upstream from Jaite, a regression model based on data collected at the site during the recreational

  20. NCCS Regression Test Harness

    Energy Science and Technology Software Center (ESTSC)

    2015-09-09

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

  1. Orthogonal Regression and Equivariance.

    ERIC Educational Resources Information Center

    Blankmeyer, Eric

    Ordinary least-squares regression treats the variables asymmetrically, designating a dependent variable and one or more independent variables. When it is not obvious how to make this distinction, a researcher may prefer to use orthogonal regression, which treats the variables symmetrically. However, the usual procedure for orthogonal regression is…

  2. Unitary Response Regression Models

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    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…

  3. A regression model for the temporal development of soil pipes and associated gullies in the alluvial-fill valley of the Rio Puerco, central New Mexico

    NASA Technical Reports Server (NTRS)

    Condit, C. D.; Elston, W. E.

    1984-01-01

    On Mars, the association of gullied escarpments and chaotic terrain is evidence for failure and scarp retreat of poorly consolidated materials. Some martian gullies have no surface outlets and may have drained through subterranean channels. Similar features, though on a much smaller scale, can be seen in alluvium along terrestrial river banks in semiarid regions, such as the Rio Puerco Valley of central New Mexico. Many of the escarpments along the Rio Puerco are developing through formation of collapse gullies, which drain through soil pipes. Gully development can be monitored on aerial photographs taken in 1935, 1962, and 1980. A regression model was developed to quantify gully evolution over a known time span. Soil pipes and their associated collapse gullies make recognizable signatures on the air photos. The areal extent of this signature can be normalized to the scarp length of each pipe-gully system, which makes comparisons between systems possible.

  4. COX-2-Specific inhibitors--the emergence of a new class of analgesic and anti-inflammatory drugs.

    PubMed

    Everts, B; Währborg, P; Hedner, T

    2000-01-01

    The prostaglandin series of bioactive compounds is formed by the interaction of two distinct but related enzymes, cyclo-oxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutive form which is present mainly in the gastric mucosa, kidney and platelets. COX-2 is mainly an inducible form, although also to some extent present constitutively in the CNS, the juxtaglomerular apparatus of the kidney and in the placenta during late gestation. Both isoforms contribute to the inflammatory process, but COX-2 is of considerable therapeutic interest as it is induced, resulting in an enhanced formation of prostaglandins, during acute as well as chronic inflammation. Conventional NSAIDs inhibit both isoforms to a similar extent and in an approximately equal dose and concentration range. The two recently developed and clinically available selective COX-2 inhibitors, celecoxib and rofecoxib, are about 100-1000 times more selective on the COX-2 than on the COX-1 isoform. In Europe rofecoxib is today indicated for the symptoms and signs of osteoarthritis, whereas celecoxib is indicated for both osteoarthritis and rheumatoid arthritis. The major clinical interest of these drugs has been related to the lower incidence of gastrointestinal bleeding which, with the conventional COX-1/COX-2 agents has been a source of hospitalisation, disablement and death, especially in the elderly. Clinical trials have convincingly demonstrated that celecoxib and rofecoxib in clinical use induce very few gastrointestinal complications compared to conventional and non-selective NSAIDs. However, the well known contraindications for NSAIDs, such as late pregnancy, aspirin-induced asthma, congestive heart failure and renal dysfunction, will so far apply also to the COX-2 inhibitors. Compared to the traditional and non-selective NSAIDs, COX-2 inhibitors may provide an insight into additional therapeutic areas, such as gastrointestinal cancer and dementia, where the potential relevance to COX-2

  5. Developing Street-Level PM2.5 and PM10 Land Use Regression Models in High-Density Hong Kong with Urban Morphological Factors.

    PubMed

    Shi, Yuan; Lau, Kevin Ka-Lun; Ng, Edward

    2016-08-01

    Monitoring street-level particulates is essential to air quality management but challenging in high-density Hong Kong due to limitations in local monitoring network and the complexities of street environment. By employing vehicle-based mobile measurements, land use regression (LUR) models were developed to estimate the spatial variation of PM2.5 and PM10 in the downtown area of Hong Kong. Sampling runs were conducted along routes measuring a total of 30 km during a selected measurement period of total 14 days. In total, 321 independent variables were examined to develop LUR models by using stepwise regression with PM2.5 and PM10 as dependent variables. Approximately, 10% increases in the model adjusted R(2) were achieved by integrating urban/building morphology as independent variables into the LUR models. Resultant LUR models show that the most decisive factors on street-level air quality in Hong Kong are frontal area index, an urban/building morphological parameter, and road network line density and traffic volume, two parameters of road traffic. The adjusted R(2) of the final LUR models of PM2.5 and PM10 are 0.633 and 0.707, respectively. These results indicate that urban morphology is more decisive to the street-level air quality in high-density cities than other cities. Air pollution hotspots were also identified based on the LUR mapping. PMID:27381187

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

    PubMed Central

    Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2009-12-15

    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

  9. Decidual Cox2 inhibition improves fetal and maternal outcomes in a preeclampsia-like mouse model

    PubMed Central

    Woods, Ashley K.; Bartos, Amanda; Heyward, Christa Y.; Lob, Heinrich E.; Isroff, Catherine E.; Butler, Scott D.; Shapiro, Stephanie E.; Dey, Sudhansu K.; Davisson, Robin L.

    2016-01-01

    Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse “ripple effects,” leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction. The precise mechanism(s) of implantation defects that lead to PE remain elusive. BPH/5 mice, which spontaneously develop the cardinal features of PE, show peri-implantation defects including upregulation of Cox2 and IL-15 at the maternal-fetal interface. This was associated with decreased decidual natural killer (dNK) cells, which have important roles in establishing placental perfusion. Interestingly, a single administration of a Cox2 inhibitor (celecoxib) during decidualization restrained Cox2 and IL-15 expression, restored dNK cell numbers, improved fetal growth, and attenuated late gestational hypertension in BPH/5 female mice. This study provides evidence that decidual overexpression of Cox2 and IL-15 may trigger the adverse pregnancy outcomes reflected in the preeclamptic syndrome, underscoring the idea that Cox2 inhibitor treatment is an effective strategy for the prevention of PE-associated fetal and maternal morbidity and mortality. PMID:27159542

  10. Image transformation into device-dependent color printer description using 4th-order polynomial regression and object-oriented programming development of image processing modules

    NASA Astrophysics Data System (ADS)

    Mongeon, Michael C.

    1996-03-01

    This paper investigates the development of printer device profiles used in color document printing system environments when devices with intrinsically different gamut capabilities communicate with one another in a common (CIELAB) color space. While the main thrust of this activity focuses on the output printer, namely the Xerox 5760 printer, and its rendition of some device independent image description, characterizations are provided which investigate relative areas of photographic, monitor, and printer gamuts using a visual hue leaf comparison between devices. The printer is modeled using 4th-order polynomial regression which maps the device independent CIELAB image representation into device dependent printer CMYK. This technique results in 1.89 AEEavg over the training data set. Some key properties of the proposed calibration method are as follows: (1) Linearized CMYK tone reproduction curves with respect to AEEpaper to improve the distribution of calibration data in color space. (2) Application of GCR strategy and linearization to the calibration target prior to the regression on the measured CIELAB and original CMY values. Each strategy employs a K addition/No CMY removal method which maximizes printer gamut and relies on the regression to determine the appropriate CMY removal. The following GCR strategies are explored: CMY only (0% K addition), 50% K addition, 100% K addition, and non-linear K addition. A library of image processing algorithms is included, using LabView object oriented programming, which provides a modular approach for key color processing tasks. In the user interface, an image is selected with appropriate GCR strategy, and the program operates on the image. In general, the pictorial image quality is excellent for each GCR strategy with subtle differences between GCR approaches. Quantitative analysis of Q60 color matching performance is included.

  11. Time-Warped Geodesic Regression

    PubMed Central

    Hong, Yi; Singh, Nikhil; Kwitt, Roland; Niethammer, Marc

    2016-01-01

    We consider geodesic regression with parametric time-warps. This allows, for example, to capture saturation effects as typically observed during brain development or degeneration. While highly-flexible models to analyze time-varying image and shape data based on generalizations of splines and polynomials have been proposed recently, they come at the cost of substantially more complex inference. Our focus in this paper is therefore to keep the model and its inference as simple as possible while allowing to capture expected biological variation. We demonstrate that by augmenting geodesic regression with parametric time-warp functions, we can achieve comparable flexibility to more complex models while retaining model simplicity. In addition, the time-warp parameters provide useful information of underlying anatomical changes as demonstrated for the analysis of corpora callosa and rat calvariae. We exemplify our strategy for shape regression on the Grassmann manifold, but note that the method is generally applicable for time-warped geodesic regression. PMID:25485368

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

    PubMed Central

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

    2015-01-01

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

  13. The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal Neovascularization and Subretinal Fibrosis

    PubMed Central

    Zhang, Ruoshuang; Liu, Zheli; Zhang, Han; Zhang, Yi; Lin, Dong

    2016-01-01

    Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium–choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-β2 in the retinal pigment epithelium–choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-β2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis. PMID:26760305

  14. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors

    PubMed Central

    Harris, Randall E; Beebe, Joanne; Alshafie, Galal A

    2012-01-01

    We conducted a series of epidemiologic studies to evaluate the chemopreventive effects of aspirin, ibuprofen, and selective cyxlooxygenase-2 (COX-2) inhibitors (coxibs) against cancers of the breast, colon, prostate, and lung. Composite results across all four cancer sites revealed that regular intake of 325 mg aspirin, 200 mg ibuprofen, or standard dosages of coxibs (200 mg celecoxib or 25 mg rofecoxib) produced risk reductions of 49%, 59%, and 64%, respectively. Use of coxibs for at least 2 years was associated with risk reductions of 71%, 70%, 55%, and 60% for breast cancer, colon cancer, prostate cancer and lung cancer, respectively. Effects of ibuprofen were similar to selective coxibs, and slightly stronger than aspirin. These observed effects are consistent with the relative COX-2 selectivity of ibuprofen, coxibs, and aspirin. Acetaminophen, an analgesic without COX-2 activity, had no effect. Overexpression of COX-2 and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. These results indicate that regular intake of nonselective or selective COX-2 inhibiting agents protects against the development of major forms of cancer.

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  18. ``Regressed experts'' as a new state in teachers' professional development: lessons from Computer Science teachers' adjustments to substantial changes in the curriculum

    NASA Astrophysics Data System (ADS)

    Liberman, Neomi; Ben-David Kolikant, Yifat; Beeri, Catriel

    2012-09-01

    Due to a program reform in Israel, experienced CS high-school teachers faced the need to master and teach a new programming paradigm. This situation served as an opportunity to explore the relationship between teachers' content knowledge (CK) and their pedagogical content knowledge (PCK). This article focuses on three case studies, with emphasis on one of them. Using observations and interviews, we examine how the teachers, we observed taught and what development of their teaching occurred as a result of their teaching experience, if at all. Our findings suggest that this situation creates a new hybrid state of teachers, which we term "regressed experts." These teachers incorporate in their professional practice some elements typical of novices and some typical of experts. We also found that these teachers' experience, although established when teaching a different CK, serve as a leverage to improve their knowledge and understanding of aspects of the new content.

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

    COX inhibitors which selectively inhibits the inducible COX-2 is an oenzyme that causes inflammation. They are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicity. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular trombotic events such as myocardial infarction. Therefore, there is still a need to develop better therapeutic effect and tolerability COX-2 inhibitor. The majority of COX-2 inhibitors are diaryl heterocycles. For optimum COX-2 selectivity and inhibitory potency a –SO3CH3 or a- SO2NH2 substituent at the para-position of phenyl ring was essential. A wide variety of heterocycles can serve as central ring system of the diaryl heterocycles structures. We report the screening of various 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety, directly or indirectly bound to the ring system, using the Protein-Ligand ANT System (PLANTS) docking software against the COX-2 enzyme. Various molecular structures of ligands were docked and scored to identify structurally similar ligands to SC-558 (reference ligand) in binding interaction to COX-2 binding site. The results show that 2,3-disubstituted-4(3H)-quinazolinones possess pbenzenesulfonamide moiety at C-2, and phenyl moiety at N-3 binds directly or indirectly to the ring system with high binding affinity. The docked ligand has orientations similar to that observed with SC-558 satisfying Lipinski's rule of five. PMID:22125393

  1. COX-2, mPGES-1 and EP2 receptor immunohistochemical expression in canine and feline malignant mammary tumours.

    PubMed

    Millanta, F; Asproni, P; Canale, A; Citi, S; Poli, A

    2016-09-01

    Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E2 (PGE2 ) tumour-promoting activity has been confirmed and its production is controlled by Cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Evidence suggests that mPGES-1 and COX-2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX-2, mPGES-1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non-neoplastic tissues. COX-2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES-1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX-2, EP2 receptor and mPGES-1 expression was significantly higher in carcinomas than in non-neoplastic tissues and adenomas. COX-2, mPGES-1 and EP2 receptor expression was strongly associated. These findings support a role of the COX-2/PGE2 pathway in the pathogenesis of these tumours. PMID:24824420

  2. Bayesian Spatial Quantile Regression

    PubMed Central

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

    2013-01-01

    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

  3. Bayesian Spatial Quantile Regression.

    PubMed

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

    2011-03-01

    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

  4. Prediction in Multiple Regression.

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2000-01-01

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

  5. Improved Regression Calibration

    ERIC Educational Resources Information Center

    Skrondal, Anders; Kuha, Jouni

    2012-01-01

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

  6. Morse-Smale Regression

    PubMed Central

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

    2012-01-01

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

  7. Morse–Smale Regression

    SciTech Connect

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

    2012-01-19

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduces 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 article 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 overfitting. 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.

  8. The immune tolerance of cancer is mediated by IDO that is inhibited by COX-2 inhibitors through regulatory T cells.

    PubMed

    Lee, Sung Yong; Choi, Hye Kyoung; Lee, Kyoung Ju; Jung, Jin Yong; Hur, Gyu Young; Jung, Ki Hwan; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Yoo, Se Hwa

    2009-01-01

    Prostaglandin (PGE2), synthesized by cyclooxygenase-2 (COX-2), is associated with cellular immune tolerance during the process of cancer development. Induction of tolerance requires a specific environment in which dendritic cells and regulatory T cells (Tregs) play an essential role. It was recently shown that maturation of dendritic cells in the presence of indoleamine 2, 3-dioxygenase (IDO) results in activation of Tregs, and inhibition of COX-2 activity regulated IDO expression within the tumor microenvironment. Thus, we hypothesized that the tumor immune tolerance would be inhibited by COX-2 inhibitor and this inhibition would be mediated by IDO-dependent Tregs inhibition. The PGE2 in Lewis lung cancer cells (3LL) and serum of mice were measured for the evaluation of COX-2 inhibitors' local and systemic effects. The production of PGE2 in 3LL cells and serum of 3LL tumor-bearing mice were decreased by COX-2 inhibition. However, there were no significant differences in serum PGE2 levels among normal control and celecoxib-treated nontumor-bearing mice. The accumulation of Tregs was reduced in the celecoxib-treated 3LL tumor-bearing mice. In addition, the expressions of COX-2, IDO, and Foxp3 were reduced in the mice treated with a COX-2 inhibitor, and this was found to correlate with a reduction in the size of tumor mass and metastasis. These results suggest that the antitumor effects of COX-2 inhibitors seemed to be correlated with the inhibition of IDO and Tregs. Therefore, COX-2 inhibitors might provide a therapeutic strategy for Tregs-induced tumor immune tolerance. PMID:19307990

  9. Development of nitrogen dioxide and volatile organic compounds land use regression models to estimate air pollution exposure near an Italian airport

    NASA Astrophysics Data System (ADS)

    Gaeta, Alessandra; Cattani, Giorgio; Di Menno di Bucchianico, Alessandro; De Santis, Antonella; Cesaroni, Giulia; Badaloni, Chiara; Ancona, Carla; Forastiere, Francesco; Sozzi, Roberto; Bolignano, Andrea; Sacco, Fabrizio

    2016-04-01

    The aim of this study was to evaluate the small scale spatial variability of nitrogen dioxide (NO2) and selected VOCs (benzene, toluene, acrolein and formaldehyde) concentrations using Land Use Regression models (LURs) in a complex multi sources domain (64 km2), containing a mid-size airport: the Ciampino Airport, located in Ciampino, Rome, Italy. 46 diffusion tube samplers were deployed within a domain centred in the airport over two 2-weekly periods (June 2011-January 2012). GIS-derived predictor variables, with varying buffer size, were evaluated to model spatial variation of NO2, benzene, toluene, formaldehyde and acrolein annual average concentrations. The airport apportionment to air quality was investigated using a Lagrangian dispersion model (SPRAY). A stepwise selection procedure was used to develop the linear regression models. The models were validated using leave one out cross validation (LOOCV) method. In this study, the use of LURs was found to be effective to explain spatial variability of NO2 (adjusted-R2 = 0.72), benzene (adjusted-R2 = 0.53), toluene (adjusted-R2 = 0.50) and acrolein (adjusted-R2 = 0.51), while limited power was achieved with the formaldehyde modeling (adjusted-R2 = 0.24). For all pollutants LURs output showed that the small scale spatial variability was mainly explained by local traffic. The airport contribution to the observed spatial variability was adequately quantified only for acrolein (0.43 (±0.69) μg/m3 in an area of about 6 km2, SW located to the airport runway), while for NO2 and formaldehyde, only a little portion of the spatial variability in a limited portion of the study domain was attributable to airport related emissions.

  10. The Effect of Cadmium on COX-1 and COX-2 Gene, Protein Expression, and Enzymatic Activity in THP-1 Macrophages.

    PubMed

    Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Piotrowska, Katarzyna; Korbecki, Jan; Kurzawski, Mateusz; Chlubek, Dariusz

    2015-06-01

    The aim of this study was to examine the effects of cadmium in concentrations relevant to those detected in human serum on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression at mRNA, protein, and enzyme activity levels in THP-1 macrophages. Macrophages were incubated with various cadmium chloride (CdCl2) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl2. The mRNA expression and protein levels of COXs were analyzed with RT-PCR and Western blotting, respectively. Prostaglandin E2 (PGE2) and stable metabolite of thromboxane B2 (TXB2) concentrations in culture media were determined using ELISA method. Our study demonstrates that cadmium at the highest tested concentrations modulates COX-1 and COX-2 at mRNA level in THP-1 macrophages; however, the lower tested cadmium concentrations appear to inhibit COX-1 protein expression. PGE2 and TXB2 production is not altered by all tested Cd concentrations; however, the significant stimulation of PGE2 and TXB2 production is observed when macrophages are exposed to both cadmium and COX-2 selective inhibitor, NS-398. The stimulatory effect of cadmium on COXs at mRNA level is not reflected at protein and enzymatic activity levels, suggesting the existence of some posttranscriptional, translational, and posttranslational events that result in silencing of those genes' expression. PMID:25645360

  11. Severe Systolic Anterior Motion After Aortic Valve Replacement and Cox MAZE Surgery.

    PubMed

    den Uil, Corstiaan A; Ter Horst, Maarten; Akin, Sakir; Galema, Tjebbe W

    2016-07-01

    Surgical aortic valve replacement may be complicated by severe dynamic left ventricular outflow tract obstruction and cardiogenic shock in the postoperative period. We present a patient who developed severe anterior motion following aortic valve and Cox MAZE surgery which necessitated a mitral valve replacement. doi: 10.1111/jocs.12763 (J Card Surg 2016;31:429-431). PMID:27212634

  12. Box-Cox Mixed Logit Model for Travel Behavior Analysis

    NASA Astrophysics Data System (ADS)

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

    2010-09-01

    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.

  13. TCDD Induced Pericardial Edema and Relative COX-2 Expression in Medaka (Oryzias Latipes) Embryos

    PubMed Central

    Dong, Wu; Matsumura, Fumio; Kullman, Seth W.

    2010-01-01

    Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in multiple, specific developmental cardiovascular phenotypes including pericardial edema and circulatory failure in small aquarium fish models. Although phenotypes are well described, mechanistic underpinnings for such toxicities remain elusive. Here we suggest that AhR activation results in stimulation of inflammation and “eicosanoid” pathways, which contribute to the observed developmental, cardiovascular phenotypes. We demonstrate that medaka embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.05–1 ppb) during early development result in a dose-related increase in the prevalence of pericardial edema and that this phenotype correlates with an increase in cyclooxygenase-2 (COX-2) gene expression. Those individuals exhibiting the edema phenotype had significantly greater COX-2 mRNA than their nonedematous cohort. Selective pharmacological inhibition of COX-2, with NS-398, and genetic knock down of COX-2 with a translation initiation morpholino significantly attenuated prevalence and severity of edema phenotype. Subsequently, exposures of medaka embryos to arachidonic acid (AA) resulted in recapitulation of the pericardial edema phenotype and significantly increased COX-2 expression only in those individuals exhibiting the edema phenotype compared with their nonedematous cohort. AA exposure does not result in significant induction of cytochrome P450 1A expression, suggesting that pericardial edema can be induced independent of AhR/aryl hydrocarbon receptor nuclear translocator/dioxin response element interactions. Results from this study demonstrate that developmental exposure to TCDD results in an induction of inflammatory mediators including COX-2, which contribute to the onset, and progression of heart dysmorphogenesis in the medaka model. PMID:20801906

  14. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures. PMID:23626706

  15. Correlation Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.; Jones, Jeff A.

    2010-01-01

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

  16. The Role of Inhibitory Control in the Development of Human Figure Drawing in Young Children

    ERIC Educational Resources Information Center

    Riggs, Kevin J.; Jolley, Richard P.; Simpson, Andrew

    2013-01-01

    We investigated the role of inhibitory control in young children's human figure drawing. We used the Bear-Dragon task as a measure of inhibitory control and used the classification system devised by Cox and Parkin to measure the development of human figure drawing. We tested 50 children aged between 40 and 64 months. Regression analysis showed…

  17. Interquantile Shrinkage in Regression Models

    PubMed Central

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

    2012-01-01

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

  18. Survival Data and Regression Models

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    We start this chapter by introducing some basic elements for the analysis of censored survival data. Then we focus on right censored data and develop two types of regression models. The first one concerns the so-called accelerated failure time models (AFT), which are parametric models where a function of a parameter depends linearly on the covariables. The second one is a semiparametric model, where the covariables enter in a multiplicative form in the expression of the hazard rate function. The main statistical tool for analysing these regression models is the maximum likelihood methodology and, in spite we recall some essential results about the ML theory, we refer to the chapter "Logistic Regression" for a more detailed presentation.

  19. Canonical variate regression.

    PubMed

    Luo, Chongliang; Liu, Jin; Dey, Dipak K; Chen, Kun

    2016-07-01

    In many fields, multi-view datasets, measuring multiple distinct but interrelated sets of characteristics on the same set of subjects, together with data on certain outcomes or phenotypes, are routinely collected. The objective in such a problem is often two-fold: both to explore the association structures of multiple sets of measurements and to develop a parsimonious model for predicting the future outcomes. We study a unified canonical variate regression framework to tackle the two problems simultaneously. The proposed criterion integrates multiple canonical correlation analysis with predictive modeling, balancing between the association strength of the canonical variates and their joint predictive power on the outcomes. Moreover, the proposed criterion seeks multiple sets of canonical variates simultaneously to enable the examination of their joint effects on the outcomes, and is able to handle multivariate and non-Gaussian outcomes. An efficient algorithm based on variable splitting and Lagrangian multipliers is proposed. Simulation studies show the superior performance of the proposed approach. We demonstrate the effectiveness of the proposed approach in an [Formula: see text] intercross mice study and an alcohol dependence study. PMID:26861909

  20. George: Gaussian Process regression

    NASA Astrophysics Data System (ADS)

    Foreman-Mackey, Daniel

    2015-11-01

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

  1. Developmental regression in autism spectrum disorder

    PubMed Central

    Al Backer, Nouf Backer

    2015-01-01

    The occurrence of developmental regression in autism spectrum disorder (ASD) is one of the most puzzling phenomena of this disorder. A little is known about the nature and mechanism of developmental regression in ASD. About one-third of young children with ASD lose some skills during the preschool period, usually speech, but sometimes also nonverbal communication, social or play skills are also affected. There is a lot of evidence suggesting that most children who demonstrate regression also had previous, subtle, developmental differences. It is difficult to predict the prognosis of autistic children with developmental regression. It seems that the earlier development of social, language, and attachment behaviors followed by regression does not predict the later recovery of skills or better developmental outcomes. The underlying mechanisms that lead to regression in autism are unknown. The role of subclinical epilepsy in the developmental regression of children with autism remains unclear. PMID:27493417

  2. Immunohistochemical analysis of COX-2 expression in dentigerous cyst, keratocystic odontogenic tumor and ameloblastoma: A comparative study

    PubMed Central

    Seyedmajidi, Maryam; Shafaee, Shahryar; Siadati, Sepideh; Moghaddam, Elham Alizadeh; Ghasemi, Nafiseh; Bijani, Ali; Najafi, Mostafa

    2015-01-01

    Background: Cyclo-oxygenase-2 (COX-2) is an early response gene that is induced by growth factors, oncogenes and carcinogens and its expression is increased in various tumors. Increased expression of COX-2 plays a significant role in the development and growth of tumors by interfering in biological processes such as cell division, cellular immunity, cell adhesion, apoptosis, and angiogenesis. This study aimed to investigate the immunohistochemical expression of COX-2 in keratocystic odontogenic tumor (KOT) in comparison with ameloblastoma and dentigerous cyst with regards to different clinical behavior and histopathological features of these lesions. Materials and Methods: Paraffined blocks of 45 cases including 15 cases of dentigerous cyst, 15 cases of KOT and 15 cases of ameloblastoma were stained with immunohistochemical method for COX-2. Five high-power fields of each sample were evaluated to determine the percentage of stained cells and the intensity of staining. Degree of immunoreactivity was obtained from the sum of two. Statistical evaluation was performed by the Kruskal-Wallis and ANOVA Mann-Whitney test (P < 0.05). Results: Overexpression of COX-2 in ameloblastoma and KOT was observed compared with dentigerous cyst (P < 0.001). However, no significant difference was observed between the expression of COX-2 in ameloblastoma and KOT (P = 0.148). Conclusion: The COX-2 expression in odontogenic tumors such as ameloblastoma and cystic neoplasm with aggressive behavior such as KOT increases. However, it does not seem that COX-2 affects the development and growth of cysts with noninvasive behavior like dentigerous cyst. PMID:26005470

  3. Development of multiple linear regression models as predictive tools for fecal indicator concentrations in a stretch of the lower Lahn River, Germany.

    PubMed

    Herrig, Ilona M; Böer, Simone I; Brennholt, Nicole; Manz, Werner

    2015-11-15

    Since rivers are typically subject to rapid changes in microbiological water quality, tools are needed to allow timely water quality assessment. A promising approach is the application of predictive models. In our study, we developed multiple linear regression (MLR) models in order to predict the abundance of the fecal indicator organisms Escherichia coli (EC), intestinal enterococci (IE) and somatic coliphages (SC) in the Lahn River, Germany. The models were developed on the basis of an extensive set of environmental parameters collected during a 12-months monitoring period. Two models were developed for each type of indicator: 1) an extended model including the maximum number of variables significantly explaining variations in indicator abundance and 2) a simplified model reduced to the three most influential explanatory variables, thus obtaining a model which is less resource-intensive with regard to required data. Both approaches have the ability to model multiple sites within one river stretch. The three most important predictive variables in the optimized models for the bacterial indicators were NH4-N, turbidity and global solar irradiance, whereas chlorophyll a content, discharge and NH4-N were reliable model variables for somatic coliphages. Depending on indicator type, the extended mode models also included the additional variables rainfall, O2 content, pH and chlorophyll a. The extended mode models could explain 69% (EC), 74% (IE) and 72% (SC) of the observed variance in fecal indicator concentrations. The optimized models explained the observed variance in fecal indicator concentrations to 65% (EC), 70% (IE) and 68% (SC). Site-specific efficiencies ranged up to 82% (EC) and 81% (IE, SC). Our results suggest that MLR models are a promising tool for a timely water quality assessment in the Lahn area. PMID:26318647

  4. Application of nonparametric regression and statistical testing to identify the impact of oil and natural gas development on local air quality

    NASA Astrophysics Data System (ADS)

    Cheng, Hanqi; Small, Mitchell J.; Pekney, Natalie J.

    2015-10-01

    The objective of the current work was to develop a statistical method and associated tool to evaluate the impact of oil and natural gas exploration and production activities on local air quality. Nonparametric regression of pollutant concentrations on wind direction was combined with bootstrap hypothesis testing to provide statistical inference regarding the existence of a local/regional air quality impact. The block bootstrap method was employed to address the effect of autocorrelation on test significance. The method was applied to short-term air monitoring data collected at three sites within Pennsylvania's Allegheny National Forest. All of the measured pollutant concentrations were well below the National Ambient Air Quality Standards, so the usual criteria and methods for data analysis were not sufficient. Using advanced directional analysis methods, test results were first applied to verify the existence of a regional impact at a background site. Next the impact of an oil field on local NOx and SO2 concentrations at a second monitoring site was identified after removal of the regional effect. Analysis of a third site also revealed air quality impacts from nearby areas with a high density of oil and gas wells. All results and conclusions were quantified in terms of statistical significance level for the associated inferences. The proposed method can be used to formulate hypotheses and verify conclusions regarding oil and gas well impacts on air quality and support better-informed decisions for their management and regulation.

  5. Development and application of a regression equation for estimating the occurrence of atrazine in shallow ground water beneath agricultural areas of the United States

    USGS Publications Warehouse

    Stackelberg, Paul E.; Gilliom, Robert J.; Wolock, David M.; Hitt, Kerie J.

    2006-01-01

    Results from 52 ground-water studies throughout the United States were used to examine relations between the occurrence of atrazine in shallow ground water in agricultural settings and explanatory variables that describe the natural setting, agricultural-management practices, and the type and amount of development in each area. The explanatory variables that were found to be correlated with atrazine occurrence were soil-infiltration rates, presence of artificial drainage (tile drains or trenches), available water-holding capacity of soils, soil permeability, amount of study area using ground water for irrigation source (as percentage of total area), amount of agricultural land (as percentage of total area), and intensity of atrazine use. Ordinary least-squares regression equations that used one or more of these explanatory variables describe as much as 58 percent of the variation in atrazine-detection frequencies. Application of a multivariate equation to unmonitored agricultural areas across the conterminous United States illustrates that atrazine use alone is insufficient for estimating the occurrence of atrazine in shallow ground water. Instead, areas in which soil characteristics and agricultural-management practices favor the movement of water from land surface to the water table and that also have intensive atrazine use are the most vulnerable to atrazine contamination.

  6. Students Speak With Gary Cox, EPIC Project Manager

    NASA Video Gallery

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

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

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

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

  8. Relationship of the Topological Distances and Activities between mPGES-1 and COX-2 versus COX-1: Implications of the Different Post-Translational Endoplasmic Reticulum Organizations of COX-1 and COX-2.

    PubMed

    Akasaka, Hironari; So, Shui-Ping; Ruan, Ke-He

    2015-06-16

    In vascular inflammation, prostaglandin E2 (PGE₂) is largely biosynthesized by microsomal PGE₂ synthase-1 (mPGES-1), competing with other downstream eicosanoid-synthesizing enzymes, such as PGIS, a synthase of a vascular protector prostacyclin (PGI₂), to isomerize the cyclooxygenase (COX)-2-derived prostaglandin H2 (PGH₂). In this study, we found that a majority of the product from the cells co-expressing human COX-2, mPGES-1, and PGIS was PGE₂. We hypothesize that the molecular and cellular mechanisms are related to the post-translational endoplasmic reticulum (ER) arrangement of those enzymes. A set of fusion enzymes, COX-2-linker [10 amino acids (aa)]-PGIS and COX-2-linker (22 amino acids)-PGIS, were created as "The Bioruler", in which the 10 and 22 amino acids are defined linkers with known helical structures and distances (14.4 and 30.8 Å, respectively). Our experiments have shown that the efficiency of PGI₂ biosynthesis was reduced when the separation distance increased from 10 to 22 amino acids. When COX-2-10aa-PGIS (with a 14.4 Å separation) was co-expressed with mPGES-1 on the ER membrane, a major product was PGE₂, but not PGI₂. However, expression of COX-2-10aa-PGIS and mPGES-1 on a separated ER with a distance of ≫30.8 Å reduced the level of PGE₂ production. These data indicated that the mPGES-1 is "complex-likely" colocalized with COX-2 within a distance of 14.4 Å. In addition, the cells co-expressing COX-1-10aa-PGIS and mPGES-1 produced PGI₂ mainly, but not PGE₂. This indicates that mPGES-1 is expressed much farther from COX-1. These findings have led to proposed models showing the different post-translational ER organization between COX-2 and COX-1 with respect to the topological arrangement of the mPGES-1 during vascular inflammation. PMID:25988363

  9. COX-2 inhibition prevents insulin-dependent diabetes in low-dose streptozotocin-treated mice.

    PubMed

    Tabatabaie, T; Waldon, A M; Jacob, J M; Floyd, R A; Kotake, Y

    2000-07-01

    Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta cells. Inducible cyclooxygenase (COX-2) is expressed under inflammatory conditions and its product prostaglandin E(2) (PGE(2)) is an important inflammation mediator. We report here that administration of the selective COX-2 inhibitor NS-398 prevents the onset of diabetes in mice brought on by multiple low-doses of streptozotocin (STZ). Histological observations indicated that STZ-mediated destruction of beta cells was prevented by NS-398 treatment. Delayed (day 3) administration of NS-398 was also protective in this model. No protective effect was observed when NS-398 was administered prior to a high, toxic dose of STZ. These results demonstrate the critical importance of COX-2 activity in autoimmune destruction of beta cells, and point to the fact that COX-2 inhibition can potentially develop into a preventive therapy against IDDM. PMID:10873667

  10. ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and MAPK signaling.

    PubMed

    A, Senthil Kumar; Bansal, Kushagra; Holla, Sahana; Verma-Kumar, Shalu; Sharma, Pawan; Balaji, Kithiganahalli Narayanaswamy

    2012-01-01

    Macrophages, as sentinels of robust host immunity, are key regulators of innate immune responses against invading mycobacteria; however, pathogenic mycobacteria survive in the infected host by subverting host innate immunity. Infection dependent expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. As a part of multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) may act as an important influencing factor towards effective host immunity. In the current investigation, we demonstrate that ESAT-6 triggers COX-2 expression both in vitro and in vivo in a TLR2 dependent manner. Signaling perturbation data suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical importance in ESAT-6 triggered expression of COX-2 in macrophages. Interestingly, ESAT-6 triggered PI3K-MAPK signaling axis holds the capacity to regulate coordinated activation of NF-κB and AP-1. Overall, current investigation provides mechanistic insights into ESAT-6 induced COX-2 expression and unravels TLR2 mediated interplay of PI3K and MAPK signaling axis as a rate-determining step during intricate host immune responses. These findings would serve as a paradigm to understand pathogenesis of mycobacterial infection and clearly pave a way towards development of novel therapeutics. PMID:22154837

  11. Antinociceptive Effects of Prim-O-Glucosylcimifugin in Inflammatory Nociception via Reducing Spinal COX-2.

    PubMed

    Wu, Liu-Qing; Li, Yu; Li, Yuan-Yan; Xu, Shi-Hao; Yang, Zong-Yong; Lin, Zheng; Li, Jun

    2016-07-01

    We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an ED50 of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNFα, IL-1β and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 (PGE2). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression. PMID:27257008

  12. Antinociceptive Effects of Prim-O-Glucosylcimifugin in Inflammatory Nociception via Reducing Spinal COX-2

    PubMed Central

    Wu, Liu-Qing; Li, Yu; Li, Yuan-Yan; Xu, Shi-hao; Yang, Zong-Yong; Lin, Zheng; Li, Jun

    2016-01-01

    We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund’s adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an ED50 of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNFα, IL-1β and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 (PGE2). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression. PMID:27257008

  13. Epigenetic deregulation of the COX pathway in cancer.

    PubMed

    Cebola, Inês; Peinado, Miguel A

    2012-10-01

    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

  14. Regression modelling of Dst index

    NASA Astrophysics Data System (ADS)

    Parnowski, Aleksei

    We developed a new approach to the problem of real-time space weather indices forecasting using readily available data from ACE and a number of ground stations. It is based on the regression modelling method [1-3], which combines the benefits of empirical and statistical approaches. Mathematically it is based upon the partial regression analysis and Monte Carlo simulations to deduce the empirical relationships in the system. The typical elapsed time per forecast is a few seconds on an average PC. This technique can be easily extended to other indices like AE and Kp. The proposed system can also be useful for investigating physical phenomena related to interactions between the solar wind and the magnetosphere -it already helped uncovering two new geoeffective parameters. 1. Parnowski A.S. Regression modeling method of space weather prediction // Astrophysics Space Science. — 2009. — V. 323, 2. — P. 169-180. doi:10.1007/s10509-009-0060-4 [arXiv:0906.3271] 2. Parnovskiy A.S. Regression Modeling and its Application to the Problem of Prediction of Space Weather // Journal of Automation and Information Sciences. — 2009. — V. 41, 5. — P. 61-69. doi:10.1615/JAutomatInfScien.v41.i5.70 3. Parnowski A.S. Statistically predicting Dst without satellite data // Earth, Planets and Space. — 2009. — V. 61, 5. — P. 621-624.

  15. Practical Session: Logistic Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

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

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

    PubMed Central

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

    2012-01-01

    The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the intermembrane space. Processing is chaperoned by Cox20, an integral inner membrane protein whose hydrophilic domains are located in the intermembrane space, and Cox20 remains associated with mature, unassembled Cox2. The Cox2 C-tail domain is exported post-translationally by the highly conserved translocase Cox18 and associated proteins. We have found that Cox20 is required for efficient export of the Cox2 C-tail. Furthermore, Cox20 interacts by co-immune precipitation with Cox18, and this interaction requires the presence of Cox2. We therefore propose that Cox20 binding to Cox2 on the trans side of the inner membrane accelerates dissociation of newly exported Cox2 from the Cox18 translocase, promoting efficient cycling of the translocase. The requirement for Cox20 in cytochrome c oxidase assembly and respiratory growth is partially bypassed by yme1, mgr1 or mgr3 mutations, each of which reduce i-AAA protease activity in the intermembrane space. Thus, Cox20 also appears to stabilize unassembled Cox2 against degradation by the i-AAA protease. Pre-Cox2 leader peptide processing by Imp1 occurs in the absence of Cox20 and i-AAA protease activity, but is greatly reduced in efficiency. Under these conditions some mature Cox2 is assembled into cytochrome c oxidase allowing weak respiratory growth. Thus, the Cox20 chaperone has important roles in leader peptide processing, C-tail export, and stabilization of Cox2. PMID:22095077

  17. Development of immune memory to glial brain tumors after tumor regression induced by immunotherapeutic Toll-like receptor 7/8 activation.

    PubMed

    Stathopoulos, Apostolis; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Kruse, Carol; Jadus, Martin; Chen, Thomas C; Schijns, Virgil E J C

    2012-05-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and immunotherapeutic treatments. We found that parenteral treatment with the TLR7/8 agonist, resiquimod, eventually induced complete tumor regression of CNS-1 glioblastoma tumors in Lewis rats. Cyclophosphamide (CY) treatment also resulted in dramatic CNS-1 remission, while the combined treatment showed similar antitumor effects. The resiquimod efficacy appeared not to be associated with direct injury to CNS-1 growth, while CY proved to exert tumoricidal cytotoxicity to the tumor cells. Rats that were cured by treatment with the innate immune response modifier resiquimod proved to be fully immune to secondary CNS-1 tumor rechallenge. They all remained tumor-free and survived. In contrast, rats that controlled CNS-1 tumor growth as a result of CY treatment did not develop immune memory, as demonstrated by their failure to reject a secondary CNS-1 tumor challenge; they showed a concomittant outgrowth of the primary tumor upon secondary tumor exposure. Rechallenge of rats that initially contained tumor growth by combination chemo-immunotherapy also failed to reject secondary tumor challenge, indicating that the cytotoxic effect of the CY likely extended to the endogenous memory immune cells as well as to the tumor. These data demonstrate strong therapeutic antitumor efficacy for the immune response modifier resiquimod leading to immunological memory, and suggest that CY treatment, although effective as chemotherapeutic agent, may be deleterious to maintenance of long-term antitumor immune memory. These data also highlight the importance of the sequence in which a multi-modal therapy is administered. PMID:22737605

  18. Expression of messenger RNA for ADAMTS subtypes changes in the periovulatory follicle after the gonadotropin surge and during luteal development and regression in cattle.

    PubMed

    Madan, Pavneesh; Bridges, Phillip J; Komar, Carolyn M; Beristain, Alexander G; Rajamahendran, Rajadurai; Fortune, Joanne E; MacCalman, Colin D

    2003-11-01

    Extensive remodeling of the extracellular matrix occurs in the ovary during the periovulatory period. Matrix metalloproteinases and their endogenous inhibitors, tissue inhibitors of metalloproteinases, are believed to play integral roles in this highly regulated series of cellular events, but their specific roles remain unclear. Recent cloning studies have identified a novel family of metalloproteinases, the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family. The regulated expression of distinct ADAMTS subtypes has been shown to be required for tissue morphogenesis during embryonic development and for maintaining the integrity of tissues in the adult. In the present studies, we have determined that multiple ADAMTS subtypes are present in the bovine ovary using a reverse transcription-polymerase chain reaction strategy. In particular, ADAMTS-1, -2, -3, -4, -5 (also known as ADAMTS-11), -7, -8, and -9, but not ADAMTS-6, -10, or -12, mRNA transcripts were detected in granulosa cells of nonatretic ovarian follicles and corpora lutea. The levels of mRNA for these ovarian ADAMTS were up- or down-regulated or remained unchanged in the granulosa and/or theca cells of the dominant follicle following the preovulatory surge of gonadotropins, depending on the subtype and/or the cell compartment, and in the corpus luteum during the luteal phase of the estrous cycle. The complex expression patterns observed for the distinct ADAMTS subtypes in the granulosa and theca cells of the periovulatory follicle and in the luteal tissues of the bovine ovary suggest that these novel proteases mediate, at least in part, the remodeling events underlying folliculogenesis and ovulation and the formation, maintenance, and regression of the corpus luteum. PMID:12855604

  19. Development of variable pathlength UV-vis spectroscopy combined with partial-least-squares regression for wastewater chemical oxygen demand (COD) monitoring.

    PubMed

    Chen, Baisheng; Wu, Huanan; Li, Sam Fong Yau

    2014-03-01

    To overcome the challenging task to select an appropriate pathlength for wastewater chemical oxygen demand (COD) monitoring with high accuracy by UV-vis spectroscopy in wastewater treatment process, a variable pathlength approach combined with partial-least squares regression (PLSR) was developed in this study. Two new strategies were proposed to extract relevant information of UV-vis spectral data from variable pathlength measurements. The first strategy was by data fusion with two data fusion levels: low-level data fusion (LLDF) and mid-level data fusion (MLDF). Predictive accuracy was found to improve, indicated by the lower root-mean-square errors of prediction (RMSEP) compared with those obtained for single pathlength measurements. Both fusion levels were found to deliver very robust PLSR models with residual predictive deviations (RPD) greater than 3 (i.e. 3.22 and 3.29, respectively). The second strategy involved calculating the slopes of absorbance against pathlength at each wavelength to generate slope-derived spectra. Without the requirement to select the optimal pathlength, the predictive accuracy (RMSEP) was improved by 20-43% as compared to single pathlength spectroscopy. Comparing to nine-factor models from fusion strategy, the PLSR model from slope-derived spectroscopy was found to be more parsimonious with only five factors and more robust with residual predictive deviation (RPD) of 3.72. It also offered excellent correlation of predicted and measured COD values with R(2) of 0.936. In sum, variable pathlength spectroscopy with the two proposed data analysis strategies proved to be successful in enhancing prediction performance of COD in wastewater and showed high potential to be applied in on-line water quality monitoring. PMID:24468377

  20. Development of an Anisotropic Geological-Based Land Use Regression and Bayesian Maximum Entropy Model for Estimating Groundwater Radon across Northing Carolina

    NASA Astrophysics Data System (ADS)

    Messier, K. P.; Serre, M. L.

    2015-12-01

    Radon (222Rn) is a naturally occurring chemically inert, colorless, and odorless radioactive gas produced from the decay of uranium (238U), which is ubiquitous in rocks and soils worldwide. Exposure to 222Rn is likely the second leading cause of lung cancer after cigarette smoking via inhalation; however, exposure through untreated groundwater is also a contributing factor to both inhalation and ingestion routes. A land use regression (LUR) model for groundwater 222Rn with anisotropic geological and 238U based explanatory variables is developed, which helps elucidate the factors contributing to elevated 222Rn across North Carolina. Geological and uranium based variables are constructed in elliptical buffers surrounding each observation such that they capture the lateral geometric anisotropy present in groundwater 222Rn. Moreover, geological features are defined at three different geological spatial scales to allow the model to distinguish between large area and small area effects of geology on groundwater 222Rn. The LUR is also integrated into the Bayesian Maximum Entropy (BME) geostatistical framework to increase accuracy and produce a point-level LUR-BME model of groundwater 222Rn across North Carolina including prediction uncertainty. The LUR-BME model of groundwater 222Rn results in a leave-one out cross-validation of 0.46 (Pearson correlation coefficient= 0.68), effectively predicting within the spatial covariance range. Modeled results of 222Rn concentrations show variability among Intrusive Felsic geological formations likely due to average bedrock 238U defined on the basis of overlying stream-sediment 238U concentrations that is a widely distributed consistently analyzed point-source data.

  1. Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase

    PubMed Central

    Bourens, Myriam; Boulet, Aren; Leary, Scot C.; Barrientos, Antoni

    2014-01-01

    Cytochrome c oxidase (CIV) deficiency is one of the most common respiratory chain defects in patients presenting with mitochondrial encephalocardiomyopathies. CIV biogenesis is complicated by the dual genetic origin of its structural subunits, and assembly of a functional holoenzyme complex requires a large number of nucleus-encoded assembly factors. In general, the functions of these assembly factors remain poorly understood, and mechanistic investigations of human CIV biogenesis have been limited by the availability of model cell lines. Here, we have used small interference RNA and transcription activator-like effector nucleases (TALENs) technology to create knockdown and knockout human cell lines, respectively, to study the function of the CIV assembly factor COX20 (FAM36A). These cell lines exhibit a severe, isolated CIV deficiency due to instability of COX2, a mitochondrion-encoded CIV subunit. Mitochondria lacking COX20 accumulate CIV subassemblies containing COX1 and COX4, similar to those detected in fibroblasts from patients carrying mutations in the COX2 copper chaperones SCO1 and SCO2. These results imply that in the absence of COX20, COX2 is inefficiently incorporated into early CIV subassemblies. Immunoprecipitation assays using a stable COX20 knockout cell line expressing functional COX20-FLAG allowed us to identify an interaction between COX20 and newly synthesized COX2. Additionally, we show that SCO1 and SCO2 act on COX20-bound COX2. We propose that COX20 acts as a chaperone in the early steps of COX2 maturation, stabilizing the newly synthesized protein and presenting COX2 to its metallochaperone module, which in turn facilitates the incorporation of mature COX2 into the CIV assembly line. PMID:24403053

  2. Explorations in Statistics: Regression

    ERIC Educational Resources Information Center

    Curran-Everett, Douglas

    2011-01-01

    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.…

  3. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

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

  4. CORRELATION AND REGRESSION

    EPA Science Inventory

    Webcast entitled Statistical Tools for Making Sense of Data, by the National Nutrient Criteria Support Center, N-STEPS (Nutrients-Scientific Technical Exchange Partnership. The section "Correlation and Regression" provides an overview of these two techniques in the context of nut...

  5. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

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

  6. Mechanisms of neuroblastoma regression

    PubMed Central

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    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

  7. Bayesian ARTMAP for regression.

    PubMed

    Sasu, L M; Andonie, R

    2013-10-01

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

  8. Cardiovascular hazard of selective COX-2 inhibitors: myth or reality?

    PubMed

    Chiolero, Arnaud; Maillard, Marc P; Burnier, Michel

    2002-05-01

    Since 1998, two selective inhibitors of COX-2 have been approved in many countries for the treatment of rheumatoid arthritis, osteoarthritis and acute pain. These new drugs have a significantly reduced gastrointestinal toxicity when compared with non-selective COX inhibitors. However, the results of two large clinical trials conducted in patients with osteoarthritis and rheumatoid arthritis have recently raised some concerns regarding the cardiovascular safety of these new drugs. The purpose of this paper is to review the potential mechanisms whereby selective COX-2 inhibitors could increase the cardiovascular risk of patients and to analyse the data indicating that this clinical risk indeed exists. The authors' analysis shows that even though there are pathophysiological mechanisms which could explain why selective COX-2 inhibition might increase the cardiovascular risk in patients, the actual level of evidence demonstrating that the risk is indeed increased is weak. Because of the importance of the issue, additional studies must be conducted with this class of agents. Meanwhile, it is crucial to emphasise that neither selective COX-2 inhibitors nor conventional NSAIDs replace aspirin in patients with a high cardiovascular risk. PMID:12904159

  9. Isoxazole-Based-Scaffold Inhibitors Targeting Cyclooxygenases (COXs).

    PubMed

    Perrone, Maria Grazia; Vitale, Paola; Panella, Andrea; Ferorelli, Savina; Contino, Marialessandra; Lavecchia, Antonio; Scilimati, Antonio

    2016-06-01

    A new set of cyclooxygenase (COX) inhibitors endowed with an additional functionality was explored. These new compounds also contained either rhodamine 6G or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, two moieties typical of efflux pump substrates and inhibitors, respectively. Among all the synthesized compounds, two new COX inhibitors with opposite selectivity were discovered: compound 8 [N-(9-{2-[(4-{2-[3-(5-chlorofuran-2-yl)-4-phenylisoxazol-5-yl]acetamido}butyl)carbamoyl]phenyl-6-(ethylamino)-2,7-dimethyl-3H-xanthen-3-ylidene}ethanaminium chloride] was found to be a selective COX-1 inhibitor, whereas 17 (2-[3,4-bis(4-methoxyphenyl)isoxazol-5-yl]-1-[6,7-dimethoxy-3,4-dihydroisoquinolin-2-(1H)-yl]ethanone) was found to be a sub-micromolar selective COX-2 inhibitor. However, both were shown to interact with P-glycoprotein. Docking experiments helped to clarify the molecular aspects of the observed COX selectivity. PMID:27136372

  10. Ridge Regression: A Regression Procedure for Analyzing Correlated Independent Variables.

    ERIC Educational Resources Information Center

    Rakow, Ernest A.

    Ridge regression is presented as an analytic technique to be used when predictor variables in a multiple linear regression situation are highly correlated, a situation which may result in unstable regression coefficients and difficulties in interpretation. Ridge regression avoids the problem of selection of variables that may occur in stepwise…

  11. Regression analysis of networked data

    PubMed Central

    Zhou, Yan; Song, Peter X.-K.

    2016-01-01

    This paper concerns regression methodology for assessing relationships between multi-dimensional response variables and covariates that are correlated within a network. To address analytical challenges associated with the integration of network topology into the regression analysis, we propose a hybrid quadratic inference method that uses both prior and data-driven correlations among network nodes. A Godambe information-based tuning strategy is developed to allocate weights between the prior and data-driven network structures, so the estimator is efficient. The proposed method is conceptually simple and computationally fast, and has appealing large-sample properties. It is evaluated by simulation, and its application is illustrated using neuroimaging data from an association study of the effects of iron deficiency on auditory recognition memory in infants. PMID:27279658

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  13. Regression Verification Using Impact Summaries

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

    Regression verification techniques are used to prove equivalence of syntactically similar programs. Checking equivalence of large programs, however, can be computationally expensive. Existing regression verification techniques rely on abstraction and decomposition techniques to reduce the computational effort of checking equivalence of the entire program. These techniques are sound but not complete. In this work, we propose a novel approach to improve scalability of regression verification by classifying the program behaviors generated during symbolic execution as either impacted or unimpacted. Our technique uses a combination of static analysis and symbolic execution to generate summaries of impacted program behaviors. The impact summaries are then checked for equivalence using an o-the-shelf decision procedure. We prove that our approach is both sound and complete for sequential programs, with respect to the depth bound of symbolic execution. Our evaluation on a set of sequential C artifacts shows that reducing the size of the summaries can help reduce the cost of software equivalence checking. Various reduction, abstraction, and compositional techniques have been developed to help scale software verification techniques to industrial-sized systems. Although such techniques have greatly increased the size and complexity of systems that can be checked, analysis of large software systems remains costly. Regression analysis techniques, e.g., regression testing [16], regression model checking [22], and regression verification [19], restrict the scope of the analysis by leveraging the differences between program versions. These techniques are based on the idea that if code is checked early in development, then subsequent versions can be checked against a prior (checked) version, leveraging the results of the previous analysis to reduce analysis cost of the current version. Regression verification addresses the problem of proving equivalence of closely related program

  14. Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors.

    PubMed

    Biava, Mariangela; Battilocchio, Claudio; Poce, Giovanna; Alfonso, Salvatore; Consalvi, Sara; Di Capua, Angela; Calderone, Vincenzo; Martelli, Alma; Testai, Lara; Sautebin, Lidia; Rossi, Antonietta; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Giordani, Antonio; Persiani, Stefano; Colovic, Milena; Dovizio, Melania; Patrignani, Paola; Anzini, Maurizio

    2014-01-15

    We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. PMID:24373735

  15. Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients.

    PubMed

    Nagatsuka, Kazuyuki; Miyata, Shigeki; Kada, Akiko; Kawamura, Atsushi; Nakagawara, Jyoji; Furui, Eisuke; Takiuchi, Shin; Taomoto, Katsushi; Kario, Kazuomi; Uchiyama, Shinichiro; Saito, Kozue; Nagao, Takehiko; Kitagawa, Kazuo; Hosomi, Naohisa; Tanaka, Keiji; Kaikita, Koichi; Katayama, Yasuo; Abumiya, Takeo; Nakane, Hiroshi; Wada, Hideo; Hattori, Akira; Kimura, Kazumi; Isshiki, Takaaki; Nishikawa, Masakatsu; Yamawaki, Takemori; Yonemoto, Naohiro; Okada, Hiromi; Ogawa, Hisao; Minematsu, Kazuo; Miyata, Toshiyuki

    2016-08-01

    Several studies have indicated that approximately 25 % of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8 %). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients. PMID:27098431

  16. COX-2 and PGE2-dependent immunomodulation in breast cancer.

    PubMed

    Chen, Edward P; Smyth, Emer M

    2011-11-01

    COX-derived prostanoids play multiple roles in inflammation and cancer. This review highlights research examining COX-2 and PGE(2)-dependent regulation of immune cell polarization and function within the tumor microenvironment, particularly as it pertains to breast cancer. Appreciating PGE(2)-mediated immunomodulation is important in understanding how tumors evade immune surveillance by re-educating infiltrating inflammatory and immune cells to support tumorigenesis. Elucidation of the multiple and complex influences exerted by tumor stromal components may lead to targeted therapies in breast and other cancers that restrain microenvironmental permissiveness and maintain natural defenses against malignancies. PMID:21907301

  17. Orthogonal Regression: A Teaching Perspective

    ERIC Educational Resources Information Center

    Carr, James R.

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. Correlation and simple linear regression.

    PubMed

    Eberly, Lynn E

    2007-01-01

    This chapter highlights important steps in using correlation and simple linear regression to address scientific questions about the association of two continuous variables with each other. These steps include estimation and inference, assessing model fit, the connection between regression and ANOVA, and study design. Examples in microbiology are used throughout. This chapter provides a framework that is helpful in understanding more complex statistical techniques, such as multiple linear regression, linear mixed effects models, logistic regression, and proportional hazards regression. PMID:18450049

  20. Combining ethnopharmacology and virtual screening for lead structure discovery: COX-inhibitors as application example.

    PubMed

    Rollinger, Judith M; Haupt, Sabine; Stuppner, Hermann; Langer, Thierry

    2004-01-01

    Virtual screening of large libraries of organic compounds combined with pharmacological high throughput screening is widely used for drug discovery in the pharmaceutical industry. Our aim was to explore the efficiency of using a biased 3D database comprising secondary metabolites from antiinflammatory medicinal plants as a source for the virtual screening. For this study pharmacophore models of cyclooxygenase I and II (COX-1, COX-2), key enzymes in the inflammation process, were generated with structure-based as well as common feature based modeling, resulting in three COX hypotheses. Four different multiconfomational 3D databases limited in molecular weight between 300 and 700 Da were applied to the screening in order to compare and analyze the obtained hit rates. Two of them were created in-house (DIOS, NPD). The database DIOS consists of 2752 compounds from phytochemical reports of antiinflammatory medicinal plants described by the ethnopharmacological source 'De material medica' of Pedanius Dioscorides, whereas NPD contains almost 80,000 compounds gathered arbitrarily from natural sources. In addition, two available multiconformational 3D libraries comprising marketed and development drug substances (DWI and NCI), mainly originating from synthesis, were used for comparison. As a test of the pharmacophore models' capability in natural sources, the models were used to search for known COX inhibitory natural products. This was achieved with some exceptions, which are discussed in the paper. Depending on the hypothesis used, DWI and NCI library searches produced hit rates in the range of 6.6% to 13.7%. A slight increase of the number of molecules assessed for binding was achieved with the database of natural products (NPD). Using the biased 3D database DIOS, however, the average increase of efficiency reached 77% to 133% compared to the hit rates resulting from WDI and NCI. The statistical benefit of a combination of an ethnopharmacological approach with the

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

    PubMed

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

    2014-12-01

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

  2. Steganalysis using logistic regression

    NASA Astrophysics Data System (ADS)

    Lubenko, Ivans; Ker, Andrew D.

    2011-02-01

    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.

  3. Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice.

    PubMed

    Kiraly, Alex J; Soliman, Eman; Jenkins, Audrey; Van Dross, Rukiyah T

    2016-01-01

    Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2. PMID:26802941

  4. Design and synthesis of [(125)I]Pyricoxib: A novel (125)I-labeled cyclooxygenase-2 (COX-2) inhibitors.

    PubMed

    Tietz, Ole; Dzandzi, James; Bhardwaj, Atul; Valliant, John F; Wuest, Frank

    2016-03-15

    Cyclooxygenase-2 (COX-2) is the key enzyme in the prostaglandin synthesis pathway which is involved in various pathophysiological conditions. The enzyme is membrane bound and located inside of the endoplasmic reticulum and nuclear membrane. Effective perfusion of inhibitors to the active site requires lipophilic drugs, which consequently display high unspecific background accumulation, for example, in fatty tissues. The objective of this work was the development of a small molecule radiolabeled with a long-lived iodine radioisotope to enable longer imaging times and better target-to-background ratios. A group of iodinated compounds (8-10) was synthesized and identified as selective COX-2 inhibitors (COX-2 IC50=0.85-13 μM). Molecular docking results provided the theoretical support for the experimental COX-2 inhibition data. Furthermore, a novel (125)I-containing trifluoro-pyrimidine compound ([(125)I]Pyricoxib) was prepared via radioiododestannylation reaction as potent and selective COX-2 inhibitor. Radiosynthesis of [(125)I]Pyricoxib was accomplished with innovative fluorous chemistry using fluorous chloroamine-T (F-CAT) as novel oxidizing agent in high radiochemical yields of 91 ± 4%. PMID:26898334

  5. English in the National Curriculum: The Cox Report.

    ERIC Educational Resources Information Center

    Use of English, 1989

    1989-01-01

    Discusses implications of the Cox Report on English instruction in Great Britain. Questions the definitions of aims and responsibilities outlined in the report. Suggests that the magnitude of what teachers are called upon to teach and assess will diffuse rather than concentrate attention on what matters most in English as a distinctive subject.…

  6. COX-2 inhibitors are contraindicated for treatment of combined injury.

    PubMed

    Jiao, W; Kiang, J G; Cary, L; Elliott, T B; Pellmar, T C; Ledney, G D

    2009-12-01

    Casualties of radiation dispersal devices, nuclear detonation or major ionizing radiation accidents, in addition to radiation exposure, may sustain physical and/or thermal trauma. Radiation exposure plus additional tissue trauma is known as combined injury. There are no definitive therapeutic agents. Cyclooxygenase-2 (COX-2), an inducible enzyme expressed in pathological disorders and radiation injury, plays an important role in inflammation and the production of cytokines and prostaglandin E(2) (PGE(2)) and could therefore affect the outcome for victims of combined injury. The COX-2 inhibitors celecoxib and meloxicam were evaluated for their therapeutic value against combined injury in mice. In survival studies, the COX-2 inhibitors had no beneficial effect on 30-day survival, wound healing or body weight gain after radiation injury alone or after combined injury. Meloxicam accelerated death in both wounded and combined injury mice. These drugs also induced severe hepatic toxicity, exaggerated inflammatory processes, and did not enhance hematopoietic cell regeneration. This study points to potential contraindications for use of COX-2 inhibitors in patients undergoing therapy for radiation injury and combined injury. PMID:19929415

  7. COX-2-derived endocannabinoid metabolites as novel inflammatory mediators.

    PubMed

    Alhouayek, Mireille; Muccioli, Giulio G

    2014-06-01

    Cyclooxygenase-2 (COX-2) is an enzyme that plays a key role in inflammatory processes. Classically, this enzyme is upregulated in inflammatory situations and is responsible for the generation of prostaglandins (PGs) from arachidonic acid (AA). One lesser-known property of COX-2 is its ability to metabolize the endocannabinoids, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). Endocannabinoid metabolism by COX-2 is not merely a means to terminate their actions. On the contrary, it generates PG analogs, namely PG-glycerol esters (PG-G) for 2-AG and PG-ethanolamides (PG-EA or prostamides) for AEA. Although the formation of these COX-2-derived metabolites of the endocannabinoids has been known for a while, their biological effects remain to be fully elucidated. Recently, several studies have focused on the role of these PG-G or PG-EA in vivo. In this review we take a closer look at the literature concerning these novel bioactive lipids and their role in inflammation. PMID:24684963

  8. MACRO FOR ESTIMATING THE BOX-COX POWER TRANSFORMATION

    EPA Science Inventory

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

  9. On nonsingular potentials of Cox-Thompson inversion scheme

    SciTech Connect

    Palmai, Tamas; Apagyi, Barnabas

    2010-02-15

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

  10. On nonsingular potentials of Cox-Thompson inversion scheme

    NASA Astrophysics Data System (ADS)

    Pálmai, Tamás; Apagyi, Barnabás

    2010-02-01

    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.

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

    PubMed

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

    2014-12-01

    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-κB, 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

  12. In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

    PubMed Central

    Dewi, Lestari

    2016-01-01

    Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Results: Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. Conclusion: The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2. PMID:27594740

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  14. Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines

    PubMed Central

    Seo, Kyoung-won; Coh, Ye-rin; Rebhun, Robert B.; Ahn, Jin-ok; Han, Sei-Myung; Lee, Hee-woo; Youn, Hwa-Young

    2016-01-01

    Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 µM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 µM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G1-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma. PMID:24656746

  15. Zeranol induces COX-2 expression through TRPC-3 activation in the placental cells JEG-3.

    PubMed

    Zhu, Yun; Yao, Xiaoqiang; Leung, Lai K

    2016-09-01

    Transient Receptor Potential Channels (TRPs) are commonly expressed in the reproductive tissues in human. Many female reproductive processes have been associated with these TRPs. The mycotoxin zeranol or α-zearalanol is derived from fungi in the Fusarium family. Limited exposure to zeranol appears to be safe. In North America, farmers are using synthetic zeranol to promote growth in livestock. As the health risks of exposure to residual zeranol have not been determined, this practice is disallowed in the European Community. In the present study the cellular calcium levels were elevated in JEG-3 cells treated with zeranol at or above 10nM. Subsequent study indicated that expressions of TRP channels were induced. In response to the calcium flow, ERK, P38 and PKCβ were activated and COX-2 expression was increased. Specific TRP inhibitors were employed to establish the connection between the ion channel activity and COX-2 expression, and TRPC-3 appeared to be the triggering mechanism. Since the involvement of COX-2 is implicated in placental development and parturition, exposure to this mycotoxin poses a potential threat to pregnant women. PMID:27224899

  16. COX-2 polymorphisms -765G→C and -1195A→G and hepatocellular carcinoma risk.

    PubMed

    Gharib, Aml F; Karam, Rehab A; Abd El Rahman, Tamer M; Elsawy, Wael H

    2014-06-15

    Cyclooxygenase-2 (COX-2) is overexpressed in hepatocellular carcinoma (HCC) and considered to play a role in hepatic carcinogenesis. Our aim was to examine the associations between polymorphisms in COX-2 -765G→C and -1195A→G and risk of HCC. We conducted a case-control study including 120 patients with HCC and 130 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. No significant difference was observed in the genotype distribution of the -765G→C polymorphism between patients and controls. The -1195AA genotype was associated with an increased risk of developing HCC (OR, 2.5; 95%CI, 1.18-5.37). The A allele was present significantly more often in HCC patients (OR 1.5; 95%CI, 1.05-2.14). In conclusion, our results demonstrated that the -1195AA genotype and A allele have an important role in HCC risk in Egyptian patients. PMID:24720952

  17. Ridge regression processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

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

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

    PubMed

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

    2014-12-30

    For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns. PMID:25345575

  19. Sparse Multivariate Regression With Covariance Estimation

    PubMed Central

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

    2014-01-01

    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

  20. Recursive Algorithm For Linear Regression

    NASA Technical Reports Server (NTRS)

    Varanasi, S. V.

    1988-01-01

    Order of model determined easily. Linear-regression algorithhm includes recursive equations for coefficients of model of increased order. Algorithm eliminates duplicative calculations, facilitates search for minimum order of linear-regression model fitting set of data satisfactory.

  1. Heteroscedastic transformation cure regression models.

    PubMed

    Chen, Chyong-Mei; Chen, Chen-Hsin

    2016-06-30

    Cure models have been applied to analyze clinical trials with cures and age-at-onset studies with nonsusceptibility. Lu and Ying (On semiparametric transformation cure model. Biometrika 2004; 91:331?-343. DOI: 10.1093/biomet/91.2.331) developed a general class of semiparametric transformation cure models, which assumes that the failure times of uncured subjects, after an unknown monotone transformation, follow a regression model with homoscedastic residuals. However, it cannot deal with frequently encountered heteroscedasticity, which may result from dispersed ranges of failure time span among uncured subjects' strata. To tackle the phenomenon, this article presents semiparametric heteroscedastic transformation cure models. The cure status and the failure time of an uncured subject are fitted by a logistic regression model and a heteroscedastic transformation model, respectively. Unlike the approach of Lu and Ying, we derive score equations from the full likelihood for estimating the regression parameters in the proposed model. The similar martingale difference function to their proposal is used to estimate the infinite-dimensional transformation function. Our proposed estimating approach is intuitively applicable and can be conveniently extended to other complicated models when the maximization of the likelihood may be too tedious to be implemented. We conduct simulation studies to validate large-sample properties of the proposed estimators and to compare with the approach of Lu and Ying via the relative efficiency. The estimating method and the two relevant goodness-of-fit graphical procedures are illustrated by using breast cancer data and melanoma data. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887342

  2. Regression Computer Programs for Setwise Regression and Three Related Analysis of Variance Techniques.

    ERIC Educational Resources Information Center

    Williams, John D.; Lindem, Alfred C.

    Four computer programs using the general purpose multiple linear regression program have been developed. Setwise regression analysis is a stepwise procedure for sets of variables; there will be as many steps as there are sets. Covarmlt allows a solution to the analysis of covariance design with multiple covariates. A third program has three…

  3. Regression modeling of ground-water flow

    USGS Publications Warehouse

    Cooley, R.L.; Naff, R.L.

    1985-01-01

    Nonlinear multiple regression methods are developed to model and analyze groundwater flow systems. Complete descriptions of regression methodology as applied to groundwater flow models allow scientists and engineers engaged in flow modeling to apply the methods to a wide range of problems. Organization of the text proceeds from an introduction that discusses the general topic of groundwater flow modeling, to a review of basic statistics necessary to properly apply regression techniques, and then to the main topic: exposition and use of linear and nonlinear regression to model groundwater flow. Statistical procedures are given to analyze and use the regression models. A number of exercises and answers are included to exercise the student on nearly all the methods that are presented for modeling and statistical analysis. Three computer programs implement the more complex methods. These three are a general two-dimensional, steady-state regression model for flow in an anisotropic, heterogeneous porous medium, a program to calculate a measure of model nonlinearity with respect to the regression parameters, and a program to analyze model errors in computed dependent variables such as hydraulic head. (USGS)

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

    PubMed Central

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

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor. PMID:26734017

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

    PubMed

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

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor. PMID:26734017

  6. Analysis of COX2 mutants reveals cytochrome oxidase subassemblies in yeast

    PubMed Central

    2005-01-01

    Cytochrome oxidase catalyses the reduction of oxygen to water. The mitochondrial enzyme contains up to 13 subunits, 11 in yeast, of which three, Cox1p, Cox2p and Cox3p, are mitochondrially encoded. The assembly pathway of this complex is still poorly understood. Its study in yeast has been so far impeded by the rapid turnover of unassembled subunits of the enzyme. In the present study, immunoblot analysis of blue native gels of yeast wild-type and Cox2p mutants revealed five cytochrome oxidase complexes or subcomplexes: a, b, c, d and f; a is likely to be the fully assembled enzyme; b lacks Cox6ap; d contains Cox7p and/or Cox7ap; f represents unassembled Cox1p; and c, observed only in the Cox2p mutants, contains Cox1p, Cox3p, Cox5p and Cox6p and lacks the other subunits. The identification of these novel cytochrome oxidase subcomplexes should encourage the reexamination of other yeast mutants. PMID:15921494

  7. Multinomial logistic regression ensembles.

    PubMed

    Lee, Kyewon; Ahn, Hongshik; Moon, Hojin; Kodell, Ralph L; Chen, James J

    2013-05-01

    This article proposes a method for multiclass classification problems using ensembles of multinomial logistic regression models. A multinomial logit model is used as a base classifier in ensembles from random partitions of predictors. The multinomial logit model can be applied to each mutually exclusive subset of the feature space without variable selection. By combining multiple models the proposed method can handle a huge database without a constraint needed for analyzing high-dimensional data, and the random partition can improve the prediction accuracy by reducing the correlation among base classifiers. The proposed method is implemented using R, and the performance including overall prediction accuracy, sensitivity, and specificity for each category is evaluated on two real data sets and simulation data sets. To investigate the quality of prediction in terms of sensitivity and specificity, the area under the receiver operating characteristic (ROC) curve (AUC) is also examined. The performance of the proposed model is compared to a single multinomial logit model and it shows a substantial improvement in overall prediction accuracy. The proposed method is also compared with other classification methods such as the random forest, support vector machines, and random multinomial logit model. PMID:23611203

  8. Some functional limit theorems for compound Cox processes

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  9. Linear regression in astronomy. I

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  10. Regression model development and computational procedures to support estimation of real-time concentrations and loads of selected constituents in two tributaries to Lake Houston near Houston, Texas, 2005-9

    USGS Publications Warehouse

    Lee, Michael T.; Asquith, William H.; Oden, Timothy D.

    2012-01-01

    In December 2005, the U.S. Geological Survey (USGS), in cooperation with the City of Houston, Texas, began collecting discrete water-quality samples for nutrients, total organic carbon, bacteria (Escherichia coli and total coliform), atrazine, and suspended sediment at two USGS streamflow-gaging stations that represent watersheds contributing to Lake Houston (08068500 Spring Creek near Spring, Tex., and 08070200 East Fork San Jacinto River near New Caney, Tex.). Data from the discrete water-quality samples collected during 2005–9, in conjunction with continuously monitored real-time data that included streamflow and other physical water-quality properties (specific conductance, pH, water temperature, turbidity, and dissolved oxygen), were used to develop regression models for the estimation of concentrations of water-quality constituents of substantial source watersheds to Lake Houston. The potential explanatory variables included discharge (streamflow), specific conductance, pH, water temperature, turbidity, dissolved oxygen, and time (to account for seasonal variations inherent in some water-quality data). The response variables (the selected constituents) at each site were nitrite plus nitrate nitrogen, total phosphorus, total organic carbon, E. coli, atrazine, and suspended sediment. The explanatory variables provide easily measured quantities to serve as potential surrogate variables to estimate concentrations of the selected constituents through statistical regression. Statistical regression also facilitates accompanying estimates of uncertainty in the form of prediction intervals. Each regression model potentially can be used to estimate concentrations of a given constituent in real time. Among other regression diagnostics, the diagnostics used as indicators of general model reliability and reported herein include the adjusted R-squared, the residual standard error, residual plots, and p-values. Adjusted R-squared values for the Spring Creek models ranged

  11. [New studies of COX-inhibitors, yet issues remain].

    PubMed

    Wollheim, Frank A

    2003-09-18

    Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized. PMID:14558211

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2011-01-01

    Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue. PMID:21668942

  14. Evaluating differential effects using regression interactions and regression mixture models

    PubMed Central

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

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design. PMID:26556903

  15. Supercomplex-associated Cox26 protein binds to cytochrome c oxidase.

    PubMed

    Strecker, Valentina; Kadeer, Zibirnisa; Heidler, Juliana; Cruciat, Cristina-Maria; Angerer, Heike; Giese, Heiko; Pfeiffer, Kathy; Stuart, Rosemary A; Wittig, Ilka

    2016-07-01

    Here we identified a hydrophobic 6.4kDa protein, Cox26, as a novel component of yeast mitochondrial supercomplex comprising respiratory complexes III and IV. Multi-dimensional native and denaturing electrophoretic techniques were used to identify proteins interacting with Cox26. The majority of the Cox26 protein was found non-covalently bound to the complex IV moiety of the III-IV supercomplexes. A population of Cox26 was observed to exist in a disulfide bond partnership with the Cox2 subunit of complex IV. No pronounced growth phenotype for Cox26 deficiency was observed, indicating that Cox26 may not play a critical role in the COX enzymology, and we speculate that Cox26 may serve to regulate or support the Cox2 protein. Respiratory supercomplexes are assembled in the absence of the Cox26 protein, however their pattern slightly differs to the wild type III-IV supercomplex appearance. The catalytic activities of complexes III and IV were observed to be normal and respiration was comparable to wild type as long as cells were cultivated under normal growth conditions. Stress conditions, such as elevated temperatures resulted in mild decrease of respiration in non-fermentative media when the Cox26 protein was absent. PMID:27091403

  16. Differential effects of selective cyclooxygenase (COX)-1 and COX-2 inhibitors on anorexic response and prostaglandin generation in various tissues induced by zymosan.

    PubMed

    Naoi, Kazuhisa; Kogure, Suguru; Saito, Masataka; Hamazaki, Tomohito; Watanabe, Shiro

    2006-07-01

    We have shown that anorexic response is induced by intraperitoneal injection of zymosan in mice, although the role of prostaglandins in this response is relatively unknown as compared with lipopolysaccharide (LPS)-induced anorexic response. Indomethacin (0.5 and 2.0 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, as well as meloxicam (0.5 mg/kg), a selective COX-2 inhibitor, but not FR122047 (2.0 mg/kg), a selective COX-1 inhibitor, attenuated zymosan-induced anorexia. Zymosan injection elevated COX-2 expression in brain and liver but not in small intestine and colon. Meloxicam (0.5 mg/kg) and FR122047 treatment (2.0 mg/kg) similarly suppressed the generation of brain prostaglandin E(2) (PGE(2)) and peritoneal prostacyclin (PGI(2)) upon zymosan injection. PGE(2) generation in liver upon zymosan injection was suppressed by meloxicam (0.5 mg/kg) but not by FR122047 treatment (2.0 mg/kg). Our observations suggest that COX-2 plays an important role in zymosan-induced anorexia, which is a similar feature in LPS-induced anorexic response. However, non-selective inhibition by selective COX-1 and COX-2 inhibitors of brain PGE(2) generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE(2) generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response. PMID:16819161

  17. Evaluating Aptness of a Regression Model

    ERIC Educational Resources Information Center

    Matson, Jack E.; Huguenard, Brian R.

    2007-01-01

    The data for 104 software projects is used to develop a linear regression model that uses function points (a measure of software project size) to predict development effort. The data set is particularly interesting in that it violates several of the assumptions required of a linear model; but when the data are transformed, the data set satisfies…

  18. Mixed-Phase Icing Simulation and Testing at the Cox Icing Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Al-Khalil, Kamel; Irani, Eddie; Miller, Dean

    2003-01-01

    A new capability was developed for indoor simulation of snow and mixed-phase icing conditions. This capability is useful for year-round testing in the Cox closed-loop Icing Wind Tunnel. Certification of aircraft for flight into these types of icing conditions is only required by the JAA in Europe. In an effort to harmonize certification requirements, the FAA in the US sponsored a preliminary program to study the effects of mixed-phase and fully glaciated icing conditions on the performance requirements of thermal ice protection systems. This paper describes the test program and the associated results.

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  20. Retro-regression--another important multivariate regression improvement.

    PubMed

    Randić, M

    2001-01-01

    We review the serious problem associated with instabilities of the coefficients of regression equations, referred to as the MRA (multivariate regression analysis) "nightmare of the first kind". This is manifested when in a stepwise regression a descriptor is included or excluded from a regression. The consequence is an unpredictable change of the coefficients of the descriptors that remain in the regression equation. We follow with consideration of an even more serious problem, referred to as the MRA "nightmare of the second kind", arising when optimal descriptors are selected from a large pool of descriptors. This process typically causes at different steps of the stepwise regression a replacement of several previously used descriptors by new ones. We describe a procedure that resolves these difficulties. The approach is illustrated on boiling points of nonanes which are considered (1) by using an ordered connectivity basis; (2) by using an ordering resulting from application of greedy algorithm; and (3) by using an ordering derived from an exhaustive search for optimal descriptors. A novel variant of multiple regression analysis, called retro-regression (RR), is outlined showing how it resolves the ambiguities associated with both "nightmares" of the first and the second kind of MRA. PMID:11410035

  1. The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells

    PubMed Central

    Caron, Marjolein M. J.; Emans, Pieter J.; Sanen, Kathleen; Surtel, Don A. M.; Cremers, Andy; Ophelders, Daan; van Rhijn, Lodewijk W.; Welting, Tim J. M.

    2016-01-01

    Objectives NSAIDs are used to relieve pain and decrease inflammation by inhibition of cyclooxygenase (COX)-catalyzed prostaglandin (PG) synthesis. PGs are fatty acid mediators involved in cartilage homeostasis, however the action of their synthesizing COX-enzymes in cartilage differentiation is not well understood. In this study we hypothesized that COX-1 and COX-2 have differential roles in chondrogenic differentiation. Methods ATDC5 cells were differentiated in the presence of COX-1 (SC-560, Mofezolac) or COX-2 (NS398, Celecoxib) specific inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin levels were determined by EIA. Prostaglandins were added during the differentiation process. Chondrogenic outcome was determined by gene- and protein expression analyses. Results Inhibition of COX-1 prevented Col2a1 and Col10a1 expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while Col2a1 remained unaffected. To explain this difference expression patterns of both COX-enzymes as well as specific prostaglandin concentrations were determined. Both COX-enzymes are upregulated during late chondrogenic differentiation, whereas only COX-2 is briefly expressed also early in differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas PGF2α and TXA2 levels remained low. Furthermore, COX inhibition resulted in decreased levels of all tested PGs, except for PGD2 and PGF2α in the COX-1 inhibited condition. Addition of PGE2 and PGF2α resulted in increased expression of chondrogenic markers, whereas TXA2 increased expression of hypertrophic markers. Conclusions Our findings point towards a differential role for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells. Ongoing research is focusing on further elucidating the functional partition of cyclooxygenases and specific prostaglandin production. PMID:27050768

  2. Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: Involvement of iNOS and COX-2

    PubMed Central

    Pandurangan, Ashok Kumar; Kumar, Suresh Ananda Sadagopan; Dharmalingam, Prakash; Ganapasam, Sudhandiran

    2014-01-01

    Colon cancer (CRC) is a serious health problem through worldwide. Development of novel drug without side effect for this cancer was crucial. Luteolin (LUT), a bioflavonoid has many beneficial effects such as antioxidant, anti-inflammatory, anti-proliferative properties. Azoxymethane (AOM), a derivative of 1, 2-Dimethyl hydrazine (DMH) was used for the induction of CRC in Balb/C mice. CRC was induced by intraperitoneal injection of AOM to mice at the dose of 15 mg/body kg weight for 3 weeks. Mouse was treated with LUT at the dose of 1.2 mg/body kg weight orally until end of the experiment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygense (COX)-2 were analyzed by RT-PCR and immunohistochemistry. The expressions of iNOS and COX-2 were increased in the case of AOM induction. Administration of LUT effectively reduced the expressions of iNOS and COX-2. The present study revealed that, LUT suppresses both iNOS and COX-2 expressions and act as an anti-inflammatory role against CRC. PMID:24991108

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

    PubMed

    Gouda, Ahmed M; Ali, Hamed I; Almalki, Waleed H; Azim, Mohamed A; Abourehab, Mohammed A S; Abdelazeem, Ahmed H

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45-5.69 µM and 0.85-3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile. PMID:26867188

  4. The Role of COX-2 in the Inflammatory and Fibrotic Response in the Lung Following Exposure to Multi-Walled Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Sayers, Brian C.

    Exposure to multiwalled carbon nanotubes (MWCNT) has been demonstrated to exacerbate airway inflammation and fibrosis in allergen-challenged mouse model. These data have led to concern that individuals with asthma could represent a susceptible population to adverse health effects following exposure to MWCNT, and possibly other engineered nanoparticles. Asthma pathogenesis is caused by the interaction of a complex genetic predisposition and environmental exposures. Because chronic airway inflammation is common to all asthma phenotypes, it is logical to investigate genes that are involved in inflammatory pathways in order to understand the genetic basis of asthma. The metabolism of arachidonic acid by cyclooxygenase (COX) enzymes is the rate-determining step in the synthesis of prostanoids, which are biologically active lipids that are important modulators of inflammation. Based on the role of COX enzymes in inflammatory pathways, we sought to investigate how COX enzymes are involved in the inflammatory response following MWCNT exposure in asthmatic airways. We report that MWCNT significantly exacerbated allergen-induced airway inflammation and mucus cell metaplasia in COX-2 deficient mice compared to wild type mice. In addition, MWCNTs significantly enhanced allergen-induced cytokines involved in Th2 (IL-13, IL-5), Th1 (CXCL10), and Th17 (IL-17A) inflammatory responses in COX-2 deficient mice but not in WT mice. We conclude that exacerbation of allergen-induced airway inflammation and mucus cell metaplasia by MWCNTs is enhanced by deficiency in COX-2 and associated with activation of a mixed Th1/Th2/Th17 immune response. Based on our observation that COX-2 deficient mice developed a mixed Th immune response following MWCNT exposure, we sought to evaluate how cytokines associated with different Th immune responses alter COX expression following MWCNT exposure. For this study, a mouse macrophage cell line (RAW264.7) was used because MWCNT were largely sequestered

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

    PubMed

    Watanabe, K I; Ohama, T

    2001-01-01

    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

  6. Application of nonparametric regression and statistical testing to identify the impact of oil and natural gas development on local air quality

    SciTech Connect

    Pekney, Natalie J.; Cheng, Hanqi; Small, Mitchell J.

    2015-11-05

    Abstract: The objective of the current work was to develop a statistical method and associated tool to evaluate the impact of oil and natural gas exploration and production activities on local air quality.

  7. Bootstrapping a change-point Cox model for survival data.

    PubMed

    Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

    2014-08-20

    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

  8. Room temperature ferromagnetic (Fe₁-xCox)₃BO₅ nanorods.

    PubMed

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

    2014-07-01

    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

  9. Electron paramagnetic resonance in Zn1-xCoxO

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  10. Cox26 is a novel stoichiometric subunit of the yeast cytochrome c oxidase.

    PubMed

    Levchenko, Maria; Wuttke, Jan-Moritz; Römpler, Katharina; Schmidt, Bernhard; Neifer, Klaus; Juris, Lisa; Wissel, Mirjam; Rehling, Peter; Deckers, Markus

    2016-07-01

    The cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain. The complex accepts electrons from cytochrome c and passes them onto molecular oxygen. This process contributes to energy capture in the form of a membrane potential across the inner membrane. The enzyme complex assembles in a stepwise process from the three mitochondria-encoded core subunits Cox1, Cox2 and Cox3, which associate with nuclear-encoded subunits and cofactors. In the yeast Saccharomyces cerevisiae, the cytochrome c oxidase associates with the bc1-complex into supercomplexes, allowing efficient energy transduction. Here we report on Cox26 as a protein found in respiratory chain supercomplexes containing cytochrome c oxidase. Our analyses reveal Cox26 as a novel stoichiometric structural subunit of the cytochrome c oxidase. A loss of Cox26 affects cytochrome c oxidase activity and respirasome organization. PMID:27083394

  11. Quality Reporting of Multivariable Regression Models in Observational Studies

    PubMed Central

    Real, Jordi; Forné, Carles; Roso-Llorach, Albert; Martínez-Sánchez, Jose M.

    2016-01-01

    Abstract Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE. Review of a representative sample of articles indexed in MEDLINE (n = 428) with observational design and use of MRMs (logistic, linear, and Cox regression). We assessed the quality of reporting about: model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model. The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0–30.3) of the articles and 18.5% (95% CI: 14.8–22.1) reported the interaction analysis. Reporting of all items assessed was higher in articles published in journals with a higher impact factor. A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature. PMID:27196467

  12. Ecological Regression and Voting Rights.

    ERIC Educational Resources Information Center

    Freedman, David A.; And Others

    1991-01-01

    The use of ecological regression in voting rights cases is discussed in the context of a lawsuit against Los Angeles County (California) in 1990. Ecological regression assumes that systematic voting differences between precincts are explained by ethnic differences. An alternative neighborhood model is shown to lead to different conclusions. (SLD)

  13. Logistic Regression: Concept and Application

    ERIC Educational Resources Information Center

    Cokluk, Omay

    2010-01-01

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

  14. [Regression grading in gastrointestinal tumors].

    PubMed

    Tischoff, I; Tannapfel, A

    2012-02-01

    Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification. PMID:22293790

  15. Development of an Agent-Based Model (ABM) to Simulate the Immune System and Integration of a Regression Method to Estimate the Key ABM Parameters by Fitting the Experimental Data

    PubMed Central

    Tong, Xuming; Chen, Jinghang; Miao, Hongyu; Li, Tingting; Zhang, Le

    2015-01-01

    Agent-based models (ABM) and differential equations (DE) are two commonly used methods for immune system simulation. However, it is difficult for ABM to estimate key parameters of the model by incorporating experimental data, whereas the differential equation model is incapable of describing the complicated immune system in detail. To overcome these problems, we developed an integrated ABM regression model (IABMR). It can combine the advantages of ABM and DE by employing ABM to mimic the multi-scale immune system with various phenotypes and types of cells as well as using the input and output of ABM to build up the Loess regression for key parameter estimation. Next, we employed the greedy algorithm to estimate the key parameters of the ABM with respect to the same experimental data set and used ABM to describe a 3D immune system similar to previous studies that employed the DE model. These results indicate that IABMR not only has the potential to simulate the immune system at various scales, phenotypes and cell types, but can also accurately infer the key parameters like DE model. Therefore, this study innovatively developed a complex system development mechanism that could simulate the complicated immune system in detail like ABM and validate the reliability and efficiency of model like DE by fitting the experimental data. PMID:26535589

  16. Development of an Agent-Based Model (ABM) to Simulate the Immune System and Integration of a Regression Method to Estimate the Key ABM Parameters by Fitting the Experimental Data.

    PubMed

    Tong, Xuming; Chen, Jinghang; Miao, Hongyu; Li, Tingting; Zhang, Le

    2015-01-01

    Agent-based models (ABM) and differential equations (DE) are two commonly used methods for immune system simulation. However, it is difficult for ABM to estimate key parameters of the model by incorporating experimental data, whereas the differential equation model is incapable of describing the complicated immune system in detail. To overcome these problems, we developed an integrated ABM regression model (IABMR). It can combine the advantages of ABM and DE by employing ABM to mimic the multi-scale immune system with various phenotypes and types of cells as well as using the input and output of ABM to build up the Loess regression for key parameter estimation. Next, we employed the greedy algorithm to estimate the key parameters of the ABM with respect to the same experimental data set and used ABM to describe a 3D immune system similar to previous studies that employed the DE model. These results indicate that IABMR not only has the potential to simulate the immune system at various scales, phenotypes and cell types, but can also accurately infer the key parameters like DE model. Therefore, this study innovatively developed a complex system development mechanism that could simulate the complicated immune system in detail like ABM and validate the reliability and efficiency of model like DE by fitting the experimental data. PMID:26535589

  17. Cyclooxygenases (COX-1 and COX-2) for tissue engineering of articular cartilage--from a developmental model to first results of tissue and scaffold expression.

    PubMed

    Brochhausen, Christoph; Zehbe, Rolf; Gross, Ulrich; Libera, Jeanette; Schubert, Helmut; Nüsing, Rolf M; Klaus, Günter; Kirkpatrick, C James

    2008-01-01

    Tissue engineering of articular cartilage remains an ongoing challenge. Since tissue regeneration recapitulates ontogenetic processes the growth plate can be regarded as an innovative model to target suitable signalling molecules and growth factors for the tissue engineering of cartilage. In the present study we analysed the expression of cyclooxygenases (COX) in a short-term chondrocyte culture in gelatin-based scaffolds and in articular cartilage of rats and compared it with that in the growth plate. Our results demonstrate the strong cellular expression of COX-1 but only a focal weak expression of COX-2 in the seeded scaffolds. Articular cartilage of rats expresses homogeneously COX-1 and COX-2 with the exception of the apical cell layer. Our findings indicate a functional role of COX in the metabolism of articular chondrocytes. The expression of COX in articular cartilage and in the seeded scaffolds opens interesting perspectives to improve the proliferation and differentiation of chondrocytes in scaffold materials by addition of specific receptor ligands of the COX system. PMID:18198403

  18. Translocation and Assembly of Mitochondrially Coded Saccharomyces cerevisiae Cytochrome c Oxidase Subunit Cox2 by Oxa1 and Yme1 in the Absence of Cox18

    PubMed Central

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

    2009-01-01

    Members of the Oxa1/YidC/Alb3 family of protein translocases are essential for assembly of energy-transducing membrane complexes. In Saccharomyces cerevisiae, Oxa1 and its paralog, Cox18, are required for assembly of Cox2, a mitochondrially encoded subunit of cytochrome c oxidase. Oxa1 is known to be required for cotranslational export of the Cox2 N-terminal domain across the inner mitochondrial membrane, while Cox18 is known to be required for post-translational export of the Cox2 C-tail domain. We find that overexpression of Oxa1 does not compensate for the absence of Cox18 at the level of respiratory growth. However, it does promote some translocation of the Cox2 C-tail domain across the inner membrane and causes increased accumulation of Cox2, which remains unassembled. This result suggests that Cox18 not only translocates the C-tail, but also must deliver it in a distinct state competent for cytochrome oxidase assembly. We identified respiring mutants from a cox18Δ strain overexpressing OXA1, whose respiratory growth requires overexpression of OXA1. The recessive nuclear mutations allow some assembly of Cox2 into cytochrome c oxidase. After failing to identify these mutations by methods based on transformation, we successfully located them to MGR1 and MGR3 by comparative hybridization to whole-genome tiling arrays and microarray-assisted bulk segregant analysis followed by linkage mapping. While Mgr1 and Mgr3 are known to associate with the Yme1 mitochondrial inner membrane i-AAA protease and to participate in membrane protein degradation, their absence does not appear to stabilize Cox2 under these conditions. Instead, Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 in the absence of Mrg1 or Mgr3, since respiratory growth and cytochrome c oxidase assembly in a cox18 mgr3 double-mutant strain overexpressing OXA1 is YME1 dependent. PMID:19307606

  19. miR-203 is involved in the laryngeal carcinoma pathogenesis via targeting VEGFA and Cox-2

    PubMed Central

    Xu, Lin; Shen, Bin; Chen, Tingting; Dong, Pin

    2016-01-01

    The development of laryngeal squamous cell carcinoma (LSCC) is a multistep process involving multiple factors. MicroRNAs, a group of important negative regulators of gene expression, have also been confirmed to be involved in the LSCC pathogenesis. In the present study, we compared the expression of nine selected microRNAs in the LSCC tissues and adjacent nontumor tissues. We found that the expression of miR-203 was significantly reduced in the LSCC tissues. Predicted by using bioinformatics tools, we found that VEGFA and cyclooxygenase-2 (Cox-2) may be direct targets of miR-203. By subsequent determination through dual-luciferase assay and Western blot, we confirmed that miR-203 suppresses the expression of VEGFA and Cox-2 by directly targeting 3′-untranslated region. Meanwhile, by analyzing the relationship between miR-203 and VEGFA in clinical tissue samples, we found that a negative correlation existed in the expression of miR-203 and VEGFA (P=0.0096, r=−0.33). Similarly, the expression of miR-203 and Cox-2 also has a negative correlation (P=0.0019, r=−0.46). Subsequently, in vitro functional study indicated that miR-203 played as a tumor suppressor by repressing proliferation, migration, and invasion of Hep-2 cells. The overexpression of VEGFA partially rescued the effect of overexpressed miR-203. Overexpressed Cox-2 partially rescued the effect of miR-203 on Hep-2 cell proliferation but not on the cell migration and invasion capacity. These findings suggest that miR-203 plays as a tumor suppressor in LSCC, partially by regulating VEGFA and Cox-2, and may serve as a potential target for therapeutic intervention. PMID:27555783

  20. Insulin resistance: regression and clustering.

    PubMed

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

    2014-01-01

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

  1. Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.

    PubMed

    Srinivas, N R

    2016-08-01

    Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins. The prediction of AUCs for various statins (pravastatin, atorvastatin, simvastatin and rosuvastatin) was carried out using the newly developed dual pharmacokinetic and pharmacodynamic model. Generally, the AUC predictions were contained within 0.5 to 2-fold difference of the observed AUC suggesting utility of the new models. The root mean square error predictions were<45% for the 2 models. On the basis of the present work, it is feasible to utilize both pharmacokinetic (Cmax) and pharmacodynamic (IC50) data for effectively predicting the AUC for statins. Such a new concept as described in the work may have utility in both drug discovery and development stages. PMID:27144659

  2. Using Regression Analysis: A Guided Tour.

    ERIC Educational Resources Information Center

    Shelton, Fred Ames

    1987-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  4. Multiple weight stepwise regression

    SciTech Connect

    Atkins, J. |; Campbell, J.

    1993-10-01

    In many science and engineering applications, there is an interest in predicting the outputs of a process for given levels of inputs. In order to develop a model, one could run the process (or a simulation of the process) at a number of points (a point would be one run at one set of possible input values) and observe the values of the outputs at those points. There observations can be used to predict the values of the outputs for other values of the inputs. Since the outputs are a function of the inputs, we can generate a surface in the space of possible inputs and outputs. This surface is called a response surface. In some cases, collecting data needed to generate a response surface can e very expensive. Thus, in these cases, there is a powerful incentive to minimize the sample size while building better response surfaces. One such case is the semiconductor equipment manufacturing industry. Semiconductor manufacturing equipment is complex and expensive. Depending upon the type of equipment, the number of control parameters may range from 10 to 30 with perhaps 5 to 10 being important. Since a single run can cost hundreds or thousands of dollars, it is very important to have efficient methods for building response surfaces. A current approach to this problem is to do the experiment in two stages. First, a traditional design (such as fractional factorial) is used to screen variables. After deciding which variables are significant, additional runs of the experiment are conducted. The original runs and the new runs are used to build a model with the significant variables. However, the original (screening) runs are not as helpful for building the model as some other points might have been. This paper presents a point selection scheme that is more efficient than traditional designs.

  5. Practical Session: Simple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

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

  6. Regression models for estimating coseismic landslide displacement

    USGS Publications Warehouse

    Jibson, R.W.

    2007-01-01

    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.

  7. Computed statistics at streamgages, and methods for estimating low-flow frequency statistics and development of regional regression equations for estimating low-flow frequency statistics at ungaged locations in Missouri

    USGS Publications Warehouse

    Southard, Rodney E.

    2013-01-01

    The weather and precipitation patterns in Missouri vary considerably from year to year. In 2008, the statewide average rainfall was 57.34 inches and in 2012, the statewide average rainfall was 30.64 inches. This variability in precipitation and resulting streamflow in Missouri underlies the necessity for water managers and users to have reliable streamflow statistics and a means to compute select statistics at ungaged locations for a better understanding of water availability. Knowledge of surface-water availability is dependent on the streamflow data that have been collected and analyzed by the U.S. Geological Survey for more than 100 years at approximately 350 streamgages throughout Missouri. The U.S. Geological Survey, in cooperation with the Missouri Department of Natural Resources, computed streamflow statistics at streamgages through the 2010 water year, defined periods of drought and defined methods to estimate streamflow statistics at ungaged locations, and developed regional regression equations to compute selected streamflow statistics at ungaged locations. Streamflow statistics and flow durations were computed for 532 streamgages in Missouri and in neighboring States of Missouri. For streamgages with more than 10 years of record, Kendall’s tau was computed to evaluate for trends in streamflow data. If trends were detected, the variable length method was used to define the period of no trend. Water years were removed from the dataset from the beginning of the record for a streamgage until no trend was detected. Low-flow frequency statistics were then computed for the entire period of record and for the period of no trend if 10 or more years of record were available for each analysis. Three methods are presented for computing selected streamflow statistics at ungaged locations. The first method uses power curve equations developed for 28 selected streams in Missouri and neighboring States that have multiple streamgages on the same streams. Statistical

  8. Uncertainty quantification in DIC with Kriging regression

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  9. Efficient Regressions via Optimally Combining Quantile Information*

    PubMed Central

    Zhao, Zhibiao; Xiao, Zhijie

    2014-01-01

    We develop a generally applicable framework for constructing efficient estimators of regression models via quantile regressions. The proposed method is based on optimally combining information over multiple quantiles and can be applied to a broad range of parametric and nonparametric settings. When combining information over a fixed number of quantiles, we derive an upper bound on the distance between the efficiency of the proposed estimator and the Fisher information. As the number of quantiles increases, this upper bound decreases and the asymptotic variance of the proposed estimator approaches the Cramér-Rao lower bound under appropriate conditions. In the case of non-regular statistical estimation, the proposed estimator leads to super-efficient estimation. We illustrate the proposed method for several widely used regression models. Both asymptotic theory and Monte Carlo experiments show the superior performance over existing methods. PMID:25484481

  10. Regional Differences in the Neuronal Expression of Cyclooxygenase-2 (COX-2) in the Newborn Pig Brain

    PubMed Central

    Oláh, Orsolya; Németh, István; Tóth-Szűki, Valéria; Bari, Ferenc; Domoki, Ferenc

    2012-01-01

    Cyclooxygenase (COX)-2 is the major constitutively expressed COX isoform in the newborn brain. COX-2 derived prostanoids and reactive oxygen species appear to play a major role in the mechanism of perinatal hypoxic-ischemic injury in the newborn piglet, an accepted animal model of the human term neonate. The study aimed to quantitatively determine COX-2 immunopositive neurons in different brain regions in piglets under normoxic conditions (n=15), and 4 hours after 10 min asphyxia (n=11). Asphyxia did not induce significant changes in neuronal COX-2 expression of any studied brain areas. In contrast, there was a marked regional difference in all experimental groups. Thus, significant difference was observed between fronto-parietal and temporo-occipital regions: 59±4% and 67±3% versus 41±2%* and 31±3%* respectively (mean±SEM, data are pooled from all subjects, n=26, *p<0.05, vs. fronto-parietal region). In the hippocampus, COX-2 immunopositivity was rare (highest expression in CA1 region: 14±2%). The studied subcortical areas showed negligible COX-2 staining. Our findings suggest that asphyxia does not significantly alter the pattern of neuronal COX-2 expression in the early reventilation period. Furthermore, based on the striking differences observed in cortical neuronal COX-2 distribution, the contribution of COX-2 mediated neuronal injury after asphyxia may also show region-specific differences. PMID:22829712

  11. iNOS signaling interacts with COX-2 pathway in colonic fibroblasts.

    PubMed

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-10-01

    COX-2 and iNOS are two major inflammatory mediators implicated in colorectal inflammation and cancer. Previously, the role of colorectal fibroblasts involved in regulation of COX-2 and iNOS expression was largely ignored. In addition, the combined interaction of COX-2 and iNOS signalings and their significance in the progression of colorectal inflammation and cancer within the fibroblasts have received little investigation. To address those issues, we investigated the role of colonic fibroblasts in the regulation of COX-2 and iNOS gene expression, and explored possible mechanisms of interaction between COX-2 and iNOS signalings using a colonic CCD-18Co fibroblast line and LPS, a potential stimulator of COX-2 and iNOS. Our results clearly demonstrated that LPS activated COX-2 gene expression and enhanced PGE(2) production, stimulated iNOS gene expression and promoted NO production in the fibroblasts. Interestingly, activation of COX-2 signaling by LPS was not involved in activation of iNOS signaling, while activation of iNOS signaling by LPS contributed in part to activation of COX-2 signaling. Further analysis indicated that PKC plays a major role in the activation and interaction of COX-2 and iNOS signalings induced by LPS in the fibroblasts. PMID:22683859

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

    SciTech Connect

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

    2007-07-12

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

  13. Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat).

    PubMed

    Theilig, F; Debiec, H; Nafz, B; Ronco, P; Nüsing, R; Seyberth, H W; Pavenstädt, H; Bouby, N; Bachmann, S

    2006-11-01

    Renal volume regulation is modulated by the action of cyclooxygenases (COX) and the resulting generation of prostanoids. Epithelial expression of COX isoforms in the cortex directs COX-1 to the distal convolutions and cortical collecting duct, and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E synthase (PGES), the downstream enzyme for renal prostaglandin E(2) (PGE(2)) generation, and the EP receptors type 1 and 3. COX-1 and related components were studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined chronic ANG II or bradykinin B(2) receptor blockade using candesartan (cand) or the B(2) antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham + cand, 2K1C + cand, sham + Hoe, 2K1C + Hoe) were treated to map expression of parameters controlling PGE(2) synthesis. In 2K1C, cortical COX isoforms did not change uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1 and PGES were uniformly downregulated in both kidneys, along with reduced urinary PGE(2) levels, and showed no clear relations with the NO status. ANG II receptor blockade confirmed negative regulation of COX-2 by ANG II but blunted the decrease in COX-1 selectively in nonclipped kidneys. B(2) receptor blockade reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct. PMID:16788145

  14. Abstract Expression Grammar Symbolic Regression

    NASA Astrophysics Data System (ADS)

    Korns, Michael F.

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

  15. Multiple Regression and Its Discontents

    ERIC Educational Resources Information Center

    Snell, Joel C.; Marsh, Mitchell

    2012-01-01

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

  16. Basis Selection for Wavelet Regression

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  17. Regression methods for spatial data

    NASA Technical Reports Server (NTRS)

    Yakowitz, S. J.; Szidarovszky, F.

    1982-01-01

    The kriging approach, a parametric regression method used by hydrologists and mining engineers, among others also provides an error estimate the integral of the regression function. The kriging method is explored and some of its statistical characteristics are described. The Watson method and theory are extended so that the kriging features are displayed. Theoretical and computational comparisons of the kriging and Watson approaches are offered.

  18. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  19. Gaussian estimation for discretely observed Cox-Ingersoll-Ross model

    NASA Astrophysics Data System (ADS)

    Wei, Chao; Shu, Huisheng; Liu, Yurong

    2016-07-01

    This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.

  20. (R)-Profens Are Substrate-Selective Inhibitors of Endocannabinoid Oxygenation by COX-2

    PubMed Central

    Duggan, Kelsey C.; Hermanson, Daniel J.; Musee, Joel; Prusakiewicz, Jeffery J.; Scheib, Jami L.; Carter, Bruce D.; Banerjee, Surajit; Oates, J.A.; Marnett, Lawrence J.

    2012-01-01

    Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids, 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak, competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R)-Enantiomers of ibuprofen, naproxen, and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent “substrate-selective inhibitors” of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R)-enantiomers relative to (S)-enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion cells. Substrate-selective inhibition provides novel tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain. PMID:22053353

  1. Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-κB- and MAPK-ERK1/2-mediated COX-2 expression

    PubMed Central

    Lin, Chun-Kuang; Tseng, Chin-Kai; Chen, Kai-Hsun; Wu, Shih-Hsiung; Liaw, Chih-Chuang; Lee, Jin-Ching

    2015-01-01

    Background and Purpose This study was designed to evaluate the effect of betulinic acid (BA), extracted from Avicennia marina, on the replication of hepatitis C virus (HCV) and to investigate the mechanism of this BA-mediated anti-HCV activity. Experimental Approach HCV replicon and infectious systems were used to evaluate the anti-HCV activity of BA. Exogenous COX-2 or knock-down of COX-2 expression was used to investigate the role of COX-2 in the anti-HCV activity of BA. The effects of BA on the phosphorylation of NF-κB and on kinases in the MAPK signalling pathway were determined. The anti-HCV activity of BA in combination with other HCV inhibitors was also determined to assess its use as an anti-HCV supplement. Key Results BA inhibited HCV replication in both Ava5 replicon cells and in a cell culture-derived infectious HCV particle system. Treatment with a combination of BA and IFN-α, the protease inhibitor telaprevir or the NS5B polymerase inhibitor sofosbuvir resulted in the synergistic suppression of HCV RNA replication. Exogenous overexpression of COX-2 gradually attenuated the inhibitory effect of BA on HCV replication, suggesting that BA reduces HCV replication by suppressing the expression of COX-2. In particular, BA down-regulated HCV-induced COX-2 expression by reducing the phosphorylation of NF-κB and ERK1/2 of the MAPK signalling pathway. Conclusions and Implications BA inhibits HCV replication by suppressing the NF-κB- and ERK1/2-mediated COX-2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV-infected patients. PMID:26102077

  2. ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells: Role of P2 Receptor-Dependent STAT3 Activation

    PubMed Central

    Cheng, Shin-Ei; Lee, I-Ta; Lin, Chih-Chung; Wu, Wan-Ling; Hsiao, Li-Der; Yang, Chuen-Mao

    2013-01-01

    Background Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE2 release remain unclear. Principal Findings Here, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin), PKC (Gö6983, Gö6976, Ro318220, and Rottlerin), ROS (Edaravone), NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin], Jak2 (AG490), and STAT3 [cucurbitacin E (CBE)] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47phox, Jak2, STAT3, and cPLA2 markedly reduced ATPγS-induced COX-2 expression and PGE2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPγS. Moreover, ATPγS-induced ROS generation and p47phox translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPγS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Gö6983, Gö6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells. Significance Taken together, these results showed that ATPγS induced COX-2 expression and PGE2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies. PMID:23326583

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed Central

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

    2015-01-01

    Introduction We have shown that diesel exhaust (DE) inhalation caused progression of atherosclerosis; however, the mechanisms are not fully understood. We hypothesize that exposure to DE upregulates cyclooxygenase (COX) expression and activity, which could play a role in DE-induced atherosclerosis. Methods ApoE knockout mice (30-week old) fed with regular chow were exposed to DE (at 200 μg/m3 of particulate matter) or filtered air (control) for 7 weeks (6 h/day, 5 days/week). The protein and mRNA expression of COX-1 and COX-2 were evaluated by immunohistochemistry analysis and quantitative real-time PCR, respectively. To examine COX activity, thoracic aortae were mounted in a wire myograph, and phenylephrine (PE)-stimulated vasoconstriction was measured with and without the presence of COX antagonists (indomethacin). COX-2 activity was further assessed by urine 2,3-dinor-6-keto PGF1α level, a major metabolite of prostacyclin I2 (PGI2). Results Immunohistochemistry analysis demonstrates that DE exposure enhanced COX-2 expression in both thoracic aorta (p < 0.01) and aortic root (p < 0.03), with no modification of COX-1 expression. The increased COX-2 expression was positively correlated with smooth muscle cell content in aortic lesions (R2 = 0.4081, p < 0.008). The fractional changes of maximal vasoconstriction in the presence of indomethacin was attenuated by 3-fold after DE exposure (p < 0.02). Urine 2,3-dinor-6-keto PGF1α level was 15-fold higher in DE group than the control (p < 0.007). The mRNA expression of COX-2 (p < 0.006) and PGI synthase (p < 0.02), but not COX-1, was significantly augmented after DE exposure. Conclusion We show that DE inhalation enhanced COX-2 expression, which is also associated with phenotypic changes of aortic lesion. PMID:22746401

  5. Synaptic and extrasynaptic NMDA receptors differentially modulate neuronal COX-2 function, lipid peroxidation, and neuroprotection

    PubMed Central

    Stark, David T.; Bazan, Nicolas G.

    2011-01-01

    Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme mediates neuronal functions, COX-2 is also regarded as a key modulator of neuroinflammation and is thought to exacerbate excitotoxicity via overproduction of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro-survival yet are essential for robust neuronal COX-2 expression. We hypothesized that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a physiological to a potentially pathological process. We combined HPLC-ESI-MS/MS-based mediator lipidomics and unbiased image analysis in mouse dissociated and organotypic cortical cultures to uncover that synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2 expression and activity. We show that synaptic NMDARs enhance neuronal COX-2 expression, while sustained synaptic stimulation limits COX-2 activity by suppressing cellular levels of the primary COX-2 substrate, arachidonic acid (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while activating phospholipase A2 (PLA2), which enhances AA levels by hydrolysis of membrane phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic events only drive induction of COX-2 expression through abnormal synaptic network excitability. Finally, we show that non-enzymatic lipid peroxidation of arachidonic and other polyunsaturated fatty acids is a function of network activity history. A new paradigm emerges from our results suggesting that pathological COX-2 signaling associated with models of stroke, epilepsy, and neurodegeneration requires specific spatio-temporal NMDAR stimulation. PMID:21957234

  6. Population death sequences and Cox processes driven by interacting Feller diffusions

    NASA Astrophysics Data System (ADS)

    Wei, Gang; Clifford, Peter; Feng, Jianfeng

    2002-11-01

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

  7. Probiotics regulate the expression of COX-2 in intestinal epithelial cells.

    PubMed

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

    2009-01-01

    Cyclooxygenase-2 (COX) 2 promotes intestinal wound healing but elicits also proinflammatory effects and has been implicated in colorectal carcinogenesis. Thus, a balanced expression of COX-2 is essential for intestinal homeostasis. This study was designed to evaluate the regulation of COX-2 by probiotic organisms and to characterize ligands and receptors involved. Colo320 and SW480 intestinal epithelial cells (IEC) were stimulated with gastrin or TNF-alpha and pre- or coincubated with commensales, bacterial supernatants, or distinct toll-like receptor (TLR) ligands. COX-2 promoter activity was determined by luciferase assays, protein expression by Western blotting, and secretion of prostaglandin E(2) (PGE(2)) by ELISA. Commensales differentially regulated COX-2 expression in IEC. E. coli Nissle 1917, the probiotic mixture VSL#3, and media conditioned by these organisms ameliorated induced COX-2 expression and PGE(2) secretion. Heat inactivation and DNase treatment significantly decreased these regulatory capacities. Lactobacillus acidophilus, however, significantly increased COX-2 expression and PGE(2) secretion. TLR agonists differentially ameliorated basal or induced COX-2 expression. Distinct probiotics specifically and significantly decrease induced COX-2 expression in IEC, most likely mediated by released factors and in part by bacterial DNA. A significant involvement of TLRs in these regulatory processes remains to be established. PMID:19116880

  8. Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer.

    PubMed

    Dash, Raju; Uddin, Mir Muhammad Nasir; Hosen, S M Zahid; Rahim, Zahed Bin; Dinar, Abu Mansur; Kabir, Mohammad Shah Hafez; Sultan, Ramiz Ahmed; Islam, Ashekul; Hossain, Md Kamrul

    2015-01-01

    Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration. PMID:26770028

  9. Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

    PubMed Central

    Dash, Raju; Uddin, Mir Muhammad Nasir; Hosen, S.M. Zahid; Rahim, Zahed Bin; Dinar, Abu Mansur; Kabir, Mohammad Shah Hafez; Sultan, Ramiz Ahmed; Islam, Ashekul; Hossain, Md Kamrul

    2015-01-01

    Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration. PMID:26770028

  10. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation

    PubMed Central

    Chennamaneni, Snigdha; Yi, Xin; Liu, lili; Pink, John J.; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2014-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100nM to 200nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100nM to 500nM. Intraperitoneal injection with a dosage of 5mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  11. Demonstration of a Fiber Optic Regression Probe

    NASA Technical Reports Server (NTRS)

    Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    The capability to provide localized, real-time monitoring of material regression rates in various applications has the potential to provide a new stream of data for development testing of various components and systems, as well as serving as a monitoring tool in flight applications. These applications include, but are not limited to, the regression of a combusting solid fuel surface, the ablation of the throat in a chemical rocket or the heat shield of an aeroshell, and the monitoring of erosion in long-life plasma thrusters. The rate of regression in the first application is very fast, while the second and third are increasingly slower. A recent fundamental sensor development effort has led to a novel regression, erosion, and ablation sensor technology (REAST). The REAST sensor allows for measurement of real-time surface erosion rates at a discrete surface location. The sensor is optical, using two different, co-located fiber-optics to perform the regression measurement. The disparate optical transmission properties of the two fiber-optics makes it possible to measure the regression rate by monitoring the relative light attenuation through the fibers. As the fibers regress along with the parent material in which they are embedded, the relative light intensities through the two fibers changes, providing a measure of the regression rate. The optical nature of the system makes it relatively easy to use in a variety of harsh, high temperature environments, and it is also unaffected by the presence of electric and magnetic fields. In addition, the sensor could be used to perform optical spectroscopy on the light emitted by a process and collected by fibers, giving localized measurements of various properties. The capability to perform an in-situ measurement of material regression rates is useful in addressing a variety of physical issues in various applications. An in-situ measurement allows for real-time data regarding the erosion rates, providing a quick method for

  12. COX-2 inhibitory NSAID-induced multiple stenosis in the small intestine diagnosed by double-balloon endoscopy

    PubMed Central

    Ueno, Yasuaki; Nakamura, Masanao; Watanabe, Osamu; Yamamura, Takeshi; Funasaka, Kohei; Ohno, Eizaburo; Miyahara, Ryoji; Kawashima, Hiroki; Goto, Hidemi; Hirooka, Yoshiki

    2016-01-01

    ABSTRACT The patient was a 72 year old man who had been given non-steroidal anti-inflammatory drug (NSAID) for two years. He repeatedly developed small intestinal ileus; therefore, he underwent several imaging examinations, but the cause was not identified. He subsequently underwent a double-balloon endoscopy (DBE). The membranous stenoses were detected in the jejunum, and the biopsy specimens were taken during the DBE. The membranous stenoses in the gastrointestinal tract were characteristic of NSAID–induced enteropathy, and he was endoscopically and histopathologically diagnosed with NSAID-induced small intestinal disorder. NSAID administration was withdrawn, and the balloon dilation was conducted for small intestinal stenosis. After that, no small intestinal ileus developed again. Some studies were conducted on the mechanism of NSAID-induced small intestinal dysfunction, but the drug that was administered to the patient was a highly selective NSAID for cyclooxygenase (COX)-2, and there are few studies that reported a dysfunctional mechanism induced by this drug. In the tissue sampled by DBE, apoptotic bodies were found; therefore, it was suggested that the stenoses in this case were caused by the COX-2 inhibitor from the relationship between COX-2 inhibition and apoptosis. Further studies are necessary to investigate the mechanism of NSAID enteropathy.

  13. Interpretation of Standardized Regression Coefficients in Multiple Regression.

    ERIC Educational Resources Information Center

    Thayer, Jerome D.

    The extent to which standardized regression coefficients (beta values) can be used to determine the importance of a variable in an equation was explored. The beta value and the part correlation coefficient--also called the semi-partial correlation coefficient and reported in squared form as the incremental "r squared"--were compared for variables…

  14. Demosaicing Based on Directional Difference Regression and Efficient Regression Priors.

    PubMed

    Wu, Jiqing; Timofte, Radu; Van Gool, Luc

    2016-08-01

    Color demosaicing is a key image processing step aiming to reconstruct the missing pixels from a recorded raw image. On the one hand, numerous interpolation methods focusing on spatial-spectral correlations have been proved very efficient, whereas they yield a poor image quality and strong visible artifacts. On the other hand, optimization strategies, such as learned simultaneous sparse coding and sparsity and adaptive principal component analysis-based algorithms, were shown to greatly improve image quality compared with that delivered by interpolation methods, but unfortunately are computationally heavy. In this paper, we propose efficient regression priors as a novel, fast post-processing algorithm that learns the regression priors offline from training data. We also propose an independent efficient demosaicing algorithm based on directional difference regression, and introduce its enhanced version based on fused regression. We achieve an image quality comparable to that of the state-of-the-art methods for three benchmarks, while being order(s) of magnitude faster. PMID:27254866

  15. Climate Change Projections Using Regional Regression Models

    NASA Astrophysics Data System (ADS)

    Griffis, V. W.; Gyawali, R.; Watkins, D. W.

    2012-12-01

    A typical approach to project climate change impacts on water resources systems is to downscale general circulation model (GCM) or regional climate model (RCM) outputs as forcing data for a watershed model. With downscaled climate model outputs becoming readily available, multi-model ensemble approaches incorporating mutliple GCMs, multiple emissions scenarios and multiple initializations are increasingly being used. While these multi-model climate ensembles represent a range of plausible futures, different hydrologic models and methods may complicate impact assessment. In particular, associated loss, flow routing, snowmelt and evapotranspiration computation methods can markedly increase hydrological modeling uncertainty. Other challenges include properly calibrating and verifying the watershed model and maintaining a consistent energy budget between climate and hydrologic models. An alternative approach, particularly appealing for ungauged basins or locations where record lengths are short, is to directly predict selected streamflow quantiles from regional regression equations that include physical basin characteristics as well as meteorological variables output by climate models (Fennessey 2011). Two sets of regional regression models are developed for the Great Lakes states using ordinary least squares and weighted least squares regression. The regional regression modeling approach is compared with physically based hydrologic modeling approaches for selected Great Lakes watersheds using downscaled outputs from the Coupled Model Intercomparison Project (CMIP3) as inputs to the Large Basin Runoff Model (LBRM) and the U.S. Army Corps Hydrologic Modeling System (HEC-HMS).

  16. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1.

    PubMed

    Islam, Abul B M M K; Dave, Mandar; Amin, Sonia; Jensen, Roderick V; Amin, Ashok R

    2016-04-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2(-/-) or COX-1(-/-) mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2(-/-)>COX-1(-/-)>WT+IL-1β. COX-1(-/-) or COX-2(-/-) cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive "anti-inflammatory, proinflammatory, and redox-activated" signature in the protein-protein interactome map was observed in COX-2(-/-) cells. The augmented COX-1 mRNA (in COX-2(-/-) cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2(-/-) cells generated an "eicosanoid storm". The genomic characteristics of COX-2(-/-) is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1(-/-) and COX-2(-/-) cells exhibited compensation of various eicosanoids at the genomic and metabolic levels. PMID:27012456

  17. Genetic Deletion of COX-2 Diminishes VEGF Production in Mouse Retinal Müller Cells

    PubMed Central

    Yanni, Susan E.; McCollum, Gary W.; Penn, John S.

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX activity, reduce the production of retinal VEGF and neovascularization in relevant models of ocular disease. We hypothesized that COX-2 mediates VEGF production in retinal Müller cells, one of its primary sources in retinal neovascular disease. The purpose of this study was to determine the role of COX-2 and its products in VEGF expression and secretion. These studies have more clearly defined the role of COX-2 and COX-2-derived prostanoids in retinal angiogenesis. Müller cells derived from wild-type and COX-2 null mice were exposed to hypoxia for 0–24 hours. COX-2 protein and activity were assessed by western blot analysis and GC-MS, respectively. VEGF production was assessed by ELISA. Wild-type mouse Müller cells were treated with vehicle (0.1% DMSO), 10 µM PGE2, or PGE2 + 5 µM H-89 (a PKA inhibitor), for 12 hours. VEGF production was assessed by ELISA. Hypoxia significantly increased COX-2 protein (p ≤ 0.05) and activity (p ≤ 0.05), and VEGF production (p ≤ 0.0003). COX-2 null Müller cells produced significantly less VEGF in response to hypoxia (p ≤ 0.05). Of the prostanoids, PGE2 was significantly increased by hypoxia (p ≤ 0.02). Exogenous PGE2 significantly increased VEGF production by Müller cells (p ≤ 0.0039), and this effect was inhibited by H-89 (p ≤ 0.055). These data demonstrate that hypoxia induces COX-2, prostanoid production, and VEGF synthesis in Müller cells, and that VEGF production is at least partially COX-2-dependent. Our study suggests that PGE2, signaling through the EP2 and/or EP4 receptor and PKA, mediates the VEGF response of Müller cells. PMID:20398651

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

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2010-01-01

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

  19. Embedded Sensors for Measuring Surface Regression

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

    The development and evaluation of new hybrid and solid rocket motors requires accurate characterization of the propellant surface regression as a function of key operational parameters. These characteristics establish the propellant flow rate and are prime design drivers affecting the propulsion system geometry, size, and overall performance. There is a similar need for the development of advanced ablative materials, and the use of conventional ablatives exposed to new operational environments. The Miniature Surface Regression Sensor (MSRS) was developed to serve these applications. It is designed to be cast or embedded in the material of interest and regresses along with it. During this process, the resistance of the sensor is related to its instantaneous length, allowing the real-time thickness of the host material to be established. The time derivative of this data reveals the instantaneous surface regression rate. The MSRS could also be adapted to perform similar measurements for a variety of other host materials when it is desired to monitor thicknesses and/or regression rate for purposes of safety, operational control, or research. For example, the sensor could be used to monitor the thicknesses of brake linings or racecar tires and indicate when they need to be replaced. At the time of this reporting, over 200 of these sensors have been installed into a variety of host materials. An MSRS can be made in either of two configurations, denoted ladder and continuous (see Figure 1). A ladder MSRS includes two highly electrically conductive legs, across which narrow strips of electrically resistive material are placed at small increments of length. These strips resemble the rungs of a ladder and are electrically equivalent to many tiny resistors connected in parallel. A substrate material provides structural support for the legs and rungs. The instantaneous sensor resistance is read by an external signal conditioner via wires attached to the conductive legs on the

  20. Cactus: An Introduction to Regression

    ERIC Educational Resources Information Center

    Hyde, Hartley

    2008-01-01

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

  1. Fungible Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2008-01-01

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

  2. Spontaneous regression of breast cancer.

    PubMed

    Lewison, E F

    1976-11-01

    The dramatic but rare regression of a verified case of breast cancer in the absence of adequate, accepted, or conventional treatment has been observed and documented by clinicians over the course of many years. In my practice limited to diseases of the breast, over the past 25 years I have observed 12 patients with a unique and unusual clinical course valid enough to be regarded as spontaneous regression of breast cancer. These 12 patients, with clinically confirmed breast cancer, had temporary arrest or partial remission of their disease in the absence of complete or adequate treatment. In most of these cases, spontaneous regression could not be equated ultimately with permanent cure. Three of these case histories are summarized, and patient characteristics of pertinent clinical interest in the remaining case histories are presented and discussed. Despite widespread doubt and skepticism, there is ample clinical evidence to confirm the fact that spontaneous regression of breast cancer is a rare phenomenon but is real and does occur. PMID:799758

  3. Regression Models of Atlas Appearance

    PubMed Central

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

    2010-01-01

    Models of object appearance based on principal components analysis provide powerful and versatile tools in computer vision and medical image analysis. A major shortcoming is that they rely entirely on the training data to extract principal modes of appearance variation and ignore underlying variables (e.g., subject age, gender). This paper introduces an appearance modeling framework based instead on generalized multi-linear regression. The training of regression appearance models is controlled by independent variables. This makes it straightforward to create model instances for specific values of these variables, which is akin to model interpolation. We demonstrate the new framework by creating an appearance model of the human brain from MR images of 36 subjects. Instances of the model created for different ages are compared with average shape atlases created from age-matched sub-populations. Relative tissue volumes vs. age in models are also compared with tissue volumes vs. subject age in the original images. In both experiments, we found excellent agreement between the regression models and the comparison data. We conclude that regression appearance models are a promising new technique for image analysis, with one potential application being the representation of a continuum of mutually consistent, age-specific atlases of the human brain. PMID:19694260

  4. Regression models of atlas appearance.

    PubMed

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

    2009-01-01

    Models of object appearance based on principal components analysis provide powerful and versatile tools in computer vision and medical image analysis. A major shortcoming is that they rely entirely on the training data to extract principal modes of appearance variation and ignore underlying variables (e.g., subject age, gender). This paper introduces an appearance modeling framework based instead on generalized multi-linear regression. The training of regression appearance models is controlled by independent variables. This makes it straightforward to create model instances for specific values of these variables, which is akin to model interpolation. We demonstrate the new framework by creating an appearance model of the human brain from MR images of 36 subjects. Instances of the model created for different ages are compared with average shape atlases created from age-matched sub-populations. Relative tissue volumes vs. age in models are also compared with tissue volumes vs. subject age in the original images. In both experiments, we found excellent agreement between the regression models and the comparison data. We conclude that regression appearance models are a promising new technique for image analysis, with one potential application being the representation of a continuum of mutually consistent, age-specific atlases of the human brain. PMID:19694260

  5. Ridge Regression for Interactive Models.

    ERIC Educational Resources Information Center

    Tate, Richard L.

    1988-01-01

    An exploratory study of the value of ridge regression for interactive models is reported. Assuming that the linear terms in a simple interactive model are centered to eliminate non-essential multicollinearity, a variety of common models, representing both ordinal and disordinal interactions, are shown to have "orientations" that are favorable to…

  6. Inhibition of 11β-Hydroxysteroid Dehydrogenase Type II Suppresses Lung Carcinogenesis by Blocking Tumor COX-2 Expression as Well as the ERK and mTOR Signaling Pathways

    PubMed Central

    Yang, Shilin; Yao, Bing; Zhang, Bixiang; Chen, Xiaoping; Pozzi, Ambra; Zhang, Ming-Zhi

    2015-01-01

    Lung cancer is by far the leading cause of cancer death. Early diagnosis and prevention remain the best approach to reduce the overall morbidity and mortality. Experimental and clinical evidence have shown that cyclooxygenase-2 (COX-2) derived prostaglandin E2 (PGE2) contributes to lung tumorigenesis. COX-2 inhibitors suppress the development and progression of lung cancer. However, increased cardiovascular risks of COX-2 inhibitors limit their use in chemoprevention of lung cancers. Glucocorticoids are endogenous and potent COX-2 inhibitors, and their local actions are down-regulated by 11β–hydroxysteroid dehydrogenase type II (11ßHSD2)-mediated metabolism. We found that 11βHSD2 expression was increased in human lung cancers and experimental lung tumors. Inhibition of 11βHSD2 activity enhanced glucocorticoid-mediated COX-2 inhibition in human lung carcinoma cells. Furthermore, 11βHSD2 inhibition suppressed lung tumor growth and invasion in association with increased tissue active glucocorticoid levels, decreased COX-2 expression, inhibition of ERK and mTOR signaling pathways, increased tumor endoplasmic reticulum stress as well as increased lifespan. Therefore, 11βHSD2 inhibition represents a novel approach for lung cancer chemoprevention and therapy by increasing tumor glucocorticoid activity, which in turn selectively blocks local COX-2 activity and/or inhibits the ERK and mTOR signaling pathways. PMID:26011146

  7. A high density COX1 barcode oligonucleotide array for identification and detection of species of Penicillium subgenus Penicillium.

    PubMed

    Chen, W; Seifert, K A; Lévesque, C A

    2009-05-01

    We developed a COX1 barcode oligonucleotide array based on 358 sequences, including 58 known and two new species of Penicillium subgenus Penicillium, and 12 allied species. The array was robotically spotted at near microarray density on membranes. Species and clade-specific oligonucleotides were selected using the computer programs SigOli and Array Designer. Robotic spotting allowed 768 spots with duplicate sets of perfect match and the corresponding mismatch and positive control oligonucleotides, to be printed on 2 × 6 cm(2) nylon membranes. The array was validated with hybridizations between the array and digoxigenin (DIG)-labelled COX1 polymerase chain reaction amplicons from 70 pure DNA samples, and directly from environmental samples (cheese and plants) without culturing. DNA hybridization conditions were optimized, but undesired cross-reactions were detected frequently, reflecting the relatively high sequence similarity of the COX1 gene among Penicillium species. Approximately 60% of the perfect match oligonucleotides were rejected because of low specificity and 76 delivered useful group-specific or species-specific reactions and could be used for detecting certain species of Penicillium in environmental samples. In practice, the presence of weak signals on arrays exposed to amplicons from environmental samples, which could have represented weak detections or weak cross reactions, made interpretation difficult for over half of the oligonucleotides. DNA regions with very few single nucleotide polymorphisms or lacking insertions/deletions among closely related species are not ideal for oligonucleotide-based diagnostics, and supplementing the COX1-based array with oligonucleotides derived from additional genes would result in a more robust hierarchical identification system. PMID:21564971

  8. AMPK potentiates hypertonicity-induced apoptosis by suppressing NFκB/COX-2 in medullary interstitial cells.

    PubMed

    Han, Qifei; Zhang, Xiaoyan; Xue, Rui; Yang, Hang; Zhou, Yunfeng; Kong, Xiaomu; Zhao, Pan; Li, Jing; Yang, Jichun; Zhu, Yi; Guan, Youfei

    2011-10-01

    Cells residing in the hypertonic, hypoxic renal medulla depend on dynamic adaptation mechanisms to respond to changes in energy supply and demand. The serine/threonine kinase 5'-AMP protein kinase (AMPK) is a sensor of cellular energy status, but whether it contributes to the survival of cells in the renal medulla is unknown. Here, hypertonic conditions induced a decrease in AMPK phosphorylation within 12 hours in renal medullary interstitial cells (RMIC), followed by a gradual return to baseline levels. Activation of AMPK markedly increased hypertonicity-induced apoptosis of RMICs and suppressed both hypertonicity-induced NFκB nuclear translocation and cyclooxygenase-2 (COX-2) activation; overexpression of COX-2 significantly attenuated these effects. AMPK activation also markedly reduced generation of reactive oxygen species and nuclear expression of tonicity-responsive enhancer-binding protein, which prevented upregulation of osmoprotective genes. In vivo, pharmacologic activation of AMPK led to massive apoptosis of RMICs and renal dysfunction in the setting of water deprivation in mice. Taken together, these results identify a critical role for AMPK in the maintenance of RMIC viability and suggest that AMPK modulates the NFκB-COX-2 survival pathway in the renal medulla. Furthermore, this study raises safety concerns for the development of AMPK activators as anti-diabetic drugs, especially for patients prone to dehydration. PMID:21903993

  9. Effects of COX inhibitors on neurodegeneration and survival in mice exposed to the marine neurotoxin domoic acid.

    PubMed

    Ryan, James C; Cross, Cheryl A; Van Dolah, Frances M

    2011-01-01

    The marine neurotoxin domoic acid (DA) is a rigid analogue of the neurotransmitter glutamate and a potent agonist of kainate subtype glutamate receptors. Persistent activation of these receptor subtypes results in rapid excitotoxicity, calcium-dependent cell death, and neuronal degeneration in regions of the brain where glutamatergic pathways are concentrated. Previous work has shown that DA promotes the expression of inflammatory genes in the brain, such as cyclooxygenase 2 (COX2). To investigate the impact of inflammation on the development of neurodegeneration, and ultimately survival following DA administration, we used selective (L745337, Merck) and non-selective (acetylsalicylic acid (ASA)) COX inhibitors in DA exposed mice. Adult male ICR mice were given a regime of either ASA or L23547 both before and after a single LD50 dose of DA. Mice were observed immediately after toxin introduction and then sacrificed at 2 days post exposure. Our lower dose of L23547 increased survival and was most effective at decreasing neuronal degeneration in the CA1 and CA3 regions of the hippocampus, areas especially sensitive to DA excitotoxicity. This study shows that COX2 plays a role in DA induced neurodegeneration and death, and that inhibitors may be of value for treatment in human and wildlife DA exposure. PMID:20934488

  10. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2—dependent mechanisms

    PubMed Central

    Shibata, Rei; Sato, Kaori; Pimentel, David R; Takemura, Yukihiro; Kihara, Shinji; Ohashi, Koji; Funahashi, Tohru; Ouchi, Noriyuki; Walsh, Kenneth

    2010-01-01

    Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-α expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-α production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-α production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-α production. Adiponectin induced cyclooxygenase (COX)-2–dependent synthesis of prostaglandin E2 in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-α production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2–dependent mechanisms. PMID:16155579

  11. Satellite rainfall retrieval by logistic regression

    NASA Technical Reports Server (NTRS)

    Chiu, Long S.

    1986-01-01

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

  12. Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice.

    PubMed

    Praticò, D; Tillmann, C; Zhang, Z B; Li, H; FitzGerald, G A

    2001-03-13

    The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet activation and vascular smooth-muscle cell migration and proliferation. Biochemically selective inhibition of COX-2 reduces PGI(2) biosynthesis substantially in humans. Because deletion of the PGI(2) receptor accelerates atherogenesis in the fat-fed low density lipoprotein receptor knockout mouse, we wished to determine whether selective inhibition of COX-2 would accelerate atherogenesis in this model. To address this hypothesis, we used dosing with nimesulide, which inhibited COX-2 ex vivo, depressed urinary 2,3 dinor 6-keto PGF(1alpha) by approximately 60% but had no effect on thromboxane formation by platelets, which only express COX-1. By contrast, the isoform nonspecific inhibitor, indomethacin, suppressed platelet function and thromboxane formation ex vivo and in vivo, coincident with effects on PGI(2) biosynthesis indistinguishable from nimesulide. Indomethacin reduced the extent of atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of atherogenesis. Despite their divergent effects on atherogenesis, both drugs depressed two indices of systemic inflammation, soluble intracellular adhesion molecule-1, and monocyte chemoattractant protein-1 to a similar but incomplete degree. Neither drug altered serum lipids and the marked increase in vascular expression of COX-2 during atherogenesis. Accelerated progression of atherosclerosis is unlikely during chronic intake of specific COX-2 inhibitors. Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis suggests that controlled evaluation of the effects of nonsteroidal anti-inflammatory drugs and/or aspirin on plaque progression in humans is timely. PMID:11248083

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

    PubMed

    Dennerlein, Sven; Rehling, Peter

    2015-03-01

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

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

    PubMed

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

    2015-12-01

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

  15. Improving VEGF-targeted therapies through inhibition of COX-2/PGE2 signaling

    PubMed Central

    Xu, Lihong; Croix, Brad St.

    2014-01-01

    Antiangiogenic agents targeting the vascular endothelial growth factor A (VEGFA) pathway play an important role in current cancer treatment modalities but are limited by alternative angiogenesis mechanisms. Recent studies suggest that enhanced signaling through a COX-2/PGE2 axis contributes to VEGF-independent tumor angiogenesis. Thus, COX-2/PGE2 inhibition may potentiate VEGF therapies.

  16. Hierarchical Adaptive Regression Kernels for Regression with Functional Predictors

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

    Vidergar, Nina; Toplak, Nataša; Kuntner, Matjaž

    2014-01-01

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

  18. A Regression Equation for Determining the Dimensionality of Data.

    ERIC Educational Resources Information Center

    Keeling, Kellie B.

    2000-01-01

    Developed a new regression equation to estimate the mean value of eigenvalues in parallel analysis and studied the performance of the equation in comparison with previously published regression equations through simulation. Performance of the new equation was comparable to that of the LCHF equation of G. Lautenschlager and others (1989). (SLD)

  19. Population-Sample Regression in the Estimation of Population Proportions

    ERIC Educational Resources Information Center

    Weitzman, R. A.

    2006-01-01

    Focusing on a single sample obtained randomly with replacement from a single population, this article examines the regression of population on sample proportions and develops an unbiased estimator of the square of the correlation between them. This estimator turns out to be the regression coefficient. Use of the squared-correlation estimator as a…

  20. COX-2 inhibitors: a novel strategy in the management of breast cancer.

    PubMed

    Regulski, Miłosz; Regulska, Katarzyna; Prukała, Wiesław; Piotrowska, Hanna; Stanisz, Beata; Murias, Marek

    2016-04-01

    Cyclooxygenase-2 (COX-2) inhibitors are common anti-inflammatory drugs with pleiotropic, endogenous actions that could be useful in the management of breast cancer. Here, we provide a complete understanding of the biochemistry of COX-2 and discuss the various molecular mechanisms behind its increased expression in breast cancer. We also analyze the possible mechanisms responsible for the anticancer effect of COX-2 inhibitors and provide an overview of the available preclinical and clinical data on the use of COX-2 inhibitors in breast cancer. Finally, we describe a mathematical model of the relation between the structure and biological potency of promising new COX-2 inhibitors (trans-stilbenes) using a 2D quantitative structure-activity relationship (QSAR) technique. PMID:26723915

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1987-09-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

  4. Implementation of a multi-variable regression analysis in the assessment of the generation rate and composition of hospital solid waste for the design of a sustainable management system in developing countries.

    PubMed

    Al-Khatib, Issam A; Abu Fkhidah, Ismail; Khatib, Jumana I; Kontogianni, Stamatia

    2016-03-01

    Forecasting of hospital solid waste generation is a critical challenge for future planning. The composition and generation rate of hospital solid waste in hospital units was the field where the proposed methodology of the present article was applied in order to validate the results and secure the outcomes of the management plan in national hospitals. A set of three multiple-variable regression models has been derived for estimating the daily total hospital waste, general hospital waste, and total hazardous waste as a function of number of inpatients, number of total patients, and number of beds. The application of several key indicators and validation procedures indicates the high significance and reliability of the developed models in predicting the hospital solid waste of any hospital. Methodology data were drawn from existent scientific literature. Also, useful raw data were retrieved from international organisations and the investigated hospitals' personnel. The primal generation outcomes are compared with other local hospitals and also with hospitals from other countries. The main outcome, which is the developed model results, are presented and analysed thoroughly. The goal is this model to act as leverage in the discussions among governmental authorities on the implementation of a national plan for safe hospital waste management in Palestine. PMID:26759435

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

    PubMed

    McCarty, Mark F

    2012-01-01

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

  6. Regression of posterior uveal melanomas following cobalt-60 plaque radiotherapy

    SciTech Connect

    Cruess, A.F.; Augsburger, J.J.; Shields, J.A.; Brady, L.W.; Markoe, A.M.; Day, J.L.

    1984-12-01

    A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that had been managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the average posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. The authors also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different from the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.

  7. Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells

    PubMed Central

    Knox, Alan J.

    2015-01-01

    Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors. Conditioned medium from BK treated HASMC induced CXCL8, VEGF, and COX-2 mRNA and protein accumulation in airway epithelial cells, which were blocked by anti-amphiregulin antibodies and amphiregulin siRNA, suggesting a paracrine effect of HASMC-derived amphiregulin on airway epithelial cells. Consistent with this, recombinant amphiregulin induced CXCL8, VEGF, and COX-2 in airway epithelial cells. Finally, we found that conditioned media from amphiregulin-stimulated airway epithelial cells induced amphiregulin expression in HASMC and that this was dependent on airway epithelial cell COX-2 activity. Our study provides evidence of a dynamic axis of interaction between HASMC and epithelial cells that amplifies CXCL8, VEGF, COX-2, and amphiregulin production. PMID:26047642

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

    SciTech Connect

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

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

  9. Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines.

    PubMed

    Nakanishi, Y; Kamijo, R; Takizawa, K; Hatori, M; Nagumo, M

    2001-08-01

    Prostaglandins (PG) are known to play important roles in the proliferation and differentiation of leukaemia cells. The effect of the inhibitors of cyclooxygenase-2 (COX-2), a rate-limiting enzyme for the synthesis of PG, on the proliferation and differentiation of leukaemia cell lines was investigated. COX-2 inhibitors, NS-398 and nabumetone, suppressed the proliferation of U-937 and ML-1 cells by inducing a G0/G1 cell-cycle arrest. Cell-cycle arrest induced by these COX-2 inhibitors was not associated with an upregulation of the cyclin-dependent kinase inhibitors. COX-2 inhibitors also inhibited the differentiation of these cells induced by interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and retinoic acid (RA). Treatment with NS-398 did not suppress the levels of PGs produced by these cells. Although COX-2 antisense oligonucleotide showed a similar inhibitory effect on these cells, its inhibitory effect was smaller than that of NS-398. These results suggest that COX-2 inhibitors may suppress the proliferation and differentiation of leukaemia cells both via COX-2-dependent and -independent pathways. PMID:11506967

  10. Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses COX-2 expression.

    PubMed

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

    2010-01-01

    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 PPARalpha and gamma. PPARgamma-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 PPARgamma. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. PMID:19578162

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

    PubMed Central

    Cunliffe, Michael

    2011-01-01

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

  12. General Regression and Representation Model for Classification

    PubMed Central

    Qian, Jianjun; Yang, Jian; Xu, Yong

    2014-01-01

    Recently, the regularized coding-based classification methods (e.g. SRC and CRC) show a great potential for pattern classification. However, most existing coding methods assume that the representation residuals are uncorrelated. In real-world applications, this assumption does not hold. In this paper, we take account of the correlations of the representation residuals and develop a general regression and representation model (GRR) for classification. GRR not only has advantages of CRC, but also takes full use of the prior information (e.g. the correlations between representation residuals and representation coefficients) and the specific information (weight matrix of image pixels) to enhance the classification performance. GRR uses the generalized Tikhonov regularization and K Nearest Neighbors to learn the prior information from the training data. Meanwhile, the specific information is obtained by using an iterative algorithm to update the feature (or image pixel) weights of the test sample. With the proposed model as a platform, we design two classifiers: basic general regression and representation classifier (B-GRR) and robust general regression and representation classifier (R-GRR). The experimental results demonstrate the performance advantages of proposed methods over state-of-the-art algorithms. PMID:25531882

  13. Methylation status and overexpression of COX-2 in Tunisian patients with ductal invasive breast carcinoma.

    PubMed

    Karray-Chouayekh, Sondes; Trifa, Fatma; Khabir, Abdelmajid; Boujelbene, Noureddine; Sellami-Boudawara, Tahia; Daoud, Jamel; Frikha, Mounir; Gargouri, Ali; Mokdad-Gargouri, Raja

    2011-06-01

    Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in solid tumours including breast cancer, which in turn affects cell proliferation, apoptosis and metastasis. The aim of this study was to investigate the expression of COX-2 and its association with clinical parameters, patient's survival, hormones receptors (oestrogen, progesterone), ERBB2 and TP53 expression in 83 cases of infiltrating ductal breast carcinomas. Moreover, the methylation status at the CpG islands of the COX-2 gene promoter was also explored in 70 specimens. We showed that tumours exhibiting moderate to intense COX-2 immunostaining were significantly more frequent in patients over 45 years old (p = 0.027). Moreover, a high level of COX-2 expression correlated with a shorter survival time (p log-rank = 0.04) and was an independent prognostic factor (p = 0.022; HR 6.4; 95% CI = 1.3-31.4). On the other hand, hypermethylation of the COX-2 gene promoter was observed in 27% of cases and strongly associated with smaller tumours (<5 cm, p = 0.011). Furthermore, patients with methylated COX-2 pattern have a better 4-year disease-free survival (p = 0.022) as well as a prolonged overall survival (p log-rank test = 0.034). In conclusion, we showed that high COX-2 expression was associated with reduced survival and was an independent prognostic factor. However, hypermethylation of the COX-2 promoter correlated with a better overall survival in Tunisian patients with breast carcinoma. PMID:21153458

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

    PubMed

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

    2011-11-15

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  18. Pain relief model for a COX-2 inhibitor in patients with postoperative dental pain

    PubMed Central

    Rohatagi, Shashank; Kastrissios, Helen; Sasahara, Kunihiro; Truitt, Kenneth; Moberly, James B; Wada, Russell; Salazar, Daniel E

    2008-01-01

    AIM To develop a pain relief model for a cyclooxygenase (COX)-2 inhibitor, CS-706, that permits prediction of doses for acute pain relief in Japanese and Western populations. METHODS A categorical response model was developed to describe the probability of pain relief (PR) over time for a Phase 2a study. Models were also developed to describe patient's use of rescue medication and onset of pain relief. RESULTS The placebo response was described by a first-order increase in PR that achieved a stable response after 4 h. The effect of CS-706 on PR was described using an Emax model; the plasma concentration of CS-706 producing 50% of the maximum response was estimated to be 87 ng ml−1, the median peak plasma concentration achieved after a 50-mg oral dose. The probability of rescue medication (REMD) decreased over time and was a function of the last observed PR score. This probability was < 16% for patients with a PR score ≥2. The probability of experiencing meaningful PR was 98% in patients who did not require REMD and 47% in those who required REMD. For patients who did not require REMD, the median onset time of meaningful pain relief (TMPR) decreased with increasing doses. In patients who required REMD, there was a saturable decline in TMPR, with the greatest improvement occurring from placebo to 50-mg doses. CONCLUSIONS The set of models developed permitted compilation of multiple dose–response curves for dose selection of CS-706 in Westerners and facilitated scaling of doses to a Japanese population. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Modelling and simulation are being increasingly used to support decision-making in new drug development.Novel modelling methods are required to capture the complexity of multiple end-points for a disease and to address questions such as dose selection in various populations.The focus of this study was to present a novel pain relief model to address such questions. WHAT THIS STUDY ADDS New contributions of this work to the

  19. Regression analysis of cytopathological data

    SciTech Connect

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

    1982-12-01

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

  20. Nuclear factor {kappa}B (NF{kappa}B) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes

    SciTech Connect

    Yeoh, Ann S.J. . E-mail: ann.yeoh@imvs.sa.gov.au; Bowen, Joanne M.; Gibson, Rachel J.; Keefe, Dorothy M.K.

    2005-12-01

    Purpose: Recent studies have proposed that mucositis development is the same throughout the gastrointestinal tract (GIT), as it is formed from one structure embryologically. Radiation-induced oral mucositis studies have outlined the key involvement of nuclear factor {kappa}B (NF{kappa}B) and cyclooxygenase-2 (Cox-2) in its pathobiology. The purpose of this study was therefore to investigate the expression of NF{kappa}B and Cox-2 in the irradiated colorectum and to correlate these with the associated histopathologic changes. Methods and Materials: Colorectal tissues from 28 colorectal cancer patients treated with preoperative radiotherapy were analyzed for histopathologic changes using a variety of tissue staining methods. The expression of NF{kappa}B and Cox-2 in these tissues was investigated using immunohistochemistry. Changes in expression of these proteins were then correlated with the histopathologic changes. Results: Radiation therapy caused injury to the normal colorectal tissue surrounding tumor site, particularly around the blood vessels. These changes were reflected in changes in NF{kappa}B and Cox-2 expression. Conclusions: We conclude that different regions of the GIT, the colorectum, and oral cavity have similar underlying mechanisms of radiation-induced mucositis. Understanding these mechanisms will allow new approaches to be developed to specifically target steps in the evolution of alimentary mucositis.

  1. Multiatlas segmentation as nonparametric regression.

    PubMed

    Awate, Suyash P; Whitaker, Ross T

    2014-09-01

    This paper proposes a novel theoretical framework to model and analyze the statistical characteristics of a wide range of segmentation methods that incorporate a database of label maps or atlases; such methods are termed as label fusion or multiatlas segmentation. We model these multiatlas segmentation problems as nonparametric regression problems in the high-dimensional space of image patches. We analyze the nonparametric estimator's convergence behavior that characterizes expected segmentation error as a function of the size of the multiatlas database. We show that this error has an analytic form involving several parameters that are fundamental to the specific segmentation problem (determined by the chosen anatomical structure, imaging modality, registration algorithm, and label-fusion algorithm). We describe how to estimate these parameters and show that several human anatomical structures exhibit the trends modeled analytically. We use these parameter estimates to optimize the regression estimator. We show that the expected error for large database sizes is well predicted by models learned on small databases. Thus, a few expert segmentations can help predict the database sizes required to keep the expected error below a specified tolerance level. Such cost-benefit analysis is crucial for deploying clinical multiatlas segmentation systems. PMID:24802528

  2. Semisupervised Clustering by Iterative Partition and Regression with Neuroscience Applications

    PubMed Central

    Qian, Guoqi; Wu, Yuehua; Ferrari, Davide; Qiao, Puxue; Hollande, Frédéric

    2016-01-01

    Regression clustering is a mixture of unsupervised and supervised statistical learning and data mining method which is found in a wide range of applications including artificial intelligence and neuroscience. It performs unsupervised learning when it clusters the data according to their respective unobserved regression hyperplanes. The method also performs supervised learning when it fits regression hyperplanes to the corresponding data clusters. Applying regression clustering in practice requires means of determining the underlying number of clusters in the data, finding the cluster label of each data point, and estimating the regression coefficients of the model. In this paper, we review the estimation and selection issues in regression clustering with regard to the least squares and robust statistical methods. We also provide a model selection based technique to determine the number of regression clusters underlying the data. We further develop a computing procedure for regression clustering estimation and selection. Finally, simulation studies are presented for assessing the procedure, together with analyzing a real data set on RGB cell marking in neuroscience to illustrate and interpret the method. PMID:27212939

  3. Mission assurance increased with regression testing

    NASA Astrophysics Data System (ADS)

    Lang, R.; Spezio, M.

    Knowing what to test is an important attribute in any testing campaign, especially when it has to be right or the mission could be in jeopardy. The New Horizons mission, developed and operated by the John Hopkins University Applied Physics Laboratory, received a planned major upgrade to their Mission Operations and Control (MOC) ground system architecture. Early in the mission planning it was recognized that the ground system platform would require an upgrade to assure continued support of technology used for spacecraft operations. With the planned update to the six year operational ground architecture from Solaris 8 to Solaris 10, it was critical that the new architecture maintain critical operations and control functions. The New Horizons spacecraft is heading to its historic rendezvous with Pluto in July 2015 and then proceeding into the Kuiper Belt. This paper discusses the Independent Software Acceptance Testing (ISAT) Regression test campaign that played a critical role to assure the continued success of the New Horizons mission. The New Horizons ISAT process was designed to assure all the requirements were being met for the ground software functions developed to support the mission objectives. The ISAT team developed a test plan with a series of test case designs. The test objectives were to verify that the software developed from the requirements functioned as expected in the operational environment. As the test cases were developed and executed, a regression test suite was identified at the functional level. This regression test suite would serve as a crucial resource in assuring the operational system continued to function as required with such a large scale change being introduced. Some of the New Horizons ground software changes required modifications to the most critical functions of the operational software. Of particular concern was the new MOC architecture (Solaris 10) is Intel based and little endian, and the legacy architecture (Solaris 8) was SPA

  4. Weather adjustment using seemingly unrelated regression

    SciTech Connect

    Noll, T.A.

    1995-05-01

    Seemingly unrelated regression (SUR) is a system estimation technique that accounts for time-contemporaneous correlation between individual equations within a system of equations. SUR is suited to weather adjustment estimations when the estimation is: (1) composed of a system of equations and (2) the system of equations represents either different weather stations, different sales sectors or a combination of different weather stations and different sales sectors. SUR utilizes the cross-equation error values to develop more accurate estimates of the system coefficients than are obtained using ordinary least-squares (OLS) estimation. SUR estimates can be generated using a variety of statistical software packages including MicroTSP and SAS.

  5. 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...

  6. Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cox Inhibitory Activity.

    PubMed

    Arisawa, Mitsuhiro; Kasaya, Yayoi; Obata, Tohru; Sasaki, Takuma; Ito, Mika; Abe, Hiroshi; Ito, Yoshihiro; Yamano, Akihito; Shuto, Satoshi

    2011-05-12

    Conformationally restricted indomethacin analogues were designed and prepared from the corresponding 2-substituted indoles, which were synthesized by a one-pot isomerization/enamide-ene metathesis as the key reaction. Conformational analysis by calculations, NMR studies, and X-ray crystallography suggested that these analogues were conformationally restricted in the s-cis or the s-trans form due to the 2-substituent as expected. Their biological activities on cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, and modulation of MRP-1-mediated multidrug resistance (MDR) are described. Some of these indomethacin analogues enhanced doxorubicin cytotoxicity, although they do not have any COX inhibitory activity, which suggests that the MDR-modulating effect of an NSAID can be unassociated with its COX-inhibitory activity. This may be an entry into the combination chemotherapy of doxorubicin with a MDR modulator. PMID:24900317

  7. Celebration of the contributions of Art Cox to stellar pulsation interpretations

    SciTech Connect

    Castor, J.I.

    1997-10-02

    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.

  8. Shape regression for vertebra fracture quantification

    NASA Astrophysics Data System (ADS)

    Lund, Michael Tillge; de Bruijne, Marleen; Tanko, Laszlo B.; Nielsen, Mads

    2005-04-01

    Accurate and reliable identification and quantification of vertebral fractures constitute a challenge both in clinical trials and in diagnosis of osteoporosis. Various efforts have been made to develop reliable, objective, and reproducible methods for assessing vertebral fractures, but at present there is no consensus concerning a universally accepted diagnostic definition of vertebral fractures. In this project we want to investigate whether or not it is possible to accurately reconstruct the shape of a normal vertebra, using a neighbouring vertebra as prior information. The reconstructed shape can then be used to develop a novel vertebra fracture measure, by comparing the segmented vertebra shape with its reconstructed normal shape. The vertebrae in lateral x-rays of the lumbar spine were manually annotated by a medical expert. With this dataset we built a shape model, with equidistant point distribution between the four corner points. Based on the shape model, a multiple linear regression model of a normal vertebra shape was developed for each dataset using leave-one-out cross-validation. The reconstructed shape was calculated for each dataset using these regression models. The average prediction error for the annotated shape was on average 3%.

  9. Regression testing in the TOTEM DCS

    NASA Astrophysics Data System (ADS)

    Rodríguez, F. Lucas; Atanassov, I.; Burkimsher, P.; Frost, O.; Taskinen, J.; Tulimaki, V.

    2012-12-01

    The Detector Control System of the TOTEM experiment at the LHC is built with the industrial product WinCC OA (PVSS). The TOTEM system is generated automatically through scripts using as input the detector Product Breakdown Structure (PBS) structure and its pinout connectivity, archiving and alarm metainformation, and some other heuristics based on the naming conventions. When those initial parameters and automation code are modified to include new features, the resulting PVSS system can also introduce side-effects. On a daily basis, a custom developed regression testing tool takes the most recent code from a Subversion (SVN) repository and builds a new control system from scratch. This system is exported in plain text format using the PVSS export tool, and compared with a system previously validated by a human. A report is sent to the developers with any differences highlighted, in readiness for validation and acceptance as a new stable version. This regression approach is not dependent on any development framework or methodology. This process has been satisfactory during several months, proving to be a very valuable tool before deploying new versions in the production systems.

  10. Preventive Inositol Hexaphosphate Extracted from Rice Bran Inhibits Colorectal Cancer through Involvement of Wnt/β-Catenin and COX-2 Pathways

    PubMed Central

    Mohd Esa, Norhaizan; Ithnin, Hairuszah; Md Akim, Abdah; Pandurangan, Ashok Kumar

    2013-01-01

    Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP6 extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP6 was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP6 markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP6 had also markedly decreased β-catenin and COX-2 in colon tumors. Thus, the downregulation of β-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP6 and thereby act as a potent anticancer agent. PMID:24260743

  11. Hydrogen sulfide promotes cell proliferation of oral cancer through activation of the COX2/AKT/ERK1/2 axis.

    PubMed

    Zhang, Shuai; Bian, Huan; Li, Xiaoxu; Wu, Huanhuan; Bi, Qingwei; Yan, Yingbin; Wang, Yixiang

    2016-05-01

    Hydrogen sulfide, the third gaseous transmitter, is one of the main causes of halitosis in the oral cavity. It is generally considered as playing a deleterious role in many oral diseases including oral cancer. However, the regulatory mechanisms involved in the effects of hydrogen sulfide on oral cancer growth remain largely unknown. In the present study, we investigated the underlying mechanisms through CCK-8 assay, EdU incorporation, real-time PCR, western blot and pathway blockade assays. Our results showed that hydrogen sulfide promoted oral cancer cell proliferation through activation of the COX2, AKT and ERK1/2 pathways in a dose-dependent manner. Blocking any of the three above pathways inhibited hydrogen sulfide-induced oral cancer cell proliferation. Meanwhile, blockade of COX2 by niflumic acid downregulated NaHS-induced p-ERK and p-AKT expression. Inactivation of the AKT pathway by GSK690693 significantly decreased NaHS‑induced p-ERK1/2 expression, and inhibition of the ERK1/2 pathway by U0126 markedly increased NaHS-induced p-AKT expression. Either the AKT or ERK1/2 inhibitor did not significantly alter the COX2 expression level. Our data revealed, for the first time, that hydrogen sulfide promotes oral cancer cell proliferation through activation of the COX2/AKT/ERK1/2 axis, suggesting new potential targets to eliminate the effect of hydrogen sulfide on the development of oral cancer. PMID:26987083

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

    PubMed Central

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

    2014-01-01

    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

  13. Meta-analysis of cyclooxygenase-2 (COX-2) 765G>C polymorphism and Alzheimer's disease.

    PubMed

    Su, Jianhua; Wen, Shihong; Zhu, Jinlong; Liu, Ruiping; Yang, Jinsong

    2016-09-01

    The cyclooxygenase-2 (COX-2) 765G>C polymorphism has been extensively investigated for association with Alzheimer's disease (AD). However, results of different studies have been inconsistent. The aim of the present meta-analysis was to evaluate the association between the 765G>C polymorphism of the COX-2 gene and susceptibility to AD. We searched all related subjects in PubMed, Embase, SinoMed, and China Knowledge Resource Integrated Database and identified seven studies that reported a relationship between the COX-2 765G>C polymorphism and AD. A total of 1260 cases and 1112 controls were included in the seven studies. Our data suggest that the COX-2 765G>C polymorphism may decrease the risk of AD in five genetic models. As a result, this meta-analysis suggests the 765G>C polymorphism of the COX-2 gene may be a protective factor for AD. As our sample size was limited, large-scale, well-designed studies are necessary to validate the association between the COX-2 765G>C polymorphism and AD. PMID:27443496

  14. Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma

    PubMed Central

    Rao, Chinthalapally V.; Janakiram, Naveena B.; Madka, Venkateshwar; Devarkonda, Vishal; Brewer, Misty; Biddick, Laura; Lightfoot, Stan; Steele, Vernon E.; Mohammed, Altaf

    2015-01-01

    Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX), and epidermal growth factor receptor (EGRF) are over-expressed in human pancreatic ductal adenocarcinoma (PDAC). Using next-generation sequencing (NGS) analysis, we show significant increase in COX-2, 5-LOX, and EGFR expression during PDAC progression. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and EGFR simultaneously, we tested effects of licofelone (dual 5-LOX-COX inhibitor), and gefitinib (EGFR inhibitor), individually and in combination, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PDAC using genetically engineered mice. Individually, licofelone (L) and gefitinib (G) significantly inhibited incidence of PDAC in male (72% L, 90% G, p < 0.0001) and female (90% L, 85% G, p < 0.0001) mice. The combination drug treatment produced complete inhibition of PDAC in both genders. Pancreata of mice receiving combination treatment showed significantly fewer Dclk1-positive cancer stem-like cells, inhibition of COX-2, 5-LOX, PCNA, EGFR and β-catenin expression (p < 0.05–0.0002), increased p21 expression. Significant changes in tumor immune responses and desmoplastic reaction was observed by NGS analysis in combination treatment (p < 0.05). In summary, early simultaneous targeting of 5-LOX-COX- and EGFR pathways may provide additive inhibitory effects leading to complete suppression of PDAC. PMID:26429877

  15. Translocation of Mitochondrially Synthesized Cox2 Domains from the Matrix to the Intermembrane Space▿

    PubMed Central

    Fiumera, Heather L.; Broadley, Sarah A.; Fox, Thomas D.

    2007-01-01

    The N-terminal and C-terminal domains of mitochondrially synthesized cytochrome c oxidase subunit II, Cox2, are translocated through the inner membrane to the intermembrane space (IMS). We investigated the distinct mechanisms of N-tail and C-tail export by analysis of epitope-tagged Cox2 variants encoded in Saccharomyces cerevisiae mitochondrial DNA. Both the N and C termini of a truncated protein lacking the Cox2 C-terminal domain were translocated to the IMS via a pathway dependent upon the conserved translocase Oxa1. The topology of this Cox2 variant, accumulated at steady state, was largely but not completely unaffected in mutants lacking proteins required for export of the C-tail domain, Cox18 and Mss2. C-tail export was blocked by truncation of the last 40 residues from the C-tail domain, indicating that sequence and/or structural features of this domain are required for its translocation. Mss2, a peripheral protein bound to the inner surface of the inner membrane, coimmunoprecipitated with full-length newly synthesized Cox2, whose leader peptide had already been cleaved in the IMS. Our data suggest that the C-tail domain is recognized posttranslationally by a specialized translocation apparatus after the N-tail has been translocated by Oxa1. PMID:17452441

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

    PubMed

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

    2014-01-01

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

  17. On penalized likelihood estimation for a non-proportional hazards regression model.

    PubMed

    Devarajan, Karthik; Ebrahimi, Nader

    2013-07-01

    In this paper, a semi-parametric generalization of the Cox model that permits crossing hazard curves is described. A theoretical framework for estimation in this model is developed based on penalized likelihood methods. It is shown that the optimal solution to the baseline hazard, baseline cumulative hazard and their ratio are hyperbolic splines with knots at the distinct failure times. PMID:24791034

  18. Practical Session: Multiple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Three exercises are proposed to illustrate the simple linear regression. In the first one investigates the influence of several factors on atmospheric pollution. It has been proposed by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr33.pdf) and is based on data coming from 20 cities of U.S. Exercise 2 is an introduction to model selection whereas Exercise 3 provides a first example of analysis of variance. Exercises 2 and 3 have been proposed by A. Dalalyan at ENPC (see Exercises 2 and 3 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_5.pdf).

  19. Impact of multicollinearity on small sample hydrologic regression models

    NASA Astrophysics Data System (ADS)

    Kroll, Charles N.; Song, Peter

    2013-06-01

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

  20. Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2.

    PubMed

    Ahmed, Musa; Azam, Faizul; Gbaj, Abdul; Zetrini, Abdulmottaleb E; Abodlal, Amna Salem; Rghigh, Abir; Elmahdi, Eman; Hamza, Amel; Salama, Mabruk; Bensaber, Salah M

    2016-01-01

    Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases. PMID:26785683

  1. Linear regression analysis of survival data with missing censoring indicators.

    PubMed

    Wang, Qihua; Dinse, Gregg E

    2011-04-01

    Linear regression analysis has been studied extensively in a random censorship setting, but typically all of the censoring indicators are assumed to be observed. In this paper, we develop synthetic data methods for estimating regression parameters in a linear model when some censoring indicators are missing. We define estimators based on regression calibration, imputation, and inverse probability weighting techniques, and we prove all three estimators are asymptotically normal. The finite-sample performance of each estimator is evaluated via simulation. We illustrate our methods by assessing the effects of sex and age on the time to non-ambulatory progression for patients in a brain cancer clinical trial. PMID:20559722

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

    PubMed Central

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

    2013-01-01

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

  3. Residuals and regression diagnostics: focusing on logistic regression.

    PubMed

    Zhang, Zhongheng

    2016-05-01

    Up to now I have introduced most steps in regression model building and validation. The last step is to check whether there are observations that have significant impact on model coefficient and specification. The article firstly describes plotting Pearson residual against predictors. Such plots are helpful in identifying non-linearity and provide hints on how to transform predictors. Next, I focus on observations of outlier, leverage and influence that may have significant impact on model building. Outlier is such an observation that its response value is unusual conditional on covariate pattern. Leverage is an observation with covariate pattern that is far away from the regressor space. Influence is the product of outlier and leverage. That is, when influential observation is dropped from the model, there will be a significant shift of the coefficient. Summary statistics for outlier, leverage and influence are studentized residuals, hat values and Cook's distance. They can be easily visualized with graphs and formally tested using the car package. PMID:27294091

  4. Metal-organic frameworks derived CoxFe1-xP nanocubes for electrochemical hydrogen evolution

    NASA Astrophysics Data System (ADS)

    Hao, Jinhui; Yang, Wenshu; Zhang, Zhe; Tang, Jilin

    2015-06-01

    Designing and developing active, cost-effective and stable electrocatalysts for hydrogen evolution reaction (HER) are still an ongoing challenge. Herein, we report the synthesis of binary transition metal phosphide (CoxFe1-xP) nanocubes with different Co and Fe ratios through a phosphidation process using metal-organic frameworks (MOFs) as templates. MOF templates contribute well-defined nanocube architectural features after phosphidation, while a suitable phosphidation temperature could allow formation of a crystal structure and maintain the well-defined structure. The incorporation of a binary transition metal results in redistribution of the valence electrons in CoxFe1-xP. The changes imply anionic states of the P and Fe atoms, which act as active sites and thus have stronger electron-donating ability. When CoxFe1-xP nanocubes are employed as electrocatalysts, these characteristic features facilitate the performance of HER. Remarkably, Co0.59Fe0.41P nanocubes prepared at 450 °C afford a current density of 10 mA cm-2 at a low overpotential of 72 mV in acidic conditions and 92 mV in alkaline conditions. Co0.59Fe0.41P nanocubes also exhibit a small Tafel slope of 52 mV decade-1 in acidic conditions and 72 mV decade-1 in alkaline conditions. Moreover, Co0.59Fe0.41P nanocubes show good stability in both acidic and alkaline conditions. Our method produces the highly active HER catalyst based on binary transition metal MOF templates, providing a new avenue for designing excellent electrocatalysts.Designing and developing active, cost-effective and stable electrocatalysts for hydrogen evolution reaction (HER) are still an ongoing challenge. Herein, we report the synthesis of binary transition metal phosphide (CoxFe1-xP) nanocubes with different Co and Fe ratios through a phosphidation process using metal-organic frameworks (MOFs) as templates. MOF templates contribute well-defined nanocube architectural features after phosphidation, while a suitable phosphidation

  5. Semiparametric regression during 2003–2007*

    PubMed Central

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

    2010-01-01

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

  6. Mechanisms by Which 17β-Estradiol (E2) Suppress Neuronal cox-2 Gene Expression.

    PubMed

    Stacey, Winfred; Bhave, Shreyas; Uht, Rosalie M

    2016-01-01

    E2 attenuates inflammatory responses by suppressing expression of pro-inflammatory genes. Given that inflammation is increasingly being associated with neurodegenerative and psychiatric processes, we sought to elucidate mechanisms by which E2 down-regulates a component of an inflammatory response, cyclooxygenase- 2 (COX-2) expression. Although inflammatory processes in the brain are usually associated with microglia and astrocytes, we found that the COX-2 gene (cox-2) was expressed in a neuronal context, specifically in an amygdalar cell line (AR-5). Given that COX-2 has been reported to be in neurons in the brain, and that the amygdala is a site involved in neurodegenerative and neuropsychiatric processes, we investigated mechanisms by which E2 could down-regulate cox-2 expression in the AR-5 line. These cells express estrogen receptors alpha (ERα) and beta (ERβ), and as shown here cox-2. At the level of RNA, E2 and the ERβ selective ligand diarylpropionitrile (DPN) both attenuated gene expression, whereas the ERα selective ligand propyl pyrazole triol (PPT) had no effect. Neither ligand increased ERβ at the cox-2 promoter. Rather, DPN decreased promoter occupancy of NF-κB p65 and histone 4 (H4) acetylation. Treatment with the non-specific HDAC inhibitor Trichostatin A (TSA) counteracted DPN's repressive effects on cox-2 expression. In keeping with the TSA effect, E2 and DPN increased histone deacetylase one (HDAC1) and switch-independent 3A (Sin3A) promoter occupancy. Lastly, even though E2 increased CpG methylation, DPN did not. Taken together, the pharmacological data indicate that ERβ contributes to neuronal cox-2 expression, as measured by RNA levels. Furthermore, ER ligands lead to increased recruitment of HDAC1, Sin3A and a concomitant reduction of p65 occupancy and Ac-H4 levels. None of the events, however, are associated with a significant recruitment of ERβ at the promoter. Thus, ERβ directs recruitment to the cox-2 promoter, but does so in the

  7. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    PubMed Central

    2010-01-01

    Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells. PMID:20961430

  8. Inhibition of miR-200c Restores Endothelial Function in Diabetic Mice Through Suppression of COX-2.

    PubMed

    Zhang, Huina; Liu, Jian; Qu, Dan; Wang, Li; Luo, Jiang-Yun; Lau, Chi Wai; Liu, Pingsheng; Gao, Zhen; Tipoe, George L; Lee, Hung Kay; Ng, Chi Fai; Ma, Ronald Ching Wan; Yao, Xiaoqiang; Huang, Yu

    2016-05-01

    Endothelial dysfunction plays a crucial role in the development of diabetic vasculopathy. Our initial quantitative PCR results showed an increased miR-200c expression in arteries from diabetic mice and patients with diabetes. However, whether miR-200c is involved in diabetic endothelial dysfunction is unknown. Overexpression of miR-200c impaired endothelium-dependent relaxations (EDRs) in nondiabetic mouse aortas, whereas suppression of miR-200c by anti-miR-200c enhanced EDRs in diabetic db/db mice. miR-200c suppressed ZEB1 expression, and ZEB1 overexpression ameliorated endothelial dysfunction induced by miR-200c or associated with diabetes. More importantly, overexpression of anti-miR-200c or ZEB1 in vivo attenuated miR-200c expression and improved EDRs in db/db mice. Mechanistic study with the use of COX-2(-/-) mice revealed that COX-2 mediated miR-200c-induced endothelial dysfunction and that miR-200c upregulated COX-2 expression in endothelial cells through suppression of ZEB1 and increased production of prostaglandin E2, which also reduced EDR. This study demonstrates for the first time to our knowledge that miR-200c is a new mediator of diabetic endothelial dysfunction and inhibition of miR-200c rescues EDRs in diabetic mice. These new findings suggest the potential usefulness of miR-200c as the target for drug intervention against diabetic vascular complications. PMID:26822089

  9. Monthly streamflow forecasting using Gaussian Process Regression

    NASA Astrophysics Data System (ADS)

    Sun, Alexander Y.; Wang, Dingbao; Xu, Xianli

    2014-04-01

    Streamflow forecasting plays a critical role in nearly all aspects of water resources planning and management. In this work, Gaussian Process Regression (GPR), an effective kernel-based machine learning algorithm, is applied to probabilistic streamflow forecasting. GPR is built on Gaussian process, which is a stochastic process that generalizes multivariate Gaussian distribution to infinite-dimensional space such that distributions over function values can be defined. The GPR algorithm provides a tractable and flexible hierarchical Bayesian framework for inferring the posterior distribution of streamflows. The prediction skill of the algorithm is tested for one-month-ahead prediction using the MOPEX database, which includes long-term hydrometeorological time series collected from 438 basins across the U.S. from 1948 to 2003. Comparisons with linear regression and artificial neural network models indicate that GPR outperforms both regression methods in most cases. The GPR prediction of MOPEX basins is further examined using the Budyko framework, which helps to reveal the close relationships among water-energy partitions, hydrologic similarity, and predictability. Flow regime modification and the resulting loss of predictability have been a major concern in recent years because of climate change and anthropogenic activities. The persistence of streamflow predictability is thus examined by extending the original MOPEX data records to 2012. Results indicate relatively strong persistence of streamflow predictability in the extended period, although the low-predictability basins tend to show more variations. Because many low-predictability basins are located in regions experiencing fast growth of human activities, the significance of sustainable development and water resources management can be even greater for those regions.

  10. Multiple linear regression for isotopic measurements

    NASA Astrophysics Data System (ADS)

    Garcia Alonso, J. I.

    2012-04-01

    There are two typical applications of isotopic measurements: the detection of natural variations in isotopic systems and the detection man-made variations using enriched isotopes as indicators. For both type of measurements accurate and precise isotope ratio measurements are required. For the so-called non-traditional stable isotopes, multicollector ICP-MS instruments are usually applied. In many cases, chemical separation procedures are required before accurate isotope measurements can be performed. The off-line separation of Rb and Sr or Nd and Sm is the classical procedure employed to eliminate isobaric interferences before multicollector ICP-MS measurement of Sr and Nd isotope ratios. Also, this procedure allows matrix separation for precise and accurate Sr and Nd isotope ratios to be obtained. In our laboratory we have evaluated the separation of Rb-Sr and Nd-Sm isobars by liquid chromatography and on-line multicollector ICP-MS detection. The combination of this chromatographic procedure with multiple linear regression of the raw chromatographic data resulted in Sr and Nd isotope ratios with precisions and accuracies typical of off-line sample preparation procedures. On the other hand, methods for the labelling of individual organisms (such as a given plant, fish or animal) are required for population studies. We have developed a dual isotope labelling procedure which can be unique for a given individual, can be inherited in living organisms and it is stable. The detection of the isotopic signature is based also on multiple linear regression. The labelling of fish and its detection in otoliths by Laser Ablation ICP-MS will be discussed using trout and salmon as examples. As a conclusion, isotope measurement procedures based on multiple linear regression can be a viable alternative in multicollector ICP-MS measurements.

  11. Building Regression Models: The Importance of Graphics.

    ERIC Educational Resources Information Center

    Dunn, Richard

    1989-01-01

    Points out reasons for using graphical methods to teach simple and multiple regression analysis. Argues that a graphically oriented approach has considerable pedagogic advantages in the exposition of simple and multiple regression. Shows that graphical methods may play a central role in the process of building regression models. (Author/LS)

  12. Regression Analysis by Example. 5th Edition

    ERIC Educational Resources Information Center

    Chatterjee, Samprit; Hadi, Ali S.

    2012-01-01

    Regression analysis is a conceptually simple method for investigating relationships among variables. Carrying out a successful application of regression analysis, however, requires a balance of theoretical results, empirical rules, and subjective judgment. "Regression Analysis by Example, Fifth Edition" has been expanded and thoroughly…

  13. Bayesian Unimodal Density Regression for Causal Inference

    ERIC Educational Resources Information Center

    Karabatsos, George; Walker, Stephen G.

    2011-01-01

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

  14. Standards for Standardized Logistic Regression Coefficients

    ERIC Educational Resources Information Center

    Menard, Scott

    2011-01-01

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

  15. Developmental Regression in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rogers, Sally J.

    2004-01-01

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

  16. Dietary Repletion with ω3 Fatty Acid or with COX Inhibition Reverses Cognitive Effects in F3 ω3 Fatty-Acid–Deficient Mice

    PubMed Central

    Hafandi, Ahmad; Begg, Denovan P; Premaratna, Shirmila D; Sinclair, Andrew J; Jois, Mark; Weisinger, Richard S

    2014-01-01

    Dietary deficiency of ω3 fatty acid during development leads to impaired cognitive function. However, the effects of multiple generations of ω3 fatty-acid deficiency on cognitive impairment remain unclear. In addition, we sought to test the hypothesis that the cognitive impairments of ω3 fatty-acid–deficient mice are mediated through the arachidonic acid–cyclooxygenase (COX) pathway. To address these issues, C57BL/6J mice were bred for 3 generations and fed diets either deficient (DEF) or sufficient (SUF) in ω3 fatty acids. At postnatal day 21, the F3 offspring remained on the dam's diet or were switched to the opposite diet, creating 4 groups. In addition, 2 groups that remained on the dam's diet were treated with a COX inhibitor. At 19 wk of age, spatial-recognition memory was tested on a Y-maze. Results showed that 16 wk of SUF diet reversed the cognitive impairment of F3 DEF mice. However, 16 wk of ω3 fatty-acid–deficient diet impaired the cognitive performance of the F3 SUF mice, which did not differ from that of the F3 DEF mice. These findings suggest that the cognitive deficits after multigenerational maintenance on ω3 fatty-acid–deficient diet are not any greater than are those after deficiency during a single generation. In addition, treatment with a COX inhibitor prevented spatial-recognition deficits in F3 DEF mice. Therefore, cognitive impairment due to dietary ω3 fatty-acid deficiency appears to be mediated by the arachidonic acid–COX pathway and can be prevented by 16 wk of dietary repletion with ω3 fatty acids or COX inhibition. PMID:24674584

  17. Shrinkage regression-based methods for microarray missing value imputation

    PubMed Central

    2013-01-01

    Background Missing values commonly occur in the microarray data, which usually contain more than 5% missing values with up to 90% of genes affected. Inaccurate missing value estimation results in reducing the power of downstream microarray data analyses. Many types of methods have been developed to estimate missing values. Among them, the regression-based methods are very popular and have been shown to perform better than the other types of methods in many testing microarray datasets. Results To further improve the performances of the regression-based methods, we propose shrinkage regression-based methods. Our methods take the advantage of the correlation structure in the microarray data and select similar genes for the target gene by Pearson correlation coefficients. Besides, our methods incorporate the least squares principle, utilize a shrinkage estimation approach to adjust the coefficients of the regression model, and then use the new coefficients to estimate missing values. Simulation results show that the proposed methods provide more accurate missing value estimation in six testing microarray datasets than the existing regression-based methods do. Conclusions Imputation of missing values is a very important aspect of microarray data analyses because most of the downstream analyses require a complete dataset. Therefore, exploring accurate and efficient methods for estimating missing values has become an essential issue. Since our proposed shrinkage regression-based methods can provide accurate missing value estimation, they are competitive alternatives to the existing regression-based methods. PMID:24565159

  18. Expression of cyclooxygenase-1 (COX-1) and COX-2 in human male gametes from normal patients, and those with varicocele and diabetes: a potential molecular marker for diagnosing male infertility disorders.

    PubMed

    Perrotta, I; Santoro, M; Guido, C; Avena, P; Tripepi, S; De Amicis, F; Gervasi, M C; Aquila, S

    2012-09-01

    Rising rates of varicocele and diabetes mellitus (DM) pose a significant problem to human fertility. Recent studies have pointed out the impact of cyclooxygenase (COX) in the regulation of testicular function and male fertility. Prominent COX-2 expression has been described recently in the testes of infertile patients, but little is known about the role and identity of COX isoforms in human sperm under certain disease states such as varicocele and DM. We therefore examined the expression profile and ultrastructural localization of COX-1 and COX-2 concomitantly in semen samples from healthy donors, and patients with varicocele and DM. Using Western blotting assay, 'varicocele' and 'diabetic' sperm showed enhanced COX isoforms expression with respect to the 'healthy' sperm. Immunogold labeling revealed human sperm anatomical regions containing COX-1 and COX-2, confirming their increased expression in pathological samples. Our data demonstrate that both COX isoforms are upregulated in the spermatozoa of varicocele and diabetic patients, suggesting the harmful effect of the diseases also at the sperm molecular level, going beyond the abnormal morphology described to date. In conclusion, COX enzymes may possess a biological relevance in the pathogenesis and/or maintenance of male factor infertility associated with varicocele and DM, and may be considered additional molecular markers for the diagnosis of male infertility disorders. PMID:22747653

  19. Expression of cyclooxygenase-1 (COX-1) and COX-2 in human male gametes from normal patients, and those with varicocele and diabetes: a potential molecular marker for diagnosing male infertility disorders

    PubMed Central

    Perrotta, I; Santoro, M; Guido, C; Avena, P; Tripepi, S; De Amicis, F; Gervasi, M C; Aquila, S

    2012-01-01

    Rising rates of varicocele and diabetes mellitus (DM) pose a significant problem to human fertility. Recent studies have pointed out the impact of cyclooxygenase (COX) in the regulation of testicular function and male fertility. Prominent COX-2 expression has been described recently in the testes of infertile patients, but little is known about the role and identity of COX isoforms in human sperm under certain disease states such as varicocele and DM. We therefore examined the expression profile and ultrastructural localization of COX-1 and COX-2 concomitantly in semen samples from healthy donors, and patients with varicocele and DM. Using Western blotting assay, ‘varicocele’ and ‘diabetic’ sperm showed enhanced COX isoforms expression with respect to the ‘healthy’ sperm. Immunogold labeling revealed human sperm anatomical regions containing COX-1 and COX-2, confirming their increased expression in pathological samples. Our data demonstrate that both COX isoforms are upregulated in the spermatozoa of varicocele and diabetic patients, suggesting the harmful effect of the diseases also at the sperm molecular level, going beyond the abnormal morphology described to date. In conclusion, COX enzymes may possess a biological relevance in the pathogenesis and/or maintenance of male factor infertility associated with varicocele and DM, and may be considered additional molecular markers for the diagnosis of male infertility disorders. PMID:22747653

  20. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues

    PubMed Central

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    Objective: To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Methods: One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. Results: The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (P<0.05). Spearman’s correlation analysis showed that the expressions of COX-2 and GLUT-1 (r=0.207, P<0.05), COX-2 and VEGF (r=0.243, P<0.05), as well as GLUT-1 and VEGF (r=0.758, P<0.05) were positively correlated. Conclusion: COX-2, GLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer. PMID:26101475

  1. Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity.

    PubMed

    Tao, Li; Wang, Sheng; Zhao, Yang; Sheng, Xiaobo; Wang, Aiyun; Zheng, Shizhong; Lu, Yin

    2014-09-25

    Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [d-(+)-β-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. PMID:24916702

  2. Pulmonary Vein Isolation and Cox-Maze Procedure Only Partially Denervate the Atrium

    PubMed Central

    Lall, Shelly C.; Foyil, Kelley V.; Sakamoto, Shun-Ichiro; Voeller, Rochus K.; Boineau, John P.; Damiano, Ralph J.; Schuessler, Richard B.

    2009-01-01

    OBJECTIVES The effects of ablation lines on myocardial innervation and response to autonomic stimuli are unclear. This study examined the effects of radiofrequency ablation on atrial autonomic innervation comparing pulmonary vein isolation and the biatrial Cox-Maze. METHODS In twelve acute canines, right and left vagosympathetic trunks and right and left stellate ganglia were isolated. Each nerve was stimulated prior to bipolar ablations, after pulmonary vein isolation, and after Cox-Maze. Nadolol (n=6) and atropine (n=6) were given to block sympathetic and parasympathetic responses, respectively. Changes in heart rate and atrioventricular interval were compared. Changes in QRST area relative to an isoelectric baseline (index of local innervation) were calculated. RESULTS Sympathetic stimulation of each nerve and parasympathetic stimulation of the vagosympathetic trunks caused significant changes in heart rate and atrioventricular interval. After pulmonary vein isolation, the effect of 33% of the nerves on heart rate changes were eliminated. The Cox-Maze procedure eliminated right stellate sympathetic effects on heart rate. Fifty percent of the nerves caused heart rate changes after the Cox-Maze. There was no significant effect of either lesion set on atrioventricular interval changes. Stimulation of 50% of nerves after pulmonary vein isolation produced local area changes significantly different from control. After Cox-Maze, a different 50% of nerves produced local changes different from pulmonary vein isolation. CONCLUSIONS Surgical ablation procedures disrupted innervation affecting heart rate, but not atrioventricular interval. Autonomic innervation affecting the atria was changed by pulmonary vein isolation and additionally by Cox-Maze. Residual autonomic effects were present even after the complete Cox-Maze. PMID:18374777

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

    PubMed Central

    Crager, Michael R.; Tang, Gong

    2015-01-01

    We propose a method for assessing an individual patient’s risk of a future clinical event using clinical trial or cohort data and Cox proportional hazards regression, combining the information from several studies using meta-analysis techniques. The method combines patient-specific estimates of the log cumulative hazard across studies, weighting by the relative precision of the estimates, using either fixed- or random-effects meta-analysis calculations. Risk assessment can be done for any future patient using a few key summary statistics determined once and for all from each study. Generalizations of the method to logistic regression and linear models are immediate. We evaluate the methods using simulation studies and illustrate their application using real data. PMID:26664111

  4. Estimating equivalence with quantile regression.

    PubMed

    Cade, Brian S

    2011-01-01

    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

  5. Streamflow forecasting using functional regression

    NASA Astrophysics Data System (ADS)

    Masselot, Pierre; Dabo-Niang, Sophie; Chebana, Fateh; Ouarda, Taha B. M. J.

    2016-07-01

    Streamflow, as a natural phenomenon, is continuous in time and so are the meteorological variables which influence its variability. In practice, it can be of interest to forecast the whole flow curve instead of points (daily or hourly). To this end, this paper introduces the functional linear models and adapts it to hydrological forecasting. More precisely, functional linear models are regression models based on curves instead of single values. They allow to consider the whole process instead of a limited number of time points or features. We apply these models to analyse the flow volume and the whole streamflow curve during a given period by using precipitations curves. The functional model is shown to lead to encouraging results. The potential of functional linear models to detect special features that would have been hard to see otherwise is pointed out. The functional model is also compared to the artificial neural network approach and the advantages and disadvantages of both models are discussed. Finally, future research directions involving the functional model in hydrology are presented.

  6. Harmonic regression and scale stability.

    PubMed

    Lee, Yi-Hsuan; Haberman, Shelby J

    2013-10-01

    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

  7. Gold-conjugated resveratrol nanoparticles attenuate the invasion and MMP-9 and COX-2 expression in breast cancer cells.

    PubMed

    Park, Sun Young; Chae, Seon Yeong; Park, Jin Oh; Lee, Kyu Jin; Park, Geuntae

    2016-06-01

    Gold nanoparticles (AuNPs) with antitumorigenic effects obstruct the initiation, development and progression of tumors via the regulation of various processes, such as proliferation and apoptosis. However, the effects of AuNPs on breast cancer metastasis have not been well studied, and their response to 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation remains unclear. Therefore, we synthesized resveratrol-capped gold nanoparticles (Rev-AuNPs) using green nanotechnology and investigated their potential anti-invasive properties in human breast cancer cells in response to TPA stimulation. The Rev-AuNPs formed spherical nanoparticles of 22.28±2.98 nm in diameter. Next, we found that non-cytotoxic concentrations of Rev-AuNPs significantly suppressed the TPA-induced migration and invasion abilities of breast cancer cells. Rev-AuNPs suppressed TPA-induced enzymatic activity and the expression of matrix metalloproteinase (MMP)-9 and cyclooxygenase-2 (COX-2). Furthermore, Rev-AuNP treatment remarkably downregulated TPA-induced nuclear translocation and transcriptional activation of nuclear transcription factor-κB (NF-κB) and activator protein-1 (AP-1). Rev-AuNPs reduced the phosphorylation of phosphoinositide 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK)1/2 signaling, but did not affect the phosphorylation of Jun N-terminal kinase (JNK) or p38 MAPK in the TPA-stimulated breast cancer cells. Notably, Rev-AuNPs generally showed better anti-invasive activity than resveratrol without cytotoxicity. The inhibitory effect of Rev-AuNPs on MMP-9, COX-2, NF-κB, AP-1, PI3K/Akt and ERK activation was stronger than that of resveratrol for the same concentrations. We also demonstrated that Rev-AuNPs induced heme oxygenase-1 (HO-1) expression and that the inhibition of MMP-9 and COX-2 expression and MMP-9 enzymatic activity of Rev-AuNPs were abrogated by siRNA knockdown of HO-1 expression. Our findings revealed that the anti-invasive effects of Rev

  8. Pathogenesis of colorectal carcinoma and therapeutic implications: the roles of the ubiquitin–proteasome system and Cox-2

    PubMed Central

    Voutsadakis, Ioannis A

    2007-01-01

    Abstract Pathways of the molecular pathogenesis of colorectal carcinoma have been extensively studied and molecular lesions during the development of the disease have been revealed. High up in the list of colorectal cancer lesions are APC (adenomatous polyposis coli), K-ras, Smad4 (or DPC4-deleted in pancreatic cancer 4) and p53 genes. All these molecules are part of important pathways for the regulation of cell proliferation and apoptosis and as a result perturbation of these processes lead to carcinogenesis. The ubiquitin–proteasome system (UPS) is comprised of a multi-unit cellular protease system that regulates several dozens of cell proteins after their ligation with the protein ubiquitin. Given that among these proteins are regulators of the cell cycle, apoptosis, angiogenesis, adhesion and cell signalling, this system plays a significant role in cell fate and carcinogenesis. UPS inhibition has been found to be a pre-requisite for apoptosis and is already clinically exploited with the proteasome inhibitor bortezomib in multiple myeloma. Cyclooxygenase-2 (Cox-2) is the inducible form of the enzyme that metabolizes the lipid arachidonic acid to prostaglandin H2, the first step of prostaglandins production. This enzyme is up-regulated in colorectal cancer and in several other cancers. Inhibition of Cox-2 by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been found to inhibit proliferation of colorectal cancer cells and in epidemiologic studies has been shown to reduce colon polyp formation in genetically predisposed populations and in the general population. NSAIDs have also Cox-independent anti-proliferative effects. Targeted therapies, the result of increasingly understanding carcinogenesis in the molecular level, have entered the field of anti-neoplastic treatment and are used by themselves and in combination with chemotherapy drugs. Combinations of targeted drugs have started also to be investigated. This article reviews the molecular

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

    PubMed Central

    Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela

    2015-01-01

    Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors. PMID:25916906

  10. Default risk modeling beyond the first-passage approximation: extended Black-Cox model.

    PubMed

    Katz, Yuri A; Shokhirev, Nikolai V

    2010-07-01

    We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm's ability to avoid default even if company's liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company's default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity. PMID:20866698

  11. Getting miles away from Terman: Did the CRPS fund Catharine Cox Miles's unsilenced psychology of sex?

    PubMed

    Hegarty, Peter

    2012-08-01

    Psychologist Catharine Cox Miles (1890-1984) is often remembered as the junior author, with Lewis Terman, of Sex and Personality. Written with support from the Committee for Research on the Problems of Sex (CRPS), Sex and Personality introduced the "masculinity-femininity" personality measure to psychology in 1936. Miles has been overlooked by some historians and constructed as a silent, indirect feminist by others. Private letters show that Terman and Miles had different assumptions about the need for library research work to precede the empirical work for Sex and Personality. Miles's 1935 chapter on the "Social Psychology of Sex" shows that her theoretical formulation of sex differed from Terman's in its emphasis on female embodiment, respect for the emerging tradition of the sex survey, and its opinions about the determinants of marital happiness, and the variability of intelligence. Ironically, CRPS monies wired to Terman may have funded Miles to develop this early formulation of the psychology of sex. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID:23397910

  12. Default risk modeling beyond the first-passage approximation: Extended Black-Cox model

    NASA Astrophysics Data System (ADS)

    Katz, Yuri A.; Shokhirev, Nikolai V.

    2010-07-01

    We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm’s ability to avoid default even if company’s liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company’s default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity.

  13. Measures to assess the prognostic ability of the stratified Cox proportional hazards model.

    PubMed

    2009-02-01

    Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures would be useful in analyses of individual participant data from multiple studies, data from multi-centre studies, and in single study analysis where stratification is used to avoid making assumptions of proportional hazards. We have chosen three measures developed for the unstratified CPH model (Schemper and Henderson's V , Harrell's C-index and Royston and Sauerbrei's D), adapted them for use with the stratified CPH model and demonstrated how their values can be represented over time. Although each of these measures is promising in principle, we found the measure of explained variation V very difficult to apply when data are combined from several studies with differing durations of participant follow-up. The two other measures considered, D and the C-index, were more applicable under such circumstances. We illustrate the methods using individual participant data from several prospective epidemiological studies of chronic disease outcomes. PMID:18833567

  14. A Survey of UML Based Regression Testing

    NASA Astrophysics Data System (ADS)

    Fahad, Muhammad; Nadeem, Aamer

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

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

    PubMed

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

    2014-11-01

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

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

    SciTech Connect

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

    2013-04-15

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

  17. Sparse logistic regression with Lp penalty for biomarker identification.

    PubMed

    Liu, Zhenqiu; Jiang, Feng; Tian, Guoliang; Wang, Suna; Sato, Fumiaki; Meltzer, Stephen J; Tan, Ming

    2007-01-01

    In this paper, we propose a novel method for sparse logistic regression with non-convex regularization Lp (p <1). Based on smooth approximation, we develop several fast algorithms for learning the classifier that is applicable to high dimensional dataset such as gene expression. To the best of our knowledge, these are the first algorithms to perform sparse logistic regression with an Lp and elastic net (Le) penalty. The regularization parameters are decided through maximizing the area under the ROC curve (AUC) of the test data. Experimental results on methylation and microarray data attest the accuracy, sparsity, and efficiency of the proposed algorithms. Biomarkers identified with our methods are compared with that in the literature. Our computational results show that Lp Logistic regression (p <1) outperforms the L1 logistic regression and SCAD SVM. Software is available upon request from the first author. PMID:17402921

  18. Estimating the exceedance probability of rain rate by logistic regression

    NASA Technical Reports Server (NTRS)

    Chiu, Long S.; Kedem, Benjamin

    1990-01-01

    Recent studies have shown that the fraction of an area with rain intensity above a fixed threshold is highly correlated with the area-averaged rain rate. To estimate the fractional rainy area, a logistic regression model, which estimates the conditional probability that rain rate over an area exceeds a fixed threshold given the values of related covariates, is developed. The problem of dependency in the data in the estimation procedure is bypassed by the method of partial likelihood. Analyses of simulated scanning multichannel microwave radiometer and observed electrically scanning microwave radiometer data during the Global Atlantic Tropical Experiment period show that the use of logistic regression in pixel classification is superior to multiple regression in predicting whether rain rate at each pixel exceeds a given threshold, even in the presence of noisy data. The potential of the logistic regression technique in satellite rain rate estimation is discussed.

  19. The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition.

    PubMed

    Palermo, Giulia; Favia, Angelo D; Convertino, Marino; De Vivo, Marco

    2016-06-20

    The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget-directed ligand named ARN2508 (2-[3-fluoro-4-[3-(hexylcarbamoyloxy)phenyl]phenyl]propanoic acid). This potent dual inhibitor combines, in a single scaffold, the pharmacophoric elements often needed to block FAAH and COX, that is, a carbamate moiety and the 2-arylpropionic acid functionality, respectively. Molecular modeling and molecular dynamics simulations suggest that ARN2508 uses a noncovalent mechanism of inhibition to block COXs, while inhibiting FAAH via the acetylation of the catalytic Ser241, in line with previous experimental evidence for covalent FAAH inhibition. This study proposes the molecular basis for the dual FAAH/COX inhibition by this novel hybrid scaffold, stimulating further experimental studies and offering new insights for the rational design of novel anti-inflammatory agents that simultaneously act on FAAH and COX. PMID:26593700

  20. Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1

    PubMed Central

    Bareth, Bettina; Nikolov, Miroslav; Lorenzi, Isotta; Hildenbeutel, Markus; Mick, David U.; Helbig, Christin; Urlaub, Henning; Ott, Martin; Rehling, Peter; Dennerlein, Sven

    2016-01-01

    The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and specialized chaperone-like assembly factors, are formed. In addition, cofactors such as heme and copper have to be inserted into the nascent complex. To regulate the assembly process, the availability of Cox1 is under control of a regulatory feedback cycle in which translation of COX1 mRNA is stalled when assembly intermediates of Cox1 accumulate through inactivation of the translational activator Mss51. Here we isolate a cytochrome c oxidase assembly intermediate in preparatory scale from coa1Δ mutant cells, using Mss51 as bait. We demonstrate that at this stage of assembly, the complex has not yet incorporated the heme a cofactors. Using quantitative mass spectrometry, we define the protein composition of the assembly intermediate and unexpectedly identify the putative methyltransferase Oms1 as a constituent. Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly synthesized Cox1. PMID:27030670

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

    PubMed

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

    2015-08-13

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

  2. In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis.

    PubMed

    Viscomi, Carlo; Bottani, Emanuela; Civiletto, Gabriele; Cerutti, Raffaele; Moggio, Maurizio; Fagiolari, Gigliola; Schon, Eric A; Lamperti, Costanza; Zeviani, Massimo

    2011-07-01

    Increased mitochondrial biogenesis by activation of PPAR- or AMPK/PGC-1α-dependent homeostatic pathways has been proposed as a treatment for mitochondrial disease. We tested this hypothesis on three recombinant mouse models characterized by defective cytochrome c-oxidase (COX) activity: a knockout (KO) mouse for Surf1, a knockout/knockin mouse for Sco2, and a muscle-restricted KO mouse for Cox15. First, we demonstrated that double-recombinant animals overexpressing PGC-1α in skeletal muscle on a Surf1 KO background showed robust induction of mitochondrial biogenesis and increase of mitochondrial respiratory chain activities, including COX. No such effect was obtained by treating both Surf1(-/-) and Cox15(-/-) mice with the pan-PPAR agonist bezafibrate, which instead showed adverse effects in either model. Contrariwise, treatment with the AMPK agonist AICAR led to partial correction of COX deficiency in all three models, and, importantly, significant motor improvement up to normal in the Sco2(KO/KI) mouse. These results open new perspectives for therapy of mitochondrial disease. PMID:21723506

  3. A Minimally Invasive Cox-Maze Procedure: Operative Technique and Results

    PubMed Central

    Lee, Anson M.; Clark, Kal; Bailey, Marci S.; Aziz, Abdulhameed; Schuessler, Richard B.; Damiano, Ralph J.

    2010-01-01

    Summary Objective The Cox-Maze procedure for the surgical treatment of atrial fibrillation traditionally has required a median sternotomy and cardiopulmonary bypass. This study describes a method using ablation technologies to create the full Cox-Maze lesion set through a 5–6 cm right mini-thoracotomy. Methods Twenty-two consecutive patients underwent a Cox-Maze procedure via a right mini-thoracotomy and cardiopulmonary bypass. All patients were followed prospectively with ECG and 24 hour Holter monitoring at 3, 6, and 12 months. The Cox-Maze procedure lesion set was created using bipolar radiofrequency energy and cryothermy. Results There was no operative mortality or major complications. Two patients required a permanent pacemaker. Five patients (23%) had early atrial tachyarrhythmias. At last follow-up (mean 18 ± 12 months), all of the patients (n=22) were free from atrial dysrhythmias. At 3 months (n=19), 84% of patients were off antiarrhythmic drugs. By 6 months (n=18), 94% of patients were free from AF and off antiarrhythmic medications. At 12 months (n=16), 81% of patients were free from AF and off antiarrhythmic drugs and three patients remained on warfarin for a mechanical mitral valve. Conclusions A full Cox-Maze procedure can be performed through a right mini-thoracotomy with outstanding short term results. This less invasive procedure can be offered to patients without compromising efficacy. PMID:21057605

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

    PubMed

    Raharjo, Sentot Joko; Fatchiyah, Fatchiyah

    2013-01-01

    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

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

    PubMed Central

    Raharjo, Sentot Joko; Fatchiyah, Fatchiyah

    2013-01-01

    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

  6. The Characterization And Role of Zinc Binding in Yeast Cox4

    SciTech Connect

    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.

    2007-07-09

    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.

  7. Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome

    PubMed Central

    2010-01-01

    Background Sinobronchial syndrome is a cause of chronic productive cough. Inflammatory mediators are involved in the pathophysiology of chronic productive cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the inducible isoforms of COX, is a key element in the pathophysiological process of a number of inflammatory disorders. However, little is known about the role of COX-2 in chronic productive cough in patients with sinobronchial syndrome known as neutrophilic bronchial inflammation. Methods The effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15 patients with sinobronchial syndrome in a randomized, placebo-controlled cross-over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. Results The cough threshold was significantly (p < 0.03) increased after two-week treatment with etodolac (200 mg twice a day orally) compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) μM]. Conclusions These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome. PMID:20696045

  8. Development of regression equations to revise estimates of historical streamflows for the St. Croix River at Stillwater, Minnesota (water years 1910-2011), and Prescott, Wisconsin (water years 1910-2007)

    USGS Publications Warehouse

    Ziegeweid, Jeffrey R.; Magdalene, Suzanne

    2015-01-01

    The new regression equations were used to calculate revised estimates of historical streamflows for Stillwater and Prescott starting in 1910 and ending when index-velocity streamgages were installed. Monthly, annual, 30-year, and period of record statistics were examined between previous and revised estimates of historical streamflows. The abilities of the new regression equations to estimate historical streamflows were evaluated by using percent differences to compare new estimates of historical daily streamflows to discrete streamflow measurements made at Stillwater and Prescott before the installation of index-velocity streamgages. Although less variability was observed between estimated and measured streamflows at Stillwater compared to Prescott, the percent difference data indicated that the new estimates closely approximated measured streamflows at both locations.

  9. Using visible and near-infrared diffuse reflectance spectroscopy for predicting soil properties based on regression with peaks parameters as derived from continuum-removed spectra

    NASA Astrophysics Data System (ADS)

    Vasat, Radim; Klement, Ales; Jaksik, Ondrej; Kodesova, Radka; Drabek, Ondrej; Boruvka, Lubos

    2014-05-01

    Visible and near-infrared diffuse reflectance spectroscopy (VNIR-DRS) provides a rapid and inexpensive tool for simultaneous prediction of a variety of soil properties. Usually, some sophisticated multivariate mathematical or statistical methods are employed in order to extract the required information from the raw spectra measurement. For this purpose especially the Partial least squares regression (PLSR) and Support vector machines (SVM) are the most frequently used. These methods generally benefit from the complexity with which the soil spectra are treated. But it is interesting that also techniques that focus only on a single spectral feature, such as a simple linear regression with selected continuum-removed spectra (CRS) characteristic (e.g. peak depth), can often provide competitive results. Therefore, we decided to enhance the potential of CRS taking into account all possible CRS peak parameters (area, width and depth) and develop a comprehensive methodology based on multiple linear regression approach. The eight considered soil properties were oxidizable carbon content (Cox), exchangeable (pHex) and active soil pH (pHa), particle and bulk density, CaCO3 content, crystalline and amorphous (Fed) and amorphous Fe (Feox) forms. In four cases (pHa, bulk density, Fed and Feox), of which two (Fed and Feox) were predicted reliably accurately (0.50 < R2cv < 0.80) and the other two (pHa and bulk density) only poorly (R2cv < 0.50), we obtained slightly better results than with PLSR and SVM. In one case (pHex) we achieved a significantly higher, although just reliable, accuracy (R2cv = 0.601) than with PLSR and SVM (R2cv = 0.448 and 0.442, resp.). But most interestingly, in the case of particle density, the presented approach outperformed the PLSR and SVM dramatically offering a fairly accurate prediction (R2cv = 0.827) against two failures (R2cv = 0.034 and 0.121 for PLSR and SVM, resp.). In last two cases (Cox and CaCO3) a slightly worse results were achieved then

  10. Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

    PubMed

    Chandak, Navneet; Kumar, Pawan; Kaushik, Pawan; Varshney, Parul; Sharma, Chetan; Kaushik, Dhirender; Jain, Sudha; Aneja, Kamal R; Sharma, Pawan K

    2014-08-01

    Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity. PMID:23777557

  11. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation.

    PubMed

    Zhong, Bo; Cai, Xiaohan; Chennamaneni, Snigdha; Yi, Xin; Liu, Lili; Pink, John J; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2012-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure-function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5  mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  12. London penetration depth in heavily over-doped Ba(Fe1-xCox)2As2

    NASA Astrophysics Data System (ADS)

    Murphy, Jason; Kim, H.; Tanata, M. A.; Thaler, A.; Canfield, P. C.; Welp, U.; Kwok, W. K.; Prozorov, R.

    2012-02-01

    The low-temperature variation of London penetration depth, δλ(T), has been previously studied in heavily over-doped Ba(Fe1-xNix)2As2 [1] and the authors suggested the development of line nodes. Similar conclusion was made from thermal conductivity measurements in Ba(Fe1-xCox)2As2 [2]. However, δλ(T) in this system has only been measured for x <=x=0.102 [3], which is not far enough from optimal doping. Here we report tunnel - diode resonator (TDR) measurements in heavily overdoped single crystals of Ba(Fe1-xCox)2As2 with Co content of x=0.108 (Tc=14.8 K) and x=0.127 (Tc=9 K. We found a robust power-law behavior of δλ= A T^n with n=2.5 and n=2.11 respectively. To test whether the nodes are symmetry imposed or accidental, samples were irradiated with heavy ions. The produced disorder, leads to a decrease in Tc and of the exponent n. These results effects will be discussed in a context of unconventional pairing in Fe-based superconductors. [4pt] [1] C. Martin et. al., Phys. Rev. B 81, 060505 (2010).[0pt] [2] J.-Ph. Reid et. al., Phys. Rev. B 82, 064501 (2010).[0pt] [3] R.T. Gordon et.al. Phys. Rev. B 82, 054507 (2010).

  13. Combined therapy with COX-2 inhibitor and 20-HETE inhibitor reduces colon tumor growth and the adverse effects of ischemic stroke associated with COX-2 inhibition.

    PubMed

    Zhang, Yi; Hoda, Md Nasrul; Zheng, Xuan; Li, Weiguo; Luo, Pengcheng; Maddipati, Krishna Rao; Seki, Tsugio; Ergul, Adviye; Wang, Mong-Heng

    2014-09-15

    20-Hydroxyeicosatetraenoic acid (20-HETE), Cyp4a-derived eicosanoid, is a lipid mediator that promotes tumor growth, as well as causing detrimental effects in cerebral circulation. We determined whether concurrent inhibition of cyclooxygenase-2 (COX-2) and 20-HETE affects colon tumor growth and ischemic stroke outcomes. The expression of Cyp4a and COXs and production of 20-HETE and PGE2 were determined in murine colon carcinoma (MC38) cells. We then examined the effects of combined treatment with rofecoxib, a potent COX-2 inhibitor, and HET0016, a potent Cyp4a inhibitor, on the growth and proliferation of MC38 cells. Subsequently, we tested the effects of HET0016 plus rofecoxib in MC38 tumor and ischemic stroke models. Cyp4a and COXs are highly expressed in MC38 cells. Respectively, HET0016 and rofecoxib inhibited 20-HETE and PGE2 formation in MC38 cells. Moreover, rofecoxib combined with HET0016 had greater inhibitory effects on the growth and proliferation of MC38 cells than did rofecoxib alone. Importantly, rofecoxib combined with HET0016 provided greater inhibition on tumor growth than did rofecoxib alone in MC38 tumor-bearing mice. Prolonged treatment with rofecoxib selectively induced circulating 20-HETE levels and caused cerebrovascular damage after ischemic stroke, whereas therapy with rofecoxib and HET0016 attenuated 20-HETE levels and reduced rofecoxib-induced cerebrovascular damage and stroke outcomes during anti-tumor therapy. Thus these results demonstrate that combination therapy with rofecoxib and HET0016 provides a new treatment of colon tumor, which can not only enhance the anti-tumor efficacy of rofecoxib, but also reduce rofecoxib-induced cerebrovascular damage and stroke outcomes. PMID:24990856

  14. Regional flood frequency analysis using spatial proximity and basin characteristics: Quantile regression vs. parameter regression technique

    NASA Astrophysics Data System (ADS)

    Ahn, Kuk-Hyun; Palmer, Richard

    2016-09-01

    Despite wide use of regression-based regional flood frequency analysis (RFFA) methods, the majority are based on either ordinary least squares (OLS) or generalized least squares (GLS). This paper proposes 'spatial proximity' based RFFA methods using the spatial lagged model (SLM) and spatial error model (SEM). The proposed methods are represented by two frameworks: the quantile regression technique (QRT) and parameter regression technique (PRT). The QRT develops prediction equations for flooding quantiles in average recurrence intervals (ARIs) of 2, 5, 10, 20, and 100 years whereas the PRT provides prediction of three parameters for the selected distribution. The proposed methods are tested using data incorporating 30 basin characteristics from 237 basins in Northeastern United States. Results show that generalized extreme value (GEV) distribution properly represents flood frequencies in the study gages. Also, basin area, stream network, and precipitation seasonality are found to be the most effective explanatory variables in prediction modeling by the QRT and PRT. 'Spatial proximity' based RFFA methods provide reliable flood quantile estimates compared to simpler methods. Compared to the QRT, the PRT may be recommended due to its accuracy and computational simplicity. The results presented in this paper may serve as one possible guidepost for hydrologists interested in flood analysis at ungaged sites.

  15. Comparison of Logistic Regression and Linear Regression in Modeling Percentage Data

    PubMed Central

    Zhao, Lihui; Chen, Yuhuan; Schaffner, Donald W.

    2001-01-01

    Percentage is widely used to describe different results in food microbiology, e.g., probability of microbial growth, percent inactivated, and percent of positive samples. Four sets of percentage data, percent-growth-positive, germination extent, probability for one cell to grow, and maximum fraction of positive tubes, were obtained from our own experiments and the literature. These data were modeled using linear and logistic regression. Five methods were used to compare the goodness of fit of the two models: percentage of predictions closer to observations, range of the differences (predicted value minus observed value), deviation of the model, linear regression between the observed and predicted values, and bias and accuracy factors. Logistic regression was a better predictor of at least 78% of the observations in all four data sets. In all cases, the deviation of logistic models was much smaller. The linear correlation between observations and logistic predictions was always stronger. Validation (accomplished using part of one data set) also demonstrated that the logistic model was more accurate in predicting new data points. Bias and accuracy factors were found to be less informative when evaluating models developed for percentage data, since neither of these indices can compare predictions at zero. Model simplification for the logistic model was demonstrated with one data set. The simplified model was as powerful in making predictions as the full linear model, and it also gave clearer insight in determining the key experimental factors. PMID:11319091

  16. Using regression equations built from summary data in the psychological assessment of the individual case: extension to multiple regression.

    PubMed

    Crawford, John R; Garthwaite, Paul H; Denham, Annie K; Chelune, Gordon J

    2012-12-01

    Regression equations have many useful roles in psychological assessment. Moreover, there is a large reservoir of published data that could be used to build regression equations; these equations could then be employed to test a wide variety of hypotheses concerning the functioning of individual cases. This resource is currently underused because (a) not all psychologists are aware that regression equations can be built not only from raw data but also using only basic summary data for a sample, and (b) the computations involved are tedious and prone to error. In an attempt to overcome these barriers, Crawford and Garthwaite (2007) provided methods to build and apply simple linear regression models using summary statistics as data. In the present study, we extend this work to set out the steps required to build multiple regression models from sample summary statistics and the further steps required to compute the associated statistics for drawing inferences concerning an individual case. We also develop, describe, and make available a computer program that implements these methods. Although there are caveats associated with the use of the methods, these need to be balanced against pragmatic considerations and against the alternative of either entirely ignoring a pertinent data set or using it informally to provide a clinical "guesstimate." Upgraded versions of earlier programs for regression in the single case are also provided; these add the point and interval estimates of effect size developed in the present article. PMID:22449035

  17. Dietary glycerol for quail: association between productive performance and COX III mRNA expression.

    PubMed

    Silva, S C C; Gasparino, E; Batista, E; Tanamati, F; Vesco, A P D; Lala, B; de Oliveira, D P

    2016-01-01

    This study was carry out to evaluate mRNA expression of mitochondrial cytochrome c oxidase III in the Pectoralis superficialis muscle of 28-day-old quails fed diets containing 0, 8, and 12% glycerol. Total RNA was extracted (N = 10) and cDNA was amplified using specifics primers for qRT-PCR. Feed efficiency and feed intake were evaluated. COX III mRNA expression in breast muscle was higher in the group fed with 12% glycerol (0.863 AU); no differences were observed in the expression of this gene between the muscle of animals fed diets without glycerol (0.357 AU) and 8% glycerol (0.415 AU). Quails that showed greater COX III mRNA expression also showed the lowest feed efficiency. These results show that there is a difference in COX III mRNA expression in breast muscle of 28-day-old quail fed diets different concentrations of glycerol. PMID:27323091

  18. Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma.

    PubMed

    Ramakrishnan, Gopalakrishnan; Elinos-Báez, Carmen Martha; Jagan, Sundaram; Augustine, Titto Alby; Kamaraj, Sattu; Anandakumar, Pandi; Devaki, Thiruvengadam

    2008-06-01

    Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer. PMID:18373278

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

    PubMed Central

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

    2009-01-01

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

  20. COX-2 dependent regulation of mechanotransduction in human breast cancer cells

    PubMed Central

    Yoon, A-Rum; Stasinopoulos, Ioannis; Kim, Jae Hun; Yong, Hwan Mee; Kilic, Onur; Wirtz, Denis; Bhujwalla, Zaver M; An, Steven S

    2015-01-01

    The ability of living cells to exert physical forces upon their surrounding is a necessary prerequisite for diverse biological processes, such as local cellular migrations in wound healing to metastatic-invasion of cancer. How forces are coopted in metastasis has remained unclear, however, because the mechanical interplay between cancer cells and the various stromal components has not been experimentally accessible. Current dogma implicates inflammation in these mechanical processes. Using Fourier transform traction microscopy, we measured the force-generating capacity of human breast cancer cells occupying a spectrum of invasiveness as well as basal and inducible COX-2 expression (MCF-7COX-2. Both COX-2-silenced and COX-2-expressing cells expressed EP2 and EP4 receptors, but not EP1 and EP3. Exogenous addition of PGE2 increased cell tractions and stiffened the underlying cytoskeletal network. To our knowledge this is the first report linking the expression of COX-2 with mechanotransduction of human breast cancer cells, and the regulation of COX-2-PGE2-EP signaling with physical properties of the tumor microenvironment. Drug treatments aimed at reducing this mechanical interplay may have therapeutic potential in the treatment of breast cancer. PMID:25701047

  1. Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARγ-dependent pathway

    PubMed Central

    Ramer, Robert; Mittag, Nadine; Hinz, Burkhard

    2016-01-01

    Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) are well-established agents to treat hyperlipidemic states. Experimental and epidemiological evidence further implies an anticancer effect of these substances. This study investigates the mechanism underlying human lung cancer cell death by lovastatin and the role of the prostaglandin (PG)-synthesizing enzyme cyclooxygenase-2 (COX-2) in this process. In A549 and H358 lung carcinoma cells the lipophilic prodrug lovastatin lactone led to a concentration-dependent decrease of viability and induction of DNA fragmentation, whereas its HMG-CoA-inhibitory, ring-open acid form was inactive in this respect. Apoptotic cell death by lovastatin was accompanied by high intracellular levels of the lactone form, by upregulation of COX-2 mRNA and protein, as well as by increased formation of peroxisome proliferator-activated receptor γ (PPARγ)-activating PGD2 and 15-deoxy-Δ12,14-PGJ2. Cells were significantly less sensitive to lovastatin-induced apoptotic cell death, when the expression or activity of COX-2 was suppressed by siRNA or by the COX-2 inhibitor NS-398. Apoptosis by lovastatin was likewise reversed by the PPARγ antagonist GW9662. Fluorescence microscopy analyses revealed a lovastatin-induced cytosol-to-nucleus translocation of PPARγ that was inhibited by NS-398. Collectively, this study demonstrates COX-2 induction and subsequent COX-2-dependent activation of PPARγ as a hitherto unknown mechanism by which lovastatin lactone induces human lung cancer cell death. PMID:26863638

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

    PubMed Central

    Liu, Sophia Z.

    2013-01-01

    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

  3. Timosaponin AIII inhibits melanoma cell migration by suppressing COX-2 and in vivo tumor metastasis.

    PubMed

    Kim, Ki Mo; Im, A-Rang; Kim, Seung Hyung; Hyun, Jin Won; Chae, Sungwook

    2016-02-01

    Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E2 (PGE2 ), and PGE2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE2 , and PGE2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL/6 mice. In addition, C57BL/6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-κB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-κB, PGE2, and PGE2 receptors. PMID:26595378

  4. Regression in schizophrenia and its therapeutic value.

    PubMed

    Yazaki, N

    1992-03-01

    Using the regression evaluation scale, 25 schizophrenic patients were classified into three groups of Dissolution/autism (DAUG), Dissolution----attachment (DATG) and Non-regression (NRG). The regression of DAUG was of the type in which autism occurred when destructiveness emerged, while the regression of DATG was of the type in which attachment occurred when destructiveness emerged. This suggests that the regressive phenomena are an actualized form of the approach complex. In order to determine the factors distinguishing these two groups, I investigated psychiatric symptoms, mother-child relationships, premorbid personalities and therapeutic interventions. I believe that these factors form a continuity in which they interrelatedly determine the regressive state. Foremost among them, I stressed the importance of the mother-child relationship. PMID:1353128

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

    SciTech Connect

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

    2012-03-09

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

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

    SciTech Connect

    Di Capua, M S

    1999-09-01

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

  7. Data Mining within a Regression Framework

    NASA Astrophysics Data System (ADS)

    Berk, Richard A.

    Regression analysis can imply a far wider range of statistical procedures than often appreciated. In this chapter, a number of common Data Mining procedures are discussed within a regression framework. These include non-parametric smoothers, classification and regression trees, bagging, and random forests. In each case, the goal is to characterize one or more of the distributional features of a response conditional on a set of predictors.

  8. LRGS: Linear Regression by Gibbs Sampling

    NASA Astrophysics Data System (ADS)

    Mantz, Adam B.

    2016-02-01

    LRGS (Linear Regression by Gibbs Sampling) implements a Gibbs sampler to solve the problem of multivariate linear regression with uncertainties in all measured quantities and intrinsic scatter. LRGS extends an algorithm by Kelly (2007) that used Gibbs sampling for performing linear regression in fairly general cases in two ways: generalizing the procedure for multiple response variables, and modeling the prior distribution of covariates using a Dirichlet process.

  9. Accounting for the correlation between fellow eyes in regression analysis.

    PubMed

    Glynn, R J; Rosner, B

    1992-03-01

    Regression techniques that appropriately use all available eyes have infrequently been applied in the ophthalmologic literature, despite advances both in the development of statistical models and in the availability of computer software to fit these models. We considered the general linear model and polychotomous logistic regression approaches of Rosner and the estimating equation approach of Liang and Zeger, applied to both linear and logistic regression. Methods were illustrated with the use of two real data sets: (1) impairment of visual acuity in patients with retinitis pigmentosa and (2) overall visual field impairment in elderly patients evaluated for glaucoma. We discuss the interpretation of coefficients from these models and the advantages of these approaches compared with alternative approaches, such as treating individuals rather than eyes as the unit of analysis, separate regression analyses of right and left eyes, or utilization of ordinary regression techniques without accounting for the correlation between fellow eyes. Specific advantages include enhanced statistical power, more interpretable regression coefficients, greater precision of estimation, and less sensitivity to missing data for some eyes. We concluded that these models should be used more frequently in ophthalmologic research, and we provide guidelines for choosing between alternative models. PMID:1543458

  10. Geodesic least squares regression on information manifolds

    SciTech Connect

    Verdoolaege, Geert

    2014-12-05

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

  11. Quantile regression applied to spectral distance decay

    USGS Publications Warehouse

    Rocchini, D.; Cade, B.S.

    2008-01-01

    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.

  12. Image segmentation via piecewise constant regression

    NASA Astrophysics Data System (ADS)

    Acton, Scott T.; Bovik, Alan C.

    1994-09-01

    We introduce a novel unsupervised image segmentation technique that is based on piecewise constant (PICO) regression. Given an input image, a PICO output image for a specified feature size (scale) is computed via nonlinear regression. The regression effectively provides the constant region segmentation of the input image that has a minimum deviation from the input image. PICO regression-based segmentation avoids the problems of region merging, poor localization, region boundary ambiguity, and region fragmentation. Additionally, our segmentation method is particularly well-suited for corrupted (noisy) input data. An application to segmentation and classification of remotely sensed imagery is provided.

  13. Hybrid fuzzy regression with trapezoidal fuzzy data

    NASA Astrophysics Data System (ADS)

    Razzaghnia, T.; Danesh, S.; Maleki, A.

    2011-12-01

    In this regard, this research deals with a method for hybrid fuzzy least-squares regression. The extension of symmetric triangular fuzzy coefficients to asymmetric trapezoidal fuzzy coefficients is considered as an effective measure for removing unnecessary fuzziness of the linear fuzzy model. First, trapezoidal fuzzy variable is applied to derive a bivariate regression model. In the following, normal equations are formulated to solve the four parts of hybrid regression coefficients. Also the model is extended to multiple regression analysis. Eventually, method is compared with Y-H.O. chang's model.

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

    PubMed Central

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

    2015-01-01

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

  15. A rotor optimization using regression analysis

    NASA Technical Reports Server (NTRS)

    Giansante, N.

    1984-01-01

    The design and development of helicopter rotors is subject to the many design variables and their interactions that effect rotor operation. Until recently, selection of rotor design variables to achieve specified rotor operational qualities has been a costly, time consuming, repetitive task. For the past several years, Kaman Aerospace Corporation has successfully applied multiple linear regression analysis, coupled with optimization and sensitivity procedures, in the analytical design of rotor systems. It is concluded that approximating equations can be developed rapidly for a multiplicity of objective and constraint functions and optimizations can be performed in a rapid and cost effective manner; the number and/or range of design variables can be increased by expanding the data base and developing approximating functions to reflect the expanded design space; the order of the approximating equations can be expanded easily to improve correlation between analyzer results and the approximating equations; gradients of the approximating equations can be calculated easily and these gradients are smooth functions reducing the risk of numerical problems in the optimization; the use of approximating functions allows the problem to be started easily and rapidly from various initial designs to enhance the probability of finding a global optimum; and the approximating equations are independent of the analysis or optimization codes used.

  16. Regression of papillomas induced by cottontail rabbit papillomavirus is associated with infiltration of CD8+ cells and persistence of viral DNA after regression.

    PubMed Central

    Selvakumar, R; Schmitt, A; Iftner, T; Ahmed, R; Wettstein, F O

    1997-01-01

    Cottontail rabbit papillomavirus (CRPV) is a highly oncogenic papillomavirus and has been successfully used as a model to develop protective vaccines against papillomaviruses. Papillomas induced by the virus may spontaneously regress, suggesting that CRPV can also serve as a model to develop therapeutic vaccines. As a first step toward this goal, we have analyzed immunologic and viral aspects associated with papilloma regression and have identified several features unique to regression. Immunohistochemical staining of biopsies from growing and regressing papillomas and from sites after complete regression showed infiltration of CD8+ cells into the basal and suprabasal layers of the epidermis only during active regression. In situ hybridizations with mRNA-specific probes were strongly positive for E6 and E7 mRNAs during regression, but no late mRNA was present. Viral DNA was detected by in situ hybridization during regression but not after regression. However, analysis by PCR revealed persistence of viral DNA for several months at the majority of regression sites. The results suggest that stimulation of a strong CD8+ response to virus-infected cells is important for an effective therapeutic vaccine and that special attention should be given to the suppression of latent infection. PMID:9188628

  17. AdipoR-increased intracellular ROS promotes cPLA2 and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells.

    PubMed

    Chen, Hsiao-Mei; Yang, Chuen-Mao; Chang, Jia-Feng; Wu, Chi-Sheng; Sia, Kee-Chin; Lin, Wei-Ning

    2016-08-01

    Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases. PMID:27288489

  18. Deriving the Regression Equation without Using Calculus

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.; Gordon, Florence S.

    2004-01-01

    Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

  19. Regression Analysis and the Sociological Imagination

    ERIC Educational Resources Information Center

    De Maio, Fernando

    2014-01-01

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

  20. Illustration of Regression towards the Means

    ERIC Educational Resources Information Center

    Govindaraju, K.; Haslett, S. J.

    2008-01-01

    This article presents a procedure for generating a sequence of data sets which will yield exactly the same fitted simple linear regression equation y = a + bx. Unless rescaled, the generated data sets will have progressively smaller variability for the two variables, and the associated response and covariate will "regress" towards their…

  1. Stepwise versus Hierarchical Regression: Pros and Cons

    ERIC Educational Resources Information Center

    Lewis, Mitzi

    2007-01-01

    Multiple regression is commonly used in social and behavioral data analysis. In multiple regression contexts, researchers are very often interested in determining the "best" predictors in the analysis. This focus may stem from a need to identify those predictors that are supportive of theory. Alternatively, the researcher may simply be interested…

  2. Cross-Validation, Shrinkage, and Multiple Regression.

    ERIC Educational Resources Information Center

    Hynes, Kevin

    One aspect of multiple regression--the shrinkage of the multiple correlation coefficient on cross-validation is reviewed. The paper consists of four sections. In section one, the distinction between a fixed and a random multiple regression model is made explicit. In section two, the cross-validation paradigm and an explanation for the occurrence…

  3. Principles of Quantile Regression and an Application

    ERIC Educational Resources Information Center

    Chen, Fang; Chalhoub-Deville, Micheline

    2014-01-01

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

  4. Regression Analysis: Legal Applications in Institutional Research

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. Dealing with Outliers: Robust, Resistant Regression

    ERIC Educational Resources Information Center

    Glasser, Leslie

    2007-01-01

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

  6. A Practical Guide to Regression Discontinuity

    ERIC Educational Resources Information Center

    Jacob, Robin; Zhu, Pei; Somers, Marie-Andrée; Bloom, Howard

    2012-01-01

    Regression discontinuity (RD) analysis is a rigorous nonexperimental approach that can be used to estimate program impacts in situations in which candidates are selected for treatment based on whether their value for a numeric rating exceeds a designated threshold or cut-point. Over the last two decades, the regression discontinuity approach has…

  7. Sulphasalazine and regression of rheumatoid nodules.

    PubMed

    Englert, H J; Hughes, G R; Walport, M J

    1987-03-01

    The regression of small rheumatoid nodules was noted in four patients after starting sulphasalazine therapy. This coincided with an improvement in synovitis and also falls in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). The relation between the nodule regression and the sulphasalazine therapy is discussed. PMID:2883940

  8. A Simulation Investigation of Principal Component Regression.

    ERIC Educational Resources Information Center

    Allen, David E.

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

  9. Three-Dimensional Modeling in Linear Regression.

    ERIC Educational Resources Information Center

    Herman, James D.

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

  10. Systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov (Hemiptera: Pseudococcidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov is presented. Nine species are treated, including D. millari which is described as new. The 8 previously described species are: Delottococcus aberiae (De Lotto), D. confusus (De Lotto), D. elisabethae (Brain), D. euphorbiae (E...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    EPA Science Inventory

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

  13. Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa.

    PubMed

    Sumalatha, Manne; Munikishore, Rachakunta; Rammohan, Aluru; Gunasekar, Duvvuru; Kumar, Kotha Anil; Reddy, Kakularam Kumar; Azad, Rajaram; Reddanna, Pallu; Bodo, Bernard

    2015-10-01

    Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 μM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species. PMID:26669106

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

    SciTech Connect

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

    2013-10-11

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

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

    PubMed

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. PMID:25770423

  16. Study of Rapid-Regression Liquefying Hybrid Rocket Fuels

    NASA Technical Reports Server (NTRS)

    Zilliac, Greg; DeZilwa, Shane; Karabeyoglu, M. Arif; Cantwell, Brian J.; Castellucci, Paul

    2004-01-01

    A report describes experiments directed toward the development of paraffin-based hybrid rocket fuels that burn at regression rates greater than those of conventional hybrid rocket fuels like hydroxyl-terminated butadiene. The basic approach followed in this development is to use materials such that a hydrodynamically unstable liquid layer forms on the melting surface of a burning fuel body. Entrainment of droplets from the liquid/gas interface can substantially increase the rate of fuel mass transfer, leading to surface regression faster than can be achieved using conventional fuels. The higher regression rate eliminates the need for the complex multi-port grain structures of conventional solid rocket fuels, making it possible to obtain acceptable performance from single-port structures. The high-regression-rate fuels contain no toxic or otherwise hazardous components and can be shipped commercially as non-hazardous commodities. Among the experiments performed on these fuels were scale-up tests using gaseous oxygen. The data from these tests were found to agree with data from small-scale, low-pressure and low-mass-flux laboratory tests and to confirm the expectation that these fuels would burn at high regression rates, chamber pressures, and mass fluxes representative of full-scale rocket motors.

  17. Hybrid rocket fuel combustion and regression rate study

    NASA Technical Reports Server (NTRS)

    Strand, L. D.; Ray, R. L.; Anderson, F. A.; Cohen, N. S.

    1992-01-01

    The objectives of this study are to develop hybrid fuels (1) with higher regression rates and reduced dependence on fuel grain geometry and (2) that maximize potential specific impulse using low-cost materials. A hybrid slab window motor system was developed to screen candidate fuels - their combustion behavior and regression rate. Combustion behavior diagnostics consisted of video and high speed motion pictures coverage. The mean fuel regression rates were determined by before and after measurements of the fuel slabs. The fuel for this initial investigation consisted of hydroxyl-terminated polybutadiene binder with coal and aluminum fillers. At low oxidizer flux levels (and corresponding fuel regression rates) the filled-binder fuels burn in a layered fashion, forming an aluminum containing binder/coal surface melt that, in turn, forms into filigrees or flakes that are stripped off by the crossflow. This melt process appears to diminish with increasing oxidizer flux level. Heat transfer by radiation is a significant contributor, producing the desired increase in magnitude and reduction in flow dependency (power law exponent) of the fuel regression rate.

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

    SciTech Connect

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

    2011-12-09

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

  19. COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic molecular markers.

    PubMed

    Millanta, F; Citi, S; Della Santa, D; Porciani, M; Poli, A

    2006-07-01

    Cyclooxygenase (COX)-2 is an inducible enzyme linked to tumor growth and angiogenesis. Its expression occurs in a wide range of preneoplastic and neoplastic conditions in humans, including colon and breast carcinomas. We evaluated the role of COX-2 as a mediator of angiogenesis in feline and canine invasive carcinomas (IMCs) and its role as a prognostic indicator. COX-2 expression was assessed in neoplastic samples and healthy mammary glands by immunohistochemistry, and related to the following clinicopathological parameters: age, tumor size, histologic type, tumor grading, vessel invasion, estrogen (ER) and progesterone receptor (PR) status, Ki-67, HER-2 overexpression, microvessel density (MVD), VEGF expression and overall survival (OS). In both species, COX-2 immunoreactivity was not observed in healthy tissues, whereas 96% of feline and 100% of canine invasive carcinomas scored positive. In queens, COX-2 overexpression was significantly correlated to ER-negative status (p=0.04) and to increased PR (p=0.038) expression, and angiogenesis assessed by VEGF expression (p=0.002). In bitches an increased COX-2 expression was significantly correlated to HER-2 overexpression (p=0.013) and to tumor dedifferentiation (p=0.03). In both species increased levels of COX-2 were correlated to poorer prognosis (p=0.03 in dogs and p=0.002 in cats). COX-2 is expressed in mammary tissues during tumorigenesis and its expression is associated with a poorer prognosis in bitches and queens. The correlation of COX-2 expression and angiogenesis provides support for a potential role of COX-2 inhibitors for the prevention and the treatment of feline IMCs via their anti-angiogenic properties. In the canine species, moreover, COX-2 may be important for mediating HER-2 induced mammary tumors. PMID:16538539

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

    SciTech Connect

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

    2012-08-31

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