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

    PubMed

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

    2014-02-20

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

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

    PubMed

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

    2014-11-30

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

  3. 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

  4. 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.

  5. Proportional assist ventilation and neurally adjusted ventilatory assist.

    PubMed

    Kacmarek, Robert M

    2011-02-01

    Patient-ventilator synchrony is a common problem with all patients actively triggering the mechanical ventilator. In many cases synchrony can be improved by vigilant adjustments by the managing clinician. However, in most institutions clinicians are not able to spend the time necessary to ensure synchrony in all patients. Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) were both developed to improve patient-ventilator synchrony by proportionally unloading ventilatory effort and turning control of the ventilatory pattern over to the patient. This paper discusses PAV's and NAVA's theory of operation, general process of application, and the supporting literature.

  6. [Clinical research XXII. From clinical judgment to Cox proportional hazards model].

    PubMed

    Pérez-Rodríguez, Marcela; Rivas-Ruiz, Rodolfo; Palacios-Cruz, Lino; Talavera, Juan O

    2014-01-01

    Survival analyses are commonly used to determine the time of an event (for example, death). However, they can be used also for other clinical outcomes on the condition that these are dichotomous, for example healing time. These analyses only consider the relationship of one variable. However, Cox proportional hazards model is a multivariate analysis of the survival analysis, in which other potentially confounding covariates of the effect of the main maneuver studied, such as age, gender or disease stage, are taken into account. This analysis can include both quantitative and qualitative variables in the model. The measure of association used is called hazard ratio (HR) or relative risk ratio, which is not the same as the relative risk or odds ratio (OR). The difference is that the HR refers to the possibility that one of the groups develops the event before it is compared with the other group. The proportional hazards multivariate model of Cox is the most widely used in medicine when the phenomenon is studied in two dimensions: time and event.

  7. Sleepiness and prediction of driver impairment in simulator studies using a Cox proportional hazard approach.

    PubMed

    Vadeby, Anna; Forsman, Asa; Kecklund, Göran; Akerstedt, Torbjörn; Sandberg, David; Anund, Anna

    2010-05-01

    Cox proportional hazard models were used to study relationships between the event that a driver is leaving the lane caused by sleepiness and different indicators of sleepiness. In order to elucidate different indicators' performance, five different models developed by Cox proportional hazard on a data set from a simulator study were used. The models consisted of physiological indicators and indicators from driving data both as stand alone and in combination. The different models were compared on two different data sets by means of sensitivity and specificity and the models' ability to predict lane departure was studied. In conclusion, a combination of blink indicators based on the ratio between blink amplitude and peak closing velocity of eyelid (A/PCV) (or blink amplitude and peak opening velocity of eyelid (A/POV)), standard deviation of lateral position and standard deviation of lateral acceleration relative road (ddy) was the most sensitive approach with sensitivity 0.80. This is also supported by the fact that driving data only shows the impairment of driving performance while blink data have a closer relation to sleepiness. Thus, an effective sleepiness warning system may be based on a combination of lane variability measures and variables related to eye movements (particularly slow eye closure) in order to have both high sensitivity (many correct warnings) and acceptable specificity (few false alarms).

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

    PubMed Central

    Lin, Chen-Yen; Halabi, Susan

    2013-01-01

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

  9. Sparse estimation of Cox proportional hazards models via approximated information criteria.

    PubMed

    Su, Xiaogang; Wijayasinghe, Chalani S; Fan, Juanjuan; Zhang, Ying

    2016-09-01

    We propose a new sparse estimation method for Cox (1972) proportional hazards models by optimizing an approximated information criterion. The main idea involves approximation of the ℓ0 norm with a continuous or smooth unit dent function. The proposed method bridges the best subset selection and regularization by borrowing strength from both. It mimics the best subset selection using a penalized likelihood approach yet with no need of a tuning parameter. We further reformulate the problem with a reparameterization step so that it reduces to one unconstrained nonconvex yet smooth programming problem, which can be solved efficiently as in computing the maximum partial likelihood estimator (MPLE). Furthermore, the reparameterization tactic yields an additional advantage in terms of circumventing postselection inference. The oracle property of the proposed method is established. Both simulated experiments and empirical examples are provided for assessment and illustration. PMID:26873398

  10. Generating survival times to simulate Cox proportional hazards models with time-varying covariates.

    PubMed

    Austin, Peter C

    2012-12-20

    Simulations and Monte Carlo methods serve an important role in modern statistical research. They allow for an examination of the performance of statistical procedures in settings in which analytic and mathematical derivations may not be feasible. A key element in any statistical simulation is the existence of an appropriate data-generating process: one must be able to simulate data from a specified statistical model. We describe data-generating processes for the Cox proportional hazards model with time-varying covariates when event times follow an exponential, Weibull, or Gompertz distribution. We consider three types of time-varying covariates: first, a dichotomous time-varying covariate that can change at most once from untreated to treated (e.g., organ transplant); second, a continuous time-varying covariate such as cumulative exposure at a constant dose to radiation or to a pharmaceutical agent used for a chronic condition; third, a dichotomous time-varying covariate with a subject being able to move repeatedly between treatment states (e.g., current compliance or use of a medication). In each setting, we derive closed-form expressions that allow one to simulate survival times so that survival times are related to a vector of fixed or time-invariant covariates and to a single time-varying covariate. We illustrate the utility of our closed-form expressions for simulating event times by using Monte Carlo simulations to estimate the statistical power to detect as statistically significant the effect of different types of binary time-varying covariates. This is compared with the statistical power to detect as statistically significant a binary time-invariant covariate.

  11. A flexible alternative to the Cox proportional hazards model for assessing the prognostic accuracy of hospice patient survival.

    PubMed

    Miladinovic, Branko; Kumar, Ambuj; Mhaskar, Rahul; Kim, Sehwan; Schonwetter, Ronald; Djulbegovic, Benjamin

    2012-01-01

    Prognostic models are often used to estimate the length of patient survival. The Cox proportional hazards model has traditionally been applied to assess the accuracy of prognostic models. However, it may be suboptimal due to the inflexibility to model the baseline survival function and when the proportional hazards assumption is violated. The aim of this study was to use internal validation to compare the predictive power of a flexible Royston-Parmar family of survival functions with the Cox proportional hazards model. We applied the Palliative Performance Scale on a dataset of 590 hospice patients at the time of hospice admission. The retrospective data were obtained from the Lifepath Hospice and Palliative Care center in Hillsborough County, Florida, USA. The criteria used to evaluate and compare the models' predictive performance were the explained variation statistic R(2), scaled Brier score, and the discrimination slope. The explained variation statistic demonstrated that overall the Royston-Parmar family of survival functions provided a better fit (R(2) =0.298; 95% CI: 0.236-0.358) than the Cox model (R(2) =0.156; 95% CI: 0.111-0.203). The scaled Brier scores and discrimination slopes were consistently higher under the Royston-Parmar model. Researchers involved in prognosticating patient survival are encouraged to consider the Royston-Parmar model as an alternative to Cox. PMID:23082220

  12. 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.

  13. A comparative study on splitting criteria of a survival tree based on the Cox proportional model.

    PubMed

    Shimokawa, Asanao; Kawasaki, Yohei; Miyaoka, Etsuo

    2016-01-01

    We treat the situations that the effect of covariates on hazard is differed in subgroups of patients. To handle this situation, we can consider the hybrid model of the Cox model and tree-structured model. Through simulation studies, we compared several splitting criteria for constructing this hybrid model. As a result, the criterion using the degree of the improvement in the negative maximum partial log-likelihood obtained by splitting showed a good performance for many situations. We also present the results obtained by applying this tree model in an actual medical research study to show its utility. PMID:26043356

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

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma

    2014-01-01

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

  15. Adjusted Wald Confidence Interval for a Difference of Binomial Proportions Based on Paired Data

    ERIC Educational Resources Information Center

    Bonett, Douglas G.; Price, Robert M.

    2012-01-01

    Adjusted Wald intervals for binomial proportions in one-sample and two-sample designs have been shown to perform about as well as the best available methods. The adjusted Wald intervals are easy to compute and have been incorporated into introductory statistics courses. An adjusted Wald interval for paired binomial proportions is proposed here and…

  16. Risk Factors of Graft Survival After Diagnosis of Post-kidney Transplant Malignancy: Using Cox Proportional Hazard Model

    PubMed Central

    Rahimi Foroushani, Abbas; Salesi, Mahmoud; Rostami, Zohreh; Mehrazmay, Ali Reza; Mohammadi, Jamile; Einollahi, Behzad; Eshraghian, Mohammad Reza

    2015-01-01

    Background: All recipients of kidney transplantation, especially those with posttransplant malignancy, are at risk of long-term graft failure. Objectives: The purpose of our study was to evaluate the risk factors associated with graft survival after diagnosis of malignancy. Patients and Methods: To reach this purpose, we conducted a historical cohort study in Iran and 266 cases with posttransplant malignancy were followed up from diagnosis of malignancy until long-term graft loss or the date of last visit. These patients were taken as a census from 16 Transplant Centers in Iran during 22 years follow-up period since October 1984 to December 2008. A Cox proportional hazards model was performed to determine the important independent predictors of graft survival after malignancy. Results: At the end of the study, long-term graft failure was seen in 27 (10.2%) cases. One-year and 2-year graft survival after diagnosis of cancer were 93.6% and 91.7%, respectively. The univariate analysis showed that the incidence of chronic graft loss was significantly higher in male patients with solid cancers, withdrawal of immunosuppressant regimen, no response to treatment, and tumor metastasis. In continuation, the Cox model indicated that the significant risk factors associated with graft survival were type of cancer (P < 0.0001), response to treatment (P < 0.0001, HR = 0.14, 95% CI: 0.06 - 0.32), metastasis (P < 0.0001, HR = 5.68, 95% CI: 2.24 - 14.42), and treatment modality (P = 0.0001). Conclusions: By controlling the modifiable risk factors and modality of treatment in our study, physicians can reach more effective treatment. PMID:26734477

  17. Effect of type traits on functional longevity of Czech Holstein cows estimated from a Cox proportional hazards model.

    PubMed

    Zavadilová, L; Němcová, E; Stípková, M

    2011-08-01

    Relationships between conformation traits and functional longevity in Holstein cows were evaluated using survival analysis. Functional longevity was defined as the number of days between the first calving and culling; that is, length of productive life. The data set consisted of 116,369 Holstein cows that first calved from 2003 to 2008. All cows used in the analysis were scored for conformation between d 30 and d 210 of their first lactation. The data included 48% censored records. Analyses were done separately for 20 linear descriptive type traits, 6 composite traits, and height at sacrum measured in centimeters. Cox proportional hazard models were fitted to analyze data. The hazard function was described as the product of a baseline hazard function and the time-independent effects of age at first calving and sire (random), and the time-dependent effects of stage of lactation and lactation number, herd, year and season, herd size, and 305-d milk production. The strongest relationship between a composite trait and functional longevity was for dairy form, followed by udder and final score. Among the descriptive type traits, the strongest relationships with longevity were found for body condition score, angularity, traits related to udder attachment, and udder depth. Foot and leg traits showed substantially lower effect on functional longevity, and the effect of foot angle was minimal. Functional longevity declined with decreased body condition score of cows. Cows with deep udders had significantly lower functional survival compared with cows with shallow udders. In addition, weak central ligament was associated with significant reduction of cow longevity. For dairy form and angularity, cows classified as very good were the worst with respect to longevity, whereas cows classified as poor were the best. An intermediate optimum was evident for rear legs rear view and rear legs set (side view), whereas cows with sickled legs had lower longevity than cows with straighter

  18. New modes of mechanical ventilation: proportional assist ventilation, neurally adjusted ventilatory assist, and fractal ventilation.

    PubMed

    Navalesi, Paolo; Costa, Roberta

    2003-02-01

    Increased knowledge of the mechanisms that determine respiratory failure has led to the development of new technologies aimed at improving ventilatory treatment. Proportional assist ventilation and neurally adjusted ventilatory assist have been designed with the goal of improving patient-ventilator interaction by matching the ventilator support with the neural output of the respiratory centers. With proportional assist ventilation, the support is continuously readjusted in proportion to the predicted inspiratory effort. Neurally adjusted ventilatory assist is an experimental mode in which the assistance is delivered in proportion to the electrical activity of the diaphragm, assessed by means of an esophageal electrode. Biologically variable (or fractal) ventilation is a new, volume-targeted, controlled ventilation mode aimed at improving oxygenation; it incorporates the breath-to-breath variability that characterizes a natural breathing pattern.

  19. Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.

    PubMed

    de Keyser, Catherine E; Leening, Maarten J G; Romio, Silvana A; Jukema, J Wouter; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Stijnen, Theo; Stricker, Bruno H

    2014-11-01

    When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.

  20. Comparison of Cox's and relative survival models when estimating the effects of prognostic factors on disease-specific mortality: a simulation study under proportional excess hazards.

    PubMed

    Le Teuff, Gwenaël; Abrahamowicz, Michal; Bolard, Philippe; Quantin, Catherine

    2005-12-30

    In many prognostic studies focusing on mortality of persons affected by a particular disease, the cause of death of individual patients is not recorded. In such situations, the conventional survival analytical methods, such as the Cox's proportional hazards regression model, do not allow to discriminate the effects of prognostic factors on disease-specific mortality from their effects on all-causes mortality. In the last decade, the relative survival approach has been proposed to deal with the analyses involving population-based cancer registries, where the problem of missing information on the cause of death is very common. However, some questions regarding the ability of the relative survival methods to accurately discriminate between the two sources of mortality remain open. In order to systematically assess the performance of the relative survival model proposed by Esteve et al., and to quantify its potential advantages over the Cox's model analyses, we carried out a series of simulation experiments, based on the population-based colon cancer registry in the French region of Burgundy. Simulations showed a systematic bias induced by the 'crude' conventional Cox's model analyses when individual causes of death are unknown. In simulations where only about 10 per cent of patients died of causes other than colon cancer, the Cox's model over-estimated the effects of male gender and oldest age category by about 17 and 13 per cent, respectively, with the coverage rate of the 95 per cent CI for the latter estimate as low as 65 per cent. In contrast, the effect of higher cancer stages was under-estimated by 8-28 per cent. In contrast to crude survival, relative survival model largely reduced such problems and handled well even such challenging tasks as separating the opposite effects of the same variable on cancer-related versus other-causes mortality. Specifically, in all the cases discussed above, the relative bias in the estimates from the Esteve et al.'s model was

  1. A new method to evaluate the effects of bacterial dosage, infection route and Vibrio strain in experimental challenges of Litopenaeus vannamei, based on the Cox proportional hazard model.

    PubMed

    Xia, Qing; Wang, Baojie; Liu, Mei; Jiang, Keyong; Wang, Lei

    2015-10-01

    In the shrimp challenge test the Vibrio dosage, infection route, and strain are considered as risk factors that result in mortality. Assessment of Vibrio/shrimp interactions, and disease dynamics following infection by Vibrio, are useful techniques needed for detailed studies on the control of risk factors. In this paper we used an application of the Cox proportional hazard model to assess relative survival probability, estimate mortality risk, and construct a prognostic model to assess predictions of estimated time to death. Results indicate that infection route was the most important prognostic factor contributing to mortality in the challenge test (β = 3.698, P < 0.000). The shrimp infection rate following injection was found to be 40.4 times greater than that following immersion (hazard ratio (HR) = 40.4; p = 0.000). Our results also indicated that the HR resulting in shrimp mortality following a high dose of 10(8) cfu/shrimp was significantly greater (HR = 5.9, P < 0.000), than that following a baseline dosage of 10(7) cfu/shrimp. Strain Vh was found to be more virulent than Strain Vp (HR = 4.8; P < 0.000). The prognostic index also indicated that the infection route is the most important prognostic factor contributing to mortality in the challenge test.

  2. Using Swiss Webster mice to model Fetal Alcohol Spectrum Disorders (FASD): An analysis of multilevel time-to-event data through mixed-effects Cox proportional hazards models.

    PubMed

    Chi, Peter; Aras, Radha; Martin, Katie; Favero, Carlita

    2016-05-15

    Fetal Alcohol Spectrum Disorders (FASD) collectively describes the constellation of effects resulting from human alcohol consumption during pregnancy. Even with public awareness, the incidence of FASD is estimated to be upwards of 5% in the general population and is becoming a global health problem. The physical, cognitive, and behavioral impairments of FASD are recapitulated in animal models. Recently rodent models utilizing voluntary drinking paradigms have been developed that accurately reflect moderate consumption, which makes up the majority of FASD cases. The range in severity of FASD characteristics reflects the frequency, dose, developmental timing, and individual susceptibility to alcohol exposure. As most rodent models of FASD use C57BL/6 mice, there is a need to expand the stocks of mice studied in order to more fully understand the complex neurobiology of this disorder. To that end, we allowed pregnant Swiss Webster mice to voluntarily drink ethanol via the drinking in the dark (DID) paradigm throughout their gestation period. Ethanol exposure did not alter gestational outcomes as determined by no significant differences in maternal weight gain, maternal liquid consumption, litter size, or pup weight at birth or weaning. Despite seemingly normal gestation, ethanol-exposed offspring exhibit significantly altered timing to achieve developmental milestones (surface righting, cliff aversion, and open field traversal), as analyzed through mixed-effects Cox proportional hazards models. These results confirm Swiss Webster mice as a viable option to study the incidence and causes of ethanol-induced neurobehavioral alterations during development. Future studies in our laboratory will investigate the brain regions and molecules responsible for these behavioral changes.

  3. Addressing Loss of Efficiency Due to Misclassification Error in Enriched Clinical Trials for the Evaluation of Targeted Therapies Based on the Cox Proportional Hazards Model

    PubMed Central

    Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-pei

    2016-01-01

    A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example. PMID:27120450

  4. Nonlinear relative-proportion-based route adjustment process for day-to-day traffic dynamics: modeling, equilibrium and stability analysis

    NASA Astrophysics Data System (ADS)

    Zhu, Wenlong; Ma, Shoufeng; Tian, Junfang; Li, Geng

    2016-11-01

    Travelers' route adjustment behaviors in a congested road traffic network are acknowledged as a dynamic game process between them. Existing Proportional-Switch Adjustment Process (PSAP) models have been extensively investigated to characterize travelers' route choice behaviors; PSAP has concise structure and intuitive behavior rule. Unfortunately most of which have some limitations, i.e., the flow over adjustment problem for the discrete PSAP model, the absolute cost differences route adjustment problem, etc. This paper proposes a relative-Proportion-based Route Adjustment Process (rePRAP) maintains the advantages of PSAP and overcomes these limitations. The rePRAP describes the situation that travelers on higher cost route switch to those with lower cost at the rate that is unilaterally depended on the relative cost differences between higher cost route and its alternatives. It is verified to be consistent with the principle of the rational behavior adjustment process. The equivalence among user equilibrium, stationary path flow pattern and stationary link flow pattern is established, which can be applied to judge whether a given network traffic flow has reached UE or not by detecting the stationary or non-stationary state of link flow pattern. The stability theorem is proved by the Lyapunov function approach. A simple example is tested to demonstrate the effectiveness of the rePRAP model.

  5. Adjusting multistate capture-recapture models for misclassification bias: manatee breeding proportions

    USGS Publications Warehouse

    Kendall, W.L.; Hines, J.E.; Nichols, J.D.

    2003-01-01

    Matrix population models are important tools for research and management of populations. Estimating the parameters of these models is an important step in applying them to real populations. Multistate capture-recapture methods have provided a useful means for estimating survival and parameters of transition between locations or life history states but have mostly relied on the assumption that the state occupied by each detected animal is known with certainty. Nevertheless, in some cases animals can be misclassified. Using multiple capture sessions within each period of interest, we developed a method that adjusts estimates of transition probabilities for bias due to misclassification. We applied this method to 10 years of sighting data for a population of Florida manatees (Trichechus manatus latirostris) in order to estimate the annual probability of transition from nonbreeding to breeding status. Some sighted females were unequivocally classified as breeders because they were clearly accompanied by a first-year calf. The remainder were classified, sometimes erroneously, as nonbreeders because an attendant first-year calf was not observed or was classified as more than one year old. We estimated a conditional breeding probability of 0.31 + 0.04 (estimate + 1 SE) when we ignored misclassification bias, and 0.61 + 0.09 when we accounted for misclassification.

  6. Adjustments to de Leva-anthropometric regression data for the changes in body proportions in elderly humans.

    PubMed

    Ho Hoang, Khai-Long; Mombaur, Katja

    2015-10-15

    Dynamic modeling of the human body is an important tool to investigate the fundamentals of the biomechanics of human movement. To model the human body in terms of a multi-body system, it is necessary to know the anthropometric parameters of the body segments. For young healthy subjects, several data sets exist that are widely used in the research community, e.g. the tables provided by de Leva. None such comprehensive anthropometric parameter sets exist for elderly people. It is, however, well known that body proportions change significantly during aging, e.g. due to degenerative effects in the spine, such that parameters for young people cannot be used for realistically simulating the dynamics of elderly people. In this study, regression equations are derived from the inertial parameters, center of mass positions, and body segment lengths provided by de Leva to be adjustable to the changes in proportion of the body parts of male and female humans due to aging. Additional adjustments are made to the reference points of the parameters for the upper body segments as they are chosen in a more practicable way in the context of creating a multi-body model in a chain structure with the pelvis representing the most proximal segment.

  7. Adjustments to de Leva-anthropometric regression data for the changes in body proportions in elderly humans.

    PubMed

    Ho Hoang, Khai-Long; Mombaur, Katja

    2015-10-15

    Dynamic modeling of the human body is an important tool to investigate the fundamentals of the biomechanics of human movement. To model the human body in terms of a multi-body system, it is necessary to know the anthropometric parameters of the body segments. For young healthy subjects, several data sets exist that are widely used in the research community, e.g. the tables provided by de Leva. None such comprehensive anthropometric parameter sets exist for elderly people. It is, however, well known that body proportions change significantly during aging, e.g. due to degenerative effects in the spine, such that parameters for young people cannot be used for realistically simulating the dynamics of elderly people. In this study, regression equations are derived from the inertial parameters, center of mass positions, and body segment lengths provided by de Leva to be adjustable to the changes in proportion of the body parts of male and female humans due to aging. Additional adjustments are made to the reference points of the parameters for the upper body segments as they are chosen in a more practicable way in the context of creating a multi-body model in a chain structure with the pelvis representing the most proximal segment. PMID:26338096

  8. Adjusting the Proportion of Electron-Withdrawing Groups in a Graft Functional Polymer for Multilevel Memory Performance.

    PubMed

    Wu, Linxin; Wang, Peng; Zhang, Chunyu; He, Jinghui; Chen, Dongyun; Jun, Jiang; Xu, Qingfeng; Lu, Jianmei

    2016-01-01

    A polymer containing aldehyde active groups (PVB) was synthesized by atom transfer radical polymerization (ATRP), acting as a polymer precursor to graft a functional moiety via nucleophilic addition reaction. DHI (2-(1,5-dimethyl-hexyl)-6-hydrazino-benzo[de]isoquinoline-1,3-dione) and NPH (nitrophenyl hydrazine) groups, which contain naphthalimides that act as narrow traps and nitro groups that act as deep traps, were anchored onto the PVB at different ratios. A series of graft polymers were obtained and named PVB-DHI, PVB-DHI4 -NPH, PVB-DHI-NPH4 , and PVB-NPH. The chemical composition of the polymers was analyzed by (1) H-NMR spectroscopy and X-ray photoelectron spectroscopy (XPS). Memory devices were prepared from the polymers, and I-V characteristics were measured to determine the performance. By adjusting the ratio of different electron acceptors (DHI and NPH) to 4:1, ternary memory behavior was achieved. The relationship between memory behavior of PVB-DHIx NPHy and acceptor groups as well as their conduction mechanism were studied in detail.

  9. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+).

    PubMed

    Georgopoulos, Dimitris; Xirouchaki, Nectaria; Tzanakis, Nikolaos; Younes, Magdy

    2016-09-01

    The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+) after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure), respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy "Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?" [1].

  10. 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.

  11. Proportional Hazards Models of Graduation

    ERIC Educational Resources Information Center

    Chimka, Justin R.; Reed-Rhoads, Teri; Barker, Kash

    2008-01-01

    Survival analysis is a statistical tool used to describe the duration between events. Many processes in medical research, engineering, and economics can be described using survival analysis techniques. This research involves studying engineering college student graduation using Cox proportional hazards models. Among male students with American…

  12. 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.

  13. Estimation of treatment effects based on possibly misspecified Cox regression.

    PubMed

    Hattori, Satoshi; Henmi, Masayuki

    2012-10-01

    In randomized clinical trials, a treatment effect on a time-to-event endpoint is often estimated by the Cox proportional hazards model. The maximum partial likelihood estimator does not make sense if the proportional hazard assumption is violated. Xu and O'Quigley (Biostatistics 1:423-439, 2000) proposed an estimating equation, which provides an interpretable estimator for the treatment effect under model misspecification. Namely it provides a consistent estimator for the log-hazard ratio among the treatment groups if the model is correctly specified, and it is interpreted as an average log-hazard ratio over time even if misspecified. However, the method requires the assumption that censoring is independent of treatment group, which is more restricted than that for the maximum partial likelihood estimator and is often violated in practice. In this paper, we propose an alternative estimating equation. Our method provides an estimator of the same property as that of Xu and O'Quigley under the usual assumption for the maximum partial likelihood estimation. We show that our estimator is consistent and asymptotically normal, and derive a consistent estimator of the asymptotic variance. If the proportional hazards assumption holds, the efficiency of the estimator can be improved by applying the covariate adjustment method based on the semiparametric theory proposed by Lu and Tsiatis (Biometrika 95:679-694, 2008). PMID:22527680

  14. COX-2 chronology

    PubMed Central

    Hawkey, C J

    2005-01-01

    The role of selective cyclooxygenase (COX)-2 inhibitors in medical practice has become controversial since evidence emerged that their use is associated with an increased risk of myocardial infarction. Selective COX-2 inhibitors were seen as successor to non-selective non-steroidal anti-inflammatory drugs, in turn successors to aspirin. The importance of pain relief means that such drugs have always attracted attention. The fact that they work through inhibition of cyclooxygenase, are widespread, and have multiple effects also means that adverse effects that were unanticipated (even though predictable) have always emerged. In this paper I therefore present an historical perspective so that the lessons of the past may be applied to the present. PMID:16227351

  15. 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

  16. Strip Diagrams: Illuminating Proportions

    ERIC Educational Resources Information Center

    Cohen, Jessica S.

    2013-01-01

    Proportional reasoning is both complex and layered, making it challenging to define. Lamon (1999) identified characteristics of proportional thinkers, such as being able to understand covariance of quantities; distinguish between proportional and nonproportional relationships; use a variety of strategies flexibly, most of which are nonalgorithmic,…

  17. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    PubMed

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method. PMID:26434910

  18. Coincidence Proportional Counter

    DOEpatents

    Manley, J H

    1950-11-21

    A coincidence proportional counter having a plurality of collecting electrodes so disposed as to measure the range or energy spectrum of an ionizing particle-emitting source such as an alpha source, is disclosed.

  19. Adaptation through proportion

    NASA Astrophysics Data System (ADS)

    Xiong, Liyang; Shi, Wenjia; Tang, Chao

    2016-08-01

    Adaptation is a ubiquitous feature in biological sensory and signaling networks. It has been suggested that adaptive systems may follow certain simple design principles across diverse organisms, cells and pathways. One class of networks that can achieve adaptation utilizes an incoherent feedforward control, in which two parallel signaling branches exert opposite but proportional effects on the output at steady state. In this paper, we generalize this adaptation mechanism by establishing a steady-state proportionality relationship among a subset of nodes in a network. Adaptation can be achieved by using any two nodes in the sub-network to respectively regulate the output node positively and negatively. We focus on enzyme networks and first identify basic regulation motifs consisting of two and three nodes that can be used to build small networks with proportional relationships. Larger proportional networks can then be constructed modularly similar to LEGOs. Our method provides a general framework to construct and analyze a class of proportional and/or adaptation networks with arbitrary size, flexibility and versatile functional features.

  20. Determinants of Under-Five Mortality in Rural Empowered Action Group States in India: An Application of Cox Frailty Model

    PubMed Central

    Mani, Kalaivani; Dwivedi, Sada Nand; Pandey, Ravindra Mohan

    2012-01-01

    Objectives In India there has been a decline in overall under-five mortality, with some states still showing very high mortality rates. It is argued that there is family clustering in mortality among children aged <5 years. We explored the effects of programmable (proximate) determinants on under-five mortality by accounting for family-level clustering and adjusting for background variables using Cox frailty model in rural Empowered Action Group states (EAG) in India and compared results with standard models. Methods Analysis included 13,785 live births that occurred five years preceding the National Family Health Survey-3 (2005-06). The Cox frailty model and the traditional Cox proportional hazards models were used. Results The Cox frailty model showed that mother’s age at birth, place of delivery, sex of the baby, composite variable of birth order and birth interval, baby size at birth, and breastfeeding were significant determinants of under-five mortality, after adjusting for the familial frailty effect. The hazard ratio was 1.41 (95% CI=1.14−1.75) for children born to mothers aged 12-19 years compared to mothers aged 20-30 years, 1.42 (95% CI=1.12−1.79) for small-sized than average-sized babies at birth, and 102 (95% CI=81−128) for non-breastfed than breastfed babies. Children had significantly lower mortality risks in the richest than poorest wealth quintile. The familial frailty effect was 2.86 in the rural EAG states. The hazard ratios for the determinants in all the three models were similar except the death of a previous child variable in the Cox frailty model, which had the highest R2 and lowest log-likelihood. Conclusions and Public Health Implications While planning for the child survival program in rural EAG states, parental competence which explains the unobserved familial effect needs to be considered along with significant programmable determinants. The frailty models that provide statistically valid estimates of the covariate effects are

  1. Keep It in Proportion.

    ERIC Educational Resources Information Center

    Snider, Richard G.

    1985-01-01

    The ratio factors approach involves recognizing a given fraction, then multiplying so that units cancel. This approach, which is grounded in concrete operational thinking patterns, provides a standard for science ratio and proportion problems. Examples are included for unit conversions, mole problems, molarity, speed/density problems, and…

  2. Multiwire proportional chamber development

    NASA Technical Reports Server (NTRS)

    Doolittle, R. F.; Pollvogt, U.; Eskovitz, A. J.

    1973-01-01

    The development of large area multiwire proportional chambers, to be used as high resolution spatial detectors in cosmic ray experiments is described. A readout system was developed which uses a directly coupled, lumped element delay-line whose characteristics are independent of the MWPC design. A complete analysis of the delay-line and the readout electronic system shows that a spatial resolution of about 0.1 mm can be reached with the MWPC operating in the strictly proportional region. This was confirmed by measurements with a small MWPC and Fe-55 X-rays. A simplified analysis was carried out to estimate the theoretical limit of spatial resolution due to delta-rays, spread of the discharge along the anode wire, and inclined trajectories. To calculate the gas gain of MWPC's of different geometrical configurations a method was developed which is based on the knowledge of the first Townsend coefficient of the chamber gas.

  3. Monitor proportional counter

    NASA Technical Reports Server (NTRS)

    Weisskopf, M. C.

    1979-01-01

    An Uhuru class Ar-CO2 gas filled proportional counter sealed with a 1.5 mil beryllium window and sensitive to X-rays in the energy bandwidth from 1.5 to 22 keV is presented. This device is coaligned with the X-ray telescope aboard the Einstein Observatory and takes data as a normal part of the Observatory operations.

  4. Proportional counter radiation camera

    DOEpatents

    Borkowski, C.J.; Kopp, M.K.

    1974-01-15

    A gas-filled proportional counter camera that images photon emitting sources is described. A two-dimensional, positionsensitive proportional multiwire counter is provided as the detector. The counter consists of a high- voltage anode screen sandwiched between orthogonally disposed planar arrays of multiple parallel strung, resistively coupled cathode wires. Two terminals from each of the cathode arrays are connected to separate timing circuitry to obtain separate X and Y coordinate signal values from pulse shape measurements to define the position of an event within the counter arrays which may be recorded by various means for data display. The counter is further provided with a linear drift field which effectively enlarges the active gas volume of the counter and constrains the recoil electrons produced from ionizing radiation entering the counter to drift perpendicularly toward the planar detection arrays. A collimator is interposed between a subject to be imaged and the counter to transmit only the radiation from the subject which has a perpendicular trajectory with respect to the planar cathode arrays of the detector. (Official Gazette)

  5. Masked Proportional Routing

    NASA Technical Reports Server (NTRS)

    Wolpert, David

    2004-01-01

    Masked proportional routing is an improved procedure for choosing links between adjacent nodes of a network for the purpose of transporting an entity from a source node ("A") to a destination node ("B"). The entity could be, for example, a physical object to be shipped, in which case the nodes would represent waypoints and the links would represent roads or other paths between waypoints. For another example, the entity could be a message or packet of data to be transmitted from A to B, in which case the nodes could be computer-controlled switching stations and the links could be communication channels between the stations. In yet another example, an entity could represent a workpiece while links and nodes could represent, respectively, manufacturing processes and stages in the progress of the workpiece towards a finished product. More generally, the nodes could represent states of an entity and the links could represent allowed transitions of the entity. The purpose of masked proportional routing and of related prior routing procedures is to schedule transitions of entities from their initial states ("A") to their final states ("B") in such a manner as to minimize a cost or to attain some other measure of optimality or efficiency. Masked proportional routing follows a distributed (in the sense of decentralized) approach to probabilistically or deterministically choosing the links. It was developed to satisfy a need for a routing procedure that 1. Does not always choose the same link(s), even for two instances characterized by identical estimated values of associated cost functions; 2. Enables a graceful transition from one set of links to another set of links as the circumstances of operation of the network change over time; 3. Is preferably amenable to separate optimization of different portions of the network; 4. Is preferably usable in a network in which some of the routing decisions are made by one or more other procedure(s); 5. Preferably does not cause an

  6. Gated strip proportional detector

    DOEpatents

    Morris, Christopher L.; Idzorek, George C.; Atencio, Leroy G.

    1987-01-01

    A gated strip proportional detector includes a gas tight chamber which encloses a solid ground plane, a wire anode plane, a wire gating plane, and a multiconductor cathode plane. The anode plane amplifies the amount of charge deposited in the chamber by a factor of up to 10.sup.6. The gating plane allows only charge within a narrow strip to reach the cathode. The cathode plane collects the charge allowed to pass through the gating plane on a set of conductors perpendicular to the open-gated region. By scanning the open-gated region across the chamber and reading out the charge collected on the cathode conductors after a suitable integration time for each location of the gate, a two-dimensional image of the intensity of the ionizing radiation incident on the detector can be made.

  7. Gated strip proportional detector

    DOEpatents

    Morris, C.L.; Idzorek, G.C.; Atencio, L.G.

    1985-02-19

    A gated strip proportional detector includes a gas tight chamber which encloses a solid ground plane, a wire anode plane, a wire gating plane, and a multiconductor cathode plane. The anode plane amplifies the amount of charge deposited in the chamber by a factor of up to 10/sup 6/. The gating plane allows only charge within a narrow strip to reach the cathode. The cathode plane collects the charge allowed to pass through the gating plane on a set of conductors perpendicular to the open-gated region. By scanning the open-gated region across the chamber and reading out the charge collected on the cathode conductors after a suitable integration time for each location of the gate, a two-dimensional image of the intensity of the ionizing radiation incident on the detector can be made.

  8. The Cox3p assembly module of yeast cytochrome oxidase

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. 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

  11. Risk Adjustment and the Assessment of Disparities in Dialysis Mortality Outcomes.

    PubMed

    Kalbfleisch, John; Wolfe, Robert; Bell, Sarah; Sun, Rena; Messana, Joseph; Shearon, Tempie; Ashby, Valarie; Padilla, Robin; Zhang, Min; Turenne, Marc; Pearson, Jeffrey; Dahlerus, Claudia; Li, Yi

    2015-11-01

    Standardized mortality ratios (SMRs) reported by Medicare compare mortality at individual dialysis facilities with the national average, and are currently adjusted for race. However, whether the adjustment for race obscures or clarifies disparities in quality of care for minority groups is unknown. Cox model-based SMRs were computed with and without adjustment for patient race for 5920 facilities in the United States during 2010. The study population included virtually all patients treated with dialysis during this period. Without race adjustment, facilities with higher proportions of black patients had better survival outcomes; facilities with the highest percentage of black patients (top 10%) had overall mortality rates approximately 7% lower than expected. After adjusting for within-facility racial differences, facilities with higher proportions of black patients had poorer survival outcomes among black and non-black patients; facilities with the highest percentage of black patients (top 10%) had mortality rates approximately 6% worse than expected. In conclusion, accounting for within-facility racial differences in the computation of SMR helps to clarify disparities in quality of health care among patients with ESRD. The adjustment that accommodates within-facility comparisons is key, because it could also clarify relationships between patient characteristics and health care provider outcomes in other settings.

  12. 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

  13. 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

  14. Visual Manipulatives for Proportional Reasoning.

    ERIC Educational Resources Information Center

    Moore, Joyce L.; Schwartz, Daniel L.

    The use of a visual representation in learning about proportional relations was studied, examining students' understandings of the invariance of a multiplicative relation on both sides of a proportion equation and the invariance of the structural relations that exist in different semantic types of proportion problems. Subjects were 49 high-ability…

  15. [Structural adjustment, cultural adjustment?].

    PubMed

    Dujardin, B; Dujardin, M; Hermans, I

    2003-12-01

    Over the last two decades, multiple studies have been conducted and many articles published about Structural Adjustment Programmes (SAPs). These studies mainly describe the characteristics of SAPs and analyse their economic consequences as well as their effects upon a variety of sectors: health, education, agriculture and environment. However, very few focus on the sociological and cultural effects of SAPs. Following a summary of SAP's content and characteristics, the paper briefly discusses the historical course of SAPs and the different critiques which have been made. The cultural consequences of SAPs are introduced and are described on four different levels: political, community, familial, and individual. These levels are analysed through examples from the literature and individual testimonies from people in the Southern Hemisphere. The paper concludes that SAPs, alongside economic globalisation processes, are responsible for an acute breakdown of social and cultural structures in societies in the South. It should be a priority, not only to better understand the situation and its determining factors, but also to intervene and act with strategies that support and reinvest in the social and cultural sectors, which is vital in order to allow for individuals and communities in the South to strengthen their autonomy and identify.

  16. Specific cyclooxygenase-2 (COX-2) inhibitors.

    PubMed

    Rubin, B R

    1999-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently among the most widely prescribed drugs worldwide. Their therapeutic benefits and their side effects in the gastrointestinal tract and kidney, as well as in hemostasis, are of great importance in modern medicine. Within the past decade, new insights into how NSAIDs produce both their therapeutic benefits and their serious side effects have been discovered. It is now known that there are two froms of the cyclooxygenase (COX) enzyme that metabolize arachidonic acid into prostaglandins. Drugs that specifically inhibit the COX-2 enzyme were formulated and put into clinical trials during the past 5 years. These drugs are now available to treat patients in the United States. Specific COX-2 inhibitors offer the benefit of being able to treat the pain and inflammation of arthritis with potentially little risk of serious gastrointestinal injury.

  17. Multiple Ways to Solve Proportions

    ERIC Educational Resources Information Center

    Ercole, Leslie K.; Frantz, Marny; Ashline, George

    2011-01-01

    When solving problems involving proportions, students may intuitively draw on strategies that connect to their understanding of fractions, decimals, and percents. These two statements--"Instruction in solving proportions should include methods that have a strong intuitive basis" and "Teachers should begin instruction with more intuitive…

  18. 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

  19. Proportional smile design using the recurring esthetic dental (red) proportion.

    PubMed

    Ward, D H

    2001-01-01

    Dentists have needed an objective way in which to evaluate a smile. A method for determining the ideal size and position of the anterior teeth has been presented here. Use of the FIVE to evaluate the RED proportion and the width-to-height ratio, tempered with sound clinical judgment, gives pleasing and consistent results. With the diversity that exists in nature, rarely does the final result follow all the mathematical rules of proportional smile design. This approach may serve as a foundation on which to base initial smile design, however. When one begins to understand the relationship between beauty, mathematics, and the surrounding world, one begins to appreciate their interdependence.

  20. 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

  1. Bayesian inference on proportional elections.

    PubMed

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software.

  2. Bayesian Inference on Proportional Elections

    PubMed Central

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software. PMID:25786259

  3. Proportional Reasoning with a Pyramid

    ERIC Educational Resources Information Center

    Mamolo, Ami; Sinclair, Margaret; Whiteley, Walter J.

    2011-01-01

    Proportional reasoning pops up in math class in a variety of places, such as while making scaled drawings; finding equivalent fractions; converting units of measurement; comparing speeds, prices, and rates; and comparing lengths, areas, and volume. Students need to be exposed to a variety of representations to develop a sound understanding of this…

  4. Social Justice and Proportional Reasoning

    ERIC Educational Resources Information Center

    Simic-Muller, Ksenija

    2015-01-01

    Ratio and proportional reasoning tasks abound that have connections to real-world situations. Examples in this article demonstrate how textbook tasks can easily be transformed into authentic real-world problems that shed light on issues of equity and fairness, such as population growth and crime rates. A few ideas are presented on how teachers can…

  5. Saving Money Using Proportional Reasoning

    ERIC Educational Resources Information Center

    de la Cruz, Jessica A.; Garney, Sandra

    2016-01-01

    It is beneficial for students to discover intuitive strategies, as opposed to the teacher presenting strategies to them. Certain proportional reasoning tasks are more likely to elicit intuitive strategies than other tasks. The strategies that students are apt to use when approaching a task, as well as the likelihood of a student's success or…

  6. 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

  7. Multiple comparisons for survival data with propensity score adjustment

    PubMed Central

    Zhu, Hong; Lu, Bo

    2015-01-01

    This article considers the practical problem in clinical and observational studies where multiple treatment or prognostic groups are compared and the observed survival data are subject to right censoring. Two possible formulations of multiple comparisons are suggested. Multiple Comparisons with a Control (MCC) compare every other group to a control group with respect to survival outcomes, for determining which groups are associated with lower risk than the control. Multiple Comparisons with the Best (MCB) compare each group to the truly minimum risk group and identify the groups that are either with the minimum risk or the practically minimum risk. To make a causal statement, potential confounding effects need to be adjusted in the comparisons. Propensity score based adjustment is popular in causal inference and can effectively reduce the confounding bias. Based on a propensity-score-stratified Cox proportional hazards model, the approaches of MCC test and MCB simultaneous confidence intervals for general linear models with normal error outcome are extended to survival outcome. This paper specifies the assumptions for causal inference on survival outcomes within a potential outcome framework, develops testing procedures for multiple comparisons and provides simultaneous confidence intervals. The proposed methods are applied to two real data sets from cancer studies for illustration, and a simulation study is also presented. PMID:25663729

  8. Evaluation of natural smile: Golden proportion, RED or Golden percentage

    PubMed Central

    Murthy, B. V. Sreenivasan; Ramani, Niketa

    2008-01-01

    Creating geometric or mathematical proportion to relate the successive width of maxillary anterior teeth is a critical aspect in Esthetic dentistry. Golden proportion, recurring esthetic dental (RED) proportion and golden percentage are new theories in this field. Aim: To investigate the existence and suitability of Golden proportion, Recurring Esthetic Dental, and Golden percentage between the widths of maxillary anterior teeth in individuals with natural dentition, with the aid of digital photographs and computer analysis. Material and Methods: Standardized frontal images of 56 dental students, 20 male and 36 female, were captured. Each maxillary anterior tooth was digitally measured. Once the measurements were recorded, the three theories were applied and the data was analyzed statistically. Results: The golden proportion was found to exist only in 14-25% of the subjects, between perceived maxillary anterior teeth in natural dentition. The value of RED proportion was not constant, and as one moved distally, this proportion gradually increased. Furthermore, the results revealed that golden percentage was rather constant in terms of relative tooth width. Central incisor represented 22%, lateral incisor 15% and canine 13% of the width of six maxillary anterior teeth, as viewed from the front. Conclusion: Both golden proportion and RED proportion are unsuitable methods to relate the successive width of the maxillary anterior teeth in natural dentition. However, the golden percentage theory can be applied if percentages are adjusted, taking into consideration the ethnicity of the population. PMID:20142879

  9. What is proportional reasoning, anyway?

    NASA Astrophysics Data System (ADS)

    Subero, Keron; Kanim, Stephen

    2007-10-01

    There appears to be a correlation between some measures of scientific reasoning skills and gain on conceptual measures of student understanding of introductory physics such as the Force Concept Inventory. At NMSU, we have established a correlation between pretest scores on proportional reasoning tasks and student performance on conceptual post-tests in the introductory lab. Proponents of a Piagetian model of cognitive development would call these scientific reasoning skills `operational capacities'' that signal the last transition in human intellectual growth from ``Concrete Operational'' to ``Formal'' reasoning. Seen in this light, the correlations described above suggest a cognitive ``deficit'' associated with development. We are exploring the possibility that proportional reasoning may in fact be a blanket term to describe many smaller elements of skills which students often seem to lack. In this talk, I will present some initial results from our investigation.

  10. Comparison of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors use in Australia and Nova Scotia (Canada)

    PubMed Central

    Barozzi, Nadia; Sketris, Ingrid; Cooke, Charmaine; Tett, Susan

    2009-01-01

    AIMS Cyclooxygenase-2 (COX-2) inhibitors were marketed aggressively and their rapid uptake caused safety concerns and budgetary challenges in Canada and Australia. The objectives of this study were to compare and contrast COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drug (ns-NSAID) use in Nova Scotia (Canada) and Australia and to identify lessons learned from the two jurisdictions. METHODS Ns-NSAID and COX-2 inhibitor Australian prescription data (concession beneficiaries) were downloaded from the Medicare Australia website (2001–2006). Similar Pharmacare data were obtained for Nova Scotia (seniors and those receiving Community services). Defined daily doses per 1000 beneficiaries day−1 were calculated. COX-2 inhibitors/all NSAIDs ratios were calculated for Australia and Nova Scotia. Ns-NSAIDs were divided into low, moderate and high risk for gastrointestinal side-effects and the proportions of use in each group were determined. Which drugs accounted for 90% of use was also calculated. RESULTS Overall NSAID use was different in Australia and Nova Scotia. However, ns-NSAID use was similar. COX-2 inhibitor dispensing was higher in Australia. The percentage of COX-2 inhibitor prescriptions over the total NSAID use was different in the two countries. High-risk NSAID use was much higher in Australia. Low-risk NSAID prescribing increased in Nova Scotia over time. The low-risk/high-risk ratio was constant throughout over the period in Australia and increased in Nova Scotia. CONCLUSIONS There are significant differences in Australia and Nova Scotia in use of NSAIDs, mainly due to COX-2 prescribing. Nova Scotia has a higher proportion of low-risk NSAID use. Interventions to provide physicians with information on relative benefits and risks of prescribing specific NSAIDs are needed, including determining their impact. PMID:19660008

  11. 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.

  12. Photodetectors for Scintillator Proportionality Measurement

    SciTech Connect

    Moses, William W.; Choong, Woon-Seng; Hull, Giulia; Payne, Steve; Cherepy, Nerine; Valentine, J.D.

    2010-10-18

    We evaluate photodetectors for use in a Compton Coincidence apparatus designed for measuring scintillator proportionality. There are many requirements placed on the photodetector in these systems, including active area, linearity, and the ability to accurately measure low light levels (which implies high quantum efficiency and high signal-to-noise ratio). Through a combination of measurement and Monte Carlo simulation, we evaluate a number of potential photodetectors, especially photomultiplier tubes and hybrid photodetectors. Of these, we find that the most promising devices available are photomultiplier tubes with high ({approx}50%) quantum efficiency, although hybrid photodetectors with high quantum efficiency would be preferable.

  13. Incisors’ proportions in smile esthetics

    PubMed Central

    Alsulaimani, Fahad F; Batwa, Waeil

    2013-01-01

    Aims: To determine whether alteration of the maxillary central and lateral incisors’ length and width, respectively, would affect perceived smile esthetics and to validate the most esthetic length and width, respectively, for the central and lateral incisors. Materials and Methods: Photographic manipulation was undertaken to produce two sets of photographs, each set of four photographs showing the altered width of the lateral incisor and length of the central length. The eight produced photographs were assessed by laypeople, dentists and orthodontists. Results: Alteration in the incisors’ proportion affected the relative smile attractiveness for laypeople (n=124), dentists (n=115) and orthodontists (n=68); dentists and orthodontists did not accept lateral width reduction of more than 0.5 mm (P<0.01), which suggests that the lateral to central incisor width ratio ranges from 54% to 62%. However, laypeople did not accept lateral width reduction of more than 1 mm (P<0.01), widening the range to be from 48% to 62%. All groups had zero tolerance for changes in central crown length (P<0.01). Conclusion: All participants recognized that the central incisors’ length changes. For lateral incisors, laypeople were more tolerant than dentists and orthodontists. This suggests that changing incisors’ proportions affects the relative smile attractiveness. PMID:24987650

  14. Recurrent events and the exploding Cox model

    PubMed Central

    Gjessing, Håkon K.; Røysland, Kjetil; Pena, Edsel A.; Aalen, Odd O.

    2014-01-01

    Counting process models have played an important role in survival and event history analysis for more than 30 years. Nevertheless, almost all models that are being used have a very simple structure. Analyzing recurrent events invites the application of more complex models with dynamic covariates. We discuss how to define valid models in such a setting. One has to check carefully that a suggested model is well defined as a stochastic process. We give conditions for this to hold. Some detailed discussion is presented in relation to a Cox type model, where the exponential structure combined with feedback lead to an exploding model. In general, counting process models with dynamic covariates can be formulated to avoid explosions. In particular, models with a linear feedback structure do not explode, making them useful tools in general modeling of recurrent events. PMID:20625827

  15. 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

  16. Correlated versus uncorrelated frailty Cox models: A comparison of different estimation procedures.

    PubMed

    Elghafghuf, Adel; Stryhn, Henrik

    2016-09-01

    In many studies in medicine, including clinical trials and epidemiological investigations, data are clustered into groups such as health centers or herds in veterinary medicine. Such data are usually analyzed by hierarchical regression models to account for possible variation between groups. When such variation is large, it is of potential interest to explore whether additionally the effect of a within-group predictor varies between groups. In survival analysis, this may be investigated by including two frailty terms at group level in a Cox proportional hazards model. Several estimation methods have been proposed to estimate this type of frailty Cox models. We review four of these methods, apply them to real data from veterinary medicine, and compare them using a simulation study. PMID:27273127

  17. Shaft adjuster

    DOEpatents

    Harry, H.H.

    1988-03-11

    Abstract and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus. 3 figs.

  18. Shaft adjuster

    DOEpatents

    Harry, Herbert H.

    1989-01-01

    Apparatus and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus.

  19. 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

  20. 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

  1. Characterization of the peroxide sensitivity of COX-deficient yeast strains reveals unexpected relationships between COX assembly proteins.

    PubMed

    Veniamin, Simona; Sawatzky, Luanne G; Banting, Graham S; Glerum, D Moira

    2011-10-15

    A number of distinct cuproproteins of the mitochondrial inner membrane are required for the assembly of cytochrome oxidase (COX), thought to function in a "bucket brigade" fashion to provide copper to the Cu(A) and Cu(B) sites. In yeast, the loss of two these proteins, Sco1p and Cox11p, leads to respiratory deficiency and a specific inability to survive exposure to hydrogen peroxide (H(2)O(2)). Using a quantitative assay, we have identified subtle differences in the peroxide-sensitive phenotypes between sco1 and cox11 mutant strains. Interestingly, the peroxide sensitivity of the sco1 null strain can be suppressed by overexpressing either SCO2 or COX11, although overexpression of neither SCO1 nor SCO2 can rescue the cox11 null strain. We also find that overexpression of either CTT1, encoding the cytosolic catalase T, or CTA1, encoding the mitochondrial matrix catalase, suppresses the peroxide sensitivity in both the sco1 and the cox11 null mutants. Direct measurement of peroxide metabolism shows that sco1 and cox11 null strains fail to degrade a significant amount of exogenously provided H(2)O(2). Taken together, our data demonstrate that although Cox11p and Sco1p play distinct roles in COX assembly, they seem to play overlapping or related roles in peroxide metabolism that require further investigation. PMID:21821119

  2. Challenging the principle of proportionality.

    PubMed

    Andersson, Anna-Karin Margareta

    2016-04-01

    The first objective of this article is to examine one aspect of the principle of proportionality (PP) as advanced by Alan Gewirth in his 1978 bookReason and Morality Gewirth claims that being capable of exercising agency to some minimal degree is a property that justifies having at least prima facie rights not to get killed. However, according to the PP, before the being possesses the capacity for exercising agency to that minimal degree, the extent of her rights depends on to what extent she approaches possession of agential capacities. One interpretation of PP holds that variations in degree of possession of the physical constitution necessary to exercise agency are morally relevant. The other interpretation holds that only variations in degree of actual mental capacity are morally relevant. The first of these interpretations is vastly more problematic than the other. The second objective is to argue that according to the most plausible interpretation of the PP, the fetus' level of development before at least the 20th week of pregnancy does not affect the fetus' moral rights status. I then suggest that my argument is not restricted to such fetuses, although extending my argument to more developed fetuses requires caution. PMID:26839114

  3. Comparing proportional hazards and accelerated failure time models for survival analysis.

    PubMed

    Orbe, Jesus; Ferreira, Eva; Núñez-Antón, Vicente

    2002-11-30

    This paper describes a method proposed for a censored linear regression model that can be used in the context of survival analysis. The method has the important characteristic of allowing estimation and inference without knowing the distribution of the duration variable. Moreover, it does not need the assumption of proportional hazards. Therefore, it can be an interesting alternative to the Cox proportional hazards models when this assumption does not hold. In addition, implementation and interpretation of the results is simple. In order to analyse the performance of this methodology, we apply it to two real examples and we carry out a simulation study. We present its results together with those obtained with the traditional Cox model and AFT parametric models. The new proposal seems to lead to more precise results.

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

    PubMed

    Liu, Zhenqiu; Jiang, Feng

    2009-01-01

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

  5. 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.

  6. 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

  7. Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

    PubMed

    Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

    2015-08-01

    Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p < 0.0001) of high compared with low MD breast tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

  8. Controlling Time-Dependent Confounding by Health Status and Frailty: Restriction Versus Statistical Adjustment

    PubMed Central

    McGrath, Leah J.; Ellis, Alan R.; Brookhart, M. Alan

    2015-01-01

    Nonexperimental studies of preventive interventions are often biased because of the healthy-user effect and, in frail populations, because of confounding by functional status. Bias is evident when estimating influenza vaccine effectiveness, even after adjustment for claims-based indicators of illness. We explored bias reduction methods while estimating vaccine effectiveness in a cohort of adult hemodialysis patients. Using the United States Renal Data System and linked data from a commercial dialysis provider, we estimated vaccine effectiveness using a Cox proportional hazards marginal structural model of all-cause mortality before and during 3 influenza seasons in 2005/2006 through 2007/2008. To improve confounding control, we added frailty indicators to the model, measured time-varying confounders at different time intervals, and restricted the sample in multiple ways. Crude and baseline-adjusted marginal structural models remained strongly biased. Restricting to a healthier population removed some unmeasured confounding; however, this reduced the sample size, resulting in wide confidence intervals. We estimated an influenza vaccine effectiveness of 9% (hazard ratio = 0.91, 95% confidence interval: 0.72, 1.15) when bias was minimized through cohort restriction. In this study, the healthy-user bias could not be controlled through statistical adjustment; however, sample restriction reduced much of the bias. PMID:25868551

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

    SciTech Connect

    Li, H.; Thompson, E.A.

    1994-09-01

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

  10. Improved Margin of Error Estimates for Proportions in Business: An Educational Example

    ERIC Educational Resources Information Center

    Arzumanyan, George; Halcoussis, Dennis; Phillips, G. Michael

    2015-01-01

    This paper presents the Agresti & Coull "Adjusted Wald" method for computing confidence intervals and margins of error for common proportion estimates. The presented method is easily implementable by business students and practitioners and provides more accurate estimates of proportions particularly in extreme samples and small…

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. 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

  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. 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

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

    PubMed

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

    2014-06-01

    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.

  19. On Estimation of Covariate-Specific Residual Time Quantiles under the Proportional Hazards Model

    PubMed Central

    Crouch, Luis Alexander; May, Susanne; Chen, Ying Qing

    2015-01-01

    Estimation and inference in time-to-event analysis typically focus on hazard functions and their ratios under the Cox proportional hazards model. These hazard functions, while popular in the statistical literature, are not always easily or intuitively communicated in clinical practice, such as in the settings of patient counseling or resource planning. Expressing and comparing quantiles of event times may allow for easier understanding. In this article we focus on residual time, i.e., the remaining time-to-event at an arbitrary time t given that the event has yet to occur by t. In particular, we develop estimation and inference procedures for covariate-specific quantiles of the residual time under the Cox model. Our methods and theory are assessed by simulations, and demonstrated in analysis of two real data sets. PMID:26058825

  20. Lipid Adjustment for Chemical Exposures: Accounting for Concomitant Variables

    PubMed Central

    Li, Daniel; Longnecker, Matthew P.; Dunson, David B.

    2013-01-01

    Background Some environmental chemical exposures are lipophilic and need to be adjusted by serum lipid levels before data analyses. There are currently various strategies that attempt to account for this problem, but all have their drawbacks. To address such concerns, we propose a new method that uses Box-Cox transformations and a simple Bayesian hierarchical model to adjust for lipophilic chemical exposures. Methods We compared our Box-Cox method to existing methods. We ran simulation studies in which increasing levels of lipid-adjusted chemical exposure did and did not increase the odds of having a disease, and we looked at both single-exposure and multiple-exposures cases. We also analyzed an epidemiology dataset that examined the effects of various chemical exposures on the risk of birth defects. Results Compared with existing methods, our Box-Cox method produced unbiased estimates, good coverage, similar power, and lower type-I error rates. This was the case in both single- and multiple-exposure simulation studies. Results from analysis of the birth-defect data differed from results using existing methods. Conclusion Our Box-Cox method is a novel and intuitive way to account for the lipophilic nature of certain chemical exposures. It addresses some of the problems with existing methods, is easily extendable to multiple exposures, and can be used in any analyses that involve concomitant variables. PMID:24051893

  1. 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

  2. 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.

  3. Masked repetition priming and proportion effects under cognitive load.

    PubMed

    Bodner, Glen E; Stalinski, Stephanie M

    2008-06-01

    The authors used a cognitive load manipulation (rehearsing a string of digits during the trial) to test the automaticity of (a) masked repetition priming and (b) the masked repetition proportion (RP) effect (i.e., greater priming when the proportion of repetition-prime trials is higher) in the lexical decision task. The RP (.2 vs. .8) was varied across blocks. Masked priming was not reduced under load compared with a no-load group. Surprisingly, only the load group showed an RP effect in response latencies, although the no-load group showed an RP effect in the error rates. Our results show that masked priming is automatic, yet the influence of masked primes can nonetheless be adjusted at an unconscious level. Implications for accounts of masked priming are discussed. PMID:18572990

  4. 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

  5. Molecular characterization of the gene cluster coxMSL encoding the molybdenum-containing carbon monoxide dehydrogenase of Oligotropha carboxidovorans.

    PubMed Central

    Schübel, U; Kraut, M; Mörsdorf, G; Meyer, O

    1995-01-01

    The CO dehydrogenase structural genes (cox) and orf4 are clustered in the transcriptional order coxM--> coxS--> coxL--> orf4 on the 128-kb megaplasmid pHCG3 of the carboxidotroph Oligotropha carboxidovorans OM5. Sequence analysis suggested association of molybdopterin cytosine dinucleotide and flavin adenine dinucleotide with CoxL and of the [2Fe-2S] clusters with CoxS. PMID:7721710

  6. External Adjustment Sensitivity Analysis for Unmeasured Confounding: An Application to Coronary Stent Outcomes, Pennsylvania 2004–2008

    PubMed Central

    Huesch, Marco D

    2013-01-01

    Background Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. Objective To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Data Sources/Study Setting Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004–2005 followed up for death through 3 years. Study Design Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. Principal Findings DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Conclusions Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. PMID:23206261

  7. Proportional Reasoning and the Visually Impaired

    ERIC Educational Resources Information Center

    Hilton, Geoff; Hilton, Annette; Dole, Shelley L.; Goos, Merrilyn; O'Brien, Mia

    2012-01-01

    Proportional reasoning is an important aspect of formal thinking that is acquired during the developmental years that approximate the middle years of schooling. Students who fail to acquire sound proportional reasoning often experience difficulties in subjects that require quantitative thinking, such as science, technology, engineering, and…

  8. CCSSM Challenge: Graphing Ratio and Proportion

    ERIC Educational Resources Information Center

    Kastberg, Signe E.; D'Ambrosio, Beatriz S.; Lynch-Davis, Kathleen; Mintos, Alexia; Krawczyk, Kathryn

    2013-01-01

    A renewed emphasis was placed on ratio and proportional reasoning in the middle grades in the Common Core State Standards for Mathematics (CCSSM). The expectation for students includes the ability to not only compute and then compare and interpret the results of computations in context but also interpret ratios and proportions as they are…

  9. Working Memory Mechanism in Proportional Quantifier Verification

    ERIC Educational Resources Information Center

    Zajenkowski, Marcin; Szymanik, Jakub; Garraffa, Maria

    2014-01-01

    The paper explores the cognitive mechanisms involved in the verification of sentences with proportional quantifiers (e.g. "More than half of the dots are blue"). The first study shows that the verification of proportional sentences is more demanding than the verification of sentences such as: "There are seven blue and eight yellow…

  10. PGE2 production in oral cancer cell lines is COX-2-dependent.

    PubMed

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

    2009-02-01

    It has been suggested that epithelial cyclooxygenase-2 (COX-2) promotes oral carcinogenesis and carcinoma malignancy through increased prostaglandin E(2) (PGE(2)) production. Although oral squamous cell carcinomas (OSCC) often express COX-2, they may also produce PGE(2) in a COX-1-dependent manner. We used 6 isolated cell lines to investigate which COX isoforms OSCC may use for PGE(2) production. COX-1 and -2 expression patterns divided the 6 OSCC cell lines into 3 distinct groups: both COX isoforms low, only COX-1 high, or both COX isoforms high. Multicolor immunohistofluorescence staining confirmed the COX-expression profiles in organotypic 3D cultures and the COX-2 dominance in OSCC tumors. Epidermal growth factor (EGF) stimulation induced COX-2 (but not COX-1) expression and increased PGE(2) production, which was attenuated by COX-2 (but not COX-1) specific inhibition or siRNA-mediated COX-2 gene knockdown. Thus, PGE(2) production in OSCC cell lines was COX-2-dependent. PMID:19278989

  11. In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

    PubMed

    Ramírez-Cisneros, M Ángeles; Rios, María Yolanda; Aguilar-Guadarrama, A Berenice; Rao, Praveen P N; Aburto-Amar, Rola; Rodríguez-López, Verónica

    2015-10-15

    A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 ± 0.6%) and COX-2 (80.8 ± 4.0%) inhibition at 10 μM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition.

  12. 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

  13. 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

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

    PubMed

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

    2015-02-01

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

  15. Proportion of recovered waterfowl bands reported

    USGS Publications Warehouse

    Geis, A.D.; Atwood, E.L.

    1961-01-01

    Data from the annual mail survey of waterfowl hunters in the United States were used to estimate the total numbers of banded waterfowl that were shot. These estimates were compared with Banding Office records to estimate the proportion of recovered bands that was reported. On the average, about two banded birds were recovered for each one reported. The proportion reported was higher for some areas and for some species than for others. The proportion reported was higher when more of the reports came through employees of conservation agencies.

  16. 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

  17. Working memory mechanism in proportional quantifier verification.

    PubMed

    Zajenkowski, Marcin; Szymanik, Jakub; Garraffa, Maria

    2014-12-01

    The paper explores the cognitive mechanisms involved in the verification of sentences with proportional quantifiers (e.g., "More than half of the dots are blue"). The first study shows that the verification of proportional sentences is more demanding than the verification of sentences such as: "There are seven blue and eight yellow dots". The second study reveals that both types of sentences are correlated with memory storage, however, only proportional sentences are associated with the cognitive control. This result suggests that the cognitive mechanism underlying the verification of proportional quantifiers is crucially related to the integration process, in which an individual has to compare in memory the cardinalities of two sets. In the third study we find that the numerical distance between two cardinalities that must be compared significantly influences the verification time and accuracy. The results of our studies are discussed in the broader context of processing complex sentences. PMID:24374596

  18. Proportionality, just war theory and weapons innovation.

    PubMed

    Forge, John

    2009-03-01

    Just wars are supposed to be proportional responses to aggression: the costs of war must not greatly exceed the benefits. This proportionality principle raises a corresponding 'interpretation problem': what are the costs and benefits of war, how are they to be determined, and a 'measurement problem': how are costs and benefits to be balanced? And it raises a problem about scope: how far into the future do the states of affairs to be measured stretch? It is argued here that weapons innovation always introduces costs, and that these costs cannot be determined in advance of going to war. Three examples, the atomic bomb, the AK-47 and the ancient Greek catapult, are given as examples. It is therefore argued that the proportionality principle is inapplicable prospectively. Some replies to the argument are discussed and rejected. Some more general defences of the proportionality principle are considered and also rejected. Finally, the significance of the argument for Just War Theory as a whole is discussed.

  19. Using Resampling to Compare Two Proportions

    ERIC Educational Resources Information Center

    Stephenson, W. Robert; Froelich, Amy G.; Duckworth, William M.

    2010-01-01

    This article shows that when applying resampling methods to the problem of comparing two proportions, students can discover that whether you resample with or without replacement can make a big difference.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. Progress in studying scintillator proportionality: Phenomenological model

    SciTech Connect

    Bizarri, Gregory; Cherepy, Nerine; Choong, Woon-Seng; Hull, Giulia; Moses, William; Payne, Sephen; Singh, Jai; Valentine, John; Vasilev, Andrey; Williams, Richard

    2009-04-30

    We present a model to describe the origin of non-proportional dependence of scintillator light yield on the energy of an ionizing particle. The non-proportionality is discussed in terms of energy relaxation channels and their linear and non-linear dependences on the deposited energy. In this approach, the scintillation response is described as a function of the deposited energy deposition and the kinetic rates of each relaxation channel. This mathematical framework allows both a qualitative interpretation and a quantitative fitting representation of scintillation non-proportionality response as function of kinetic rates. This method was successfully applied to thallium doped sodium iodide measured with SLYNCI, a new facility using the Compton coincidence technique. Finally, attention is given to the physical meaning of the dominant relaxation channels, and to the potential causes responsible for the scintillation non-proportionality. We find that thallium doped sodium iodide behaves as if non-proportionality is due to competition between radiative recombinations and non-radiative Auger processes.

  5. Boron-10 Lined Proportional Counter Wall Effects

    SciTech Connect

    Siciliano, Edward R.; Kouzes, Richard T.

    2012-05-01

    The Department of Energy Office of Nuclear Safeguards (NA-241) is supporting the project 'Coincidence Counting With Boron-Based Alternative Neutron Detection Technology' at Pacific Northwest National Laboratory (PNNL) for development of an alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a boron-lined proportional tube based system in the configuration of a coincidence counter. This report provides information about how variations in proportional counter radius and gas pressure in a typical coincident counter design might affect the observed signal from boron-lined tubes. A discussion comparing tubes to parallel plate counters is also included.

  6. Proportional hazards models with discrete frailty.

    PubMed

    Caroni, Chrys; Crowder, Martin; Kimber, Alan

    2010-07-01

    We extend proportional hazards frailty models for lifetime data to allow a negative binomial, Poisson, Geometric or other discrete distribution of the frailty variable. This might represent, for example, the unknown number of flaws in an item under test. Zero frailty corresponds to a limited failure model containing a proportion of units that never fail (long-term survivors). Ways of modifying the model to avoid this are discussed. The models are illustrated on a previously published set of data on failures of printed circuit boards and on new data on breaking strengths of samples of cord.

  7. 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

  8. 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

  9. Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on COX-1, COX-2 activity and nitric oxide production on whole-blood assay.

    PubMed

    Anauate, Maria Cecilia; Torres, Luce Maria; de Mello, Suzana Beatriz Veríssimo

    2010-09-01

    The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil's claw crude extract could antagonize or increase the synthesis of inflammatory mediators. PMID:20812280

  10. 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

  11. Ratio, Proportion and Scaling. Mathematics Resource Project.

    ERIC Educational Resources Information Center

    Hoffer, Shirley Ann, Ed.

    The Mathematics Resource Project has as its goal the production of topical resources for teachers, drawn from the vast amounts of available material. This experimental edition on Ratio, Proportion, and Scaling, contains a teaching emphasis section, a classroom materials section, and teacher commentaries. The teaching emphasis section stresses…

  12. Augmented mixed models for clustered proportion data

    PubMed Central

    Bandyopadhyay, Dipankar; Galvis, Diana M; Lachos, Victor H

    2015-01-01

    Often in biomedical research, we deal with continuous (clustered) proportion responses ranging between zero and one quantifying the disease status of the cluster units. Interestingly, the study population might also consist of relatively disease-free as well as highly diseased subjects, contributing to proportion values in the interval [0, 1]. Regression on a variety of parametric densities with support lying in (0, 1), such as beta regression, can assess important covariate effects. However, they are deemed inappropriate due to the presence of zeros and/or ones. To evade this, we introduce a class of general proportion density, and further augment the probabilities of zero and one to this general proportion density, controlling for the clustering. Our approach is Bayesian and presents a computationally convenient framework amenable to available freeware. Bayesian case-deletion influence diagnostics based on q-divergence measures are automatic from the Markov chain Monte Carlo output. The methodology is illustrated using both simulation studies and application to a real dataset from a clinical periodontology study. PMID:25491718

  13. Golden Proportions for the Generalized Tribonacci Numbers

    ERIC Educational Resources Information Center

    Shah, Devbhadra V.; Mehta, Darshana A.

    2009-01-01

    It is known that the ratios of consecutive terms of Fibonacci and Tribonacci sequences converge to the fixed ratio. In this article, we consider the generalized form of Tribonacci numbers and derive the "golden proportion" for the whole family of this generalized sequence. (Contains 2 tables.)

  14. Indices of body proportionality in neonates.

    PubMed

    Tsou Yau, K I; Chang, M H

    1993-01-01

    The inadequacy of using body weight alone to evaluate fetal skeletal and soft-tissue growth has long been recognized. Body proportionality indices could identify symptomatic newborn infants better than size-for-date classification. Lack of normative data precludes its being used, practically, in Chinese newborns. Thus body weight, body length, head circumference and mid-arm circumference were measured in 240 neonates appropriate for gestational age, 27-42 weeks, 960-3918 g, to construct reference indices of body proportionality: ponderal index (PI), body mass index (BMI), weight/length ratio (W/L), head circumference/body length ratio (HC/L) and mid-arm circumference/head circumference ratio (MAC/HC). All the five indices of body proportionality but HC/L were statistically correlated with gestational age (GA). For full-term newborns, PI did not correlate with GA. Furthers, the MAC/HC ratio decreased after 40 weeks' gestation. Therefore, when these indices of body proportionality are used to evaluate intrauterine nutritional status of a newborn, the appropriate standard for GA should be considered. PMID:8372678

  15. Canine Conjectures: Using Data for Proportional Reasoning

    ERIC Educational Resources Information Center

    Westenskow, Arla; Moyer-Packenham, Patricia S.

    2011-01-01

    No person, place, or thing can capture the attention of a class of sixth graders like "man's best friend." To prompt students' interest in a series of lessons on proportional relationships, the authors brought in a unique teaching aid--a dog. A family dog was used to supply the measurements for scatter plots and variables so that students could…

  16. Kitchen Gardens: Contexts for Developing Proportional Reasoning

    ERIC Educational Resources Information Center

    Hilton, Annette; Hilton, Geoff; Dole, Shelley; Goos, Merrilyn; O'Brien, Mia

    2013-01-01

    It is great to see how the sharing of ideas sparks new ideas. In 2011 Lyon and Bragg wrote an "Australian Primary Mathematics Classroom" (APMC) article on the mathematics of kitchen gardens. In this article the authors show how the kitchen garden may be used as a starting point for proportional reasoning. The authors highlight different…

  17. Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2.

    PubMed

    Salvado, M Dolores; Alfranca, Arántzazu; Haeggström, Jesper Z; Redondo, Juan Miguel

    2012-04-01

    Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. Although prostanoid biosynthetic enzymes and signaling have been extensively analyzed in inflammation, little is known about how prostanoids mediate tumor-induced angiogenesis. Targeted cyclooxygenase (COX)-2 inhibition in tumor, stromal and endothelial cells is an attractive antiangiogenic strategy; however, the associated cardiovascular side effects have led to the development of a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) acting downstream of COX. These agents target terminal prostanoid synthases and prostanoid receptors, which may also include several peroxisome proliferator-activated receptors (PPARs). Here, we discuss the role of prostanoids as modulators of tumor angiogenesis and how prostanoid metabolism reflects complex cell-cell crosstalk that determines tumor growth. Finally, we discuss the potential of new NSAIDs for the treatment of angiogenesis-dependent tumor development.

  18. Intermediate Moral Respect and Proportionality Reasoning.

    PubMed

    Finegan, Thomas

    2016-10-01

    In a recent article in this journal Jonathan Pugh critiques the idea of intermediate 'moral respect' which some say is owed to embryos. This concept is inherent within the 'principle of proportionality', the principle that destructive research on embryos is permissable only if the research serves an important purpose. Pugh poses two specific questions to proponents of the idea of intermediate moral respect. This article argues that while the questions posed by Pugh are certainly pertinent to the debate, the hypothetical responses he suggests to these questions do not quite get to the core of what is troublesome about the concept. The article suggests alternative responses to Pugh's questions in order to focus attention on more fundamental problems facing the idea of intermediate moral respect, while also pointing to how the intermediate moral respect proponent might best develop these responses. It goes on to argue that these hypothetical responses fail to answer convincingly the questions posed. More specifically, this article challenges two possible justifications for the distinct idea of intermediate moral respect, namely the argument from potentiality (the argument raised by Pugh) and an argument from the proportionality of fundamental moral status (not considered by Pugh). The article also raises a dilemma inherent in the application of the principle of proportionality to cases involving beings to which intermediate moral respect is owed even where it is allowed, ex hypothesi, that both the category of intermediate moral respect and the general proportionality reasoning underpinning the principle of proportionality are basically cogent. This article thus develops and adds to the challenge laid down by Pugh to proponents of the idea of intermediate moral respect. PMID:27212688

  19. Intermediate Moral Respect and Proportionality Reasoning.

    PubMed

    Finegan, Thomas

    2016-10-01

    In a recent article in this journal Jonathan Pugh critiques the idea of intermediate 'moral respect' which some say is owed to embryos. This concept is inherent within the 'principle of proportionality', the principle that destructive research on embryos is permissable only if the research serves an important purpose. Pugh poses two specific questions to proponents of the idea of intermediate moral respect. This article argues that while the questions posed by Pugh are certainly pertinent to the debate, the hypothetical responses he suggests to these questions do not quite get to the core of what is troublesome about the concept. The article suggests alternative responses to Pugh's questions in order to focus attention on more fundamental problems facing the idea of intermediate moral respect, while also pointing to how the intermediate moral respect proponent might best develop these responses. It goes on to argue that these hypothetical responses fail to answer convincingly the questions posed. More specifically, this article challenges two possible justifications for the distinct idea of intermediate moral respect, namely the argument from potentiality (the argument raised by Pugh) and an argument from the proportionality of fundamental moral status (not considered by Pugh). The article also raises a dilemma inherent in the application of the principle of proportionality to cases involving beings to which intermediate moral respect is owed even where it is allowed, ex hypothesi, that both the category of intermediate moral respect and the general proportionality reasoning underpinning the principle of proportionality are basically cogent. This article thus develops and adds to the challenge laid down by Pugh to proponents of the idea of intermediate moral respect.

  20. 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.

  1. 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

  2. Log Gaussian Cox processes and spatially aggregated disease incidence data.

    PubMed

    Li, Ye; Brown, Patrick; Gesink, Dionne C; Rue, Håvard

    2012-10-01

    This article presents a methodology for modeling aggregated disease incidence data with the spatially continuous log-Gaussian Cox process. Statistical models for spatially aggregated disease incidence data usually assign the same relative risk to all individuals in the same reporting region (census areas or postal regions). A further assumption that the relative risks in two regions are independent given their neighbor's risks (the Markov assumption) makes the commonly used Besag-York-Mollié model computationally simple. The continuous model proposed here uses a data augmentation step to sample from the posterior distribution of the exact locations at each step of an Markov chain Monte Carlo algorithm, and models the exact locations with an log-Gaussian Cox process. A simulation study shows the log-Gaussian Cox process model consistently outperforming the Besag-York-Mollié model. The method is illustrated by making inference on the spatial distribution of syphilis risk in North Carolina. The effect of several known social risk factors are estimated, and areas with risk well in excess of that expected given these risk factors are identified.

  3. Pyrimidine-based fluorescent COX-2 inhibitors: synthesis and biological evaluation.

    PubMed

    Tietz, Ole; Kaur, Jatinder; Bhardwaj, Atul; Wuest, Frank R

    2016-07-26

    The cyclooxygenase-2 (COX-2) enzyme is overexpressed in a variety of cancers and mediates inflammatory processes that aid the growth and progression of malignancies. Three novel and selective fluorescent COX-2 inhibitors have been designed and synthesized on the basis of previously reported pyrimidine-based COX-2 inhibitors and the 7-nitrobenzofurazan fluorophore. In vitro evaluation of COX-1/COX-2 isozyme inhibition identified N-(2-((7-nitro-benzo[c][1,2,5]oxadiazol-4-yl)amino)propyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoro-methyl)-pyrimidin-2-amine (6) as a novel potent and selective COX-2 inhibitor (IC50 = 1.8 μM). Lead compound (6) was further evaluated for its ability to selectively visualize COX-2 isozyme in COX-2 expressing human colon cancer cell line HCA-7 using confocal microscopy experiments. PMID:27383140

  4. Proportionally off-mass-shell equation for unequal mass systems

    NASA Astrophysics Data System (ADS)

    Maung Maung, Khin; Norbury, John W.; Kahana, David E.

    1996-03-01

    A new two-body relativistic equation is presented. The major advantage of the proposed equation over existing equations in the literature is that this equation automatically adjusts itself for different mass systems. Besides unitarity and covariance, this equation gives a physically meaningful prescription of how the particles go off-mass-shell in the intermediate states. It allows the particles to go off-mass-shell proportionally to their masses so that when one of the masses becomes infinite, it automatically becomes a one-body equation for the lighter particle and for equal mass systems, it reduces to the Todorov equation. Because of the off-mass-shell prescription for the intermediate states, it will be useful for systems with a wide variety of masses such as mesons, positronium, muonium, pionium, the deuteron and light hadronic atoms.

  5. Preferred female body proportions among child-free men.

    PubMed

    Burris, Christopher T; Munteanu, Armand R

    2012-12-01

    Based on conceptual extrapolations from sociobiological models concerning the significance of secondary sex characteristics as markers of a female's capacity to produce and nurture offspring, we reasoned that men's greater unwillingness to reproduce would be linked to preference for a female body type characterized by the relative absence of such markers. Heterosexual undergraduate men (N = 67) indicated their ideal (most arousing) female body type on-line by means of an adjustable female figure. As expected, the desire to remain childfree was linked to erotic preference for a combination of smaller breasts and larger waist-to-hip ratio. Additional research into individual factors that map onto variations in the preferred body proportions of erotic targets is thus encouraged. PMID:22722955

  6. 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

  7. ADJUSTABLE DOUBLE PULSE GENERATOR

    DOEpatents

    Gratian, J.W.; Gratian, A.C.

    1961-08-01

    >A modulator pulse source having adjustable pulse width and adjustable pulse spacing is described. The generator consists of a cross coupled multivibrator having adjustable time constant circuitry in each leg, an adjustable differentiating circuit in the output of each leg, a mixing and rectifying circuit for combining the differentiated pulses and generating in its output a resultant sequence of negative pulses, and a final amplifying circuit for inverting and square-topping the pulses. (AEC)

  8. Expression of gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors.

    PubMed

    Lipari, L; Mauro, A; Gallina, S; Tortorici, S; Buscemi, M; Tete, S; Gerbino, A

    2012-01-01

    Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthin's tumor through immunohistochemistry and Reverse Transcription - Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.

  9. Proportional Reasoning of Preservice Elementary Education Majors: An Epistemic Model of the Proportional Reasoning Construct.

    ERIC Educational Resources Information Center

    Fleener, M. Jayne

    Current research and learning theory suggest that a hierarchy of proportional reasoning exists that can be tested. Using G. Vergnaud's four complexity variables (structure, content, numerical characteristics, and presentation) and T. E. Kieren's model of rational number knowledge building, an epistemic model of proportional reasoning was…

  10. 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

  11. Processing of Numerical and Proportional Quantifiers.

    PubMed

    Shikhare, Sailee; Heim, Stefan; Klein, Elise; Huber, Stefan; Willmes, Klaus

    2015-09-01

    Quantifier expressions like "many" and "at least" are part of a rich repository of words in language representing magnitude information. The role of numerical processing in comprehending quantifiers was studied in a semantic truth value judgment task, asking adults to quickly verify sentences about visual displays using numerical (at least seven, at least thirteen, at most seven, at most thirteen) or proportional (many, few) quantifiers. The visual displays were composed of systematically varied proportions of yellow and blue circles. The results demonstrated that numerical estimation and numerical reference information are fundamental in encoding the meaning of quantifiers in terms of response times and acceptability judgments. However, a difference emerges in the comparison strategies when a fixed external reference numerosity (seven or thirteen) is used for numerical quantifiers, whereas an internal numerical criterion is invoked for proportional quantifiers. Moreover, for both quantifier types, quantifier semantics and its polarity (positive vs. negative) biased the response direction (accept/reject). Overall, our results indicate that quantifier comprehension involves core numerical and lexical semantic properties, demonstrating integrated processing of language and numbers. PMID:25631283

  12. NASA CONNECT: Proportionality: Modeling the Future

    NASA Technical Reports Server (NTRS)

    2000-01-01

    'Proportionality: Modeling the Future' is the sixth of seven programs in the 1999-2000 NASA CONNECT series. Produced by NASA Langley Research Center's Office of Education, NASA CONNECT is an award-winning series of instructional programs designed to enhance the teaching of math, science and technology concepts in grades 5-8. NASA CONNECT establishes the 'connection' between the mathematics, science, and technology concepts taught in the classroom and NASA research. Each program in the series supports the national mathematics, science, and technology standards; includes a resource-rich teacher guide; and uses a classroom experiment and web-based activity to complement and enhance the math, science, and technology concepts presented in the program. NASA CONNECT is FREE and the programs in the series are in the public domain. Visit our web site and register. http://connect.larc.nasa.gov 'Proportionality: Modeling the Future', students will examine how patterns, measurement, ratios, and proportions are used in the research, development, and production of airplanes.

  13. Evaluation of Facial Beauty Using Anthropometric Proportions

    PubMed Central

    Milutinovic, Jovana

    2014-01-01

    The improvement of a patient's facial appearance is one of the main goals of contemporary orthodontic treatment. The aim of this investigation was to evaluate the difference in facial proportions between attractive and anonymous females in order to establish objective facial features which are widely considered as beautiful. The study included two groups: first group consisted of 83 Caucasian female subjects between 22 and 28 years of age who were selected from the population of students at the University of Belgrade, and the second group included 24 attractive celebrity Caucasian females. The en face facial photographs were taken in natural head position (NHP). Numerous parameters were recorded on these photographs, in order to establish facial symmetry and correlation with the ideal set of proportions. This study showed significant difference between anonymous and attractive females. Attractive females showed smaller face in general and uniformity of the facial thirds and fifths, and most of the facial parameters meet the criteria of the ideal proportions. PMID:24701166

  14. The PEP Quark Search Proportional Chambers

    NASA Astrophysics Data System (ADS)

    Parker, S. I.; Harris, F.; Karliner, I.; Yount, D.; Ely, R.; Hamilton, R.; Pun, T.; Guryn, W.; Miller, D.; Fries, R.

    1981-04-01

    Proportional chambers are used in the PEP Free Quark Search to identify and remove possible background sources such as particles traversing the edges of counters, to permit geometric corrections to the dE/dx and TOF information from the scintillator and Cerenkov counters, and to look for possible high cross section quarks. The present beam pipe has a thickness of 0.007 interaction lengths (λi) and is followed in both arms (each with 45° <= θ <= 135°. Δphi = 90°) by 5 proportional chambers, each 0.0008 λi thick with 32 channels of pulse height readout, and by 3 thin scintillator planes, each 0.003 λi thick. Following this thin front end, each arm of the detector has 8 layers of scintillator (one with scintillating light pipes) interspersed with 4 proportional chambers and a layer of lucite Cerenkov counters. Both the calculated ion statistics and measurements using He-CH4 gas in a test chamber indicate that the chamber efficiencies should be > 98% for q = 1/3. The Landau spread measured in the test was equal to that observed for normal q = 1 traversals. One scintillator plane and thin chamber in each arm will have an extra set of ADC's with a wide gate bracketing the normal one so timing errors and tails of earlier pulses should not produce fake quarks.

  15. The use of polycarbonate in proportional counters

    SciTech Connect

    Trow, M.; Smith, A. )

    1992-01-01

    Proportional counters are relatively sensitive to contamination through outgassing and the range of electrical insulators suitable for use in their manufacture is quite limited. Although small amounts of plastics such as polychlorotrifluoroethylene have been used as feedthroughs, ceramics are most commonly used when sealed counters with long lives are required. Ceramics have poor and widely scattered mechanical properties and the use of a more robust material is often highly desirable. Of particular interest is the use of polymers and this work examines polycarbonate in particular. To investigate its suitability in terms of outgassing a simple cylindrical, single anode proportional counter containing a large sample of polycarbonate was baked at {similar to}100 {degree}C and filled with a CO{sub 2}/Ar/Xe mixture (5:47.5:47.5 by pressure, respectively). Subsequent measurements of the counter indicated an increase in gain, which, after a second similar filling, was identified to be associated with a preferential loss of CO{sub 2} to the polycarbonate. The consequences of this result and the circumstances under which polycarbonate could be used on a large scale in the construction of proportional counters are discussed.

  16. 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

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

    PubMed

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

    2014-01-01

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

  18. 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

  19. Tissue equivalent proportional counter neutron monitor

    SciTech Connect

    Smith, R.C.; Strode, J.N.

    1980-06-01

    The Tissue Equivalent Proportional Counter (TEPC) is a sensitive area monitoring instrument that can be used either in place at fixed locations or as a portable neutron exposure measuring device. The system monitors low levels of neutron radiation exposure and has the capability of accurately measuring neutron exposure rates as low as 0.1 mrem/hr. The computerized analysis system calculates the quality factor which is important for situations where the neutron to gamma ratio may vary significantly and irregularly such as in fuel fabrication or handling facilities.

  20. Neutron spectrometry with He-3 proportional counters

    SciTech Connect

    Manolopoulou, M.; Fragopoulou, M.; Stoulos, S.; Vagena, E.; Westmeier, W.; Zamani, M.

    2011-07-01

    Helium filled proportional counters are widely used in the field of neutron detection and spectrometry. In this work the response of a commercially available He-3 counter is studied experimentally and calculated with Monte Carlo for the neutron energy range from 230 keV up to about 7 MeV. The calculated response of the system is used to determine neutron yield energy distribution emitted from an extended {sup nat}U/Pb assembly irradiated with 1.6 GeV deuterons. The results are in acceptable agreement with the calculated neutron distribution with DCM-DEM code. (authors)

  1. 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

  2. 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.

  3. Energy Proportionality for Disk Storage Using Replication

    SciTech Connect

    Kim, Jinoh; Rotem, Doron

    2010-09-09

    Energy saving has become a crucial concern in datacenters as several reports predict that the anticipated energy costs over a three year period will exceed hardware acquisition. In particular, saving energy for storage is of major importance as storage devices (and cooling them off) may contribute over 25 percent of the total energy consumed in a datacenter. Recent work introduced the concept of energy proportionality and argued that it is a more relevant metric than just energy saving as it takes into account the tradeoff between energy consumption and performance. In this paper, we present a novel approach, called FREP (Fractional Replication for Energy Proportionality), for energy management in large datacenters. FREP includes areplication strategy and basic functions to enable flexible energy management. Specifically, our method provides performance guarantees by adaptively controlling the power states of a group of disks based on observed and predicted workloads. Our experiments, using a set of real and synthetic traces, show that FREP dramatically reduces energy requirements with a minimal response time penalty.

  4. ProPortal: A Database for Prochlorococcus

    DOE Data Explorer

    Huang, Katherine [Chisholm lab, MIT

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans, and is the smallest known oxygenic phototroph. All isolates described thus far can be assigned to either a tightly clustered high-light (HL) adapted clade, or a more divergent low-light (LL) adapted group. They are closely related to, but distinct from, marine Synechococcus. The genomes of 12 strains have been sequenced and they range in size from 1.6 to 2.6 Mbp. They represent diverse lineages, spanning the rRNA diversity (97 to 99.93% similarity) of cultured representatives of this group. Our analyses of these genomes inform our understanding of how adaptation occurs in the oceans along gradients of light, nutrients, and other environmental factors, providing essential context for interpreting rapidly expanding metagenomic datasets. [Copied from http://proportal.mit.edu/project/prochlorococcus/] ProPortal allows users to browse and search genome date for not only Prochlorococcus, but Cyanophage and Synechococcus. Microarray data, environmental cell concentration data, and metagenome information are also available.

  5. Kalman-predictive-proportional-integral-derivative (KPPID)

    SciTech Connect

    Fluerasu, A.; Sutton, M.

    2004-12-17

    With third generation synchrotron X-ray sources, it is possible to acquire detailed structural information about the system under study with time resolution orders of magnitude faster than was possible a few years ago. These advances have generated many new challenges for changing and controlling the state of the system on very short time scales, in a uniform and controlled manner. For our particular X-ray experiments on crystallization or order-disorder phase transitions in metallic alloys, we need to change the sample temperature by hundreds of degrees as fast as possible while avoiding over or under shooting. To achieve this, we designed and implemented a computer-controlled temperature tracking system which combines standard Proportional-Integral-Derivative (PID) feedback, thermal modeling and finite difference thermal calculations (feedforward), and Kalman filtering of the temperature readings in order to reduce the noise. The resulting Kalman-Predictive-Proportional-Integral-Derivative (KPPID) algorithm allows us to obtain accurate control, to minimize the response time and to avoid over/under shooting, even in systems with inherently noisy temperature readings and time delays. The KPPID temperature controller was successfully implemented at the Advanced Photon Source at Argonne National Laboratories and was used to perform coherent and time-resolved X-ray diffraction experiments.

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

    PubMed

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

    2009-06-01

    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 cox18Delta strain overexpressing OXA1, whose respiratory growth requires overexpression of OXA1. The recessive nuclear mutations allow some assembly of Cox2 into cytochrome c oxidase. After failing to identify these mutations by methods based on transformation, we successfully located them to MGR1 and MGR3 by comparative hybridization to whole-genome tiling arrays and microarray-assisted bulk segregant analysis followed by linkage mapping. While Mgr1 and Mgr3 are known to associate with the Yme1 mitochondrial inner membrane i-AAA protease and to participate in membrane protein degradation, their absence does not appear to stabilize Cox2 under these conditions. Instead, Yme1 probably chaperones the folding and/or assembly of Oxa1-exported Cox2 in the absence of Mrg1 or Mgr3, since respiratory growth and cytochrome c oxidase assembly in a cox18 mgr3 double-mutant strain overexpressing OXA1 is YME1 dependent.

  7. 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

  8. Cox regression methods for two-stage randomization designs.

    PubMed

    Lokhnygina, Yuliya; Helterbrand, Jeffrey D

    2007-06-01

    Two-stage randomization designs (TSRD) are becoming increasingly common in oncology and AIDS clinical trials as they make more efficient use of study participants to examine therapeutic regimens. In these designs patients are initially randomized to an induction treatment, followed by randomization to a maintenance treatment conditional on their induction response and consent to further study treatment. Broader acceptance of TSRDs in drug development may hinge on the ability to make appropriate intent-to-treat type inference within this design framework as to whether an experimental induction regimen is better than a standard induction regimen when maintenance treatment is fixed. Recently Lunceford, Davidian, and Tsiatis (2002, Biometrics 58, 48-57) introduced an inverse probability weighting based analytical framework for estimating survival distributions and mean restricted survival times, as well as for comparing treatment policies at landmarks in the TSRD setting. In practice Cox regression is widely used and in this article we extend the analytical framework of Lunceford et al. (2002) to derive a consistent estimator for the log hazard in the Cox model and a robust score test to compare treatment policies. Large sample properties of these methods are derived, illustrated via a simulation study, and applied to a TSRD clinical trial. PMID:17425633

  9. Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

    PubMed

    Rodríguez-Salinas, Elizabeth; Riveros-Rosas, Héctor; Li, Zhongkui; Fucíková, Karolina; Brand, Jerry J; Lewis, Louise A; González-Halphen, Diego

    2012-07-01

    In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae.

  10. How do college students solve proportion problems?

    NASA Astrophysics Data System (ADS)

    Thornton, Melvin C.; Fuller, Robert G.

    Problems which could be solved using proportional reasoning were administered nationwide by college faculty to their own science classes during a three year period. The reasoning of more than 8000 students covering three sections of the country was classified as concrete, transitional, or formal using Piagetian categories. Data from the West closely replicated that from the Midwest on similar metric conversion tasks. Student performance changed noticeably with a different problem format. The percentages of students using a ratio formula, ratio attempt, or intuitive methods of solution held approximately constant over time, task, and section of the country. The data shows the use of additive and conversion methods of solution depends upon the problem presentation.

  11. A proportional temperature controller with automatic shutoff

    NASA Astrophysics Data System (ADS)

    Lucich, G. M.; Holland, P. W.

    1980-08-01

    A sensitive, proportional temperature controller useful in the temperature range from 40 to 400 C with an accuracy of plus or minus 0.1 C is described. It is potentially useful for regulating temperatures in air chambers, liquid baths, furnaces and reaction vessels and for other applications. This instrument was developed to control the duration and temperature of the heating cycle of a charcoal filled adsorber that is part of a special helium analyzer. The controller was made from commercially available parts and can be easily modified to provide continuous temperature control. The circuit is solid state and employs no electromechanical devices. Over a 2 year period of use as a component of the special helium analyzer, this temperature controller performed successfully and required no maintenance.

  12. Boron-10 Lined Proportional Counter Model Validation

    SciTech Connect

    Lintereur, Azaree T.; Siciliano, Edward R.; Kouzes, Richard T.

    2012-06-30

    The Department of Energy Office of Nuclear Safeguards (NA-241) is supporting the project “Coincidence Counting With Boron-Based Alternative Neutron Detection Technology” at Pacific Northwest National Laboratory (PNNL) for the development of an alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a boron-lined proportional tube-based alternative system in the configuration of a coincidence counter. This report discusses the validation studies performed to establish the degree of accuracy of the computer modeling methods current used to simulate the response of boron-lined tubes. This is the precursor to developing models for the uranium neutron coincidence collar under Task 2 of this project.

  13. TRIAC/SCR proportional control circuit

    DOEpatents

    Hughes, W.J.

    1999-04-06

    A power controller device is disclosed which uses a voltage-to-frequency converter in conjunction with a zero crossing detector to linearly and proportionally control AC power being supplied to a load. The output of the voltage-to frequency converter controls the ``reset`` input of a R-S flip flop, while an ``0`` crossing detector controls the ``set`` input. The output of the flip flop triggers a monostable multivibrator controlling the SCR or TRIAC firing circuit connected to the load. Logic gates prevent the direct triggering of the multivibrator in the rare instance where the ``reset`` and ``set`` inputs of the flip flop are in coincidence. The control circuit can be supplemented with a control loop, providing compensation for line voltage variations. 9 figs.

  14. TRIAC/SCR proportional control circuit

    DOEpatents

    Hughes, Wallace J.

    1999-01-01

    A power controller device which uses a voltage-to-frequency converter in conjunction with a zero crossing detector to linearly and proportionally control AC power being supplied to a load. The output of the voltage-to frequency converter controls the "reset" input of a R-S flip flop, while an "0" crossing detector controls the "set" input. The output of the flip flop triggers a monostable multivibrator controlling the SCR or TRIAC firing circuit connected to the load. Logic gates prevent the direct triggering of the multivibrator in the rare instance where the "reset" and "set" inputs of the flip flop are in coincidence. The control circuit can be supplemented with a control loop, providing compensation for line voltage variations.

  15. Gaseous fuel and air proportioning device

    SciTech Connect

    Lassanske, G. G.; Poshlman, A. G.

    1984-01-10

    The device for proportioning a gaseous fuel and air for combustion in an internal combustion engine includes a plate-like first member having a peripheral edge portion and a second member cooperating with the first member having a peripheral edge portion and a second member cooperating with the first member to define a mixing chamber having an outlet adapted to be connected in communication with the air intake of the engine carburetor. The second member also includes an annular portion having an arcuate first wall which is convex to and spaced from the peripheral edge portion of the first member to define an annular venturi having an inlet in communication with the atmosphere and an annular outlet in communication with the mixing chamber. A base member or second wall cooperates with the arcuate wall to form a substantially closed, annular plenum chamber into which a gaseous fuel, such as natural gas, is admitted when the engine is to be operated on the gaseous fuel. The gaseous fuel is admitted into the mixing chamber from the plenum chamber through one or more ports in the arcuate wall at or in the vicinity of the throat of the annular venturi. A pair of circumferentially spaced radially extending partitions located on the opposite sides of each port define a radially extending venturi which has a throat located at or in the vicinity of the port and serves to induce flow of the gaseous fuel through the corresponding port. The proportioning device preferably is arranged to fit inside the housing of an existing air cleaner.

  16. Genetic analysis of the DNA recognition sequence of the P2 Cox protein.

    PubMed Central

    Cores de Vries, G; Wu, X S; Haggård-Ljungquist, E

    1991-01-01

    The Cox protein of temperate Escherichia coli phage P2 is involved in three important biological processes: (i) excision of the integrated prophage genome (G. Lindahl and M. Sunshine, Virology 49:180-187, 1972), (ii) transcriptional repression of the P2 Pc promoter, which controls the expression of the immunity repressor C and the integrase (S. Saha, E. Haggård-Ljungquist, and K. Nordström, EMBO J. 6:3191-3199, 1987), and (iii) transcriptional activation of the late PII promoter of the unrelated satellite phage P4 (S. Saha, E. Haggård-Ljungquist, and K. Nordström, Proc. Natl. Acad. Sci. USA 86:3973-3977, 1989). A comparison of the DNA regions protected by Cox from DNaseI degradation has revealed a presumptive Cox recognition sequence (Saha et al., Proc. Natl. Acad. Sci. USA). The binding region of Cox in the P2 Pc promoter contains three presumptive recognition sequences, "Cox boxes," located in tandem. P2 vir3 and P2 vir24 are virulent deletion mutants unable to plate on Cox-producing strains, most likely because the deletions locate the new early promoters too close to the Cox-binding region (Saha et al., EMBO J.). In this report, spontaneous P2 vir3 and vir24 mutants, no longer sensitive to repression by the Cox protein, have been isolated. These mutants plate with equal efficiency on strains with or without a Cox-producing plasmid, and they have been named cor for cox resistance. Three types are recognized; the four P2 vir3 cor mutants have a 1-base deletion in the first Cox box, while the P2 vir24 cor mutants were of two types; four have a base substitution in the first Cox box, and one has a base substitution in the second Cox box. The effect of the Cox protein on the mutated P2 vir3 and vir24 promoters was analyzed in vivo by using fusions to a promoterless cat (chloramphenicol acetyltransferase) gene. The activities of the P2 vir3 and vir24 early promoters, as opposed to the wild-type early Pe promoter, are drastically reduced by the Cox protein, and

  17. Dynamic Proportional Share Scheduling in Hadoop

    NASA Astrophysics Data System (ADS)

    Sandholm, Thomas; Lai, Kevin

    We present the Dynamic Priority (DP) parallel task scheduler for Hadoop. It allows users to control their allocated capacity by adjusting their spending over time. This simple mechanism allows the scheduler to make more efficient decisions about which jobs and users to prioritize and gives users the tool to optimize and customize their allocations to fit the importance and requirements of their jobs. Additionally, it gives users the incentive to scale back their jobs when demand is high, since the cost of running on a slot is then also more expensive. We envision our scheduler to be used by deadline or budget optimizing agents on behalf of users. We describe the design and implementation of the DP scheduler and experimental results. We show that our scheduler enforces service levels more accurately and also scales to more users with distinct service levels than existing schedulers.

  18. 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

  19. 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

  20. Stretch-induced myoblast proliferation is dependent on the COX2 pathway

    SciTech Connect

    Otis, Jeffrey S.; Burkholder, Thomas J.; Pavlath, Grace K. . E-mail: gpavlat@emory.edu

    2005-11-01

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

  1. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    PubMed

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  2. 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

  3. Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

    PubMed Central

    Wilson, Andrew J.; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md. Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D.; Pietenpol, Jennifer A.; Crispens, Marta A.; Marnett, Lawrence J.; Khabele, Dineo

    2015-01-01

    Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors. PMID:25972361

  4. Altered proportions of RCS-rat eyes.

    PubMed

    Schreckenberger, M; Eichhorn, M; Gottanka, J; Döbig, C; Lütjen-Drecoll, E

    1994-10-01

    The growth pattern of RCS-rat eyes with hereditary retinal degeneration was analysed morphometrically, evaluating midsagittal sections of the entire globe and sections of the chamber angle region. No changes of the axial diameter of RCS-rat eyes were found if compared with eyes of age-matched controls. There were, however, characteristic proportional changes in the anterior eye segment of RCS rats. The distance between the peripheral end of Descemet's membrane (DM) and both the posterior end of Schlemm's canal and the ora serrata were significantly elongated indicating that this region might be most susceptible to growth factors. The length of the posterior globe up to the level of the ora serrata was shorter in RCS rats than in control rats. In addition, in RCS-rat eyes the pars plana was significantly elongated and the pars plicata shortened. Ultrastructural changes of ciliary epithelium were not seen before 7 months of age in RCS rats. They were only present in those parts of the circumference in which the stromal capillaries also revealed structural changes. The ciliary epithelial alterations were therefore considered secondary to narrowing or rarefication in the adjacent blood vessels.

  5. 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.

  6. COX-2 inhibitors: a CLASS act or Just VIGORously promoted.

    PubMed

    Malhotra, Samir; Shafiq, N; Pandhi, P

    2004-03-23

    Abstract Selective cyclo-oxygenase (COX)-2 inhibitors were developed with the hope of producing lesser gastrointestinal (GI) side effects as compared with the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Soon after their introduction into the market, the sales of celecoxib and rofecoxib went up considerably. Most of this was attributed to the results of the Celecoxib Long-term Arthritis Safety Study (CLASS) and Vioxx Gastrointestinal Outcome Research (VIGOR) trials. However, several discrepancies were noted in the presentation of the actual trial results submitted to the US Food and Drug Administration (FDA) and those used for the purpose of publication in scientific journals. These issues were discussed subsequently by the way of scientific communications. Moreover, with increasing use of these agents, evidence of their adverse effects is coming to light. The present review aims at discussing the above issues, with emphasis on the results of the CLASS and VIGOR trials.

  7. (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

  8. 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.

  9. Perpendicular magnetic anisotropy in Fe2Cr1 - xCoxSi Heusler alloy

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Pu; Qiu, Jin-Jun; Lu, Hui; Ji, Rong; Han, Gu-Chang; Teo, Kie-Leong

    2014-12-01

    Perpendicular magnetic anisotropy (PMA) was achieved in annealed Fe2Cr1 - xCoxSi (FCCS) Heusler alloys with different Co compositions x. The Co composition is varied to tune the Fermi level in order to achieve both higher spin polarization and better thermal stability. The PMA is thermally stable up to 400 oC for FCCS with x = 0, 0.3, 0.5 and 350 oC for FCCS with x = 0.7, 0.9, 1. The thickness of FCCS films with PMA ranges from 0.6 to 1.2 nm. The annealing temperature and FCCS thickness are found to greatly affect the PMA. The magnetic anisotropy energy density KU is 2.8  ×  106 erg cm-3 for 0.8 nm Fe2CrSi, and decreases as the Co composition x increases, suggesting that the PMA induced at the FCCS/MgO interface is dominated by the contribution of Fe atoms. There is a trade-off between high spin polarization and strong PMA by adjusting the Co composition.

  10. 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

  11. 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.

  12. COX-2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus

    PubMed Central

    Kreiss, C; Birder, L A; Kiss, S; VanBibber, M M; Bauer, A J

    2003-01-01

    Background and aims: Cyclooxygenase 2 (COX-2) and prostaglandins (PGs) participate in the pathogenesis of inflammatory postoperative ileus. We sought to determine whether the emerging neuronal modulator COX-2 plays a significant role in primary afferent activation during postoperative ileus using spinal Fos expression as a marker. Methods: Rats, and COX-2+/+ and COX-2−/− mice underwent simple intestinal manipulation. The effect of intestinal manipulation on Fos immunoreactivity (IR) in the L5-S1 spinal cord, in situ circumference, and postoperative leucocytic infiltrate of the intestinal muscularis was measured. Postoperative PGE2 production was measured in peritoneal lavage fluid. The dependence of these parameters on COX-2 was studied in pharmacological (DFU, Merck- Frosst, selective COX-2 inhibitor) and genetic (COX-2−/− mice) models. Results: Postoperative Fos IR increased 3.7-fold in rats and 2.2-fold in mice. Both muscularis leucocytic infiltrate and the circumference of the muscularis increased significantly in rats and COX-2+/+ mice postoperatively, indicating dilating ileus. Surgical manipulation markedly increased PGE2 levels in the peritoneal cavity. DFU pretreatment and the genetic absence of COX-2−/− prevented dilating ileus, and leucocytic infiltrate was diminished by 40% with DFU and by 54% in COX-2−/− mice. DFU reversed postsurgical intra- abdominal PGE2 levels to normal. Fos IR after intestinal manipulation was attenuated by approximately 50% in DFU treated rats and in COX-2−/− mice. Conclusions: Postoperatively, small bowel manipulation causes a significant and prolonged increase in spinal Fos expression, suggesting prolonged primary afferent activation. COX-2 plays a key role in this response. This activation of primary afferents may subsequently initiate inhibitory motor reflexes to the gut, contributing to postoperative ileus. PMID:12631664

  13. SLIT ADJUSTMENT CLAMP

    DOEpatents

    McKenzie, K.R.

    1959-07-01

    An electrode support which permits accurate alignment and adjustment of the electrode in a plurality of planes and about a plurality of axes in a calutron is described. The support will align the slits in the electrode with the slits of an ionizing chamber so as to provide for the egress of ions. The support comprises an insulator, a leveling plate carried by the insulator and having diametrically opposed attaching screws screwed to the plate and the insulator and diametrically opposed adjusting screws for bearing against the insulator, and an electrode associated with the plate for adjustment therewith.

  14. Attachment style and adjustment to divorce.

    PubMed

    Yárnoz-Yaben, Sagrario

    2010-05-01

    Divorce is becoming increasingly widespread in Europe. In this study, I present an analysis of the role played by attachment style (secure, dismissing, preoccupied and fearful, plus the dimensions of anxiety and avoidance) in the adaptation to divorce. Participants comprised divorced parents (N = 40) from a medium-sized city in the Basque Country. The results reveal a lower proportion of people with secure attachment in the sample group of divorcees. Attachment style and dependence (emotional and instrumental) are closely related. I have also found associations between measures that showed a poor adjustment to divorce and the preoccupied and fearful attachment styles. Adjustment is related to a dismissing attachment style and to the avoidance dimension. Multiple regression analysis confirmed that secure attachment and the avoidance dimension predict adjustment to divorce and positive affectivity while preoccupied attachment and the anxiety dimension predicted negative affectivity. Implications for research and interventions with divorcees are discussed.

  15. 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.

  16. 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

  17. 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

  18. Alteration of femoral bone morphology and density in COX-2−/− mice

    PubMed Central

    Robertson, Galen; Xie, Chao; Chen, Di; Awad, Hani; Schwarz, Edward M.; O’Keefe, Regis J.; Guldberg, Robert E.; Zhang, Xinping

    2009-01-01

    A role of COX-2 in pathological bone destruction and fracture repair has been established; however, few studies have been conducted to examine the involvement of COX-2 in maintaining bone mineral density and bone micro-architecture. In this study, we examined bone morphology in multiple trabecular and cortical regions within the distal and diaphyseal femur of 4-month-old wild-type and COX-2−/− mice using micro-computed tomography. Our results demonstrated that while COX-2−/− female mice had normal bone geometry and trabecular microarchitecture at 4 months of age, the male knockout mice displayed reduced bone volume fraction within the distal femoral metaphysis. Furthermore, male COX-2−/− mice had a significant reduction in cortical bone mineral density within the central cortical diaphysis and distal epiphysis and metaphysis. Consistent with the observed reduction in cortical mineral density, biomechanical testing via 4-point-bending showed that male COX-2−/− mice had a significant increase in postyield deformation, indicating a ductile bone phenotype in male COX-2−/− mice. In conclusion, our study suggests that genetic ablation of COX-2 may have a sex-related effect on cortical bone homeostasis and COX-2 plays a role in maintaining normal bone micro-architecture and density in mice. PMID:16731065

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

    PubMed

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

    2013-01-01

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

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. Proportional-plus-integral semiactive control using magnetorheological dampers

    NASA Astrophysics Data System (ADS)

    Aguirre, N.; Ikhouane, F.; Rodellar, J.

    2011-05-01

    Magnetorheological (MR) dampers are a promising alternative to structural active actuators as they provide adjustable damping over a wide range of frequencies without large power requirements. However, the complex dynamics that characterizes these devices makes it difficult to formulate control laws based on the MR damper model. Instead, many semiactive control strategies proposed in the literature have been based on the idea of "clipping" the voltage signal so that the MR damper force "tracks" a desired active control force which is computed on-line. With this idea many algorithms have been proposed using, among others, techniques such as optimal control, H∞ control, sliding mode control, backstepping and QFT. This work presents a semiactive control strategy based on the same idea of "clipping" the voltage signal but using a simpler PI design. The proportional and integral gains of the controller are calculated so that the controller guarantees stability, minimization of the closed loop response and robustness against modeling errors. Effectiveness of the control strategy is compared to some others techniques and passive cases as well. Simulation results shows that this simple strategy can effectively improve the structural responses and achieve performance index comparable to that of more complex algorithms.

  3. Electron doping evolution of the neutron spin resonance in NaFe1-xCoxAs

    DOE PAGES

    Zhang, Chenglin; Song, Yu; Carr, Scott Victor; Chi, Songxue; Christianson, Andrew D.; Matsuda, Masaaki; Fernandez-Baca, Jaime A.; Dai, Pengcheng; Lv, Weicheng; Tan, Guotai; et al

    2016-05-31

    Neutron spin resonance, a collective magnetic excitation coupled to superconductivity, is one of the most prominent features shared by a broad family of unconventional superconductors including copper oxides, iron pnictides, and heavy fermions. In this paper, we study the doping evolution of the resonances in NaFe1–xCoxAs covering the entire superconducting dome. For the underdoped compositions, two resonance modes coexist. As doping increases, the low-energy resonance gradually loses its spectral weight to the high-energy one but remains at the same energy. By contrast, in the overdoped regime we only find one single resonance, which acquires a broader width in both energymore » and momentum but retains approximately the same peak position even when Tc drops by nearly a half compared to optimal doping. Furthermore, these results suggest that the energy of the resonance in electron overdoped NaFe1–xCoxAs is neither simply proportional to Tc nor the superconducting gap but is controlled by the multiorbital character of the system and doped impurity scattering effect.« less

  4. Electron doping evolution of the neutron spin resonance in NaFe1 -xCoxAs

    NASA Astrophysics Data System (ADS)

    Zhang, Chenglin; Lv, Weicheng; Tan, Guotai; Song, Yu; Carr, Scott V.; Chi, Songxue; Matsuda, M.; Christianson, A. D.; Fernandez-Baca, J. A.; Harriger, L. W.; Dai, Pengcheng

    2016-05-01

    Neutron spin resonance, a collective magnetic excitation coupled to superconductivity, is one of the most prominent features shared by a broad family of unconventional superconductors including copper oxides, iron pnictides, and heavy fermions. In this paper, we study the doping evolution of the resonances in NaFe1 -xCoxAs covering the entire superconducting dome. For the underdoped compositions, two resonance modes coexist. As doping increases, the low-energy resonance gradually loses its spectral weight to the high-energy one but remains at the same energy. By contrast, in the overdoped regime we only find one single resonance, which acquires a broader width in both energy and momentum but retains approximately the same peak position even when Tc drops by nearly a half compared to optimal doping. These results suggest that the energy of the resonance in electron overdoped NaFe1 -xCoxAs is neither simply proportional to Tc nor the superconducting gap but is controlled by the multiorbital character of the system and doped impurity scattering effect.

  5. Remotely Adjustable Hydraulic Pump

    NASA Technical Reports Server (NTRS)

    Kouns, H. H.; Gardner, L. D.

    1987-01-01

    Outlet pressure adjusted to match varying loads. Electrohydraulic servo has positioned sleeve in leftmost position, adjusting outlet pressure to maximum value. Sleeve in equilibrium position, with control land covering control port. For lowest pressure setting, sleeve shifted toward right by increased pressure on sleeve shoulder from servovalve. Pump used in aircraft and robots, where hydraulic actuators repeatedly turned on and off, changing pump load frequently and over wide range.

  6. Weighted triangulation adjustment

    USGS Publications Warehouse

    Anderson, Walter L.

    1969-01-01

    The variation of coordinates method is employed to perform a weighted least squares adjustment of horizontal survey networks. Geodetic coordinates are required for each fixed and adjustable station. A preliminary inverse geodetic position computation is made for each observed line. Weights associated with each observed equation for direction, azimuth, and distance are applied in the formation of the normal equations in-the least squares adjustment. The number of normal equations that may be solved is twice the number of new stations and less than 150. When the normal equations are solved, shifts are produced at adjustable stations. Previously computed correction factors are applied to the shifts and a most probable geodetic position is found for each adjustable station. Pinal azimuths and distances are computed. These may be written onto magnetic tape for subsequent computation of state plane or grid coordinates. Input consists of punch cards containing project identification, program options, and position and observation information. Results listed include preliminary and final positions, residuals, observation equations, solution of the normal equations showing magnitudes of shifts, and a plot of each adjusted and fixed station. During processing, data sets containing irrecoverable errors are rejected and the type of error is listed. The computer resumes processing of additional data sets.. Other conditions cause warning-errors to be issued, and processing continues with the current data set.

  7. GSFC's Multi-Wire Gas Proportional Counter

    NASA Astrophysics Data System (ADS)

    Serlemitsos, Peter J.

    2013-01-01

    The Goddard X-ray group made its appearance in 1964 as a one person (Elihu Boldt) appendage to the well established cosmic ray group, then headed by Frank MacDonald. This discipline proximity was crucial because it meant superb technical support from the start, which allowed the fledging group to quickly advance toward directions of choice. When I became the 2nd member of the group in 1966, the new discipline still relied on bulky gas counters, stacked to make up a usable detection area. Slim opportunities existed for timing or spectral inferences. Elihu's strong interest in pursuing the reported diffuse cosmic radiation had to be set aside, as improving this situation appeared to be years away. Cosmic ray researchers had long used charged particle timing techniques for cleaning up their data, but those appeared irrelevant for our purposes because of the large, background generating, mass of the gas containment vessels and the slow drift in the counter gas of the charge from photon interaction sites to the counter anode. We had to deal with these realities in whatever choices we made for our future instruments. The multi-wire gas proportional counter emerged from our still small group in the late1960s, demonstrating on several rocket and balloon flights a greatly reduced detector background, improved event timing and adequate resolution for addressing key spectral features. Three of these detectors, flown in 1975 on NASA's 8th orbiting solar observatory, were successfully used for some 3 years to conduct non dispersive, 1-10 keV spectroscopy on many galactic and extragalactic sources, including several clusters of galaxies. In 1977 we flew a set of larger detectors on the first of NASA's High Energy Astrophysical Observatories (HEAO). These were specifically designed for the study of the X-ray background. Finally, the largest instruments of this family were flown in 1995 by our group on NASA's Rossi X-ray Timing Explorer, RXTE, which observed over a remarkable 16

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

    PubMed

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

    2012-11-01

    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.

  9. miR-101 inhibits glioma cell invasion via the downregulation of COX-2

    PubMed Central

    Ma, Chunyang; Zheng, Chuanyi; Bai, Enqi; Yang, Kun

    2016-01-01

    Glioma is the most common type of primary tumor of the central nervous system. The present study aimed to demonstrate the role of miR-101 and cyclooxygenase-2 (COX-2) in the initiation and development of glioma. The expression of miR-101 and COX-2 in normal and malignant human glial cells and tissues was determined by western blotting and quantitative polymerase chain reaction analysis. The role of miR-101 on COX-2 expression was evaluated by a dual-luciferase reporter assay. The effects of miR-101 and COX-2 in glioma cell proliferation and invasion was verified by CCK-8 test and Transwell assays, respectively. The present study demonstrated that miR-101 expression was downregulated while COX-2 was upregulated in glioma tissues and cells. Furthermore, transfection of miR-101 significantly downregulated COX-2 expression in both U373 and U87 glioma cells. In addition, further experiments revealed that overexpression of miR-101 resulted in significant inhibition of the in vitro proliferation and migration of glioma cells, and the in vivo growth of established tumors. Direct downregulation of COX-2 by transfection with corresponding small interfering RNA also inhibited the proliferation and invasion of glioma cells. These results indicate that downregulation of miR-101 is involved in the initiation and development of glioma via COX-2 upregulation.

  10. 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…

  11. 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.

  12. 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.

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

    PubMed Central

    2013-01-01

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

  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.

  15. 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

  16. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

    PubMed

    Gao, Shui-Ping; Sun, He-Fen; Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-12-22

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

  17. miR-101 inhibits glioma cell invasion via the downregulation of COX-2

    PubMed Central

    Ma, Chunyang; Zheng, Chuanyi; Bai, Enqi; Yang, Kun

    2016-01-01

    Glioma is the most common type of primary tumor of the central nervous system. The present study aimed to demonstrate the role of miR-101 and cyclooxygenase-2 (COX-2) in the initiation and development of glioma. The expression of miR-101 and COX-2 in normal and malignant human glial cells and tissues was determined by western blotting and quantitative polymerase chain reaction analysis. The role of miR-101 on COX-2 expression was evaluated by a dual-luciferase reporter assay. The effects of miR-101 and COX-2 in glioma cell proliferation and invasion was verified by CCK-8 test and Transwell assays, respectively. The present study demonstrated that miR-101 expression was downregulated while COX-2 was upregulated in glioma tissues and cells. Furthermore, transfection of miR-101 significantly downregulated COX-2 expression in both U373 and U87 glioma cells. In addition, further experiments revealed that overexpression of miR-101 resulted in significant inhibition of the in vitro proliferation and migration of glioma cells, and the in vivo growth of established tumors. Direct downregulation of COX-2 by transfection with corresponding small interfering RNA also inhibited the proliferation and invasion of glioma cells. These results indicate that downregulation of miR-101 is involved in the initiation and development of glioma via COX-2 upregulation. PMID:27698824

  18. 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

  19. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

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

    PubMed

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

    2001-06-01

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

  1. Mathematically modelling proportions of Japanese populations by industry

    NASA Astrophysics Data System (ADS)

    Hirata, Yoshito

    2016-10-01

    I propose a mathematical model for temporal changes of proportions for industrial sectors. I prove that the model keeps the proportions for the primary, the secondary, and the tertiary sectors between 0 and 100% and preserves their total as 100%. The model fits the Japanese historical data between 1950 and 2005 for the population proportions by industry very well. The model also predicts that the proportion for the secondary industry becomes negligible and becomes less than 1% at least around 2080.

  2. Evaluation of facial divine proportion in North Indian Population

    PubMed Central

    Khan, Naseem Ahmad; Nagar, Amit; Tandon, Pradeep; Singh, Gulshan Kumar; Singh, Alka

    2016-01-01

    Objective: To evaluate the facial divine proportion and its relationship with facial attractiveness in North Indian population. Materials and Methods: For evaluation of various facial proportions, standardized frontal facial photographs of total 300 subjects between 18 and 30 years of age were obtained. Black and white copies of these photographs were presented in front of an evaluation jury for assigning scores of facial attractiveness and finally 130 attractive subjects were selected. These subjects were divided into two groups, Group I (attractive females n = 65) and Group II (attractive males n = 65) and they were further analyzed for various parameters of facial proportions. Unpaired Student's t-test was used to compare both groups. Results: Group I showed that five of seven vertical facial proportions were close to divine proportion (1.618) whereas only two vertical proportions in Group II were close to it. Transverse facial proportions in both groups deviated more from divine proportion (1.618) and were closer to silver proportion (1.414). Conclusions: Most of the facial proportions of attractive females in the North-Indian population were close to the divine proportion. Thus, facial divine proportion could be an important factor in the perception of facial attractiveness of North-Indian attractive females.

  3. Spatial Proportional Reasoning Is Associated with Formal Knowledge about Fractions

    ERIC Educational Resources Information Center

    Möhring, Wenke; Newcombe, Nora S.; Levine, Susan C.; Frick, Andrea

    2016-01-01

    Proportional reasoning involves thinking about parts and wholes (i.e., about fractional quantities). Yet, research on proportional reasoning and fraction learning has proceeded separately. This study assessed proportional reasoning and formal fraction knowledge in 8- to 10-year-olds. Participants (N = 52) saw combinations of cherry juice and water…

  4. Evaluation of facial divine proportion in North Indian Population

    PubMed Central

    Khan, Naseem Ahmad; Nagar, Amit; Tandon, Pradeep; Singh, Gulshan Kumar; Singh, Alka

    2016-01-01

    Objective: To evaluate the facial divine proportion and its relationship with facial attractiveness in North Indian population. Materials and Methods: For evaluation of various facial proportions, standardized frontal facial photographs of total 300 subjects between 18 and 30 years of age were obtained. Black and white copies of these photographs were presented in front of an evaluation jury for assigning scores of facial attractiveness and finally 130 attractive subjects were selected. These subjects were divided into two groups, Group I (attractive females n = 65) and Group II (attractive males n = 65) and they were further analyzed for various parameters of facial proportions. Unpaired Student's t-test was used to compare both groups. Results: Group I showed that five of seven vertical facial proportions were close to divine proportion (1.618) whereas only two vertical proportions in Group II were close to it. Transverse facial proportions in both groups deviated more from divine proportion (1.618) and were closer to silver proportion (1.414). Conclusions: Most of the facial proportions of attractive females in the North-Indian population were close to the divine proportion. Thus, facial divine proportion could be an important factor in the perception of facial attractiveness of North-Indian attractive females. PMID:27630502

  5. Simple, Internally Adjustable Valve

    NASA Technical Reports Server (NTRS)

    Burley, Richard K.

    1990-01-01

    Valve containing simple in-line, adjustable, flow-control orifice made from ordinary plumbing fitting and two allen setscrews. Construction of valve requires only simple drilling, tapping, and grinding. Orifice installed in existing fitting, avoiding changes in rest of plumbing.

  6. Self Adjusting Sunglasses

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Corning Glass Works' Serengeti Driver sunglasses are unique in that their lenses self-adjust and filter light while suppressing glare. They eliminate more than 99% of the ultraviolet rays in sunlight. The frames are based on the NASA Anthropometric Source Book.

  7. Rural to Urban Adjustment

    ERIC Educational Resources Information Center

    Abramson, Jane A.

    Personal interviews with 100 former farm operators living in Saskatoon, Saskatchewan, were conducted in an attempt to understand the nature of the adjustment process caused by migration from rural to urban surroundings. Requirements for inclusion in the study were that respondents had owned or operated a farm for at least 3 years, had left their…

  8. Self adjusting inclinometer

    DOEpatents

    Hunter, Steven L.

    2002-01-01

    An inclinometer utilizing synchronous demodulation for high resolution and electronic offset adjustment provides a wide dynamic range without any moving components. A device encompassing a tiltmeter and accompanying electronic circuitry provides quasi-leveled tilt sensors that detect highly resolved tilt change without signal saturation.

  9. Inference for survival prediction under the regularized Cox model.

    PubMed

    Sinnott, Jennifer A; Cai, Tianxi

    2016-10-01

    When a moderate number of potential predictors are available and a survival model is fit with regularization to achieve variable selection, providing accurate inference on the predicted survival can be challenging. We investigate inference on the predicted survival estimated after fitting a Cox model under regularization guaranteeing the oracle property. We demonstrate that existing asymptotic formulas for the standard errors of the coefficients tend to underestimate the variability for some coefficients, while typical resampling such as the bootstrap tends to overestimate it; these approaches can both lead to inaccurate variance estimation for predicted survival functions. We propose a two-stage adaptation of a resampling approach that brings the estimated error in line with the truth. In stage 1, we estimate the coefficients in the observed data set and in [Formula: see text] resampled data sets, and allow the resampled coefficient estimates to vote on whether each coefficient should be 0. For those coefficients voted as zero, we set both the point and interval estimates to [Formula: see text] In stage 2, to make inference about coefficients not voted as zero in stage 1, we refit the penalized model in the observed data and in the [Formula: see text] resampled data sets with only variables corresponding to those coefficients. We demonstrate that ensemble voting-based point and interval estimators of the coefficients perform well in finite samples, and prove that the point estimator maintains the oracle property. We extend this approach to derive inference procedures for survival functions and demonstrate that our proposed interval estimation procedures substantially outperform estimators based on asymptotic inference or standard bootstrap. We further illustrate our proposed procedures to predict breast cancer survival in a gene expression study. PMID:27107008

  10. THE COX-MAZE IV PROCEDURE: PREDICTORS OF LATE RECURRENCE

    PubMed Central

    Damiano, Ralph J.; Schwartz, Forrest H.; Bailey, Marci S.; Maniar, Hersh S.; Munfakh, Nabil A.; Moon, Marc R.; Schuessler, Richard B.

    2010-01-01

    Objectives The Cox-Maze III procedure(CMP) achieved high cure rates and became the surgical gold standard for the treatment of atrial fibrillation(AF). Due to its invasiveness, a more simplified ablation-assisted procedure(CMP-IV) has been performed at our institution since January, 2002. The study examined multiple preoperative and perioperative variables to determine predictors of late recurrence. Methods Data were collected prospectively on 282 patients who underwent the CMP-IV from January 2002 through December 2009. Forty-two percent of patients had paroxysmal and 58% had either persistent or long-standing persistent AF. All patients were available for follow-up. Follow-up included ECGs in all patients. Since 2006, 24 hour holter monitoring was obtained in 94% of patients at 3, 6 and 12 months. Data were analyzed by logistic regression analysis at 12 months with 13 preoperative and perioperative variables used as co-variants. Results Sixty-six percent of patients had a concomitant procedure. Following an ablation-assisted CMP, the freedom from AF was 89%, 93%, and 89% at 3, 6, and 12 months, respectively. The freedom from both AF and antiarrhythmic drugs was 63%, 79%, and 78% at 3, 6, and 12 months. The risk factors for AF recurrence at one year were enlarged left atrial(LA) diameter(p=0.027), failure to isolate the entire posterior left atrium(p=0.022), and early atrial tachyarrhythmias (ATAs)(p=0.010). Conclusions The CMP-IV has a high success rate at one year, even with improved follow-up and stricter definitions of failure. In patients with large LA, there may be a need for more extensive size reduction or expanded lesion sets. PMID:21168019

  11. Inference for survival prediction under the regularized Cox model.

    PubMed

    Sinnott, Jennifer A; Cai, Tianxi

    2016-10-01

    When a moderate number of potential predictors are available and a survival model is fit with regularization to achieve variable selection, providing accurate inference on the predicted survival can be challenging. We investigate inference on the predicted survival estimated after fitting a Cox model under regularization guaranteeing the oracle property. We demonstrate that existing asymptotic formulas for the standard errors of the coefficients tend to underestimate the variability for some coefficients, while typical resampling such as the bootstrap tends to overestimate it; these approaches can both lead to inaccurate variance estimation for predicted survival functions. We propose a two-stage adaptation of a resampling approach that brings the estimated error in line with the truth. In stage 1, we estimate the coefficients in the observed data set and in [Formula: see text] resampled data sets, and allow the resampled coefficient estimates to vote on whether each coefficient should be 0. For those coefficients voted as zero, we set both the point and interval estimates to [Formula: see text] In stage 2, to make inference about coefficients not voted as zero in stage 1, we refit the penalized model in the observed data and in the [Formula: see text] resampled data sets with only variables corresponding to those coefficients. We demonstrate that ensemble voting-based point and interval estimators of the coefficients perform well in finite samples, and prove that the point estimator maintains the oracle property. We extend this approach to derive inference procedures for survival functions and demonstrate that our proposed interval estimation procedures substantially outperform estimators based on asymptotic inference or standard bootstrap. We further illustrate our proposed procedures to predict breast cancer survival in a gene expression study.

  12. As-built design specification for proportion estimate software subsystem

    NASA Technical Reports Server (NTRS)

    Obrien, S. (Principal Investigator)

    1980-01-01

    The Proportion Estimate Processor evaluates four estimation techniques in order to get an improved estimate of the proportion of a scene that is planted in a selected crop. The four techniques to be evaluated were provided by the techniques development section and are: (1) random sampling; (2) proportional allocation, relative count estimate; (3) proportional allocation, Bayesian estimate; and (4) sequential Bayesian allocation. The user is given two options for computation of the estimated mean square error. These are referred to as the cluster calculation option and the segment calculation option. The software for the Proportion Estimate Processor is operational on the IBM 3031 computer.

  13. The inflammatory effect of infection with Hymenolepis diminuta via the increased expression and activity of COX-1 and COX-2 in the rat jejunum and colon.

    PubMed

    Kosik-Bogacka, D I; Baranowska-Bosiacka, I; Kolasa-Wołosiuk, A; Lanocha-Arendarczyk, N; Gutowska, I; Korbecki, J; Namięta, H; Rotter, I

    2016-10-01

    The aim of this study was to determine whether Hymenolepis diminuta may affect the expression and activity of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), resulting in the altered levels of their main products - prostaglandins (PGE2) and thromboxane B2 (TXB2). The study used the same experimental model as in our previous studies in which we had observed changes in the transepithelial ion transport, tight junctions and in the indicators of oxidative stress, in both small and large intestines of rats infected with H. diminuta. In this paper, we investigated not only the site of immediate presence of the tapeworm (jejunum), but also a distant site (colon). Inflammation related to H. diminuta infection is associated with the increased expression and activation of cyclooxygenase (COX), enzyme responsible for the synthesis of PGE2 and TXB2, local hormones contributing to the enhanced inflammatory reaction in the jejunum and colon in the infected rats. The increased COX expression and activity is probably caused by the increased levels of free radicals and the weakening of the host's antioxidant defense induced by the presence of the parasite. Our immunohistochemical analysis showed that H. diminuta infection affected not only the intensity of the immunodetection of COX but also the enzyme protein localization within intestinal epithelial cells - from the entire cytoplasm to apical/basal regions of cells, or even to the nucleus. PMID:27466058

  14. Dietary Proportions of Carbohydrates, Fat, and Protein and Risk of Oesophageal Cancer by Histological Type

    PubMed Central

    Lagergren, Katarina; Lindam, Anna; Lagergren, Jesper

    2013-01-01

    Background Dietary habits influence the risk of cancer of the oesophagus and oesophago-gastric junction, but the role of proportions of the main dietary macronutrients carbohydrates, fats and proteins is uncertain. Methods Data was derived from a nationwide Swedish population-based case-control study conducted in 1995–1997, in which case ascertainment was rapid, and all cases were uniformly classified. Information on the subjects' history of dietary intake was collected in personal interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, with adjustment for potentially confounding factors. Results Included were 189 oesophageal adenocarcinomas, 262 oesophago-gastric adenocarcinomas, 167 oesophageal squamous cell carcinomas, and 820 control subjects. Regarding oesophageal or oesophago-gastric junctional adenocarcinoma, a high dietary proportion of carbohydrates decreased the risk (OR 0.50, CI 0.34–0.73), and a high portion of fat increased the risk (OR 1.96, CI 1.34–2.87), while a high proportion of protein did not influence the risk (OR 1. 08, 95% CI 0.75–1.56). Regarding oesophageal squamous cell carcinoma, the single macronutrients did not influence the risk statistically significantly. Conclusions A diet with a low proportion of carbohydrates and a high proportion of fat might increase the risk of oesophageal adenocarcinoma. PMID:23349988

  15. Students' Understanding of Proportional, Inverse Proportional, and Affine Functions: Two Studies on the Role of External Representations

    ERIC Educational Resources Information Center

    De Bock, Dirk; Van Dooren, Wim; Verschaffel, Lieven

    2015-01-01

    We investigated students' understanding of proportional, inverse proportional, and affine functions and the way this understanding is affected by various external representations. In a first study, we focus on students' ability to model textual descriptions of situations with different kinds of representations of proportional, inverse…

  16. The Identification and Validation Process of Proportional Reasoning Attributes: An Application of a Proportional Reasoning Modeling Framework

    ERIC Educational Resources Information Center

    Tjoe, Hartono; de la Torre, Jimmy

    2014-01-01

    In this paper, we discuss the process of identifying and validating students' abilities to think proportionally. More specifically, we describe the methodology we used to identify these proportional reasoning attributes, beginning with the selection and review of relevant literature on proportional reasoning. We then continue with the…

  17. Estimating sighting proportions of American alligator nests during helicopter survey

    USGS Publications Warehouse

    Rice, Kenneth G.; Percival, H. Franklin; Woodward, Allan R.

    2000-01-01

    Proportions of American alligator (Alligator mississippiensis) nests sighted during aerial survey in Florida were estimated based upon multiple surveys by different observers. We compared sighting proportions across habitats, nesting seasons, and observer experience levels. The mean sighting proportion across all habitats and years was 0.736 (SE=0.024). Survey counts corrected by the mean sighting proportion reliably predicted total nest counts (7?2=0.933). Sighting proportions did not differ by habitat type (P=0.668) or year P=0.328). Experienced observers detected a greater proportion of nests (P<0.0001) than did either less experienced or inexperienced observers. Reliable estimates of nest abundance can be derived from aerial counts of alligator nests when corrected by the appropriate sighting proportion.

  18. 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

  19. 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.

  20. Citral, a component of lemongrass oil, activates PPARα and γ and suppresses COX-2 expression.

    PubMed

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

    2010-11-01

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

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

    PubMed

    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.

  2. 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

  3. Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance.

    PubMed

    Queiroga, Felisbina Luisa; Perez-Alenza, Maria Dolores; Silvan, Gema; Peña, Laura; Lopes, Carlos; Illera, Juan Carlos

    2005-01-01

    Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p < 0.001) and tumor size (p < 0.001). The follow-up study revealed that high Cox-2 levels were related with recurrence (p = 0.002), metastases (p < 0.001), disease-free survival (p < 0.001) and overall survival (p < 0.001). This study demonstrates an association between intra-tumor Cox-2 levels and poor prognosis. The high levels found in IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.

  4. Case-mix adjustment for evaluation of mortality in cystic fibrosis.

    PubMed

    O'Connor, Gerald T; Quinton, Hebe B; Kahn, Richard; Robichaud, Priscilla; Maddock, Joanne; Lever, Thomas; Detzer, Mark; Brooks, John G

    2002-02-01

    Comparison of patient mortality rates in cystic fibrosis (CF) obtained from different institutions requires the use of case-mix adjustment methods to account for baseline differences in patient and disease characteristics. There is no current professional consensus on the use of case-mix adjustment methods for use in comparing mortality rates in CF. Characteristics used for this case-mix adjustment should include those that are different across institutions and are associated with patient survival. They should not include characteristics of disease severity that may be a consequence of effectiveness of treatment. The goal of these analyses was to identify a set of these characteristics of patients or disease that would be useful for case-mix adjustment of CF mortality rates. Data from the Cystic Fibrosis Foundation Patient Registry and from the United States Census of the Population (1990) were used in these analyses. Kaplan-Meier techniques, the log-rank test, and Cox proportional hazards regression were used to estimate survivorship, calculate hazard ratios (HR), 95% confidence intervals (CI(95%)), and to conduct tests of statistical significance. The data set included all 30,469 CF patients seen at CF Care Centers from 1982-1998. There were 5,906 deaths during 508,721 person-years of follow-up. In multivariate analyses, female gender (HR 1.30, CI(95%) (1.16, 1,47), P < 0.001), nonwhite race (HR 1.48, CI(95%) (1.07, 2.04), P = 0.018), Hispanic ethnicity (HR 1.85, CI(95%) (1.42, 2.43), P < 0.001), and symptomatic presentation (respiratory, gastrointestinal, respiratory and gastrointestinal, meconium ileus, and other symptomatic presentations; HRs 1.38-1.83; P values, 0.028 to < 0.001) were associated with higher risk of death. The homozygous Delta F508 genotype (HR 1.36, CI(95%) (1.19, 1.55), P < 0.001) and neither mutation being Delta F508 (HR 1.40, CI(95%) (1.15, 1.71), P = 0.001) were also associated with higher risk of death. Patients diagnosed after 36 months

  5. HGF/MET signaling promotes glioma growth via up-regulation of Cox-2 expression and PGE2 production

    PubMed Central

    Zhao, Yan; Sun, Ying; Zhang, Haiyan; Liu, Xing; Du, Wenzong; Li, Yongli; Zhang, Junhe; Chen, Lingchao; Jiang, Chuanlu

    2015-01-01

    Cyclooxygenase2 (Cox-2) is well known for glioma growth through up-regulation of prostaglandin E2 (PGE2) levels. MET, a hepatocyte growth factor (HGF) receptor, is also frequently high expressed in glioma, which promotes glioma growth and invasion. Here, we demonstrate that HGF/MET signaling can promote PGE2 production in glioma cells via Cox-2 up-regulation. RNA inhibition of MET suggested that MET signaling is essential for Cox-2 up-regulation. Moreover, HGF could enhance Cox-2 expression and PGE2 release. Knockdown of Cox-2 inhibited growth-promoting effects of HGF, suggesting that HGF/MET functioned via Cox-2/PGE2 pathway. Therefore, our work reveals a critical relationship of Cox-2/PGE2 and HGF/MET signaling in promoting glioma cells proliferation. Further, targeting MET and Cox-2 may represent an attractive target therapy for glioma. PMID:26097553

  6. 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

  7. 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.

  8. Precision adjustable stage

    DOEpatents

    Cutburth, Ronald W.; Silva, Leonard L.

    1988-01-01

    An improved mounting stage of the type used for the detection of laser beams is disclosed. A stage center block is mounted on each of two opposite sides by a pair of spaced ball bearing tracks which provide stability as well as simplicity. The use of the spaced ball bearing pairs in conjunction with an adjustment screw which also provides support eliminates extraneous stabilization components and permits maximization of the area of the center block laser transmission hole.

  9. Adjustable vane windmills

    SciTech Connect

    Ducker, W.L.

    1982-09-14

    A system of rotatably and pivotally mounted radially extended bent supports for radially extending windmill rotor vanes in combination with axially movable radially extended control struts connected to the vanes with semi-automatic and automatic torque and other sensing and servo units provide automatic adjustment of the windmill vanes relative to their axes of rotation to produce mechanical output at constant torque or at constant speed or electrical quantities dependent thereon.

  10. Adjustable vane windmills

    SciTech Connect

    Ducker, W.L.

    1980-01-15

    A system of rotatably and pivotally mounted radially extended bent supports for radially extending windmill rotor vanes in combination with axially movable radially extended control struts connected to the vanes with semi-automatic and automatic torque and other sensing and servo units provide automatic adjustment of the windmill vanes relative to their axes of rotation to produce mechanical output at constant torque or at constant speed or electrical quantities dependent thereon.

  11. Adjustable vane windmills

    SciTech Connect

    Ducker, W.L.

    1982-09-07

    A system of rotatably and pivotally mounted radially extended bent supports for radially extending windmill rotor vanes in combination with axially movable radially extended control struts connected to the vanes with semi-automatic and automatic torque and other sensing and servo units provide automatic adjustment of the windmill vanes relative to their axes of rotation to produce mechanical output at constant torque or at constant speed or electrical quantities dependent thereon.

  12. Adjustable Autonomy Testbed

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.; Schrenkenghost, Debra K.

    2001-01-01

    The Adjustable Autonomy Testbed (AAT) is a simulation-based testbed located in the Intelligent Systems Laboratory in the Automation, Robotics and Simulation Division at NASA Johnson Space Center. The purpose of the testbed is to support evaluation and validation of prototypes of adjustable autonomous agent software for control and fault management for complex systems. The AA T project has developed prototype adjustable autonomous agent software and human interfaces for cooperative fault management. This software builds on current autonomous agent technology by altering the architecture, components and interfaces for effective teamwork between autonomous systems and human experts. Autonomous agents include a planner, flexible executive, low level control and deductive model-based fault isolation. Adjustable autonomy is intended to increase the flexibility and effectiveness of fault management with an autonomous system. The test domain for this work is control of advanced life support systems for habitats for planetary exploration. The CONFIG hybrid discrete event simulation environment provides flexible and dynamically reconfigurable models of the behavior of components and fluids in the life support systems. Both discrete event and continuous (discrete time) simulation are supported, and flows and pressures are computed globally. This provides fast dynamic simulations of interacting hardware systems in closed loops that can be reconfigured during operations scenarios, producing complex cascading effects of operations and failures. Current object-oriented model libraries support modeling of fluid systems, and models have been developed of physico-chemical and biological subsystems for processing advanced life support gases. In FY01, water recovery system models will be developed.

  13. Sensitivity of health risk estimates to air quality adjustment procedure

    SciTech Connect

    Whitfield, R.G.

    1997-06-30

    This letter is a summary of risk results associated with exposure estimates using two-parameter Weibull and quadratic air quality adjustment procedures (AQAPs). New exposure estimates were developed for children and child-occurrences, six urban areas, and five alternative air quality scenarios. In all cases, the Weibull and quadratic results are compared to previous results, which are based on a proportional AQAP.

  14. 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.

  15. 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...

  16. The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase.

    PubMed Central

    Akarasereenont, Pravit C; Techatraisak, Kitirat; Thaworn, Athiwat; Chotewuttakorn, Sirikul

    2002-01-01

    Cyclooxygenase (COX), existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF) has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC). The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX-2 was assessed by measuring the production of 6-keto-prostaglandin F1alpha in the presence of exogenous arachidonic acids (10 microM, 10 min) by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml), COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml) was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 microg/ml), but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml). Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role. PMID:11926591

  17. Cyclooxygenase-2 (COX-2) expression in high-risk premalignant oral lesions.

    PubMed

    Sudbø, Jon; Ristimäki, Ari; Sondresen, Jan Erik; Kildal, Wanja; Boysen, Morten; Koppang, Hanna S; Reith, Albrecht; Risberg, Björn; Nesland, Jahn M; Bryne, Magne

    2003-07-01

    Emerging data indicate a link between genetic instability and up-regulation of cyclooxygenase-2 (COX-2). To see if individuals at high risk of oral cancer are candidates for treatment with selective COX-2 inhibitors (coxibs), levels of COX-2 expression in healthy, premalignant and cancerous oral mucosa were compared with the occurrence of DNA ploidy status as a genetic risk marker of oral cancer. COX-2 gene product was evaluated immunohistochemically in 30 healthy persons, in 22 patients with dysplastic lesions without previous or concomitant carcinomas, and in 29 patients with oral carcinomas. The immunohistochemical findings were verified by western blotting. COX-2 expression was correlated to DNA content as a genetic risk marker of oral cancer. COX-2 was up-regulated from healthy to premalignant to cancerous oral mucosa. Thus, COX-2 expression was found in 1 case of healthy oral mucosa (3%). All specimens from healthy mucosa had a normal DNA content. In patients with premalignancies. In 29 patients with oral carcinomas, cyclooxygenase-2 expression was observed in 26 (88%), and aneuploidy was observed in 25 cases (94%, P=0.04). Notably, of 22 patients with dysplastic lesions, COX-2 was exclusively expressed in a subgroup of nine patients (41%) identified to be at high risk of cancer by the aberrant DNA content of their lesions. Seven of these patients were followed for 5 years or more. An oral carcinoma developed in six of them (85%; P=0.02). These findings emphasize the need to determine whether coxibs can reduce the risk of oral cancer in patients with high-risk precancerous lesions. PMID:12747975

  18. Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.

    PubMed

    Rose, Tyler M; Reilly, Christopher A; Deering-Rice, Cassandra E; Brewster, Clinton; Brewster, Chelsea

    2014-12-15

    Serotonin was linked by amidation to the carboxylic acid groups of a series of structurally diverse NSAIDs. The resulting NSAID-serotonin conjugates were tested in vitro for their ability to inhibit FAAH, TRPV1, and COX2. Ibuprofen-5-HT and Flurbiprofen-5-HT inhibited all three targets with approximately the same potency as N-arachidonoyl serotonin (AA-5-HT), while Fenoprofen-5-HT and Naproxen-5-HT showed activity as dual inhibitors of TRPV1 and COX2.

  19. Inhibition of FAAH, TRPV1, and COX2 by NSAID-Serotonin Conjugates

    PubMed Central

    Rose, Tyler M.; Reilly, Christopher A.; Deering-Rice, Cassandra E.; Brewster, Clinton; Brewster, Chelsea

    2014-01-01

    Serotonin was linked by amidation to the carboxylic acid groups of a series of structurally diverse NSAIDs. The resulting NSAID-serotonin conjugates were tested in vitro for their ability to inhibit FAAH, TRPV1, and COX2. Ibuprofen-5-HT and Flurbiprofen-5-HT inhibited all three targets with approximately the same potency as N-arachidonoyl serotonin (AA-5-HT), while Fenoprofen-5-HT and Naproxen-5-HT showed activity as dual inhibitors of TRPV1 and COX2. PMID:25467164

  20. Human fecal water inhibits COX-2 in colonic HT-29 cells: role of phenolic compounds.

    PubMed

    Karlsson, Pernilla C; Huss, Ulrika; Jenner, Andrew; Halliwell, Barry; Bohlin, Lars; Rafter, Joseph J

    2005-10-01

    The inducible enzyme cyclooxygenase-2 (COX-2) plays a major role in the regulation of inflammation and possibly in the development of colon cancer. The aim of the present study was to screen for COX-2 inhibitors in samples of fecal water (the aqueous phase of feces) and investigate whether phenolic compounds are responsible for any observed effects on COX-2. Volunteers (n = 20) were recruited and asked to supply a 24-h stool sample. Fecal water samples were prepared and analyzed by GC-MS for their content of phenolic compounds. These samples were also evaluated for their effects on COX-2 protein levels (Western blot) and prostaglandin (PG)E2 production in tumor necrosis-alpha-stimulated HT-29 cells and pure enzymatic activity in a COX-2-catalyzed prostaglandin biosynthesis in vitro assay. The major phenolic compounds identified were phenylpropionic acid, phenylacetic acid, cinnamic acid, and benzoic acid derivatives. Of 13 fecal water samples analyzed, 12 significantly decreased PGE2 production (range 5.4-39.7% inhibition, P-value < 0.05) compared with control cells and 13 of 14 samples analyzed decreased COX-2 protein levels in HT-29 cells (19-63% inhibition). Of the 20 fecal water samples, 2 also weakly inhibited enzymatic activity of purified COX-2 (22-24% inhibition). Three compounds identified in fecal water, 3-phenylpropionic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, decreased the protein level at 250 micromol/L (15-62% inhibition). This study shows for the first time that human fecal water contains components that can affect both the COX-2 protein level and enzymatic activity. PMID:16177193

  1. Axinelline A, a new COX-2 inhibitor from Streptomyces axinellae SCSIO02208.

    PubMed

    Ai, Wen; Lin, Xiu-Ping; Tu, Zhengchao; Tian, Xin-Peng; Lu, Xin; Mangaladoss, Fredimoses; Zhong, Zhi-Long; Liu, Yonghong

    2014-01-01

    Axinelline A, a new cyclooxygenase-2 (COX-2) inhibitor, was isolated from Streptomyces axinellae SCSIO02208. The structures of compounds 1-9 were determined by analysing the NMR and MS data. The absolute configuration of 1 was determined by using optical rotation and comparing with the reported data. Compound 1 exhibited COX-2 inhibitory activity, the IC50 value being 2.8 μM.

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

    SciTech Connect

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

    2008-05-23

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

  3. Estrogen protects the heart from ischemia-reperfusion injury via COX-2-derived PGI2.

    PubMed

    Booth, Erin Anne; Flint, RaShonda Renee; Lucas, Kathryn Louise; Knittel, Andrea Kathleen; Lucchesi, Benedict R

    2008-09-01

    There is an accumulating body of data to suggest that estrogen mediates its cardioprotective effects via cyclooxygenase activation and synthesis of prostaglandins (PG), specifically PGI2. We hypothesized that inhibition of COX-2 would prevent estrogen's cardioprotective effects after myocardial ischemia-reperfusion. Acute treatment with 17beta-estradiol (E2; 20 microg/rabbit) increased COX-2 protein expression and activity in the myocardium. To determine the effects of COX-2 inhibition on infarct size after E2 treatment, New Zealand white rabbits were anesthetized and administered the COX-2 inhibitor nimesulide (5 mg/kg) or vehicle intravenously 30 minutes before an intravenous injection of E2. Thirty minutes after estrogen treatment, the coronary artery was occluded for 30 minutes followed by 4 hours of reperfusion. E2 significantly decreased infarct size as a percent of area at risk when compared to vehicle (18.9 +/- 3.1 versus 47.0 +/- 4.1; P < 0.001). Pretreatment with nimesulide nullified the infarct size sparing effect of E2 (55.8 +/- 5.6). Treatment with the PGI2 receptor antagonist RO3244794 also abolished the protective effects of E2 (45.3 +/- 4.5). The results indicate that estrogen protects the myocardium from ischemia-reperfusion injury through increased production of COX-2-derived PGI2. The data indicate that selective COX-2 inhibitors might counteract the potential cytoprotective effects of estrogen in premenopausal or postmenopausal women.

  4. 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

  5. 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

  6. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    PubMed Central

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention. PMID:23875171

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

  9. First birth cesarean proportion: A missed indicator in controlling policies

    PubMed Central

    Safari-Faramani, Roya; Haghdoost, Ali Akbar; Nakhaei, Nouzar; Foroudnia, Shohreh; Mahmoodabadi, Zahra; Safizadeh, Mansooreh

    2016-01-01

    Background: Around one out of two mothers give births by cesarean section (CS) surgery in Iran and about half of this number is due to previous CS. Recently Health Sector Evolution (HSEP) program (started in April 2014) targets the high rate of CS in Iran. To assess the impact of the interventions, we emphasized that the First Birth Cesarean (FBC) proportion is one of the main indicators to assess the controlling programs. Methods: Data on the mode of delivery were collected in Kerman province between 21 March and 20 March 2015 classified by hospital ownership. FBC proportion is defined as the number of CS in the first pregnancies divided by the total number of first births. Chi-square test for trend was used to assess the trends. Results: Total number of births was around 34000. There were 8.9 and 13.1 percent reduction in CS and FBC proportion respectively. CS proportion was 54.5 at the end of the first quarter of the studied period and reached to 49.6 at the end of the period (p<0.0001). Also, FBC proportion was 54.1 percent at first and reached to 47 percent at the end of the study period. The main reason for CS was due to previous CS. At the hospital level, the highest reduction in CS and FBC proportion were in public hospitals. Conclusion: Results suggested more reduction in FBC proportion than the CS proportion, so this is a very good sign since more potential CS cases will be prevented. As repeated CS is one of the main indications for the operation, in the short term, even effective policies may change the overall proportion slightly, while the FBC proportion is more sensitive to reflect the impacts. Therefore, it is necessary to target the main fuel to reduce CS proportion effectively. PMID:27579285

  10. Reducing magnetic zero drift by optimizing proportions of neon dual isotopes in laser gyros

    NASA Astrophysics Data System (ADS)

    Di, Nan; Zhao, Jian-lin

    2012-03-01

    The relationships among the proportions of the neon dual isotopes ratio, scale factor corrections (SFCs), light intensities, environmental magnetic field and magnetic zero drift are discussed in detail by numerical simulations. The results show that the unification of the optimal operating point (OP) and the frequency stabilization operating point (FSP) is achievable by adjusting the proportions of neon dual isotopes accurately and tuning the cavity length with frequency stabilization system exactly. In that case, the left-rotation and right-rotation gyros can obtain the same SFC, which can decrease the magnetic sensitivity of the laser gyro efficiently. The Zeeman effect zero drift and the Faraday bias zero drift are both reduced by two orders of magnitude, while the magnetic shielding requirement of laser tube is decreased by 1-2 orders of magnitude.

  11. Large-proportional shrunken bio-replication of shark skin based on UV-curing shrinkage

    NASA Astrophysics Data System (ADS)

    Chen, Huawei; Che, Da; Zhang, Xin; Yue, Yue; Zhang, Deyuan

    2015-01-01

    The shark skin effect has attracted worldwide attention because of its superior drag reduction. As the product of natural selection, the maximum drag reduction of shark skin is found in its normal living environment. Large-proportional shrinkage of shark skin morphology is greatly anticipated for its adaptation to faster fluid flow. One novel approach, large-proportional shrunken bio-replication, is proposed as a method to adjust the optimal drag reduction region of shark skin based on the shrinkage of UV-cured material. The shark skin is taken as a replica template to allow large-proportional shrinking in the drag reduction morphology by taking advantage of the shrinkage of UV-curable material. The accuracy of the large-proportional shrunken bio-replication approach is verified by a comparison between original and shrunken bio-replicated shark skin, which shows that the shrinking ratio can reach 23% and the bio-replication accuracy is higher than 95%. In addition, the translation of the optimum drag reduction peak of natural surface function to various applications and environments is proved by drag reduction experiments.

  12. Effects of load proportioning on the capacity of multiple-hole composite joints

    NASA Technical Reports Server (NTRS)

    Hyer, M. W.; Chastain, P. A.

    1985-01-01

    This study addresses the issue of adjusting the proportion of load transmitted by each hole in a multiple-hole joint so that the joint capacity is a maximum. Specifically two-hole-in-series joints are examined. The results indicate that when each hole reacts 50% of the total load, the joint capacity is not a maximum. One hole generally is understressed at joint failure. The algorithm developed to determine the load proportion at each hole which results in maximum capacity is discussed. The algorithm includes two-dimensional finite-element stress analysis and failure criteria. The algorithm is used to study the effects of joint width, hole spacing, and hole to joint-end distance on load proportioning and capacity. To study hole size effects, two hole diameters are considered. Three laminates are considered: a quasi-isotropic laminate; a cross-ply laminate; and a 45 degree angle-ply laminate. By proportioning the load, capacity can be increased generally from 5 to 10%. In some cases a greater increase is possible.

  13. Subsea adjustable choke valves

    SciTech Connect

    Cyvas, M.K. )

    1989-08-01

    With emphasis on deepwater wells and marginal offshore fields growing, the search for reliable subsea production systems has become a high priority. A reliable subsea adjustable choke is essential to the realization of such a system, and recent advances are producing the degree of reliability required. Technological developments have been primarily in (1) trim material (including polycrystalline diamond), (2) trim configuration, (3) computer programs for trim sizing, (4) component materials, and (5) diver/remote-operated-vehicle (ROV) interfaces. These five facets are overviewed and progress to date is reported. A 15- to 20-year service life for adjustable subsea chokes is now a reality. Another factor vital to efficient use of these technological developments is to involve the choke manufacturer and ROV/diver personnel in initial system conceptualization. In this manner, maximum benefit can be derived from the latest technology. Major areas of development still required and under way are listed, and the paper closes with a tabulation of successful subsea choke installations in recent years.

  14. Attention Modulation by Proportion Congruency: The Asymmetrical List Shifting Effect

    ERIC Educational Resources Information Center

    Abrahamse, Elger L.; Duthoo, Wout; Notebaert, Wim; Risko, Evan F.

    2013-01-01

    Proportion congruency effects represent hallmark phenomena in current theorizing about cognitive control. This is based on the notion that proportion congruency determines the relative levels of attention to relevant and irrelevant information in conflict tasks. However, little empirical evidence exists that uniquely supports such an attention…

  15. Longitudinal Enrollment Dynamics and Changes in Ethnic Proportionality.

    ERIC Educational Resources Information Center

    Greaves, Fred

    The Federal Racial/Ethnic Surveys of the Salinas Union High School District were examined to identify changes in ethnic proportions within a particular class from its entry in the 9th grade until the 12th grade. The 9th, 10th, 11th, and 12th grade proportional distributions are reported by school (Alisal High School, North Salinas High School, and…

  16. Development of Proportional Reasoning: Where Young Children Go Wrong

    ERIC Educational Resources Information Center

    Boyer, Ty W.; Levine, Susan C.; Huttenlocher, Janellen

    2008-01-01

    Previous studies have found that children have difficulty solving proportional reasoning problems involving discrete units until 10 to 12 years of age, but can solve parallel problems involving continuous quantities by 6 years of age. The present studies examine where children go wrong in processing proportions that involve discrete quantities. A…

  17. The Failings of the Law of Definite Proportions

    ERIC Educational Resources Information Center

    Suchow, Lawrence

    1975-01-01

    Indicates that the concept of definite proportions or constant composition should be introduced with qualification. Presents arguments against the Law of Definite Proportions and cites examples in the areas of solid solutions, compounds of the transition and inner transition elements, and in some compounds of the representative elements. (GS)

  18. 16 CFR 240.9 - Proportionally equal terms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Proportionally equal terms. 240.9 Section 240.9 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.9 Proportionally equal terms....

  19. Understanding Proportional Reasoning in Pre-Service Teachers

    ERIC Educational Resources Information Center

    Johnson, Kim H.

    2013-01-01

    The purpose of this study is to examine the proportional reasoning of pre-service teachers at the beginning of their teacher preparation program using the developmental shifts described by Lobato and Ellis (2010). They cast changes in proportional reasoning as transitions or "shifts" in students' thinking and these shifts can serve as…

  20. The influence of lower face vertical proportion on facial attractiveness.

    PubMed

    Johnston, D J; Hunt, O; Johnston, C D; Burden, D J; Stevenson, M; Hepper, P

    2005-08-01

    This study investigated the influence of changing lower face vertical proportion on the attractiveness ratings scored by lay people.Ninety-two social science students rated the attractiveness of a series of silhouettes with normal, reduced or increased lower face proportions. The random sequences of 10 images included an image with the Eastman normal lower face height relative to total face height [lower anterior face height/total anterior face height (LAFH/TAFH) of 55 per cent], and images with LAFH/TAFH increased or decreased by up to four standard deviations (SD) from the Eastman norm. All the images had a skeletal Class I antero-posterior (AP) relationship. A duplicate image in each sequence assessed repeatability. The participants scored each image using a 10 point numerical scale and also indicated whether they would seek treatment if the image was their own profile. The profile image with normal vertical facial proportions was rated by the lay people as the most attractive. Attractiveness scores reduced as the vertical facial proportions diverged from the normal value. Images with a reduced lower face proportion were rated as significantly more attractive than the corresponding images with an increased lower face proportion. Images with a reduced lower face proportion were also significantly less likely to be judged as needing treatment than the corresponding images with an increased lower face proportion. PMID:15961569

  1. ESTIMATING PROPORTION OF AREA OCCUPIED UNDER COMPLEX SURVEY DESIGNS

    EPA Science Inventory

    Estimating proportion of sites occupied, or proportion of area occupied (PAO) is a common problem in environmental studies. Typically, field surveys do not ensure that occupancy of a site is made with perfect detection. Maximum likelihood estimation of site occupancy rates when...

  2. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor

    PubMed Central

    Riendeau, D; Percival, M D; Boyce, S; Brideau, C; Charleson, S; Cromlish, W; Ethier, D; Evans, J; Falgueyret, J -P; Ford-Hutchinson, A W; Gordon, R; Greig, G; Gresser, M; Guay, J; Kargman, S; Léger, S; Mancini, J A; O'Neill, G; Ouellet, M; Rodger, I W; Thérien, M; Wang, Z; Webb, J K; Wong, E; Xu, L; Young, R N; Zamboni, R; Prasit, P; Chan, C -C

    1997-01-01

    DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) was identified as a novel orally active and highly selective cyclo-oxygenase-2 (COX-2) inhibitor.In CHO cells stably transfected with human COX isozymes, DFU inhibited the arachidonic acid-dependent production of prostaglandin E2 (PGE2) with at least a 1,000 fold selectivity for COX-2 (IC50=41±14 nM) over COX-1 (IC50>50 μM). Indomethacin was a potent inhibitor of both COX-1 (IC50=18±3 nM) and COX-2 (IC50=26±6 nM) under the same assay conditions. The large increase in selectivity of DFU over indomethacin was also observed in COX-1 mediated production of thromboxane B2 (TXB2) by Ca2+ ionophore-challenged human platelets (IC50>50 μM and 4.1±1.7 nM, respectively).DFU caused a time-dependent inhibition of purified recombinant human COX-2 with a Ki value of 140±68 μM for the initial reversible binding to enzyme and a k2 value of 0.11±0.06 s−1 for the first order rate constant for formation of a tightly bound enzyme-inhibitor complex. Comparable values of 62±26 μM and 0.06±0.01 s−1, respectively, were obtained for indomethacin. The enzyme-inhibitor complex was found to have a 1 : 1 stoichiometry and to dissociate only very slowly (t1/2=1–3 h) with recovery of intact inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased by co-incubation with arachidonic acid under non-turnover conditions, consistent with reversible competitive inhibition at the COX active site.Inhibition of purified recombinant human COX-1 by DFU was very weak and observed only at low concentrations of substrate (IC50=63±5 μM at 0.1 μM arachidonic acid). In contrast to COX-2, inhibition was time-independent and rapidly reversible. These data are consistent with a reversible competitive inhibition of COX-1.DFU inhibited lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50=0.28±0.04 μM) similar

  3. Mechanisms by Which 17β-Estradiol (E2) Suppress Neuronal cox-2 Gene Expression

    PubMed Central

    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

  4. 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

  5. Adolescent Mothers' Adjustment to Parenting.

    ERIC Educational Resources Information Center

    Samuels, Valerie Jarvis; And Others

    1994-01-01

    Examined adolescent mothers' adjustment to parenting, self-esteem, social support, and perceptions of baby. Subjects (n=52) responded to questionnaires at two time periods approximately six months apart. Mothers with higher self-esteem at Time 1 had better adjustment at Time 2. Adjustment was predicted by Time 2 variables; contact with baby's…

  6. Prescription channeling of COX-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs: a population-based case-control study.

    PubMed

    Moride, Yola; Ducruet, Thierry; Boivin, Jean-François; Moore, Nicholas; Perreault, Sylvie; Zhao, Sean

    2005-01-01

    This pharmacoepidemiologic study was conducted to determine whether risk factors for upper gastrointestinal bleeding influenced the prescription of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) at the time when COX-2 inhibitors were first included in the formulary of reimbursed medications. A population-based case-control study was conducted in which the prevalence of risk factors and the medical histories of patients prescribed COX-2 inhibitors and traditional nonselective NSAIDs were compared. The study population consisted of a random sample of members of the Quebec drug plan (age 18 years or older) who received at least one dispensation of celecoxib (n = 42,422; cases), rofecoxib (n = 25,674; cases), or traditional nonselective NSAIDs (n = 12,418; controls) during the year 2000. All study data were obtained from the Quebec health care databases. Adjusting for income level, Chronic Disease Score, prior use of low-dose acetylsalicylic acid, acetaminophen, antidepressants, benzodiazepines, prescriber specialty, and time period, the following factors were significantly associated with the prescription of COX-2 inhibitors: age 75 years or older (odds ratio [OR] 4.22, 95% confidence interval [CI] 3.95-4.51), age 55-74 years (OR 3.23, 95% CI 3.06-3.40), female sex (OR 1.52, 95% CI 1.45-1.58), prior diagnosis of gastropathy (OR 1.21, 95% CI 1.08-1.36) and prior dispensation of gastroprotective agents (OR 1.57, 95% CI 1.47-1.67). Patients who received a traditional nonselective NSAID recently were more likely to switch to a coxib, especially first-time users (OR 2.17, 95% CI 1.93-2.43). Associations were significantly greater for celecoxib than rofecoxib for age, chronic NSAID use, and last NSAID use between 1 and 3 months before the index date. At the time of introduction of COX-2 inhibitors into the formulary, prescription channeling could confound risk comparisons across products. PMID:15743481

  7. Impact of Medicaid Prior Authorization Requirement for COX-2 Inhibitor Drugs in Nebraska

    PubMed Central

    Siracuse, Mark V; Vuchetich, Phillip J

    2008-01-01

    Objective Determine the impact of a Prior Authorization Requirement (PAR) program on Medicaid pharmacy expenditures and utilization. Data Source Prescription claims for Nebraska Medicaid recipients who received a cyclooxygenase-2 (COX-2) inhibitor, a nonselective nonsteroidal antiinflammatory (NSAID) drug, or other pain relievers between July 2001 and June 2003. Study Design and Data Collection/Extraction This was a retrospective cross-sectional study with a 12-month pre-PAR implementation period and a 12-month post-PAR implementation period. Pharmacy transactions for COX-2 inhibitors, NSAIDs, other pain relievers, and gastroprotectants were identified by their National Drug Code (NDC) in a Microsoft SQL query. The PAR was designed to approve COX-2 inhibitor use only for recipients at high risk of GI side effects while restricting access to those patients at low to moderate risk of GI side effects. Principal Findings One year following implementation of the PAR, overall expenditures on COX-2 inhibitors for Nebraska Medicaid dropped 50 percent. The overall impact on pharmacy expenditures, including NSAIDs, pain relief medications, and gastroprotectants when necessary to relieve gastrointestinal (GI) side effects, for those recipients who switched from a COX-2 inhibitor to an NSAID or other pain relievers was a decline of approximately 35 percent. Conclusion and Implications for State Policy PAR for COX-2 inhibitors successfully reduced Medicaid prescription expenditures. Recipients at high risk for GI side effects appropriately received COX-2 inhibitors. Recipients at low to moderate risk for GI side effects who were switched to NSAIDs or other pain relievers had lower overall prescription expenditures. Further research is needed to determine the impact of PAR on overall health outcomes and costs. In this study, rather than take a “one size fits all” approach to prescription drug cost-saving strategies, Medicaid policy makers understood that patient variation

  8. Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.

    PubMed

    Clemente, Mónica; Sánchez-Archidona, Ana Rodríguez; Sardón, David; Díez, Lucía; Martín-Ruiz, Asunción; Caceres, Sara; Sassi, Francesco; Dolores Pérez-Alenza, M; Illera, Juan C; Dunner, Susana; Peña, Laura

    2013-08-01

    Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC. PMID:23489848

  9. 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

  10. 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

  11. 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

  12. Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.

    PubMed

    Clemente, Mónica; Sánchez-Archidona, Ana Rodríguez; Sardón, David; Díez, Lucía; Martín-Ruiz, Asunción; Caceres, Sara; Sassi, Francesco; Dolores Pérez-Alenza, M; Illera, Juan C; Dunner, Susana; Peña, Laura

    2013-08-01

    Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC.

  13. Estimation of lithofacies proportions using well and well test data

    SciTech Connect

    Hu, L.Y.; Blanc, G.; Noetinger, B.

    1996-12-31

    A crucial step of the commonly used geostatistical methods for modeling heterogeneous reservoirs (e.g. the sequential indicator simulation and the truncated Gaussian functions) is the estimation of the lithofacies local proportion (or probability density) functions. Well-test derived permeabilities show good correlation with lithofacies proportions around wells. Integrating well and well-test data in estimating lithofacies proportions could permit the building of more realistic models of reservoir heterogeneity. However this integration is difficult because of the different natures and measurement scales of these two types of data. This paper presents a two step approach to integrating well and well-test data into heterogeneous reservoir modeling. First lithofacies proportions in well-test investigation areas are estimated using a new kriging algorithm called KISCA. KISCA consists in kriging jointly the proportions of all lithofacies in a well-test investigation area so that the corresponding well-test derived permeability is respected through a weighted power averaging of lithofacies permeabilities. For multiple well-tests, an iterative process is used in KISCA to account for their interaction. After this, the estimated proportions are combined with lithofacies indicators at wells for estimating proportion (or probability density) functions over the entire reservoir field using a classical kriging method. Some numerical examples were considered to test the proposed method for estimating lithofacies proportions. In addition, a synthetic lithofacies reservoir model was generated and a well-test simulation was performed. The comparison between the experimental and estimated proportions in the well-test investigation area demonstrates the validity of the proposed method.

  14. System training and assessment in simultaneous proportional myoelectric prosthesis control

    PubMed Central

    2014-01-01

    Background Pattern recognition control of prosthetic hands take inputs from one or more myoelectric sensors and controls one or more degrees of freedom. However, most systems created allow only sequential control of one motion class at a time. Additionally, only recently have researchers demonstrated proportional myoelectric control in such systems, an option that is believed to make fine control easier for the user. Recent developments suggest improved reliability if the user follows a so-called prosthesis guided training (PGT) scheme. Methods In this study, a system for simultaneous proportional myoelectric control has been developed for a hand prosthesis with two motor functions (hand open/close, and wrist pro-/supination). The prosthesis has been used with a prosthesis socket equivalent designed for normally-limbed subjects. An extended version of PGT was developed for use with proportional control. The control system’s performance was tested for two subjects in the Clothespin Relocation Task and the Southampton Hand Assessment Procedure (SHAP). Simultaneous proportional control was compared with three other control strategies implemented on the same prosthesis: mutex proportional control (the same system but with simultaneous control disabled), mutex on-off control, and a more traditional, sequential proportional control system with co-contractions for state switching. Results The practical tests indicate that the simultaneous proportional control strategy and the two mutex-based pattern recognition strategies performed equally well, and superiorly to the more traditional sequential strategy according to the chosen outcome measures. Conclusions This is the first simultaneous proportional myoelectric control system demonstrated on a prosthesis affixed to the forearm of a subject. The study illustrates that PGT is a promising system training method for proportional control. Due to the limited number of subjects in this study, no definite conclusions can be

  15. Goodness-of-fit test for proportional subdistribution hazards model.

    PubMed

    Zhou, Bingqing; Fine, Jason; Laird, Glen

    2013-09-30

    This paper concerns using modified weighted Schoenfeld residuals to test the proportionality of subdistribution hazards for the Fine-Gray model, similar to the tests proposed by Grambsch and Therneau for independently censored data. We develop a score test for the time-varying coefficients based on the modified Schoenfeld residuals derived assuming a certain form of non-proportionality. The methods perform well in simulations and a real data analysis of breast cancer data, where the treatment effect exhibits non-proportional hazards.

  16. 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

  17. 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.

  18. Box-Cox transformation of firm size data in statistical analysis

    NASA Astrophysics Data System (ADS)

    Chen, Ting Ting; Takaishi, Tetsuya

    2014-03-01

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

  19. 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

  20. 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.

  1. Selective cyclooxygenase-2 (COX-2) inhibitors used for preventing or regressing cancer.

    PubMed

    de Souza Pereira, Ricardo

    2009-06-01

    The current use of antineoplastic drugs in human therapy causes a substancial number of toxic or side effects which consequently lead to a reduction of the amount of drug to be administered, and in some cases to discontinuation of the therapy. A reduction of the amount of drug to be administered or discontinuation of the therapy causes an increase in primary tumour growth and/or the occurrence of tumour metastases. For this reason, the development of new anti-cancer drugs with lower side effects is necessary. This review gives a general idea about the origins of cancer and the importance of cyclooxygenase-2 (COX-2) in oncogenesis. Evidence from clinical and preclinical studies indicates that COX-2-derived prostaglandins participate in carcinogenesis, inflammation, immune response suppression, apoptosis inhibition, angiogenesis, and tumour cell invasion and metastasis. The recent anti-tumour drugs are based on tests of known selective COX-2 inhibitors and on the drawing and synthesis of new potent derivatives. Maybe, this can be the way to obtain new anti-tumour drugs with very low collateral effects. Selective COX-2 inhibitors are being mixtured with new anti-cancer drugs in order to obtain better results in the regression of cancers. Some natural products are selective COX-2 inhibitors and have anti-inflammatory and anti-cancer properties. The relevant patents are discussed.

  2. Ca2+ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts.

    PubMed

    Ogata, Sachie; Kubota, Yasutaka; Satoh, Shinji; Ito, Shinich; Takeuchi, Hiroshi; Ashizuka, Megumi; Shirasuna, Kanemitsu

    2006-12-29

    Fibroblasts isolated from jaw cysts expressed calcium-sensing receptor (CasR). In the fibroblasts elevated extracellular Ca(2+) ([Ca(2+)](o)) increased fluo-3 fluorescence intensity, and the production of inositol(1,4,5)trisphosphate and active protein kinase C. Phospholipase C inhibitor U-73122 attenuated the Ca(2+)-induced increase in fluo-3 fluorescence intensity. Elevated [Ca(2+)](o) enhanced the expression of cyclooxygenase-2 (COX-2) mRNA and protein, and the secretion of prostaglandin E(2) in the fibroblasts. CasR activator neomycin also increased the expression of COX-2 mRNA, and U-73122 attenuated the Ca(2+)-induced expression of COX-2 mRNA. Elevated [Ca(2+)](o)-induced phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK), and U-73122 inhibited the Ca(2+)-induced phosphorylation. The inhibitors for each kinase, PD98059, SB203580, and SP600125, attenuated the Ca(2+)-induced expression of COX-2 mRNA. These results suggest that in jaw cyst fibroblasts elevated extracellular Ca(2+) may enhance COX-2 expression via the activation of ERK1/2, p38 MAPK, and JNK through CasR.

  3. 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

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

    PubMed Central

    Sones, Jenny L.; Cha, Jeeyeon; 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

  5. The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition

    PubMed Central

    Palermo, Giulia; Favia, Angelo D.; Convertino, Marino

    2015-01-01

    Abstract 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

  6. 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

  7. 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

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

    PubMed

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

    2013-12-01

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

  9. Proportional proximity sensing for telerobots using Coherent Laser Radar

    NASA Technical Reports Server (NTRS)

    Vazquez, Sixto L.; Goode, Plesent W.; Slotwinski, Anthony R.

    1992-01-01

    The ability of a telerobotic manipulator to operate in confined spaces while avoiding unwanted collisions is enhanced by the accurate sensing of its proximate environment. To achieve the fidelity required for precise manipulator control, a proportional proximity sensor system with a sufficiently large measurement envelope is required. Current proximity sensors provide a binary indication of the presence of obstacles within a small envelope with coarse or no proportional measurement of their location. A proportional proximity sensor system configured as a Frequency Modulated Continuous Wave (FMCW) Coherent Laser Radar (CLR) using a semiconductor laser as the energy source is described and analyzed. The source and reflected energies mix coherently to generate a radio frequency (RF) signal whose frequency is proportional to the range. The system is tested for accuracy, range, depth of range, speed, and sensitivity and the results are presented. Techniques to derive orientation information and an application to telerobotic control are also described.

  10. Proportionality: a valid alternative to correlation for relative data.

    PubMed

    Lovell, David; Pawlowsky-Glahn, Vera; Egozcue, Juan José; Marguerat, Samuel; Bähler, Jürg

    2015-03-01

    In the life sciences, many measurement methods yield only the relative abundances of different components in a sample. With such relative-or compositional-data, differential expression needs careful interpretation, and correlation-a statistical workhorse for analyzing pairwise relationships-is an inappropriate measure of association. Using yeast gene expression data we show how correlation can be misleading and present proportionality as a valid alternative for relative data. We show how the strength of proportionality between two variables can be meaningfully and interpretably described by a new statistic ϕ which can be used instead of correlation as the basis of familiar analyses and visualisation methods, including co-expression networks and clustered heatmaps. While the main aim of this study is to present proportionality as a means to analyse relative data, it also raises intriguing questions about the molecular mechanisms underlying the proportional regulation of a range of yeast genes.

  11. DC motor proportional control system for orthotic devices

    NASA Technical Reports Server (NTRS)

    Blaise, H. T.; Allen, J. R.

    1972-01-01

    Multi-channel proportional control system for operation of dc motors for use with externally-powered orthotic arm braces is described. Components of circuitry and principles of operation are described. Schematic diagram of control circuit is provided.

  12. Description of an ionization calorimeter complemented with proportional counters

    NASA Technical Reports Server (NTRS)

    Babayan, K. P.; Boyadzhyan, N. G.; Vasiltsov, V. V.; Grigorov, N. L.; Sobinyakov, V. A.; Shestoperov, V. Y.

    1975-01-01

    An ionization calorimeter is described with a system of proportional counters which are used to determine the charge of the particles incident to the calorimeter and to estimate the number of the secondary charged particles.

  13. Improvements in estimating proportions of objects from multispectral data

    NASA Technical Reports Server (NTRS)

    Horwitz, H. M.; Hyde, P. D.; Richardson, W.

    1974-01-01

    Methods for estimating proportions of objects and materials imaged within the instantaneous field of view of a multispectral sensor were developed further. Improvements in the basic proportion estimation algorithm were devised as well as improved alien object detection procedures. Also, a simplified signature set analysis scheme was introduced for determining the adequacy of signature set geometry for satisfactory proportion estimation. Averaging procedures used in conjunction with the mixtures algorithm were examined theoretically and applied to artificially generated multispectral data. A computationally simpler estimator was considered and found unsatisfactory. Experiments conducted to find a suitable procedure for setting the alien object threshold yielded little definitive result. Mixtures procedures were used on a limited amount of ERTS data to estimate wheat proportion in selected areas. Results were unsatisfactory, partly because of the ill-conditioned nature of the pure signature set.

  14. Proportional reasoning in the learning of chemistry: levels of complexity

    NASA Astrophysics Data System (ADS)

    Ramful, Ajay; Narod, Fawzia Bibi

    2014-03-01

    This interdisciplinary study sketches the ways in which proportional reasoning is involved in the solution of chemistry problems, more specifically, problems involving quantities in chemical reactions (commonly referred to as stoichiometry problems). By building on the expertise of both mathematics and chemistry education research, the present paper shows how the theoretical constructs in proportional reasoning in mathematics education offer rich explanatory accounts of the complexities involved in solving stoichiometry problems. Using Vergnaud's concept of measure spaces, the theoretical analysis shows that proportionality situations are relatively more intricate, involving various layers of complexity in chemistry as compared to those in the mathematics curriculum. Knowledge of proportionality and chemistry are simultaneously required to provide solutions to chemical reactions. Our analysis of a range of stoichiometry situations led us to propose a problem analysis framework involving five levels of difficulty. Further, the specificity of proportionality in stoichiometry is that it can only be established when quantities are interpreted in the unit "mole," a unit which does not have any physical embodiment in terms of a measure of quantity unlike mass and volume. Our analysis of student-teachers' solution to the stoichiometry problems, shows that they tend to incorrectly (probably intuitively) set proportional relationships when two quantities in a reaction are expressed in non-molar quantities such as mass. The data also bring to the fore the primarily formulaic approach that student-teachers use in setting inherent proportionality relationships. An important finding is the interpretation of a chemical equation as a mathematical equation, rather than a statement of proportionality.

  15. 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

  16. Delay Adjusted Incidence Infographic

    Cancer.gov

    This Infographic shows the National Cancer Institute SEER Incidence Trends. The graphs show the Average Annual Percent Change (AAPC) 2002-2011. For Men, Thyroid: 5.3*,Liver & IBD: 3.6*, Melanoma: 2.3*, Kidney: 2.0*, Myeloma: 1.9*, Pancreas: 1.2*, Leukemia: 0.9*, Oral Cavity: 0.5, Non-Hodgkin Lymphoma: 0.3*, Esophagus: -0.1, Brain & ONS: -0.2*, Bladder: -0.6*, All Sites: -1.1*, Stomach: -1.7*, Larynx: -1.9*, Prostate: -2.1*, Lung & Bronchus: -2.4*, and Colon & Rectum: -3/0*. For Women, Thyroid: 5.8*, Liver & IBD: 2.9*, Myeloma: 1.8*, Kidney: 1.6*, Melanoma: 1.5, Corpus & Uterus: 1.3*, Pancreas: 1.1*, Leukemia: 0.6*, Brain & ONS: 0, Non-Hodgkin Lymphoma: -0.1, All Sites: -0.1, Breast: -0.3, Stomach: -0.7*, Oral Cavity: -0.7*, Bladder: -0.9*, Ovary: -0.9*, Lung & Bronchus: -1.0*, Cervix: -2.4*, and Colon & Rectum: -2.7*. * AAPC is significantly different from zero (p<.05). Rates were adjusted for reporting delay in the registry. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  17. 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 Central

    Zhang, Yi; Hoda, Md Nasrul; Zheng, Xuan; Li, Weiguo; Luo, Pengcheng; Maddipati, Krishna Rao; Seki, Tsugio; Ergul, Adviye

    2014-01-01

    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

  18. The respiratory chain supercomplex organization is independent of COX7a2l isoforms.

    PubMed

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-12-01

    The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research.

  19. Cox's chair: 'a moral and a medical mean in the treatment of maniacs'.

    PubMed

    Wade, Nicholas J; Norrsell, U; Presly, A

    2005-03-01

    Two hundred years ago Joseph Cox published his book on the treatment of insanity. His novel technique was rotating the body in a specially designed chair. Initially modest and later extravagant claims were made for the therapeutic benefit of 'Cox's chair'. It was widely adopted in Europe in the first decades of the nineteenth century, but lost favour thereafter. Its benefits have proved to be scientific rather than medical because it was adopted by students of the senses to investigate vertigo; a century later it re-emerged as the Bárány chair for the clinical assessment of vestibular function. The legacy of Cox's chair, and its related treatment of swinging, are to be found in funfairs throughout the world.

  20. 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

  1. 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

  2. ["Golden proportion" and its application to calculate dentition].

    PubMed

    Vadachkoriia, N R; Gumberidze, N Sh; Mandzhavidze, N A

    2007-01-01

    Within an evolutionary process, the nature has created the standard of aesthetics - a "gold proportion" on the basis of which, the parts of human body, to be more exact, teeth and denture correspond to each other and to own parts by the size, which is the ideal precondition for ideal appearance. The charming smile serves as the proof, that teeth in denture are located by a principle of "gold proportion". A "gold proportion" is the corner stone of beauty and it can be applied with success in stomatology. Proportion is the certain ratio between parts, and proportional means a proper correlation of parts among themselves. It is reputed, that knowledge about "gold proportion" Pythagor has got from products of the Egyptian and Babylon scientists. And this is true, proportions of cult constructions, bas-relieves, pyramids in Giza, home appliances and ornaments from Tutanhamon tomb testify, that under their creation the Egyptian masters were guided by a principle of "gold proportion". The facade of ancient Greek temple Parthenon is built by a principle of "gold proportion". During archeological digs of this temple the compasses which sculptors and architects of an ancient world used has been found. The "gold proportion" is mentioned in the work which has reached us "Beginning" the author is the scientist of antique epoch Euclid. In 1509, in Venice the book of Luka Pacholi the "Divine proportion" has been published, its illustration is attributed to Leonardo de Vinci. This work has been recognized as a "Hymn of a gold proportion". In 1885 the German researcher professor Zeising published his work - "Aesthetic researches". When Zeising has received numerical values of piece length, he saw that they coincided with figures of some numerical sequence, which was offered by the great Italian mathematician of Middle Ages Fibonacci (or Leonardo Pisano). In his composition the "Abacus Book" Leonardo Fibonacci showed aforesaid sequence of numbers, by means of which he has explained

  3. ["Golden proportion" and its application to calculate dentition].

    PubMed

    Vadachkoriia, N R; Gumberidze, N Sh; Mandzhavidze, N A

    2007-01-01

    Within an evolutionary process, the nature has created the standard of aesthetics - a "gold proportion" on the basis of which, the parts of human body, to be more exact, teeth and denture correspond to each other and to own parts by the size, which is the ideal precondition for ideal appearance. The charming smile serves as the proof, that teeth in denture are located by a principle of "gold proportion". A "gold proportion" is the corner stone of beauty and it can be applied with success in stomatology. Proportion is the certain ratio between parts, and proportional means a proper correlation of parts among themselves. It is reputed, that knowledge about "gold proportion" Pythagor has got from products of the Egyptian and Babylon scientists. And this is true, proportions of cult constructions, bas-relieves, pyramids in Giza, home appliances and ornaments from Tutanhamon tomb testify, that under their creation the Egyptian masters were guided by a principle of "gold proportion". The facade of ancient Greek temple Parthenon is built by a principle of "gold proportion". During archeological digs of this temple the compasses which sculptors and architects of an ancient world used has been found. The "gold proportion" is mentioned in the work which has reached us "Beginning" the author is the scientist of antique epoch Euclid. In 1509, in Venice the book of Luka Pacholi the "Divine proportion" has been published, its illustration is attributed to Leonardo de Vinci. This work has been recognized as a "Hymn of a gold proportion". In 1885 the German researcher professor Zeising published his work - "Aesthetic researches". When Zeising has received numerical values of piece length, he saw that they coincided with figures of some numerical sequence, which was offered by the great Italian mathematician of Middle Ages Fibonacci (or Leonardo Pisano). In his composition the "Abacus Book" Leonardo Fibonacci showed aforesaid sequence of numbers, by means of which he has explained

  4. The first characterization of free radicals formed from cellular COX-catalyzed peroxidation.

    PubMed

    Gu, Yan; Xu, Yi; Law, Benedict; Qian, Steven Y

    2013-04-01

    Through free radical-mediated peroxidation, cyclooxygenase (COX) can metabolize dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) to form well-known bioactive metabolites, namely, the 1-series of prostaglandins (PGs1) and the 2-series of prostaglandins (PGs2), respectively. Unlike PGs2, which are generally viewed as proinflammatory and procarcinogenic PGs, PGs1 may possess anti-inflammatory and anti-cancer activity. Previous studies using ovine COX along with spin trapping and the LC/ESR/MS technique have shown that certain exclusive free radicals are generated from different free radical reactions in DGLA and AA peroxidation. However, it has been unclear whether the differences were associated with the contrasting bioactivity of DGLA vs AA. The aim of this study was to refine the LC/MS and spin trapping technique to make it possible for the association between free radicals and cancer cell growth to be directly tested. Using a colon cancer cell line, HCA-7 colony 29, and LC/MS along with a solid-phase extraction, we were able to characterize the reduced forms of radical adducts (hydroxylamines) as the free radicals generated from cellular COX-catalyzed peroxidation. For the first time, free radicals formed in the COX-catalyzed peroxidation of AA vs DGLA and their association with cancer cell growth were assessed (cell proliferation via MTS and cell cycle distribution via propidium iodide staining) in the same experimental setting. The exclusive free radicals formed from the COX-catalyzed peroxidation of AA and DGLA were shown to be correlated with the cell growth response. Our results indicate that free radicals generated from the distinct radical reactions in COX-catalyzed peroxidation may represent the novel metabolites of AA and DGLA that correspond to their contrasting bioactivity.

  5. 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

  6. 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.

  7. Signal Transduction Pathway Analysis in Desmoid-type Fibromatosis: TGFβ, COX2 and Sex Steroid Receptors

    PubMed Central

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

    2014-01-01

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

  8. 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

  9. COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells.

    PubMed

    Fujita, Mitsugu; Kohanbash, Gary; Fellows-Mayle, Wendy; Hamilton, Ronald L; Komohara, Yoshihiro; Decker, Stacy A; Ohlfest, John R; Okada, Hideho

    2011-04-01

    Epidemiologic studies have highlighted associations between the regular use of nonsteroidal anti-inflammatory drugs (NSAID) and reduced glioma risks in humans. Most NSAIDs function as COX-2 inhibitors that prevent production of prostaglandin E₂ (PGE₂). Because PGE₂ induces expansion of myeloid-derived suppressor cells (MDSC), we hypothesized that COX-2 blockade would suppress gliomagenesis by inhibiting MDSC development and accumulation in the tumor microenvironment (TME). In mouse models of glioma, treatment with the COX-2 inhibitors acetylsalicylic acid (ASA) or celecoxib inhibited systemic PGE₂ production and delayed glioma development. ASA treatment also reduced the MDSC-attracting chemokine CCL2 (C-C motif ligand 2) in the TME along with numbers of CD11b(+)Ly6G(hi)Ly6C(lo) granulocytic MDSCs in both the bone marrow and the TME. In support of this evidence that COX-2 blockade blocked systemic development of MDSCs and their CCL2-mediated accumulation in the TME, there were defects in these processes in glioma-bearing Cox2-deficient and Ccl2-deficient mice. Conversely, these mice or ASA-treated wild-type mice displayed enhanced expression of CXCL10 (C-X-C motif chemokine 10) and infiltration of cytotoxic T lymphocytes (CTL) in the TME, consistent with a relief of MDSC-mediated immunosuppression. Antibody-mediated depletion of MDSCs delayed glioma growth in association with an increase in CXCL10 and CTLs in the TME, underscoring a critical role for MDSCs in glioma development. Finally, Cxcl10-deficient mice exhibited reduced CTL infiltration of tumors, establishing that CXCL10 limited this pathway of immunosuppression. Taken together, our findings show that the COX-2 pathway promotes gliomagenesis by directly supporting systemic development of MDSCs and their accumulation in the TME, where they limit CTL infiltration. PMID:21324923

  10. 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

  11. Proportional counter for X-ray analysis of lunar and planetary surfaces. [a position sensitive scintillating imaging proportional counter

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A position sensitive proportional scintillation detector was developed and evaluated for use in applications involving X-ray imaging as well as spectroscopy. Topics covered include limitations of the proportional scintillation counter for use in space; purification of the xenon gas in the detector, and the operation of the detector system. Results show that the light signal in a proportional scintillation detector remains well localized. With modest electric fields in xenon, the primary electrons from a photoelectric absorption of an X-ray can be brought a distance of a few millimeters to a higher field region without spreading more than a millimeter or so. Therefore, it is possible to make a proportional scintillation detector with good position sensitivity that could be used to calibrate out the difference in light collection over its sensitive volume.

  12. A comparison of the newer COX-2 drugs and older nonnarcotic oral analgesics.

    PubMed

    Sunshine, A

    2000-09-01

    The newer COX-2 drugs are safer analgesics than the older NSAIDs. At the usual dose used in osteoarthritis, they have less analgesic effect than the older NSAIDs. The non-narcotic analgesics such as acetaminophen, salicylate, NSAIDs, and the newer COX-2 drugs seem to have distinctly different mechanisms of action. In limited clinical trials, some of these drugs in combination give additive analgesia. Consideration should be given to using these drugs in combination, after suitable clinical trials, to enhance the efficacy of this category of analgesics.

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

    PubMed Central

    Kong, Shengchun; Nan, Bin

    2013-01-01

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

  14. Global structure in spatiotemporal chaos of the Matthews-Cox equations.

    PubMed

    Sakaguchi, Hidetsugu; Tanaka, Dan

    2007-08-01

    We find that an amplitude death state and a spatiotemporally chaotic state coexist spontaneously in the Matthews-Cox equations and this coexistence is robust. Although the entire system is far from equilibrium, the domain wall between the two states is stabilized by a negative-feedback effect due to a conservation law. This is analogous to the phase separation in conserved systems that exhibit spinodal decompositions. We observe similar phenomena also in the Nikolaevskii equation, from which the Matthews-Cox equations were derived. A Galilean invariance of the former equation corresponds to the conservation law of the latter equations.

  15. 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.

  16. COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis.

    PubMed

    Majumder, Mousumi; Xin, Xiping; Liu, Ling; Tutunea-Fatan, Elena; Rodriguez-Torres, Mauricio; Vincent, Krista; Postovit, Lynne-Marie; Hess, David; Lala, Peeyush K

    2016-09-01

    Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids. These changes were reversed with COX-2-inhibitor or EP4-antagonist (EP4A), indicating dependence on COX-2/EP4 activities. COX-2 over-expression or EP4-agonist treatments of COX-2-low cells caused up-regulation of NOTCH/WNT genes, blocked with PI3K/AKT inhibitors. NOTCH/WNT inhibitors also blocked COX-2/EP4 induced SLC induction. Microarray analysis showed up-regulation of numerous SLC-regulatory and EMT-associated genes. MCF-7-COX-2 cells showed increased mammary tumorigenicity and spontaneous multiorgan metastases in NOD/SCID/IL-2Rγ-null mice for successive generations with limiting cell inocula. These tumors showed up-regulation of VEGF-A/C/D, Vimentin and phospho-AKT, down-regulation of E-Cadherin and enrichment of SLC marker positive and spheroid forming cells. MCF-7-COX-2 cells also showed increased lung colonization in NOD/SCID/GUSB-null mice, an effect reversed with EP4-knockdown or EP4A treatment of the MCF-7-COX-2 cells. COX-2/EP4/ALDH1A mRNA expression in human breast cancer tissues were highly correlated with one other, more marked in progressive stage of disease. In situ immunostaining of human breast tumor tissues revealed co-localization of SLC markers with COX-2, supporting COX-2 inducing SLCs. High COX-2/EP4 mRNA expression was linked with reduced survival. Thus, EP4 represents a novel SLC

  17. 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

  18. Sp1 and COX2 expression is positively correlated with a poor prognosis in pancreatic ductal adenocarcinoma

    PubMed Central

    Han, Ting; Zhuo, Meng; Zhou, Yangyang; Wang, Lei; Wang, Yi; Jiao, Feng; Wang, Liwei

    2016-01-01

    Previous studies showed that celecoxib, a cyclooxygenase-2 (COX2) inhibitor, can inhibit angiogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC) via the suppression of specificity protein 1 (Sp1). In this study, we investigated the prognostic value of Sp1 and COX2 in 88 PDAC patients. Our study showed there was a positive correlation between Sp1 and COX2 expression (P=0.001) by using the Spearman's rank test. Pearson Chi-square test revealed that Sp1 and COX2 expression were positively associated with lymph node metastasis (P<0.05, both). In addition, the Kaplan–Meier analysis showed that patients with Sp1- or COX2-positive expression exhibited poorer overall survival (OS) than those with Sp1- or COX2-negative expression (P<0.05, all). Most importantly, Sp1- and COX2-negative patients had the best OS (P=0.01). In multivariate analysis, Sp1 expression (P=0.03), COX2 expression (P=0.04), and nuclear grade (P=0.009) were found to be independent predictors for OS. Moreover, we confirmed that Sp1 could upregulate the expression of COX2 in PDAC cell lines by western blot analysis, and both are of important prognostic value in PDAC. PMID:27057636

  19. Wing spar stress charts and wing truss proportions

    NASA Technical Reports Server (NTRS)

    Warner, Edward P

    1926-01-01

    In order to simplify the calculation of beams continuous over three supports, a series of charts have been calculated giving the bending moments at all the critical points and the reactions at all supports for such members. Using these charts as a basis, calculations of equivalent bending moments, representing the total stresses acting in two bay-wing trusses of proportions varying over a wide range, have been determined, both with and without allowance for column effect. This leads finally to the determination of the best proportions for any particular truss or the best strut locations in any particular airplane. The ideal proportions are found to vary with the thickness of the wing section used, the aspect ratio, and the ratio of gap to chord.

  20. Student reasoning about ratio and proportion in introductory physics

    NASA Astrophysics Data System (ADS)

    Boudreaux, Andrew

    2012-02-01

    To many students, introductory physics must seem a fast-moving parade of abstract and somewhat mysterious quantities. Most such quantities are rooted in proportional reasoning. Using ratio, physicists construct the force experienced by a unit charge, and attach the name electric field, or characterize a motion with the velocity change that occurs in a unit time. While physicists reason about these ratios without conscious effort, students tend to resort to memorized algorithms, and at times struggle to match the appropriate algorithm to the situation encountered. Although the term ``proportional reasoning'' is prevalent, skill in reasoning with these ratio quantities is neither acquired nor applied as a single cognitive entity. Expert ability seems to be characterized by the intentional use of a variety of components, or elements of proportional reasoning, by a fluency in shifting from one component to another, and by a skill in selecting from among these components. Based on this perspective, it is natural to expect students to develop proportional reasoning ability in fits and starts as various facets are acquired and integrated into existing understandings. In an ongoing collaboration between Western Washington University, New Mexico State University, and Rutgers, we are attempting to map the rich cognitive terrain of proportional reasoning, and to use our findings to guide the design of instruction that develops fluency. This talk will present a provisional set of proportional reasoning components, along with research tasks that have been developed to measure student ability along these components. Student responses will be presented as evidence of specific modes of thinking. The talk will conclude with a brief outline of our approach to improving student understanding.

  1. Proportion of hospital readmissions deemed avoidable: a systematic review

    PubMed Central

    van Walraven, Carl; Bennett, Carol; Jennings, Alison; Austin, Peter C.; Forster, Alan J.

    2011-01-01

    Background Readmissions to hospital are increasingly being used as an indicator of quality of care. However, this approach is valid only when we know what proportion of readmissions are avoidable. We conducted a systematic review of studies that measured the proportion of readmissions deemed avoidable. We examined how such readmissions were measured and estimated their prevalence. Methods We searched the MEDLINE and EMBASE databases to identify all studies published from 1966 to July 2010 that reviewed hospital readmissions and that specified how many were classified as avoidable. Results Our search strategy identified 34 studies. Three of the studies used combinations of administrative diagnostic codes to determine whether readmissions were avoidable. Criteria used in the remaining studies were subjective. Most of the studies were conducted at single teaching hospitals, did not consider information from the community or treating physicians, and used only one reviewer to decide whether readmissions were avoidable. The median proportion of readmissions deemed avoidable was 27.1% but varied from 5% to 79%. Three study-level factors (teaching status of hospital, whether all diagnoses or only some were considered, and length of follow-up) were significantly associated with the proportion of admissions deemed to be avoidable and explained some, but not all, of the heterogeneity between the studies. Interpretation All but three of the studies used subjective criteria to determine whether readmissions were avoidable. Study methods had notable deficits and varied extensively, as did the proportion of readmissions deemed avoidable. The true proportion of hospital readmissions that are potentially avoidable remains unclear. PMID:21444623

  2. Mood Adjustment via Mass Communication.

    ERIC Educational Resources Information Center

    Knobloch, Silvia

    2003-01-01

    Proposes and experimentally tests mood adjustment approach, complementing mood management theory. Discusses how results regarding self-exposure across time show that patterns of popular music listening among a group of undergraduate students differ with initial mood and anticipation, lending support to mood adjustment hypotheses. Describes how…

  3. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  4. Development of proportional counters using photosensitive gases and liquids

    SciTech Connect

    Anderson, D.F.

    1985-02-01

    An introduction to the history and to the principle of operation of wire chambers using photosensitive gases and liquids is presented. Their use as light sensors coupled to Gas Scintillation Proportional Counters and BaF/sub 2/, as well as their use in Cherenkov Ring Imaging, is discussed in some detail. The development of wire chambers using photosensitive gases, and later photosensitive liquids, has gone in three major directions. The first is as a replacement for photomultiplier tubes for gas scintillation proportional counters. The second is for Ring Imaging Cherenkov detectors. The third is as the photon sensor for the scintillator BaF/sub 2/. We discuss all three fields here.

  5. Parental Divorce and Children's Adjustment.

    PubMed

    Lansford, Jennifer E

    2009-03-01

    This article reviews the research literature on links between parental divorce and children's short-term and long-term adjustment. First, I consider evidence regarding how divorce relates to children's externalizing behaviors, internalizing problems, academic achievement, and social relationships. Second, I examine timing of the divorce, demographic characteristics, children's adjustment prior to the divorce, and stigmatization as moderators of the links between divorce and children's adjustment. Third, I examine income, interparental conflict, parenting, and parents well-being as mediators of relations between divorce and children's adjustment. Fourth, I note the caveats and limitations of the research literature. Finally, I consider notable policies related to grounds for divorce, child support, and child custody in light of how they might affect children s adjustment to their parents divorce.

  6. 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.

  7. 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...

  8. 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

  9. 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

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

    PubMed Central

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

    2004-01-01

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

  11. 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.

  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. Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals.

    PubMed

    Murakami, Akira; Ohigashi, Hajime

    2007-12-01

    Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.

  14. 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.

  15. COX-2-Derived PGE2 Promotes Injury-induced Vascular Neointimal Hyperplasia through the EP3 Receptor

    PubMed Central

    Zhang, Jian; Zou, Fangfang; Tang, Juan; Zhang, Qianqian; Gong, Yanjun; Wang, Qingsong; Shen, Yujun; Xiong, Lixia; Breyer, Richard; Lararus, Michael; Funk, Colin D.; Yu, Ying

    2014-01-01

    Rationale Vascular smooth muscle cell (VSMC) migration and proliferation are the hallmarks of restenosis pathogenesis after angioplasty. Cyclooxygenase (COX)-derived prostaglandin (PG)E2 is implicated in the vascular remodeling response to injury. However, its precise molecular role remains unknown. Objective This study investigates the impact of COX-2-derived PGE2 on neointima formation after injury. Methods and Results Vascular remodeling was induced by wire-injury in femoral arteries of mice. Both neointima formation and the restenosis ratio were diminished in COX-2 KO mice as compared to controls, whereas these parameters were enhanced in COX-1>COX-2 mice where COX-1 is governed by COX-2 regulatory elements. PG profile analysis revealed that the reduced PGE2 by COX-2 deficiency, but not PGI2, could be rescued by COX-1 replacement, indicating COX-2-derived PGE2 enhanced neointima formation. Through multiple approaches, the EP3 receptor was identified to mediate the VSMC migration response to various stimuli. Disruption of EP3 impaired VSMC polarity for directional migration by depressing small GTPase activity and retarded vascular neointimal hyperplasia while overexpression of EP3α and EP3β aggravated neointima formation. Inhibition or deletion of EP3α/β, a Gαs protein-coupled receptor, activated thecAMP/PKA pathway and depressed activation of RhoA in VSMCs. PGE2 could stimulate PI3K/Akt/GSK3β signaling in VSMCs through Gβγ subunits upon EP3α/β activation. Abolition of EP3 suppressed PI3K signaling and reduced GTPase activity in VSMCs, and altered cell polarity and directional migration. Conclusions COX-2-derived PGE2 facilitated the neointimal hyperplasia response to injury through EP3α/β-mediated cAMP/PKA and PI3K pathways, indicating EP3 inhibition maybe a promising therapeutic strategy for percutaneous transluminal coronary angioplasty. PMID:23595951

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

    SciTech Connect

    Zhu, Yingting; 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.

  17. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats.

    PubMed

    Khayyal, M T; El-Ghazaly, Mona A; El-Hazek, R M; Nada, A S

    2009-10-01

    The potential value of selective and non-selective COX-2 inhibitors in preventing some of the biochemical changes induced by ionizing radiation was studied in rats exposed to carrageenan-induced paw edema and 6-day-old air pouch models. The animals were exposed to different exposure levels of gamma-radiation, namely either to single doses of 2 and 7.5 Gy or a fractionated dose level of 7.5 Gy delivered as 0.5 Gy twice weekly for 7.5 weeks. The inflammatory response produced by carrageenan in irradiated rats was markedly higher than that induced in non-irradiated animals, and depended on the extent of irradiation. Celecoxib, a selective COX-2 inhibitor, in doses of 3, 5, 10, and 15 mg/kg was effective in reducing paw edema in irradiated and non-irradiated rats in a dose-dependent manner as well as diclofenac (3 mg/kg), a non-selective COX inhibitor. Irradiation of animals before the induction of the air pouch by an acute dose of 2 Gy led to a significant increase in leukocytic count, as well as in the level of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), LTB(4), PGE(2) (as an index of COX-2 activity), TXB(2) (as an index of COX-1 activity), and the plasma level of MDA. This increase in level of these parameters was more marked than that observed in the non-irradiated animals subjected to the inflammagen. The blood GSH level was not affected by the dose of irradiation used, whereas superoxide dismutase (SOD) activity was suppressed. In many respects, celecoxib (5 mg/kg) was as potent as diclofenac in decreasing the elevated levels of IL-6, IL-1beta, TNF-alpha, LTB(4), PGE(2), but lacked any significant effect on TXB(2) level. Since it is mostly selective for COX-2 with a rare effect on COX-1 enzyme, both drugs at the selected dose levels showed no effect on level of MDA, GSH, and SOD activity.

  18. Adjustment versus no adjustment when using adjustable sutures in strabismus surgery

    PubMed Central

    Liebermann, Laura; Hatt, Sarah R.; Leske, David A.; Holmes, Jonathan M.

    2013-01-01

    Purpose To compare long-term postoperative outcomes when performing an adjustment to achieve a desired immediate postoperative alignment versus simply tying off at the desired immediate postoperative alignment when using adjustable sutures for strabismus surgery. Methods We retrospectively identified 89 consecutive patients who underwent a reoperation for horizontal strabismus using adjustable sutures and also had a 6-week and 1-year outcome examination. In each case, the intent of the surgeon was to tie off and only to adjust if the patient was not within the intended immediate postoperative range. Postoperative success was predefined based on angle of misalignment and diplopia at distance and near. Results Of the 89 patients, 53 (60%) were adjusted and 36 (40%) were tied off. Success rates were similar between patients who were simply tied off immediately after surgery and those who were adjusted. At 6 weeks, the success rate was 64% for the nonadjusted group versus 81% for the adjusted group (P = 0.09; difference of 17%; 95% CI, −2% to 36%). At 1 year, the success rate was 67% for the nonadjusted group versus 77% for the adjusted group (P = 0.3; difference of 11%; 95% CI, −8% to 30%). Conclusions Performing an adjustment to obtain a desired immediate postoperative alignment did not yield inferior long-term outcomes to those obtained by tying off to obtain that initial alignment. If patients were who were outside the desired immediate postoperative range had not been not adjusted, it is possible that their long-term outcomes would have been worse, therefore, overall, an adjustable approach may be superior to a nonadjustable approach. PMID:23415035

  19. Adjustable electronic load-alarm relay

    DOEpatents

    Mason, Charles H.; Sitton, Roy S.

    1976-01-01

    This invention is an improved electronic alarm relay for monitoring the current drawn by an AC motor or other electrical load. The circuit is designed to measure the load with high accuracy and to have excellent alarm repeatability. Chattering and arcing of the relay contacts are minimal. The operator can adjust the set point easily and can re-set both the high and the low alarm points by means of one simple adjustment. The relay includes means for generating a signal voltage proportional to the motor current. In a preferred form of the invention a first operational amplifier is provided to generate a first constant reference voltage which is higher than a preselected value of the signal voltage. A second operational amplifier is provided to generate a second constant reference voltage which is lower than the aforementioned preselected value of the signal voltage. A circuit comprising a first resistor serially connected to a second resistor is connected across the outputs of the first and second amplifiers, and the junction of the two resistors is connected to the inverting terminal of the second amplifier. Means are provided to compare the aforementioned signal voltage with both the first and second reference voltages and to actuate an alarm if the signal voltage is higher than the first reference voltage or lower than the second reference voltage.

  20. Improving Students' Proportional Thinking Using Schema-Based Instruction

    ERIC Educational Resources Information Center

    Jitendra, Asha K.; Star, Jon R.; Rodriguez, Michael; Lindell, Mary; Someki, Fumio

    2011-01-01

    This study investigated the effectiveness of an instructional program (schema-based instruction, SBI) designed to teach 7th graders how to comprehend and solve proportion problems involving ratios/rates, scale drawings, and percents. The SBI program emphasized the underlying mathematical structure of problems via schematic diagrams, focused on a…

  1. High condylectomy versus proportional condylectomy: is secondary orthognathic surgery necessary?

    PubMed

    Fariña, R; Olate, S; Raposo, A; Araya, I; Alister, J P; Uribe, F

    2016-01-01

    The objective of this study was to assess the need for secondary orthognathic surgery in patients undergoing two different condylectomy protocols for active unilateral condylar hyperplasia (UCH). A retrospective cohort study evaluated UCH patients treated by condylectomy. Two groups were established: group 1 comprised those who had undergone a high condylectomy (5 mm removed) and group 2 comprised those who had undergone a proportional condylectomy (removing the difference observed between the measurements of the hyperplastic and the healthy side). Data analysis was done with the Levene test and t-test; a P-value of <0.05 indicated a statistically significant relationship. Forty-nine patients, with an average age of 19.83 years, were analyzed; 11 were included in group 1 and 38 in group 2. There was no statistical difference between the two groups with regard to age or sex (P=0.781). An average of 5.81 mm was removed in the high condylectomy group, while an average of 9.28 mm was removed in the proportional condylectomy group; this difference was statistically significant (P=0.042). Comparing the two groups, proportional condylectomy reduced the need for secondary orthognathic surgery (P<0.001). The proportional condylectomy can be used as the sole surgical treatment in cases of UCH, thus avoiding the need for secondary orthognathic surgery. PMID:26275962

  2. Making Sense of Fractions, Ratios, and Proportions. 2002 Yearbook.

    ERIC Educational Resources Information Center

    Litwiller, Bonnie, Ed.; Bright, George, Ed.

    This yearbook contains articles that give insight into students' thinking about factions, ratios, and proportions. Suggestions are offered on how to develop the concepts and skills associated with these topics. The book is divided into elementary, middle school, and professional development sections. Chapters include: (1) "The Development of…

  3. Prospective Elementary Teachers' Misunderstandings in Solving Ratio and Proportion Problems

    ERIC Educational Resources Information Center

    Monteiro, Cecilia

    2003-01-01

    This study explores difficulties that prospective elementary mathematics teachers have with the concepts of ratio and proportion, mainly when they are engaged in solving problems using algorithm procedures. These difficulties can be traced back to earlier experiences when they were students of junior and high school. The reflection on these…

  4. Development of proportional counters using photosensitive gases and liquids

    SciTech Connect

    Anderson, D.F.

    1984-10-01

    An introduction to the history and to the principle of operation of wire chambers using photosensitive gases and liquids is presented. Their use as light sensors coupled to Gas Scintillation Proportional Counters and BaF/sub 2/, as well as their use in Cherenkov Ring imaging, is discussed in some detail. 42 references, 21 figures.

  5. Proportional Reasoning Tasks as a Measure of Formal Reasoning Ability.

    ERIC Educational Resources Information Center

    Shemesh, Michal

    A nonequivalent control group design study, with a math unit on ratio and proportion as the treatment, was conducted to examine the validity of some written tasks as a measure of formal reasoning. Subjects in the study were 68 fifth grade students who enrolled in two classes in a small urban school. The experimental group learned a 12-lesson math…

  6. Augmented mixed beta regression models for periodontal proportion data

    PubMed Central

    Galvis, Diana M.; Bandyopadhyay, Dipankar; Lachos, Victor H.

    2014-01-01

    Continuous (clustered) proportion data often arise in various domains of medicine and public health where the response variable of interest is a proportion (or percentage) quantifying disease status for the cluster units, ranging between zero and one. However, because of the presence of relatively disease-free as well as heavily diseased subjects in any study, the proportion values can lie in the interval [0, 1]. While beta regression can be adapted to assess covariate effects in these situations, its versatility is often challenged because of the presence/excess of zeros and ones because the beta support lies in the interval (0, 1). To circumvent this, we augment the probabilities of zero and one with the beta density, controlling for the clustering effect. Our approach is Bayesian with the ability to borrow information across various stages of the complex model hierarchy and produces a computationally convenient framework amenable to available freeware. The marginal likelihood is tractable and can be used to develop Bayesian case-deletion influence diagnostics based on q-divergence measures. Both simulation studies and application to a real dataset from a clinical periodontology study quantify the gain in model fit and parameter estimation over other ad hoc alternatives and provide quantitative insight into assessing the true covariate effects on the proportion responses. PMID:24764045

  7. Collaboration Promotes Proportional Reasoning about Resource Distribution in Young Children

    ERIC Educational Resources Information Center

    Ng, Rowena; Heyman, Gail D.; Barner, David

    2011-01-01

    The authors investigated how children and adults evaluate the "niceness" of individuals who engage in resource distribution, with a focus on their sensitivity to the proportion of resources given. Across 3 experiments, subjects evaluated the niceness of a child who gave a quantity of pennies to another child. In Study 1 (N = 30), adults showed…

  8. Attentional Control and the Relatedness Proportion Effect in Semantic Priming

    ERIC Educational Resources Information Center

    Hutchison, Keith A.

    2007-01-01

    In 2 experiments, participants completed both an attentional control battery (OSPAN, antisaccade, and Stroop tasks) and a modified semantic priming task. The priming task measured relatedness proportion (RP) effects within subjects, with the color of the prime indicating the probability that the to-be-named target would be related. In Experiment…

  9. Modelling boron-lined proportional counter response to neutrons.

    PubMed

    Shahri, A; Ghal-Eh, N; Etaati, G R

    2013-09-01

    The detailed Monte Carlo simulation of a boron-lined proportional counter response to a neutron source has been presented. The MCNP4C and experimental data on different source-moderator geometries have been given for comparison. The influence of different irradiation geometries and boron-lining thicknesses on the detector response has been studied.

  10. System proportions fluid-flow in response to demand signals

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Control system provides proportioned fluid flow rates in response to demand signals. It compares a digital signal, representing a flow demand, with a reference signal to yield a control voltage to one or more solenoid valves connected to orifices of a predetermined size.

  11. 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…

  12. Proportional Reasoning in the Learning of Chemistry: Levels of Complexity

    ERIC Educational Resources Information Center

    Ramful, Ajay; Narod, Fawzia Bibi

    2014-01-01

    This interdisciplinary study sketches the ways in which proportional reasoning is involved in the solution of chemistry problems, more specifically, problems involving quantities in chemical reactions (commonly referred to as stoichiometry problems). By building on the expertise of both mathematics and chemistry education research, the present…

  13. Simulation of dynamics of hydraulic system with proportional control valve

    NASA Astrophysics Data System (ADS)

    Bureček, Adam; Hružík, Lumír; Vašina, Martin

    2016-03-01

    Dynamics of a hydraulic system is influenced by several parameters, in this case mainly by proportional control valve, oil bulk modulus, oil viscosity, mass load etc. This paper will be focused on experimental measurement and mathematical simulation of dynamics of a hydraulic system with proportional control valve, linear hydraulic cylinder and mass load. The measurement is performed on experimental equipment that enables realization of dynamic processes of the hydraulic system. Linear hydraulic cylinder with mass load is equipped with position sensor of piston. The movement control of piston rod is ensured by the proportional control valve. The equipment enables to test an influence of parameter settings of regulator of the proportional control valve on position and pressure system responses. The piston position is recorded by magnetostrictive sensor that is located in drilled piston rod side of the linear hydraulic cylinder. Pressures are measured by piezoresistive sensors on the piston side and the piston rod side of the hydraulic cylinder. The measurement is performed during movement of the piston rod with mass load to the required position. There is realized and verified a mathematical model using Matlab SimHydraulics software for this hydraulic system.

  14. A Refined Item Digraph Analysis of a Proportional Reasoning Test.

    ERIC Educational Resources Information Center

    Bart, William M.; Williams-Morris, Ruth

    1990-01-01

    Refined item digraph analysis (RIDA) is a way of studying diagnostic and prescriptive testing. It permits assessment of a test item's diagnostic value by examining the extent to which the item has properties of ideal items. RIDA is illustrated with the Orange Juice Test, which assesses the proportionality concept. (TJH)

  15. High condylectomy versus proportional condylectomy: is secondary orthognathic surgery necessary?

    PubMed

    Fariña, R; Olate, S; Raposo, A; Araya, I; Alister, J P; Uribe, F

    2016-01-01

    The objective of this study was to assess the need for secondary orthognathic surgery in patients undergoing two different condylectomy protocols for active unilateral condylar hyperplasia (UCH). A retrospective cohort study evaluated UCH patients treated by condylectomy. Two groups were established: group 1 comprised those who had undergone a high condylectomy (5 mm removed) and group 2 comprised those who had undergone a proportional condylectomy (removing the difference observed between the measurements of the hyperplastic and the healthy side). Data analysis was done with the Levene test and t-test; a P-value of <0.05 indicated a statistically significant relationship. Forty-nine patients, with an average age of 19.83 years, were analyzed; 11 were included in group 1 and 38 in group 2. There was no statistical difference between the two groups with regard to age or sex (P=0.781). An average of 5.81 mm was removed in the high condylectomy group, while an average of 9.28 mm was removed in the proportional condylectomy group; this difference was statistically significant (P=0.042). Comparing the two groups, proportional condylectomy reduced the need for secondary orthognathic surgery (P<0.001). The proportional condylectomy can be used as the sole surgical treatment in cases of UCH, thus avoiding the need for secondary orthognathic surgery.

  16. Are Explicit Apologies Proportional to the Offenses They Address?

    ERIC Educational Resources Information Center

    Heritage, John; Raymond, Chase Wesley

    2016-01-01

    We consider here Goffman's proposal of proportionality between virtual offenses and remedial actions, based on the examination of 102 cases of explicit apologies. To this end, we offer a typology of the primary apology formats within the dataset, together with a broad categorization of the types of virtual offenses to which these apologies are…

  17. A FORTRAN program for testing trend and homogeneity in proportions.

    PubMed

    Thakur, A K; Berry, K J; Mielke, P W

    1985-01-01

    A FORTRAN program is provided for testing linear trend and homogeneity in proportions. Trend is evaluated by the Cochran-Armitage method and homogeneity is tested by an overall X2 test as well by multiple pairwise comparisons by the Fisher-Irwin exact method. The program should be easy to implement on any size of computer with a FORTRAN compiler.

  18. Sci-Math: Applications in Proportional Problem Solving. Module One.

    ERIC Educational Resources Information Center

    Goodstein, Madeline P.

    Sci-Math is an interdisciplinary curriculum intended to help students develop the math skills needed for science, especially dimensional analysis, ratio, and the concept of proportion. Sci-Math is divided into two modules with each module having a student and teacher's guide. This module is a pre-algebra module dealing with the arithmetic and…

  19. Applying the Mean Proportional Principle to Graphical Solutions.

    ERIC Educational Resources Information Center

    Barton, Lyndon O.

    1991-01-01

    A graphical illustration is presented indicating how the mean proportional (geometric mean), once established for one set of conditions of a geometric identity, can be used to generate other sets of conditions for the same identity. Exemplified is the application of this principle in developing graphical solutions to engineering problems. (JJK)

  20. Map Scale, Proportion, and Google[TM] Earth

    ERIC Educational Resources Information Center

    Roberge, Martin C.; Cooper, Linda L.

    2010-01-01

    Aerial imagery has a great capacity to engage and maintain student interest while providing a contextual setting to strengthen their ability to reason proportionally. Free, on-demand, high-resolution, large-scale aerial photography provides both a bird's eye view of the world and a new perspective on one's own community. This article presents an…

  1. COX-2 rs20417 polymorphism is associated with stroke and white matter disease

    PubMed Central

    Oliveira-Filho, Jamary; Ornellas, Ana C.P.; Zhang, Cathy R.; Oliveira, Luciana M.B.; Araújo-Santos, Théo; Borges, Valeria M.; Ventura, Laís M.G.B.; Reis, Francisco J. F. B.; Aras, Roque; Fernandes, André M.; Rosand, Jonathan; Greenberg, Steven M.; Furie, Karen L.; Rost, Natalia S.

    2015-01-01

    Goals To investigate the effect of COX-2 polymorphism and its product, prostaglandin-E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Methods Cases were outpatients with ischemic stroke; controls were stroke-free subjects from two outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (ELISA) were performed to confirm T. cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain MRIs of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. Findings We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic, 486 non-cardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (p=5x10−6) and decreased PGE2 levels (p=4x10−5); similarly, Chagas was associated with stroke (p=4x10−3) and decreased PGE2 levels (p=7x10−3). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among non-cardioembolic (p=0.037), but not among cardioembolic stroke patients. Conclusions Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples. PMID:25957909

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

    PubMed

    Riehl, Terrence E; Foster, Lynne; Stenson, William F

    2012-02-01

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

  3. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    PubMed

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic

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

    PubMed Central

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

    2014-01-01

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

  5. Abnormal COX2 Protein Expression May Be Correlated with Poor Prognosis in Oral Cancer: A Meta-Analysis

    PubMed Central

    Wang, Zhi-Ming; Liu, Jie; Liu, Hong-Bo; Ye, Ming; Zhang, Yu-Fei; Yang, Dong-Sheng

    2014-01-01

    Background. The prognostic significance of COX2 for survival of patients with oral cancer remains controversial. Thus, the meta-analysis was performed in order to identify COX2 expression impact on prognosis of oral cancer. Method. Relevant literatures were searched using the following electronic databases without any language restrictions: Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and CBM. Version 12.0 STATA software (Stata Corporation, College Station, Texas, USA) was used for the current meta-analysis. Odds ratios (ORs) and hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between COX2 expression and prognosis of oral cancer. Results. Final analysis of 979 oral cancer patients from 12 clinical cohort studies was performed. The meta-analysis results show that COX2 expression in cancer tissues was significantly higher than those in normal and benign tissues (all P < 0.05). Combined HR of COX2 suggests that positive COX2 expression has a shorter overall survival (OS) than those of negative COX2 expression (P < 0.05). Conclusion. The meta-analysis study shows that elevated COX2 expression may be associated with the pathogenesis of oral cancer and with a worse prognosis in oral cancer patients. PMID:25028647

  6. DNA compaction by the bacteriophage protein Cox studied on the single DNA molecule level using nanofluidic channels.

    PubMed

    Frykholm, Karolin; Berntsson, Ronnie Per-Arne; Claesson, Magnus; de Battice, Laura; Odegrip, Richard; Stenmark, Pål; Westerlund, Fredrik

    2016-09-01

    The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA-Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 and WΦ affect DNA. By measuring the extension of nanoconfined DNA in absence and presence of Cox we show that the protein compacts DNA and that the binding is highly cooperative, in agreement with the model of a Cox filament around which DNA is wrapped. Furthermore, comparing microscopy images for the wild-type P2 Cox protein and two mutants allows us to discriminate between compaction due to filament formation and compaction by monomeric Cox. P2 and WΦ Cox have similar effects on the physical properties of DNA and the subtle, but significant, differences in DNA binding are due to differences in binding affinity rather than binding mode. The presented work highlights the use of single DNA molecule studies to confirm structural predictions from X-ray crystallography. It also shows how a small protein by oligomerization can have great impact on the organization of DNA and thereby fulfill multiple regulatory functions.

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

    ERIC Educational Resources Information Center

    Albrecht, Doris

    2007-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  9. COX-2 is involved in ET-1-induced hypertrophy of neonatal rat cardiomyocytes: role of NFATc3.

    PubMed

    Li, Hong; Gao, Si; Ye, Jiantao; Feng, Xiaojun; Cai, Yi; Liu, Zhiping; Lu, Jing; Li, Qin; Huang, Xiaoyang; Chen, Shaorui; Liu, Peiqing

    2014-02-15

    Endothelin-1 (ET-1) is a critical molecule that involved in heart failure. It has been proved that ET-1 stimulation results in cardiac hypertrophy both in vitro and in vivo, but the mechanisms underlying remain largely unknown. In this study, we reported that cyclooxygenase-2 (COX-2) might be an important mediator of hypertrophic responses to ET-1 stimulation. In the cultured rat neonatal cardiomyocytes, ET-1 significantly upregulated the expression and activity of COX-2, which was accompanied by increase in cell surface area and BNP mRNA level. In contrast, ET-1-dependent cardiomyocyte hypertrophy was abolished by COX-2 selective inhibitors, NS-398 and celecoxib, or by COX-2 RNA interference, but the inhibitory effects could be diminished by pretreatment with PGE2. Furthermore, cyclosporin A (CsA) and knockdown of nuclear factor of activated T-cells c3 (NFATc3) inhibited the expression of COX-2 induced by ET-1, and NFATc3 could also bound to the -GGAAA- sequence in the promoter region of rat COX-2 gene, indicating that calcineurin/NFATc3 signaling participated in the transcriptional regulation of COX-2 following ET-1 treatment. These findings provided further insight into the roles of ET-1 in cardiac hypertrophy and suggested a potential therapeutic strategy against cardiac hypertrophy by inhibiting COX-2.

  10. DNA compaction by the bacteriophage protein Cox studied on the single DNA molecule level using nanofluidic channels.

    PubMed

    Frykholm, Karolin; Berntsson, Ronnie Per-Arne; Claesson, Magnus; de Battice, Laura; Odegrip, Richard; Stenmark, Pål; Westerlund, Fredrik

    2016-09-01

    The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA-Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 and WΦ affect DNA. By measuring the extension of nanoconfined DNA in absence and presence of Cox we show that the protein compacts DNA and that the binding is highly cooperative, in agreement with the model of a Cox filament around which DNA is wrapped. Furthermore, comparing microscopy images for the wild-type P2 Cox protein and two mutants allows us to discriminate between compaction due to filament formation and compaction by monomeric Cox. P2 and WΦ Cox have similar effects on the physical properties of DNA and the subtle, but significant, differences in DNA binding are due to differences in binding affinity rather than binding mode. The presented work highlights the use of single DNA molecule studies to confirm structural predictions from X-ray crystallography. It also shows how a small protein by oligomerization can have great impact on the organization of DNA and thereby fulfill multiple regulatory functions. PMID:27131370

  11. DNA compaction by the bacteriophage protein Cox studied on the single DNA molecule level using nanofluidic channels

    PubMed Central

    Frykholm, Karolin; Berntsson, Ronnie Per-Arne; Claesson, Magnus; de Battice, Laura; Odegrip, Richard; Stenmark, Pål; Westerlund, Fredrik

    2016-01-01

    The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA–Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 and WΦ affect DNA. By measuring the extension of nanoconfined DNA in absence and presence of Cox we show that the protein compacts DNA and that the binding is highly cooperative, in agreement with the model of a Cox filament around which DNA is wrapped. Furthermore, comparing microscopy images for the wild-type P2 Cox protein and two mutants allows us to discriminate between compaction due to filament formation and compaction by monomeric Cox. P2 and WΦ Cox have similar effects on the physical properties of DNA and the subtle, but significant, differences in DNA binding are due to differences in binding affinity rather than binding mode. The presented work highlights the use of single DNA molecule studies to confirm structural predictions from X-ray crystallography. It also shows how a small protein by oligomerization can have great impact on the organization of DNA and thereby fulfill multiple regulatory functions. PMID:27131370

  12. Digital dual-parameter data acquisition for SP2 hydrogen-filled proportional counters.

    PubMed

    Hawkes, N P; Roberts, N J

    2014-10-01

    Hydrogen-filled proportional counters perform well as neutron spectrometers in the energy region from a few tens of keV up to ∼1.5 MeV. Unfortunately, gamma rays also generate signals in these detectors. It is possible in principle to distinguish the two types of event via the rise time of their respective signal pulses, but the data acquisition system needed for this is complex to assemble and adjust if one uses conventional modular analogue electronics. In this work a digital sampling system, in conjunction with custom software, was used to measure and acquire amplitude and rise time data from type SP2 counters. The interpretation of the data was supported by a Monte Carlo calculation. The performance of the system is compared with that of a conventional 1-parameter analogue system, and the potential of the digital technique to supplant conventional methods is discussed.

  13. The cytosol-synthesized subunit II (Cox2) precursor with the point mutation W56R is correctly processed in yeast mitochondria to rescue cytochrome oxidase.

    PubMed

    Cruz-Torres, Valentín; Vázquez-Acevedo, Miriam; García-Villegas, Rodolfo; Pérez-Martínez, Xochitl; Mendoza-Hernández, Guillermo; González-Halphen, Diego

    2012-12-01

    Deletion of the yeast mitochondrial gene COX2 encoding subunit 2 (Cox2) of cytochrome c oxidase (CcO) results in loss of respiration (Δcox2 strain). Supekova et al. (2010) [1] transformed a Δcox2 strain with a vector expressing Cox2 with a mitochondrial targeting sequence (MTS) and the point mutation W56R (Cox2(W56R)), restoring respiratory growth. Here, the CcO carrying the allotopically-expressed Cox2(W56R) was characterized. Yeast mitochondria from the wild-type (WT) and the Δcox2+Cox2(W56R) strains were subjected to Blue Native electrophoresis. In-gel activity of CcO and spectroscopic quantitation of cytochromes revealed that only 60% of CcO is present in the complemented strain, and that less CcO is found associated in supercomplexes as compared to WT. CcOs from the WT and the mutant exhibited similar subunit composition, although activity was 20-25% lower in the enzyme containing Cox2(W56R) than in the one with Cox2(WT). Tandem mass spectrometry confirmed that W(56) was substituted by R(56) in Cox2(W56R). In addition, Cox2(W56R) exhibited the same N-terminus than Cox2(WT), indicating that the MTS of Oxa1 and the leader sequence of 15 residues were removed from Cox2(W56R) during maturation. Thus, Cox2(W56R) is identical to Cox2(WT) except for the point mutation W56R. Mitochondrial Cox1 synthesis is strongly reduced in Δcox2 mutants, but the Cox2(W56R) complemented strain led to full restoration of Cox1 synthesis. We conclude that the cytosol-synthesized Cox2(W56R) follows a rate-limiting process of import, maturation or assembly that yields lower steady-state levels of CcO. Still, the allotopically-expressed Cox2(W56R) restores CcO activity and allows mitochondrial Cox1 synthesis to advance at WT levels.

  14. Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.

    PubMed

    He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming

    2014-02-01

    High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.

  15. Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells.

    PubMed

    Gharghabi, Mehdi; Rezaei, Farhang; Mir Mohammadrezaei, Fereshteh; Ghahremani, Mohammad Hossein

    2016-01-01

    Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2expression in A549 cells. Cell viability was assessed using MTT and protein expression was measured using Western Blot assay. Results revealed that Celecoxib dose-dependently induced growth inhibition within 24 h. However, prolonged exposure to the drug up to 48 h led to increase cell viability compared to the corresponding control. Western blot analysis demonstrated that Celecoxib could augment p53 expression within 24 h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induced COX-2 expression within 48 h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48 h. These findings represent p53 as a molecular target being interconnected with COX-2 signaling axis upon Celecoxib treatment. Moreover, our data point toward the possibility that Celecoxib treatment may not be a proper therapeutic strategy in lung cancer cells owing to its potential role in the activation of oncogenes, including COX-2 and MDM2 which seemingly confers a chemoresistance circumstance to the cell. Consequently, these results underscore intensive preclinical assessment prior to applying COX-2 inhibitors in the treatment of lung tumors. PMID:27642319

  16. Long-Term Ambient Residential Traffic–Related Exposures and Measurement Error–Adjusted Risk of Incident Lung Cancer in the Netherlands Cohort Study on Diet and Cancer

    PubMed Central

    Spiegelman, Donna; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schouten, Leo J.; van den Brandt, Piet

    2015-01-01

    Background The International Agency for Research on Cancer (IARC) recently declared air pollution carcinogenic to humans. However, no study of air pollution and lung cancer to date has incorporated adjustment for exposure measurement error, and few have examined specific histological subtypes. Objectives Our aim was to assess the association of air pollution and incident lung cancer in the Netherlands Cohort Study on Diet and Cancer and the impact of measurement error on these associations. Methods The cohort was followed from 1986 through 2003, and 3,355 incident cases were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals, for long-term exposures to nitrogen dioxide (NO2), black smoke (BS), PM2.5 (particulate matter with diameter ≤ 2.5 μm), and measures of roadway proximity and traffic volume, adjusted for potential confounders. Information from a previous validation study was used to correct the effect estimates for measurement error. Results We observed elevated risks of incident lung cancer with exposure to BS [hazard ratio (HR) = 1.16; 95% CI: 1.02, 1.32, per 10 μg/m3], NO2 (HR = 1.29; 95% CI: 1.08, 1.54, per 30 μg/m3), PM2.5 (HR = 1.17; 95% CI: 0.93, 1.47, per 10 μg/m3), and with measures of traffic at the baseline address. The exposures were positively associated with all lung cancer subtypes. After adjustment for measurement error, the HRs increased and the 95% CIs widened [HR = 1.19 (95% CI: 1.02, 1.39) for BS and HR = 1.37 (95% CI: 0.86, 2.17) for PM2.5]. Conclusions These findings add support to a growing body of literature on the effects of air pollution on lung cancer. In addition, they highlight variation in measurement error by pollutant and support the implementation of measurement error corrections when possible. Citation Hart JE, Spiegelman D, Beelen R, Hoek G, Brunekreef B, Schouten LJ, van den Brandt P. 2015. Long-term ambient residential traffic–related exposures and

  17. The critical proportion of immune individuals needed to control hepatitis B

    NASA Astrophysics Data System (ADS)

    Ospina, Juan; Hincapié-Palacio, Doracelly

    2016-05-01

    We estimate the critical proportion of immunity (Pc) to control hepatitis B in Medellin - Colombia, based on a random population survey of 2077 individuals of 6-64 years of age. The force of infection (Fi) was estimated according to empirical data of susceptibility by age S(a), assuming a quadratic expression. Parameters were estimated by adjusting data to a nonlinear regression. Fi was defined by -(ds(a)/da)/s(a) and according to the form of the empirical curve S(a) we assume a quadratic expression given by S(a)= Ea2+Ba+C. Then we have the explicit expression for the accumulated Fi by age given by F(a) = -a(Ea+B)/c. The expression of average infection age A is obtained as A = L + EL3/(3C)+BL2/(2C) and the basic reproductive number R0 is obtained as R0 = 1 + 6C/(6C+2EL2+3BL). From the las result we obtain the Pc given by Pc= 6C/(12C+2EL2+3BL). Numerical simulations were performed with the age-susceptibility proportion and initial values (a=0.02, b=20, c=100), obtaining an adjusted coefficient of multiple determination of 64.83%. According to the best estimate, the algebraic expressions for S(a) and the Fi were derived. Using the result of Fi, we obtain A = 30, L =85; R0 CI 95%: 1.42 - 1.64 and Pc: 0-0.29. These results indicate that at the worst case, to maintain control of the disease should be immunes at least 30% of susceptible individuals. Similar results were obtained by sex and residential area.

  18. Adjustable Induction-Heating Coil

    NASA Technical Reports Server (NTRS)

    Ellis, Rod; Bartolotta, Paul

    1990-01-01

    Improved design for induction-heating work coil facilitates optimization of heating in different metal specimens. Three segments adjusted independently to obtain desired distribution of temperature. Reduces time needed to achieve required temperature profiles.

  19. Time-adjusted variable resistor

    NASA Technical Reports Server (NTRS)

    Heyser, R. C.

    1972-01-01

    Timing mechanism was developed effecting extremely precisioned highly resistant fixed resistor. Switches shunt all or portion of resistor; effective resistance is varied over time interval by adjusting switch closure rate.

  20. 78 FR 62712 - Rate Adjustment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... noticing a recent Postal Service filing seeking postal rate adjustments based on exigent circumstances...,'' is ``premised on the recent recession as an exigent event.'' Id. at 1, 2. In Order No. 1059,...

  1. Robotic Lower Limb Exoskeletons Using Proportional Myoelectric Control

    PubMed Central

    Ferris, Daniel P.; Lewis, Cara L.

    2010-01-01

    Robotic lower limb exoskeletons have been built for augmenting human performance, assisting with disabilities, studying human physiology, and re-training motor deficiencies. At the University of Michigan Human Neuromechanics Laboratory, we have built pneumatically-powered lower limb exoskeletons for the last two purposes. Most of our prior research has focused on ankle joint exoskeletons because of the large contribution from plantar flexors to the mechanical work performed during gait. One way we control the exoskeletons is with proportional myoelectric control, effectively increasing the strength of the wearer with a physiological mode of control. Healthy human subjects quickly adapt to walking with the robotic ankle exoskeletons, reducing their overall energy expenditure. Individuals with incomplete spinal cord injury have demonstrated rapid modification of muscle recruitment patterns with practice walking with the ankle exoskeletons. Evidence suggests that proportional myoelectric control may have distinct advantages over other types of control for robotic exoskeletons in basic science and rehabilitation. PMID:19964579

  2. Measurements of the performance of multiwire proportional chambers

    NASA Technical Reports Server (NTRS)

    Austin, R. W.; Eglitis, A.; Gregory, J. C.; Metzger, S. A.; Parnell, T. A.; Rutledge, H. F.; Selig, W.; Cumings, N. P.

    1973-01-01

    Data are presented that may be useful in formulating engineering specifications and test procedures for the proportional counter hodoscope to be flown as part of the High Energy Cosmic Ray Experiment on the High Energy Astronomy Observatory (HEAO), Mission A. A collection of preliminary data taken in laboratory tests of multiwire counters with an anode wire spacing of 5 mm and cathode gap spacing of 1 cm is presented. The data are from laboratory development models or counters for balloon flights and were selected to illustrate several aspects of proper and improper counter performance. Most of the data were taken from a large proportional counter hodoscope which has an active area of 0.5 by 0.5 m and 104 wires per plane.

  3. Multianode cylindrical proportional counter for high count rates

    DOEpatents

    Hanson, J.A.; Kopp, M.K.

    1980-05-23

    A cylindrical, multiple-anode proportional counter is provided for counting of low-energy photons (< 60 keV) at count rates of greater than 10/sup 5/ counts/sec. A gas-filled proportional counter cylinder forming an outer cathode is provided with a central coaxially disposed inner cathode and a plurality of anode wires disposed in a cylindrical array in coaxial alignment with and between the inner and outer cathodes to form a virtual cylindrical anode coaxial with the inner and outer cathodes. The virtual cylindrical anode configuration improves the electron drift velocity by providing a more uniform field strength throughout the counter gas volume, thus decreasing the electron collection time following the detection of an ionizing event. This avoids pulse pile-up and coincidence losses at these high count rates. Conventional RC position encoding detection circuitry may be employed to extract the spatial information from the counter anodes.

  4. Multianode cylindrical proportional counter for high count rates

    DOEpatents

    Hanson, James A.; Kopp, Manfred K.

    1981-01-01

    A cylindrical, multiple-anode proportional counter is provided for counting of low-energy photons (<60 keV) at count rates of greater than 10.sup.5 counts/sec. A gas-filled proportional counter cylinder forming an outer cathode is provided with a central coaxially disposed inner cathode and a plurality of anode wires disposed in a cylindrical array in coaxial alignment with and between the inner and outer cathodes to form a virtual cylindrical anode coaxial with the inner and outer cathodes. The virtual cylindrical anode configuration improves the electron drift velocity by providing a more uniform field strength throughout the counter gas volume, thus decreasing the electron collection time following the detection of an ionizing event. This avoids pulse pile-up and coincidence losses at these high count rates. Conventional RC position encoding detection circuitry may be employed to extract the spatial information from the counter anodes.

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

    PubMed

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

    2016-07-01

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

  6. Proportion cured models applied to 23 cancer sites in Norway.

    PubMed

    Cvancarova, Milada; Aagnes, Bjarte; Fosså, Sophie D; Lambert, Paul C; Møller, Bjørn; Bray, Freddie

    2013-04-01

    Statistical cure is reached when a group of patients has the same mortality as cancer-free individuals. Cure models predict the cured proportion and the median survival of fatal cases. Cure models have seldom been applied and tested systematically across all major cancer sites. Incidence and follow-up data on 23 cancer sites recorded at the Cancer Registry of Norway 1963-2007 were obtained. Mixture cure models were fitted to obtain trends and up-to-date estimates (based on period approach) assuming cured and uncured groups exist. The model converged for cancers of the mouth and pharynx, oesophagus, stomach, colon, rectum, liver, gallbladder, pancreas, lung and trachea, ovary, kidney, bladder, CNS, non-Hodgkin lymphoma (only for males) and leukemia. The proportion of cured patients increased 1963-2002 for both sexes, with the largest changes (in percent) seen for leukemia (46.4 and 46.7) and CNS (35.9, 42.0), males given first. Median survival time for the uncured cases increased for colon and rectal cancer, and there was a three- fold increase in median survival time for patients with fatal ovarian cancers. Cancers of bladder and CNS had the highest up-to-date proportion cured (in percent), 67.4 and 64.0, respectively, pancreas and liver were amongst the lowest (5.7 and 9.9, respectively). Cure models are useful when monitoring progress in cancer care, but must be applied and interpreted with caution. The absolute estimates of the cure proportion are speculative and should not be calculated where cure is not medically anticipated.

  7. Proportional drift tubes for large area muon detectors

    NASA Technical Reports Server (NTRS)

    Cho, C.; Higashi, S.; Hiraoka, N.; Maruyama, A.; Okusawa, T.; Sato, T.; Suwada, T.; Takahashi, T.; Umeda, H.

    1985-01-01

    A proportional drift chamber which consists of eight rectangular drift tubes with cross section of 10 cm x 5 cm, a sense wire of 100 micron phi gold-plated tungsten wire and the length of 6 m, was tested using cosmic ray muons. Spatial resolution (rms) is between 0.5 and 1 mm over drift space of 50 mm, depending on incident angle and distance from sense wire.

  8. A complete database for the Einstein imaging proportional counter

    NASA Technical Reports Server (NTRS)

    Helfand, David J.

    1991-01-01

    A complete database for the Einstein Imaging Proportional Counter (IPC) was completed. The original data that makes up the archive is described as well as the structure of the database, the Op-Ed analysis system, the technical advances achieved relative to the analysis of (IPC) data, the data products produced, and some uses to which the database has been put by scientists outside Columbia University over the past year.

  9. Wide-range neutron spectrometer on gas proportional counters

    SciTech Connect

    Shvetsov, A.M.; Fomushkin, E.F.

    1994-12-31

    A neutron spectrometer with four cylindrical gas proportional counters was developed, produced and tested in VNIIEF. Active lengths of the counters are concentrated in the range of {approximately}10-100 cm, while the diameters - in the range of {approximately}2-8 cm. Hydrogen, methane, argon, krypton and {sup 3}He were used as working gases. Energy range of the spectrometer constitutes {approximately}0.01

  10. Proportion cured models applied to 23 cancer sites in Norway.

    PubMed

    Cvancarova, Milada; Aagnes, Bjarte; Fosså, Sophie D; Lambert, Paul C; Møller, Bjørn; Bray, Freddie

    2013-04-01

    Statistical cure is reached when a group of patients has the same mortality as cancer-free individuals. Cure models predict the cured proportion and the median survival of fatal cases. Cure models have seldom been applied and tested systematically across all major cancer sites. Incidence and follow-up data on 23 cancer sites recorded at the Cancer Registry of Norway 1963-2007 were obtained. Mixture cure models were fitted to obtain trends and up-to-date estimates (based on period approach) assuming cured and uncured groups exist. The model converged for cancers of the mouth and pharynx, oesophagus, stomach, colon, rectum, liver, gallbladder, pancreas, lung and trachea, ovary, kidney, bladder, CNS, non-Hodgkin lymphoma (only for males) and leukemia. The proportion of cured patients increased 1963-2002 for both sexes, with the largest changes (in percent) seen for leukemia (46.4 and 46.7) and CNS (35.9, 42.0), males given first. Median survival time for the uncured cases increased for colon and rectal cancer, and there was a three- fold increase in median survival time for patients with fatal ovarian cancers. Cancers of bladder and CNS had the highest up-to-date proportion cured (in percent), 67.4 and 64.0, respectively, pancreas and liver were amongst the lowest (5.7 and 9.9, respectively). Cure models are useful when monitoring progress in cancer care, but must be applied and interpreted with caution. The absolute estimates of the cure proportion are speculative and should not be calculated where cure is not medically anticipated. PMID:22927104

  11. Quench gases for xenon- (and krypton-) filled proportional counters

    NASA Technical Reports Server (NTRS)

    Ramsey, B. D.; Agrawal, P. C.

    1988-01-01

    Xenon-filled proportional counters are used extensively in astronomy, particularly in the hard X-ray region. The choice of quench gas can have a significant effect on the operating characteristics of the instrument although the data necessary to make the choice are not easily obtainable. Results which detail the performance obtained from both cylindrical and parallel field geometries for a wide variety of readily available, ultrahigh or research grade purity, quench gases are presented.

  12. Maximum-likelihood estimation of admixture proportions from genetic data.

    PubMed Central

    Wang, Jinliang

    2003-01-01

    For an admixed population, an important question is how much genetic contribution comes from each parental population. Several methods have been developed to estimate such admixture proportions, using data on genetic markers sampled from parental and admixed populations. In this study, I propose a likelihood method to estimate jointly the admixture proportions, the genetic drift that occurred to the admixed population and each parental population during the period between the hybridization and sampling events, and the genetic drift in each ancestral population within the interval between their split and hybridization. The results from extensive simulations using various combinations of relevant parameter values show that in general much more accurate and precise estimates of admixture proportions are obtained from the likelihood method than from previous methods. The likelihood method also yields reasonable estimates of genetic drift that occurred to each population, which translate into relative effective sizes (N(e)) or absolute average N(e)'s if the times when the relevant events (such as population split, admixture, and sampling) occurred are known. The proposed likelihood method also has features such as relatively low computational requirement compared with previous ones, flexibility for admixture models, and marker types. In particular, it allows for missing data from a contributing parental population. The method is applied to a human data set and a wolflike canids data set, and the results obtained are discussed in comparison with those from other estimators and from previous studies. PMID:12807794

  13. Energy Proportionality and Performance in Data Parallel Computing Clusters

    SciTech Connect

    Kim, Jinoh; Chou, Jerry; Rotem, Doron

    2011-02-14

    Energy consumption in datacenters has recently become a major concern due to the rising operational costs andscalability issues. Recent solutions to this problem propose the principle of energy proportionality, i.e., the amount of energy consumedby the server nodes must be proportional to the amount of work performed. For data parallelism and fault tolerancepurposes, most common file systems used in MapReduce-type clusters maintain a set of replicas for each data block. A coveringset is a group of nodes that together contain at least one replica of the data blocks needed for performing computing tasks. In thiswork, we develop and analyze algorithms to maintain energy proportionality by discovering a covering set that minimizesenergy consumption while placing the remaining nodes in lowpower standby mode. Our algorithms can also discover coveringsets in heterogeneous computing environments. In order to allow more data parallelism, we generalize our algorithms so that itcan discover k-covering sets, i.e., a set of nodes that contain at least k replicas of the data blocks. Our experimental results showthat we can achieve substantial energy saving without significant performance loss in diverse cluster configurations and workingenvironments.

  14. L and M cone proportions in polymorphic New World monkeys.

    PubMed

    Jacobs, Gerald H; Williams, Gary A

    2006-01-01

    Platyrrhine monkeys typically have only a single X-chromosome opsin gene. Alleles of this gene code for multiple versions of middle- to long-wavelength cone photopigments. X-chromosome inactivation provides heterozygous females with a retinal mosaic of cones containing either of two types of M and L pigment, thus establishing the photopigment basis for trichromatic color vision. This study examined the proportions of L and M cones created by this process. For that purpose, electroretinogram flicker photometry was used to obtain complete spectral sensitivity functions from 60 heterozygous female monkeys drawn from seven genera of platyrrhine monkeys. To obtain estimates of cone proportions, these functions were subsequently fit with linear combinations of L and M cone fundamentals that were derived from similar recordings made on conspecific animals having only one type of M/L pigment. Consistent with a random X-chromosome inactivation process, the average L:M cone weighting across the sample was close to unity. At the same time, there were significant individual variations in L:M cone proportions. The genesis of this variation and its implications for seeing are discussed. PMID:16961968

  15. Proportional mortality patterns among chemical plant workers exposed to formaldehyde.

    PubMed Central

    Marsh, G M

    1982-01-01

    To examine the possible health risks associated with occupational exposure to formaldehyde a proportional mortality analysis was conducted on deaths occurring between 1950 and 1976 among 136 men who had been employed a month or more in one of five formaldehyde-related areas of a large chemical producing plant located in Springfield, Massachusetts, USA. Overall, no statistically significant excesses or deficits in proportional mortality were observed among the formaldehyde-exposed group based on comparisons with both United States men and men from the local county area. In addition, no important differences in mortality were observed among this group when comparisons were made with 456 male decedents from the same plant who had not had a month or more of formaldehyde exposure. Within the calendar period examined, no deaths from sinonasal cancer were observed among the chemical workers studied nor was mention made on any death certificate of sinonasal cancer as a contributory cause of death. No important excesses, trends, or patterns in cancer mortality were observed among white male formadelhyde-exposed workers when consideration was given to age and time period of death, type and duration of formaldehyde exposure, and the lapse period from the onset of the first formaldehyde-related job assignment. Although certain limitations of this study do not allow definite conclusions to be drawn, the results indicate no trends or patterns in proportional mortality that could be directly linked to exposures to formaldehyde. PMID:7138792

  16. NASA CONNECT: Proportionality: The X-Plane Generation

    NASA Technical Reports Server (NTRS)

    2000-01-01

    'Proportionality: The X-Plane Generation' is the fifth of seven programs in the 1999-2000 NASA CONNECT series. Produced by NASA Langley Research Center's Office of Education, NASA CONNECT is an award-winning series of instructional programs designed to enhance the teaching of math, science and technology concepts in grades 5-8. NASA CONNECT establishes the 'connection' between the mathematics, science, and technology concepts taught in the classroom and NASA research. Each program in the series supports the national mathematics, science, and technology standards; includes a resource-rich teacher guide; and uses a classroom experiment and web-based activity to complement and enhance the math, science, and technology concepts presented in the program. NASA CONNECT is FREE and the programs in the series are in the public domain. Visit our web site and register. http://connect.larc.nasa.gov In 'Proportionality: The X-Plane Generation', students will learn why scaling and proportion are important factors in spacecraft design.

  17. Is proportion burned severely related to daily area burned?

    NASA Astrophysics Data System (ADS)

    Birch, Donovan S.; Morgan, Penelope; Kolden, Crystal A.; Hudak, Andrew T.; Smith, Alistair M. S.

    2014-05-01

    The ecological effects of forest fires burning with high severity are long-lived and have the greatest impact on vegetation successional trajectories, as compared to low-to-moderate severity fires. The primary drivers of high severity fire are unclear, but it has been hypothesized that wind-driven, large fire-growth days play a significant role, particularly on large fires in forested ecosystems. Here, we examined the relative proportion of classified burn severity for individual daily areas burned that occurred during 42 large forest fires in central Idaho and western Montana from 2005 to 2007 and 2011. Using infrared perimeter data for wildfires with five or more consecutive days of mapped perimeters, we delineated 2697 individual daily areas burned from which we calculated the proportions of each of three burn severity classes (high, moderate, and low) using the differenced normalized burn ratio as mapped for large fires by the Monitoring Trends in Burn Severity project. We found that the proportion of high burn severity was weakly correlated (Kendall τ = 0.299) with size of daily area burned (DAB). Burn severity was highly variable, even for the largest (95th percentile) in DAB, suggesting that other variables than fire extent influence the ecological effects of fires. We suggest that these results do not support the prioritization of large runs during fire rehabilitation efforts, since the underlying assumption in this prioritization is a positive relationship between severity and area burned in a day.

  18. Proportional inhibition in the cricket medial giant interneuron.

    PubMed

    Baba, Y; Masuda, H; Shimozawa, T

    2001-02-01

    Inhibitory effects on the number of wind-evoked impulses were studied in the medial giant interneuron of the cricket, Gryllus bimaculatus. The interneuron receives an inhibitory input from wind receptors on cercus ipsilateral to its soma. Using a dual channel wind stimulator, the intensity of inhibitory input was changed over 1,000-fold and effects on the number of spikes were observed. The ipsilateral inhibition reduced the number of outgoing spikes from a level elicited by excitation alone and it did so in proportion to the level of wind responsiveness displayed by each cell. A proportional coefficient of inhibition was derived and its value depended on the level of total excitation of the medial giant interneuron. The medial giant interneurons with high excitation showed a smaller value of the coefficient than those with low excitation. The proportional inhibition of the medial giant interneuron by the ipsilateral cercus suppresses the number of its spikes to a reasonable level for a wide range of stimulus intensities under natural conditions.

  19. An upper-limb power-assist exoskeleton using proportional myoelectric control.

    PubMed

    Tang, Zhichuan; Zhang, Kejun; Sun, Shouqian; Gao, Zenggui; Zhang, Lekai; Yang, Zhongliang

    2014-01-01

    We developed an upper-limb power-assist exoskeleton actuated by pneumatic muscles. The exoskeleton included two metal links: a nylon joint, four size-adjustable carbon fiber bracers, a potentiometer and two pneumatic muscles. The proportional myoelectric control method was proposed to control the exoskeleton according to the user's motion intention in real time. With the feature extraction procedure and the classification (back-propagation neural network), an electromyogram (EMG)-angle model was constructed to be used for pattern recognition. Six healthy subjects performed elbow flexion-extension movements under four experimental conditions: (1) holding a 1-kg load, wearing the exoskeleton, but with no actuation and for different periods (2-s, 4-s and 8-s periods); (2) holding a 1-kg load, without wearing the exoskeleton, for a fixed period; (3) holding a 1-kg load, wearing the exoskeleton, but with no actuation, for a fixed period; (4) holding a 1-kg load, wearing the exoskeleton under proportional myoelectric control, for a fixed period. The EMG signals of the biceps brachii, the brachioradialis, the triceps brachii and the anconeus and the angle of the elbow were collected. The control scheme's reliability and power-assist effectiveness were evaluated in the experiments. The results indicated that the exoskeleton could be controlled by the user's motion intention in real time and that it was useful for augmenting arm performance with neurological signal control, which could be applied to assist in elbow rehabilitation after neurological injury.

  20. An Upper-Limb Power-Assist Exoskeleton Using Proportional Myoelectric Control

    PubMed Central

    Tang, Zhichuan; Zhang, Kejun; Sun, Shouqian; Gao, Zenggui; Zhang, Lekai; Yang, Zhongliang

    2014-01-01

    We developed an upper-limb power-assist exoskeleton actuated by pneumatic muscles. The exoskeleton included two metal links: a nylon joint, four size-adjustable carbon fiber bracers, a potentiometer and two pneumatic muscles. The proportional myoelectric control method was proposed to control the exoskeleton according to the user's motion intention in real time. With the feature extraction procedure and the classification (back-propagation neural network), an electromyogram (EMG)-angle model was constructed to be used for pattern recognition. Six healthy subjects performed elbow flexion-extension movements under four experimental conditions: (1) holding a 1-kg load, wearing the exoskeleton, but with no actuation and for different periods (2-s, 4-s and 8-s periods); (2) holding a 1-kg load, without wearing the exoskeleton, for a fixed period; (3) holding a 1-kg load, wearing the exoskeleton, but with no actuation, for a fixed period; (4) holding a 1-kg load, wearing the exoskeleton under proportional myoelectric control, for a fixed period. The EMG signals of the biceps brachii, the brachioradialis, the triceps brachii and the anconeus and the angle of the elbow were collected. The control scheme's reliability and power-assist effectiveness were evaluated in the experiments. The results indicated that the exoskeleton could be controlled by the user's motion intention in real time and that it was useful for augmenting arm performance with neurological signal control, which could be applied to assist in elbow rehabilitation after neurological injury. PMID:24727501

  1. Phenotype-genotype correlations of facial width and height proportions in patients with Class II malocclusion

    PubMed Central

    Uribe, L.M. Moreno; Ray, A.; Blanchette, D. R.; Dawson, D.V.; Southard, T.E.

    2015-01-01

    Objectives To characterize soft tissue facial height and width variation in Class II malocclusion and test for correlations with genes HMGA2, AJUBA and ADK. Setting and Sample Population Nine facial proportions were estimated from 2D frontal repose photographs of 330 Caucasian adults with Class II malocclusion. Material & Methods After adjustments for age and gender, the facial proportions were submitted to a principal component analyses (PCA). The most meaningful phenotypic variations were correlated with SNPS rs7924176 (ADK), rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals. Results PCA resulted in 4 principal components (PCs) which explained 75% of total variation. PC1 captured variation in the intercanthus distance and explained 28% of total variation. PC2 explained 21% of the variations in facial taper and facial index. PC3 explained 14% and reflected variations in the vertical dimension of the lower face. PC4 explained 12% and captured variations in distance between the eyes, width of the commissures, and the length of the superior aspect of the lower face height, corresponding to the vertical dimension of the philtrum of the upper lip. A suggestive association (p<0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in variation of facial dimensions. Conclusion 2D frontal photographs can be used to derive quantitative measures of soft tissue phenotypes that are of clinical relevance. The methods described are suitable for discovery and replication of associations between genotypes and malocclusion phenotypes. PMID:25865538

  2. LDPC Codes with Minimum Distance Proportional to Block Size

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Jones, Christopher; Dolinar, Samuel; Thorpe, Jeremy

    2009-01-01

    Low-density parity-check (LDPC) codes characterized by minimum Hamming distances proportional to block sizes have been demonstrated. Like the codes mentioned in the immediately preceding article, the present codes are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. The previously mentioned codes have low decoding thresholds and reasonably low error floors. However, the minimum Hamming distances of those codes do not grow linearly with code-block sizes. Codes that have this minimum-distance property exhibit very low error floors. Examples of such codes include regular LDPC codes with variable degrees of at least 3. Unfortunately, the decoding thresholds of regular LDPC codes are high. Hence, there is a need for LDPC codes characterized by both low decoding thresholds and, in order to obtain acceptably low error floors, minimum Hamming distances that are proportional to code-block sizes. The present codes were developed to satisfy this need. The minimum Hamming distances of the present codes have been shown, through consideration of ensemble-average weight enumerators, to be proportional to code block sizes. As in the cases of irregular ensembles, the properties of these codes are sensitive to the proportion of degree-2 variable nodes. A code having too few such nodes tends to have an iterative decoding threshold that is far from the capacity threshold. A code having too many such nodes tends not to exhibit a minimum distance that is proportional to block size. Results of computational simulations have shown that the decoding thresholds of codes of the present type are lower than those of regular LDPC codes. Included in the simulations were a few examples from a family of codes characterized by rates ranging from low to high and by thresholds that adhere closely to their respective channel capacity thresholds; the simulation results from these examples showed that the codes in question have low

  3. Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness

    PubMed Central

    McCurry, Melanie P.; Marino, Anna; South, Mark A.; Howell, Mary E. A.; Layne, Andrew S.; Ramsey, Michael W.; Stone, Michael H.

    2013-01-01

    Context: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes. Objective: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition. Design: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry. Participants and Setting: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. Main Outcome Measures: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated. Results: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. Conclusion: Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects. PMID:23515448

  4. The measurement of radon working levels at a mineral separation pilot plant in Cox's Bazar, Bangladesh.

    PubMed

    Hamid Khan, M A; Chowdhury, M S

    2003-10-01

    Beach Sand Exploitation Centre at Cox's Bazar, Bangladesh, produces commercial grade concentrations of magnetite, ilmenite, zircon, etc., from the high-grade accumulations available along the beach and foredune of Cox's Bazar. Solid state nuclear track detectors (CR-39 foils) were used to determine indoor radon concentration of radioactive mineral sands and the technologically enhanced radiation level inside the pilot plant of the Centre. It is found that the concentrations at processed mineral stock areas are high, and the maximum concentration was found to be 2,103 +/- 331 Bq m(-3) (0.23 +/- 0.03 WL). The indoor concentration of radon and its decay products in the raw sand stock area and at other locations was in the range of 116 +/- 27 Bq m(-3) (0.03 +/- 0.003 WL) to 2,042 +/- 233 Bq m(-3) (0.22 +/- 0.03 WL).

  5. O-desmethylquinine as a cyclooxygenase-2 (COX-2) inhibitors using AutoDock Vina

    NASA Astrophysics Data System (ADS)

    Damayanti, Sophi; Mahardhika, Andhika Bintang; Ibrahim, Slamet; Chong, Wei Lim; Lee, Vannajan Sanghiran; Tjahjono, Daryono Hadi

    2014-10-01

    Computational approach was employed to evaluate the biological activity of novel cyclooxygenase-2 COX-2 inhibitor, O-desmethylquinine, in comparison to quinine as common inhibitor which can also be used an agent of antipyretic, antimalaria, analgesic and antiinflamation. The molecular models of the compound were constructed and optimized with the density function theory with at the B3LYP/6-31G (d,p) level using Gaussian 09 program. Molecular docking studies of the compounds were done to obtain the COX-2 complex structures and their binding energies were analyzed using the AutoDock Vina. The results of docking of the two ligands were comparable and cannot be differentiated from the energy scoring function with AutoDock Vina.

  6. Aerobic oxidation of hydroxymethylfurfural and furfural by using heterogeneous Cox Oy -N@C catalysts.

    PubMed

    Deng, Jin; Song, Hai-Jie; Cui, Min-Shu; Du, Yi-Ping; Fu, Yao

    2014-12-01

    2,5-Furandicarboxylic acid (FDCA) is considered to be a promising replacement for terephthalic acid since they share similar structures and properties. In contrast to FDCA, 2,5-furandicarboxylic acid methyl (FDCAM) has properties that allow it to be easily purified. In this work, we reported an oxidative esterification of 5-hydroxymethylfurfural (HMF) and furfural to prepare corresponding esters over Cox Oy -N@C catalysts using O2 as benign oxidant. High yield and selectivity of FDCAM and methyl 2-furoate were obtained under optimized conditions. Factors which influenced the product distribution were examined thoroughly. The Cox Oy -N@C catalysts were recycled five times and no significant loss of activity was detected. Characterization of the catalysts could explain such phenomena. Using XPS and TGA, we made a thorough investigation of the effects of ligand and pyrolysis temperature on catalyst activity.

  7. Three case definitions of malaria and their effect on diagnosis, treatment and surveillance in Cox's Bazar district, Bangladesh.

    PubMed Central

    Montanari, R. M.; Bangali, A. M.; Talukder, K. R.; Baqui, A.; Maheswary, N. P.; Gosh, A.; Rahman, M.; Mahmood, A. H.

    2001-01-01

    In countries where malaria is endemic, routine blood slide examinations remain the major source of data for the public health surveillance system. This approach has become inadequate, however, as the public health emphasis has changed from surveillance of laboratory-confirmed malaria infections to the early detection and treatment of the disease. As a result, it has been advocated that the information collected about malaria be changed radically and should include the monitoring of morbidity and mortality, clinical practice and quality of care. To improve the early diagnosis and prompt treatment (EDPT) of malaria patients, three malaria case definitions (MCDs) were developed, with treatment and reporting guidelines, and used in all static health facilities of Cox's Bazar district, Bangladesh (population 1.5 million). The three MCDs were: uncomplicated malaria (UM); treatment failure malaria (TFM); and severe malaria (SM). The number of malaria deaths was also reported. This paper reviews the rationale and need for MCDs in malaria control programmes and presents an analysis of the integrated surveillance information collected during the three-year period, 1995-97. The combined analysis of slide-based and clinical data and their related indicators shows that blood slide analysis is no longer used to document fever episodes but to support EDPT, with priority given to SM and TFM patients. Data indicate a decrease in the overall positive predictive value of the three MCDs as malaria prevalence decreases. Hence the data quantify the extent to which the mainly clinical diagnosis of UM leads to over-diagnosis and over-treatment in changing epidemiological conditions. Also the new surveillance data show: a halving in the case fatality rate among SM cases (from 6% to 3.1%) attributable to improved quality of care, and a stable proportion of TFM cases (around 7%) against a defined population denominator. Changes implemented in the EDPT of malaria patients and in the

  8. 7 CFR 251.7 - Formula adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Formula adjustments. 251.7 Section 251.7 Agriculture... GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION THE EMERGENCY FOOD ASSISTANCE PROGRAM § 251.7 Formula adjustments. Formula adjustments. (a) Commodity adjustments. The Department will make annual adjustments...

  9. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  10. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  11. 12 CFR 1209.80 - Inflation adjustments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Inflation adjustments. 1209.80 Section 1209.80... PROCEDURE Civil Money Penalty Inflation Adjustments § 1209.80 Inflation adjustments. The maximum amount of... thereafter adjusted in accordance with the Inflation Adjustment Act, on a recurring four-year cycle, is...

  12. Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans.

    PubMed

    Lenz, Harald; Raeder, Johan; Draegni, Tomas; Heyerdahl, Fridtjof; Schmelz, Martin; Stubhaug, Audun

    2011-06-01

    Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double-blind, placebo-controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib+remifentanil, and ketorolac+remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30-minute infusion of either remifentanil or saline. The cold-pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P < 0.001 and P = 0.005, respectively). Pretreatment with parecoxib or ketorolac reduced the postinfusion area of pinprick hyperalgesia (P < 0.001 and P = 0.001, respectively), compared to the remifentanil group. Parecoxib reduced the area significantly more than ketorolac (P = 0.009). In the CPT, pretreatment with parecoxib or ketorolac did not prevent postinfusion hyperalgesia. These results demonstrated OIH in both models, and may suggest that COX-2 inhibition is more important than COX-1 inhibition in reducing hyperalgesia. Remifentanil-induced hyperalgesia was demonstrated for both electrically induced pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.

  13. COxSwAIN: Compressive Sensing for Advanced Imaging and Navigation

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Apoptosis Inducing Effect of Plumbagin on Colonic Cancer Cells Depends on Expression of COX-2

    PubMed Central

    Subramaniya, Bharathi Raja; Srinivasan, Gayathri; Mohammed Sadullah, Sakeena Sadullah; Davis, Nimitha; Baddi Reddi Subhadara, Lakshmi; Halagowder, Devaraj; Sivasitambaram, Niranjali Devaraj

    2011-01-01

    Plumbagin, a quinonoid found in the plants of the Plumbaginaceae, possesses medicinal properties. In this study we investigated the anti-proliferative and apoptotic activity of plumbagin by using two human colonic cancer cell lines, HT29 and HCT15. IC50 of Plumbagin for HCT15 and HT29 cells (22.5 µM and 62.5 µM, respectively) were significantly different. To study the response of cancer cells during treatment strategies, cells were treated with two different concentrations, 15 µM, 30 µM for HCT15 and 50 µM, 75 µM for HT29 cells. Though activation of NFκB, Caspases-3, elevated levels of TNF-α, cytosolic Cytochrome C were seen in both HCT15 cells HT29 treated with plumbagin, aberrant apoptosis with decreased level of pEGFR, pAkt, pGsk-3β, PCNA and Cyclin D1was observed only in 15 µM and 30 µM plumbagin treated HCT15 and 75 µM plumbagin treated HT29 cells. This suggests that plumbagin induces apoptosis in both HCT15 cells and HT29 treated, whereas, proliferation was inhibited only in 15 µM and 30 µM plumbagin treated HCT15 and 75 µM plumbagin treated HT29 cells, but not in 50 µM plumbagin treated HT29 cells. Expression of COX-2 was decreased in 75 µM plumbagin treated HT29 cells when compared to 50 µM plumbagin treated HT29 cells, whereas HCT15 cells lack COX. Hence the observed resistance to induction of apoptosis in 50 µM plumbagin treated HT29 cells are attributed to the expression of COX-2. In conclusion, plumbagin induces apoptosis in colonic cancer cells through TNF-α mediated pathway depending on expression of COX-2 expression. PMID:21559086

  16. A simple approach to power and sample size calculations in logistic regression and Cox regression models.

    PubMed

    Vaeth, Michael; Skovlund, Eva

    2004-06-15

    For a given regression problem it is possible to identify a suitably defined equivalent two-sample problem such that the power or sample size obtained for the two-sample problem also applies to the regression problem. For a standard linear regression model the equivalent two-sample problem is easily identified, but for generalized linear models and for Cox regression models the situation is more complicated. An approximately equivalent two-sample problem may, however, also be identified here. In particular, we show that for logistic regression and Cox regression models the equivalent two-sample problem is obtained by selecting two equally sized samples for which the parameters differ by a value equal to the slope times twice the standard deviation of the independent variable and further requiring that the overall expected number of events is unchanged. In a simulation study we examine the validity of this approach to power calculations in logistic regression and Cox regression models. Several different covariate distributions are considered for selected values of the overall response probability and a range of alternatives. For the Cox regression model we consider both constant and non-constant hazard rates. The results show that in general the approach is remarkably accurate even in relatively small samples. Some discrepancies are, however, found in small samples with few events and a highly skewed covariate distribution. Comparison with results based on alternative methods for logistic regression models with a single continuous covariate indicates that the proposed method is at least as good as its competitors. The method is easy to implement and therefore provides a simple way to extend the range of problems that can be covered by the usual formulas for power and sample size determination.

  17. mTORC1-mediated downregulation of COX2 restrains tumor growth caused by TSC2 deficiency.

    PubMed

    Li, Hongwu; Jin, Fuquan; Jiang, Keguo; Ji, Shuang; Wang, Li; Ni, Zhaofei; Chen, Xianguo; Hu, Zhongdong; Zhang, Hongbing; Liu, Yehai; Qin, Yide; Zha, Xiaojun

    2016-05-10

    Tuberous sclerosis complex (TSC), caused by loss-of-function mutations in the TSC1 or TSC2 gene, is characterized by benign tumor formation in multiple organs. Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is the primary alteration underlying TSC tumors. By analyzing Tsc2-null mouse embryonic fibroblasts (MEFs) and rat uterine leiomyoma-derived Tsc2-null ELT3 cells, we detected evidence for the involvement of cyclooxygenase 2 (COX2) as a downstream target of mTORC1 in the development of TSC tumors. We showed that loss of TSC2 led to decreased COX2 expression through activation of an mTORC1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Overexpression of COX2 promoted proliferation and tumoral growth of Tsc2-null cells. COX2 knockdown inhibited the proliferation of the control cells. COX2 enhanced Tsc2-null cell growth through upregulation of interleukin-6 (IL-6). In addition, rapamycin in combination with celecoxib, a COX2 inhibitor, strongly inhibited Tsc2-deficient cell growth. We conclude that downregulation of COX2 exerts a protective effect against hyperactivated mTORC1-mediated tumorigenesis caused by the loss of TSC2, and the combination of rapamycin and celecoxib may be an effective new approach to treating TSC.

  18. Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma.

    PubMed

    Kuźbicki, Łukasz; Lange, Dariusz; Stanek-Widera, Agata; Chwirot, Barbara W

    2016-10-01

    Because of the well-known heterogeneity of melanomas, prognosis of the disease is often difficult to assess even for lesions classified in similar stages. The aim of this study was to assess the usefulness of COX-2 as a melanoma prognostic marker and to establish an optimum algorithm for analysis of COX-2 expression levels in lesions of interest. Expression of COX-2 was detected immunohistochemically in standard sections of formalin-fixed paraffin-embedded tissue samples of 85 primary melanomas, 36 lymph node metastases, and five skin metastases including 39 cases of paired primary and metastatic lesions obtained from the same patient. Enhanced expression of COX-2 in primary melanomas is an indicator of poorer prognosis. A significant correlation was found between high expression of COX-2 in primary lesions and shorter survival. The enhancement of COX-2 expression is also positively correlated with other prognostic factors such as tumor thickness and infiltration level, ulceration, high mitotic index, more invasive histologic type, vertical growth phase, and lymph node metastasis. On the whole, the results suggest that intratumoral expression of COX-2 is a strong negative prognostic marker for patients with melanoma. Moreover, our work shows that a simple and objective immunohistochemical scoring algorithm involving the determination of only a percentage fraction of positively stained cells is sufficient to obtain the prognostic information.

  19. Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression[S

    PubMed Central

    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 PPARα and γ. PPARγ-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 PPARγ. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. PMID:19578162

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

    PubMed

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

    2012-11-01

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

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

    PubMed

    Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

    2015-10-01

    Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples.

  2. COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis.

    PubMed

    Zidan, Haidy E; Rezk, Noha A; Alnemr, Amr Abd Almohsen; Abd El Ghany, Amany M

    2015-11-01

    The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis.

  3. LincRNA-Cox2 Promotes Late Inflammatory Gene Transcription in Macrophages through Modulating SWI/SNF-Mediated Chromatin Remodeling.

    PubMed

    Hu, Guoku; Gong, Ai-Yu; Wang, Yang; Ma, Shibin; Chen, Xiqiang; Chen, Jing; Su, Chun-Jen; Shibata, Annemarie; Strauss-Soukup, Juliane K; Drescher, Kristen M; Chen, Xian-Ming

    2016-03-15

    Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. One of the most highly induced lincRNAs in macrophages upon TLR ligation is lincRNA-Cox2, which was recently shown to mediate the activation and repression of distinct classes of immune genes in innate immune cells. We report that lincRNA-Cox2, located at chromosome 1 proximal to the PG-endoperoxide synthase 2 (Ptgs2/Cox2) gene, is an early-primary inflammatory gene controlled by NF-κB signaling in murine macrophages. Functionally, lincRNA-Cox2 is required for the transcription of NF-κB-regulated late-primary inflammatory response genes stimulated by bacterial LPS. Specifically, lincRNA-Cox2 is assembled into the switch/sucrose nonfermentable (SWI/SNF) complex in cells after LPS stimulation. This resulting lincRNA-Cox2/SWI/SNF complex can modulate the assembly of NF-κB subunits to the SWI/SNF complex, and ultimately, SWI/SNF-associated chromatin remodeling and transactivation of the late-primary inflammatory-response genes in macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role for NF-κB-induced lincRNA-Cox2 as a coactivator of NF-κB for the transcription of late-primary response genes in innate immune cells through modulation of epigenetic chromatin remodeling.

  4. mTORC1-mediated downregulation of COX2 restrains tumor growth caused by TSC2 deficiency

    PubMed Central

    Ji, Shuang; Wang, Li; Ni, Zhaofei; Chen, Xianguo; Hu, Zhongdong; Zhang, Hongbing; Liu, Yehai; Qin, Yide; Zha, Xiaojun

    2016-01-01

    Tuberous sclerosis complex (TSC), caused by loss-of-function mutations in the TSC1 or TSC2 gene, is characterized by benign tumor formation in multiple organs. Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is the primary alteration underlying TSC tumors. By analyzing Tsc2-null mouse embryonic fibroblasts (MEFs) and rat uterine leiomyoma-derived Tsc2-null ELT3 cells, we detected evidence for the involvement of cyclooxygenase 2 (COX2) as a downstream target of mTORC1 in the development of TSC tumors. We showed that loss of TSC2 led to decreased COX2 expression through activation of an mTORC1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Overexpression of COX2 promoted proliferation and tumoral growth of Tsc2-null cells. COX2 knockdown inhibited the proliferation of the control cells. COX2 enhanced Tsc2-null cell growth through upregulation of interleukin-6 (IL-6). In addition, rapamycin in combination with celecoxib, a COX2 inhibitor, strongly inhibited Tsc2-deficient cell growth. We conclude that downregulation of COX2 exerts a protective effect against hyperactivated mTORC1-mediated tumorigenesis caused by the loss of TSC2, and the combination of rapamycin and celecoxib may be an effective new approach to treating TSC. PMID:27078846

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

    PubMed Central

    Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

    2015-01-01

    Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples. PMID:26537044

  6. Empirical Bayes estimation of proportions with application to cowbird parasitism rates

    USGS Publications Warehouse

    Link, W.A.; Hahn, D.C.

    1996-01-01

    Bayesian models provide a structure for studying collections of parameters such as are considered in the investigation of communities, ecosystems, and landscapes. This structure allows for improved estimation of individual parameters, by considering them in the context of a group of related parameters. Individual estimates are differentially adjusted toward an overall mean, with the magnitude of their adjustment based on their precision. Consequently, Bayesian estimation allows for a more credible identification of extreme values in a collection of estimates. Bayesian models regard individual parameters as values sampled from a specified probability distribution, called a prior. The requirement that the prior be known is often regarded as an unattractive feature of Bayesian analysis and may be the reason why Bayesian analyses are not frequently applied in ecological studies. Empirical Bayes methods provide an alternative approach that incorporates the structural advantages of Bayesian models while requiring a less stringent specification of prior knowledge. Rather than requiring that the prior distribution be known, empirical Bayes methods require only that it be in a certain family of distributions, indexed by hyperparameters that can be estimated from the available data. This structure is of interest per se, in addition to its value in allowing for improved estimation of individual parameters; for example, hypotheses regarding the existence of distinct subgroups in a collection of parameters can be considered under the empirical Bayes framework by allowing the hyperparameters to vary among subgroups. Though empirical Bayes methods have been applied in a variety of contexts, they have received little attention in the ecological literature. We describe the empirical Bayes approach in application to estimation of proportions, using data obtained in a community-wide study of cowbird parasitism rates for illustration. Since observed proportions based on small sample

  7. 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

  8. 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.

  9. CoxFey@C Composites with Tunable Atomic Ratios for Excellent Electromagnetic Absorption Properties

    PubMed Central

    Lv, Hualiang; Ji, Guangbin; Zhang, Haiqian; Li, Meng; Zuo, Zhongzheng; Zhao, Yue; Zhang, Baoshan; Tang, Dongming; Du, Youwei

    2015-01-01

    The shell on the nano-magnetic absorber can prevent oxidation, which is very important for its practical utilization. Generally, the nonmagnetic shell will decrease the integral magnetic loss and thus weaken the electromagnetic absorption. However, maintaining the original absorption properties of the magnetic core is a major challenge. Here, we designed novel and facile CoxFey@C composites by reducing CoxFe3−xO4@phenolic resin (x = 1, 0.5 and 0.25). High saturation magnetization value (Ms) of CoxFey particle, as a core, shows the interesting magnetic loss ability. Meanwhile, the carbon shell may increase the integral dielectric loss. The resulting composite shows excellent electromagnetic absorption properties. For example, at a coating thickness of 2 mm, the RLmin value can reach to −23 dB with an effective frequency range of 7 GHz (11–18 GHz). The mechanisms of the improved microwave absorption properties are discussed. PMID:26659124

  10. Effects of COX inhibition and LPS on Formalin Induced Pain in the Infant Rat

    PubMed Central

    Hunter, Deirtra; Chai, Christina; Barr, Gordon A.

    2014-01-01

    In the adult, immune and neural processes jointly modulate pain. During development, both are in transition and little is known about the role that the immune system plays in pain processing in infants and children. The objective of this study was to determine if inhibition or augmentation of the immune system would alter pain processing in the infant rat, as it does in the adult. In Experiment 1, rat pups aged 3, 10 or 21 (PN3, PN10, PN21) days of age were pre-treated with NS398 (selective COX-2 inhibitor) or SC560 (selective COX-1 inhibitor) and tested in the intraplantar formalin test to assess effects of COX inhibition on nociception. Neither drug had an effect on the behavioral response at PN3 or PN10 pups but both drugs attenuated nociceptive scores in PN21 pups. cFos expression in the spinal cord likewise was reduced only at PN21. In Experiment 2, pups were injected with LPS prior to the formalin test at PN3 and PN21. LPS increased the nociceptive response more robustly at PN21 than at PN3, while increasing cytokine mRNA equally at both ages. The augmentation of pain responding at PN21 was largely during the late stages of the formalin test, as reported in the adult. These data support previous findings demonstrating late maturing immune modulation of nociceptive behaviors. PMID:25205468

  11. The Respiratory Chain Supercomplex Organization Is Independent of COX7a2l Isoforms

    PubMed Central

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-01-01

    Summary The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research. PMID:25470551

  12. CoxFey@C Composites with Tunable Atomic Ratios for Excellent Electromagnetic Absorption Properties

    NASA Astrophysics Data System (ADS)

    Lv, Hualiang; Ji, Guangbin; Zhang, Haiqian; Li, Meng; Zuo, Zhongzheng; Zhao, Yue; Zhang, Baoshan; Tang, Dongming; Du, Youwei

    2015-12-01

    The shell on the nano-magnetic absorber can prevent oxidation, which is very important for its practical utilization. Generally, the nonmagnetic shell will decrease the integral magnetic loss and thus weaken the electromagnetic absorption. However, maintaining the original absorption properties of the magnetic core is a major challenge. Here, we designed novel and facile CoxFey@C composites by reducing CoxFe3-xO4@phenolic resin (x = 1, 0.5 and 0.25). High saturation magnetization value (Ms) of CoxFey particle, as a core, shows the interesting magnetic loss ability. Meanwhile, the carbon shell may increase the integral dielectric loss. The resulting composite shows excellent electromagnetic absorption properties. For example, at a coating thickness of 2 mm, the RLmin value can reach to -23 dB with an effective frequency range of 7 GHz (11-18 GHz). The mechanisms of the improved microwave absorption properties are discussed.

  13. Imidazolineoxyl N-oxide induces COX-2 in endothelial cells: role of free radicals.

    PubMed

    Camacho, Mercedes; Martinez-Gonzalez, Jose; Rodriguez, Cristina; Siguero, Laura; Seriola, Cristina; Romero, Jose-Maria; Vila, Luis

    2012-01-01

    cPTIO (2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) exerts beneficial actions on systemic inflammatory response. Besides its nitric oxide (NO) scavenging properties cPTIO could exert beneficial effects through modulation of arachidonic acid metabolism. We studied the effect of cPTIO on the biosynthesis of vasoactive prostaglandins (PG) by endothelial cells. Human cord umbilical vein endothelial cells (HUVEC) were treated with cPTIO, and expression of cycloxygenase (COX) isoenzymes in terms of mRNA and protein was determined by real-time-PCR and immunoblotting. Release of PGE2 (as index of untransformed PGH2 release) and 6-oxo-PGF1alpha (PGI2 stable metabolite) was determined by enzyme-immunoassay. cPTIO significantly increases the release of untransformed PGH2 associated to the induction of COX-2 expression. Experiments with NO-synthase inhibitors and radical scavengers showed that induction of COX-2 by cPTIO was mediated by free radical species, likely caused by the mobilization of NO from cellular stores. Finally, using specific signal-transduction inhibitors we show the involvement of Src/PI3-K/PKC pathway. Additional effects other than a direct NO scavenging activity may confer therapeutic advantages to cPTIO as compared with NO-synthase inhibitors for the treatment of systemic inflammation-associated vascular hyporeactivity. PMID:22652668

  14. Comparing Smoothing Techniques for Fitting the Nonlinear Effect of Covariate in Cox Models

    PubMed Central

    Roshani, Daem; Ghaderi, Ebrahim

    2016-01-01

    Background and Objective: Cox model is a popular model in survival analysis, which assumes linearity of the covariate on the log hazard function, While continuous covariates can affect the hazard through more complicated nonlinear functional forms and therefore, Cox models with continuous covariates are prone to misspecification due to not fitting the correct functional form for continuous covariates. In this study, a smooth nonlinear covariate effect would be approximated by different spline functions. Material and Methods: We applied three flexible nonparametric smoothing techniques for nonlinear covariate effect in the Cox models: penalized splines, restricted cubic splines and natural splines. Akaike information criterion (AIC) and degrees of freedom were used to smoothing parameter selection in penalized splines model. The ability of nonparametric methods was evaluated to recover the true functional form of linear, quadratic and nonlinear functions, using different simulated sample sizes. Data analysis was carried out using R 2.11.0 software and significant levels were considered 0.05. Results: Based on AIC, the penalized spline method had consistently lower mean square error compared to others to selection of smoothed parameter. The same result was obtained with real data. Conclusion: Penalized spline smoothing method, with AIC to smoothing parameter selection, was more accurate in evaluate of relation between covariate and log hazard function than other methods. PMID:27041809

  15. [Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib].

    PubMed

    Ortiz, M; Mon, C; Fernández, M J; Sánchez, R; Mampaso, F; Alvarez Ude, F

    2005-01-01

    The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

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

    PubMed Central

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

    2013-01-01

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

  17. Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

    PubMed Central

    Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

    2011-01-01

    Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

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

    PubMed

    Xiao, Yongling; Abrahamowicz, Michal

    2010-03-30

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

  19. PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

    PubMed Central

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

    2015-01-01

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radio-chemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. PMID:24832612

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

    SciTech Connect

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

    2008-10-01

    Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca{sup 2+} concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes.

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

    PubMed

    Zuo, Z; Ouyang, W; Li, J; Costa, M; Huang, C

    2012-07-01

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

  2. The Pet309 pentatricopeptide repeat motifs mediate efficient binding to the mitochondrial COX1 transcript in yeast

    PubMed Central

    Zamudio-Ochoa, Angélica; Camacho-Villasana, Yolanda; García-Guerrero, Aldo E; Pérez-Martínez, Xochitl

    2014-01-01

    Mitochondrial synthesis of Cox1, the largest subunit of the cytochrome c oxidase complex, is controlled by Mss51 and Pet309, two mRNA-specific translational activators that act via the COX1 mRNA 5′-UTR through an unknown mechanism. Pet309 belongs to the pentatricopeptide repeat (PPR) protein family, which is involved in RNA metabolism in mitochondria and chloroplasts, and its sequence predicts at least 12 PPR motifs in the central portion of the protein. Deletion of these motifs selectively disrupted translation but not accumulation of the COX1 mRNA. We used RNA coimmunoprecipitation assays to show that Pet309 interacts with the COX1 mRNA in vivo and that this association is present before processing of the COX1 mRNA from the ATP8/6 polycistronic mRNA. This association was not affected by deletion of 8 of the PPR motifs but was undetectable after deletion of the entire 12-PPR region. However, interaction of the Pet309 protein lacking 12 PPR motifs with the COX1 mRNA was detected after overexpression of the mutated form of the protein, suggesting that deletion of this region decreased the binding affinity for the COX1 mRNA without abolishing it entirely. Moreover, binding of Pet309 to the COX1 mRNA was affected by deletion of Mss51. This work demonstrates an in vivo physical interaction between a yeast mitochondrial translational activator and its target mRNA and shows the cooperativity of the PPR domains of Pet309 in interaction with the COX1 mRNA. PMID:25181249

  3. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by μCT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  4. High proportion of male faeces in jaguar populations.

    PubMed

    Palomares, Francisco; Roques, Séverine; Chávez, Cuauhtémoc; Silveira, Leandro; Keller, Claudia; Sollmann, Rahel; do Prado, Denise Mello; Torres, Patricia Carignano; Adrados, Begoña; Godoy, José Antonio; de Almeida Jácomo, Anah Tereza; Tôrres, Natália Mundim; Furtado, Mariana Malzoni; López-Bao, José Vicente

    2012-01-01

    Faeces provide relevant biological information which includes, with the application of genetic techniques, the sex and identity of individuals that defecated, thus providing potentially useful data on the behaviour and ecology of individuals, as well as the dynamics and structure of populations. This paper presents estimates of the sex ratio of different felid species (jaguar, Panthera onca; puma, Puma concolor; and ocelot/margay, Leopardus pardalis/Leopardus wiedi) as observed in field collected faeces, and proposes several hypotheses that could explain the strikingly high proportion of faeces from male jaguars. The proportion of male and female faeces was estimated using a non-invasive faecal sampling method in 14 study areas in Mexico and Brazil. Faecal samples were genetically analysed to identify the species, the sex and the individual (the latter only for samples identified as belonging to jaguars). Considering the three species, 72.6% of faeces (n = 493) were from males; however, there were significant differences among them, with the proportion from males being higher for jaguars than for pumas and ocelots/margays. A male-bias was consistently observed in all study areas for jaguar faeces, but not for the other species. For jaguars the trend was the same when considering the number of individuals identified (n = 68), with an average of 4.2±0.56 faeces per male and 2.0±0.36 per female. The observed faecal marking patterns might be related to the behaviour of female jaguars directed toward protecting litters from males, and in both male and female pumas, to prevent interspecific aggressions from male jaguars. The hypothesis that there are effectively more males than females in jaguar populations cannot be discarded, which could be due to the fact that females are territorial and males are not, or a tendency for males to disperse into suboptimal areas for the species.

  5. High proportion of male faeces in jaguar populations.

    PubMed

    Palomares, Francisco; Roques, Séverine; Chávez, Cuauhtémoc; Silveira, Leandro; Keller, Claudia; Sollmann, Rahel; do Prado, Denise Mello; Torres, Patricia Carignano; Adrados, Begoña; Godoy, José Antonio; de Almeida Jácomo, Anah Tereza; Tôrres, Natália Mundim; Furtado, Mariana Malzoni; López-Bao, José Vicente

    2012-01-01

    Faeces provide relevant biological information which includes, with the application of genetic techniques, the sex and identity of individuals that defecated, thus providing potentially useful data on the behaviour and ecology of individuals, as well as the dynamics and structure of populations. This paper presents estimates of the sex ratio of different felid species (jaguar, Panthera onca; puma, Puma concolor; and ocelot/margay, Leopardus pardalis/Leopardus wiedi) as observed in field collected faeces, and proposes several hypotheses that could explain the strikingly high proportion of faeces from male jaguars. The proportion of male and female faeces was estimated using a non-invasive faecal sampling method in 14 study areas in Mexico and Brazil. Faecal samples were genetically analysed to identify the species, the sex and the individual (the latter only for samples identified as belonging to jaguars). Considering the three species, 72.6% of faeces (n = 493) were from males; however, there were significant differences among them, with the proportion from males being higher for jaguars than for pumas and ocelots/margays. A male-bias was consistently observed in all study areas for jaguar faeces, but not for the other species. For jaguars the trend was the same when considering the number of individuals identified (n = 68), with an average of 4.2±0.56 faeces per male and 2.0±0.36 per female. The observed faecal marking patterns might be related to the behaviour of female jaguars directed toward protecting litters from males, and in both male and female pumas, to prevent interspecific aggressions from male jaguars. The hypothesis that there are effectively more males than females in jaguar populations cannot be discarded, which could be due to the fact that females are territorial and males are not, or a tendency for males to disperse into suboptimal areas for the species. PMID:23285226

  6. The elite athlete - assessing body shape, size, proportion and composition.

    PubMed

    Kerr, D A; Ackland, T R; Schreiner, A B

    1995-03-01

    In the quest to optimize performance of the elite athlete the sport scientist has sought to determine the ideal physique for a given sport or event. For some sports, specific structural characteristics offer definite performance advantages; for example in rowing, in addition to height, a large arm span has been identified as important. In other sports. such as long distance running, low levels of adiposity or 'fatness' appear to be linked with faster running times. There are four areas where appraisal of the athlete's physique can provide useful information: (1) identification of talented athletes; (2) to assess and monitor the growing athlete; (3) to monitor training and performance; and (4) to determine 'race weight' in weight-category sports. As a research tool a particular method must be reliable and valid. Other considerations include how expensive the method is, if it is suitable for a field situation and if large amounts of data on a number of subjects can be collected quickly. The method should be safe for both the athlete and the tester and provide useful feedback for the athlete or coach. Anthropometry, with training is able to fulfil most of these criteria and is the most widely used method of physique assessment in sports science. Large anthropometric data bases have been collected on elite athletes at Olympic games and world championships according to a standard protocol. Kinanthropometry, which has developed from anthropometry, is concerned with measurement and evaluation of different aspects of human movement and individual variation in body shape, size, proportion and composition. For the assessment of adiposity a sum of skinfolds, usually over six sites, is most commonly used rather than percentage body fat formulae. Muscle mass can be assessed indirectly through girth and corrected girth measurements. Limb lengths and breadths are used to assess skeletal structure and proportional differences in limb size. The anthropometric methods most commonly

  7. High Proportion of Male Faeces in Jaguar Populations

    PubMed Central

    Palomares, Francisco; Roques, Séverine; Chávez, Cuauhtémoc; Silveira, Leandro; Keller, Claudia; Sollmann, Rahel; do Prado, Denise Mello; Torres, Patricia Carignano; Adrados, Begoña; Godoy, José Antonio; de Almeida Jácomo, Anah Tereza; Tôrres, Natália Mundim; Furtado, Mariana Malzoni; López-Bao, José Vicente

    2012-01-01

    Faeces provide relevant biological information which includes, with the application of genetic techniques, the sex and identity of individuals that defecated, thus providing potentially useful data on the behaviour and ecology of individuals, as well as the dynamics and structure of populations. This paper presents estimates of the sex ratio of different felid species (jaguar, Panthera onca; puma, Puma concolor; and ocelot/margay, Leopardus pardalis/Leopardus wiedi) as observed in field collected faeces, and proposes several hypotheses that could explain the strikingly high proportion of faeces from male jaguars. The proportion of male and female faeces was estimated using a non-invasive faecal sampling method in 14 study areas in Mexico and Brazil. Faecal samples were genetically analysed to identify the species, the sex and the individual (the latter only for samples identified as belonging to jaguars). Considering the three species, 72.6% of faeces (n = 493) were from males; however, there were significant differences among them, with the proportion from males being higher for jaguars than for pumas and ocelots/margays. A male-bias was consistently observed in all study areas for jaguar faeces, but not for the other species. For jaguars the trend was the same when considering the number of individuals identified (n = 68), with an average of 4.2±0.56 faeces per male and 2.0±0.36 per female. The observed faecal marking patterns might be related to the behaviour of female jaguars directed toward protecting litters from males, and in both male and female pumas, to prevent interspecific aggressions from male jaguars. The hypothesis that there are effectively more males than females in jaguar populations cannot be discarded, which could be due to the fact that females are territorial and males are not, or a tendency for males to disperse into suboptimal areas for the species. PMID:23285226

  8. Proportional counting techniques for routine tritium analyses at environmental levels

    SciTech Connect

    Bowman, W W; Hughes, M B

    1981-01-01

    Techniques and procedures were developed to routinely analyze samples for tritium as part of research and monitoring programs on the transport of radionuclides released from the Savannah River Plant site. Because tritium concentrations in the environment are low, trace analysis methods were developed. The primary analysis technique involves converting aqueous samples to hydrogen gas which is mixed with propane and assayed in proportional counters. Counter background is reduced by massive shielding, anticoincidence gating with plastic scintillators, and pulse shape discrimination. The overall sensitivity for tritium is 0.02 pCi/g of water with a demonstrated precision of 6.3% at 1 pCi/g of water.

  9. Asbestos disease in sheet metal workers: proportional mortality update.

    PubMed

    Michaels, D; Zoloth, S

    1988-01-01

    This paper, updating the findings of an earlier study, provides additional evidence that sheet metal workers in the construction trades are at increased risk for asbestos-related disease. A proportional analysis of cause of death among 331 New York sheet metal workers found a significantly elevated PMR for lung cancer (PMR = 186). In addition, there were six deaths attributable to mesothelioma (three classified as lung cancer deaths) and three death certificates mentioned asbestosis or pulmonary fibrosis, although none of these three deaths were attributed to these diseases.

  10. Proportional EMG control for upper-limb powered exoskeletons.

    PubMed

    Lenzi, T; De Rossi, S M M; Vitiello, N; Carrozza, M C

    2011-01-01

    Electromyography (EMG) has been frequently proposed as the driving signal for controlling powered exoskeletons. Lot of effort has been spent to design accurate algorithms for muscular torque estimation, while very few studies attempted to understand to what extent an accurate torque estimate is indeed necessary to provide effective movement assistance through powered exoskeletons. In this study, we focus on the latter aspect by using a simple and "low-accuracy" torque estimate, an EMG-proportional control, to provide assistance through an elbow exoskeleton. Preliminary results show that subjects adapt almost instantaneously to the assistance provided by the exoskeleton and can reduce their effort while keeping full control of the movement. PMID:22254387

  11. [Body build and body proportions in children with bronchial asthma].

    PubMed

    Umławska, Wioleta

    2011-01-01

    This paper is a literature review of somatic development in children with chronic bronchial asthma. Asthma is the most common chronic inflammatory disease of the respiratory system in children and youth that is increasing in prevalence. In spite of significant progress in treatment, growth problems are often observed in children with asthma. Growth delay in asthmatic children, increased incidence of short stature, distorted body proportions and nutritional status impairment are reported frequently, in spite of inhaled corticosteroid drugs treatment. The severity of the asthma influences growth outcomes. The issue of growth in children with chronic asthma requires further detailed studies in its clinical and auxological aspects.

  12. Wealth distribution under Yard-Sale exchange with proportional taxes

    NASA Astrophysics Data System (ADS)

    Bustos-Guajardo, R.; Moukarzel, Cristian F.

    2016-03-01

    Recent analysis of a Yard-Sale (YS) exchange model supplemented with redistributive proportional taxation suggested an asymptotic behavior P(w)˜1/wμ for the wealth distribution, with a parameter-dependent exponent μ. Revisiting this problem, it is here shown analytically, and confirmed by extensive numerical simulation, that the asymptotic behavior of P(w) is not power-law but rather a Gaussian. When taxation is weak, we furthermore show that a restricted-range power-law behavior appears for wealths around the mean value. The corresponding power-law exponent equals 3/2 when the return distribution has zero mean.

  13. Proportion of recovered goose and brant bands that are reported

    USGS Publications Warehouse

    Martinson, R.K.; McCann, J.A.

    1966-01-01

    A few more than one-third of the goose and brant bands recovered by hunters were reported to the Bird Banding Laboratory (a rate of 0.361) during the 1962-64 hunting seasons. We calculated this band-reporting rate by comparing the estimated number of goose and brant bands recovered by hunters, based on a mail questionnaire survey, with the number of bands actually reported to the Bird Banding Laboratory. This band-reporting rate is probably representative only of the 1962-65 period. It is likely that, in earlier years, a greater proportion (perhaps about 0.60) of recovered goose and brant bands were reported.

  14. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling☆

    PubMed Central

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P.N.; Kashfi, Khosrow

    2015-01-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5 mM at 24 h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. PMID:26319435

  15. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

    PubMed

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P N; Kashfi, Khosrow

    2015-12-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential.

  16. Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma

    PubMed Central

    Sousa, A.; Pfister, R.; Christie, P. E.; Lane, S. J.; Nasser, S. M.; Schmitz-Schumann, M.; Lee, T. H.

    1997-01-01

    BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX- 1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX- 1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX- 2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma. 


 PMID:9487340

  17. MCCB warm adjustment testing concept

    NASA Astrophysics Data System (ADS)

    Erdei, Z.; Horgos, M.; Grib, A.; Preradović, D. M.; Rodic, V.

    2016-08-01

    This paper presents an experimental investigation in to operating of thermal protection device behavior from an MCCB (Molded Case Circuit Breaker). One of the main functions of the circuit breaker is to assure protection for the circuits where mounted in for possible overloads of the circuit. The tripping mechanism for the overload protection is based on a bimetal movement during a specific time frame. This movement needs to be controlled and as a solution to control this movement we choose the warm adjustment concept. This concept is meant to improve process capability control and final output. The warm adjustment device design will create a unique adjustment of the bimetal position for each individual breaker, determined when the testing current will flow thru a phase which needs to trip in a certain amount of time. This time is predetermined due to scientific calculation for all standard types of amperages and complies with the IEC 60497 standard requirements.

  18. Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids

    PubMed Central

    Staniaszek, LE; Norris, LM; Kendall, DA; Barrett, DA; Chapman, V

    2010-01-01

    Background and purpose: Recent studies suggest that the effects of cyclooxygenase-2 (COX-2) inhibition are mediated by cannabinoid receptor activation. However, some non-steroidal anti-inflammatory drugs inhibit the enzyme fatty acid amide hydrolase, which regulates levels of some endocannabinoids. Whether COX-2 directly regulates levels of endocannabinoids in vivo is unclear. Here, the effect of the COX-2 inhibitor nimesulide, which does not inhibit fatty acid amide hydrolase, on spinal nociceptive processing was determined. Effects of nimesulide on tissue levels of endocannabinoids and related compounds were measured and the role of cannabinoid 1 (CB1) receptors was determined. Experimental approach: Effects of spinal and peripheral administration of nimesulide (1–100 µg per 50 µL) on mechanically evoked responses of rat dorsal horn neurones were measured, and the contribution of the CB1 receptor was determined with the antagonist AM251 (N-(piperidin-1-yl)-5-(-4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide), in anaesthetized rats. Effects of nimesulide on spinal levels of endocannabinoids and related compounds were quantified using liquid chromatography-tandem mass spectrometry. Key results: Spinal, but not peripheral, injection of nimesulide (1–100 µg per 50 µL) significantly reduced mechanically evoked responses of dorsal horn neurones. Inhibitory effects of spinal nimesulide were blocked by the CB1 receptor antagonist AM251 (1 µg per 50 µL), but spinal levels of endocannabinoids were not elevated. Indeed, both anandamide and N-oleoylethanolamide (OEA) were significantly decreased by nimesulide. Conclusions and implications: Although the inhibitory effects of COX-2 blockade on spinal neuronal responses by nimesulide were dependent on CB1 receptors, we did not detect a concomitant elevation in anandamide or 2-AG. Further understanding of the complexities of endocannabinoid catabolism by multiple enzymes is essential to

  19. Directly Adjusting Node's Impacts to Realize the Synchronization of Complex Networks

    NASA Astrophysics Data System (ADS)

    Zhang, Haifeng; Zhao, Ming; Wang, Binghong

    Most previous studies on the synchronization of complex networks were based on that each node managed to adjust its neighbors coupling strength to enhance synchronizability, i.e. each node tried to adjust its total input coupling strength in a proper way and the neighbor nodes were passively adjusted. From practical and engineering viewpoints, each node should manage to adjust its total output coupling strength to realize synchronization. Moreover, each node's total output coupling strength can be distributed to its neighbors with different proportions. In view of the above reasons, in this paper, we study the synchronization of complex networks under the assumptions that the total output coupling strength of each node is voluntarily/directly distributed to its neighbors with different proportions. What is more, we assume that the total output coupling strength of each node can be nonlinear to its degree. Our analysis and numerical simulations show that the synchronizability can be enhanced dramatically when the parameters are properly selected.

  20. Convective adjustment in baroclinic atmospheres

    NASA Technical Reports Server (NTRS)

    Emanuel, Kerry A.

    1986-01-01

    Local convection in planetary atmospheres is generally considered to result from the action of gravity on small regions of anomalous density. That in rotating baroclinic fluids the total potential energy for small scale convection contains a centrifugal as well as a gravitational contribution is shown. Convective adjustment in such an atmosphere results in the establishment of near adiabatic lapse rates of temperature along suitably defined surfaces of constant angular momentum, rather than in the vertical. This leads in general to sub-adiabatic vertical lapse rates. That such an adjustment actually occurs in the earth's atmosphere is shown by example and the magnitude of the effect for several other planetary atmospheres is estimated.

  1. Adaptive differences in the body proportions of large felids.

    PubMed

    Gonyea, W J

    1976-01-01

    Body proportions of eight species of large felids were studied and the relationship between their morphology, habitat structure and habitat utilization was analyzed. Both Panthera onca and Neofelis nebulosa are exclusive forest dwellers (found exclusively in high densly structured habitats). These felids have the relatively shortest anterior limbs and lumbar spine. In addition, P. onca has the relatively shortest posterior limbs of the large felids, while the posterior limbs of N. nebulosa are relatively long when compared with those of P. onca which seems to be an adaptation for jumping. All large fields use the anterior limbs to make primary contact with their prey. In addition, the prey taken by the forest fields can exceed their own body weight. On the other hand, the cheetah is found in low structured habitats (savanna), and it has the relatively longest limbs and lumbarspine of the large felids. But the cheetah's prey usually weigh less than its own body weight. The cheetah also employs a 'rapid pursuit phase' in hunting and is capable of overtaking its prey. The lion, however, was found to have the body proportions of a forest felid, yet it also resides in low structured habitats. It is postulated that the utilization of large prey by the lion limits the possibilities for morphological adaptations for speed. To increase hunting efficiency, reproductive success, and territorial defense on the plains, lions form prides.

  2. Human patellar articular proportions: recent and Pleistocene patterns

    PubMed Central

    TRINKAUS, ERIK

    2000-01-01

    The degrees of mediolateral asymmetry of the patellar articular facet, as well as the median and lateral articular angles of the facet, were compared across samples of recent humans and of Pleistocene archaic and modern fossil humans. All samples exhibit considerable variability in these patellar proportions. The articular angles are similar across the different samples, but there is a trend towards decreasing lateral angles with decreasing robusticity. The archaic humans exhibit significantly more symmetry of the medial and lateral facets than do any of the recent human samples. However, given the variability in medial versus lateral patellofemoral contact forces documented for extant humans and the roles of the distal oblique portions of vastus medialis and vastus lateralis in patellar stabilisation, it is unclear to what extent this variation in patellar articular proportions may affect knee kinesiology. The contrasts may be related to different levels of patellar stability and/or musculoskeletal hypertrophy, but they appear unlikely to have affected primary knee function. PMID:10853969

  3. Monte Carlo simulations of microgap gas-filled proportional counters

    NASA Astrophysics Data System (ADS)

    Kundu, Ashoke; Morton, Edward J.; Key, Martyn J.; Luggar, Russell D.

    1999-09-01

    Monte Carlo calculations have been widely employed to model the interactions of electrons and photons as they travel through and collide with matter. This approach has been applied with some success to the problem of simulating the response of gas-filled proportional counters, mapping out electron transport through the electric field on an interaction-by-interaction basis. These studies focus on the multiplication of electrons as they drift into the high electric field region of the detector and subsequently avalanche. We are using this technique in our new simulation code to depict avalanching in microgap gas-filled proportional counters, in order to investigate the variation of two principle detector properties with the anode pitch used in the detector. Spatial resolution information can be obtained by measuring the lateral diffusion distance of an electron from the point where it is liberated to the point in the detector where it initiates an avalanche. By also modeling the motion of the positive ions that are left behind from the initial avalanche, we are able to gauge the effect of space charge distortion on subsequent avalanches. This effect is particularly important at the high X-ray count rates that we are interested in for our ultimate aim, which is to use the detectors as part of a high-speed tomography system for imaging multiphase oil/water/gas flows.

  4. The arcsine is asinine: the analysis of proportions in ecology.

    PubMed

    Warton, David I; Hui, Francis K C

    2011-01-01

    The arcsine square root transformation has long been standard procedure when analyzing proportional data in ecology, with applications in data sets containing binomial and non-binomial response variables. Here, we argue that the arcsine transform should not be used in either circumstance. For binomial data, logistic regression has greater interpretability and higher power than analyses of transformed data. However, it is important to check the data for additional unexplained variation, i.e., overdispersion, and to account for it via the inclusion of random effects in the model if found. For non-binomial data, the arcsine transform is undesirable on the grounds of interpretability, and because it can produce nonsensical predictions. The logit transformation is proposed as an alternative approach to address these issues. Examples are presented in both cases to illustrate these advantages, comparing various methods of analyzing proportions including untransformed, arcsine- and logit-transformed linear models and logistic regression (with or without random effects). Simulations demonstrate that logistic regression usually provides a gain in power over other methods.

  5. Fiber Contraction Approaches for Improving CMC Proportional Limit

    NASA Technical Reports Server (NTRS)

    DiCarlo, James A.; Yun, Hee Mann

    1997-01-01

    The fact that the service life of ceramic matrix composites (CMC) decreases dramatically for stresses above the CMC proportional limit has triggered a variety of research activities to develop microstructural approaches that can significantly improve this limit. As discussed in a previous report, both local and global approaches exist for hindering the propagation of cracks through the CMC matrix, the physical source for the proportional limit. Local approaches include: (1) minimizing fiber diameter and matrix modulus; (2) maximizing fiber volume fraction, fiber modulus, and matrix toughness; and (3) optimizing fiber-matrix interfacial shear strength; all of which should reduce the stress concentration at the tip of cracks pre existing or created in the matrix during CMC service. Global approaches, as with pre-stressed concrete, center on seeking mechanisms for utilizing the reinforcing fiber to subject the matrix to in-situ compressive stresses which will remain stable during CMC service. Demonstrated CMC examples for the viability of this residual stress approach are based on strain mismatches between the fiber and matrix in their free states, such as, thermal expansion mismatch and creep mismatch. However, these particular mismatch approaches are application limited in that the residual stresses from expansion mismatch are optimum only at low CMC service temperatures and the residual stresses from creep mismatch are typically unidirectional and difficult to implement in complex-shaped CMC.

  6. Sample size calculation for the proportional hazards cure model.

    PubMed

    Wang, Songfeng; Zhang, Jiajia; Lu, Wenbin

    2012-12-20

    In clinical trials with time-to-event endpoints, it is not uncommon to see a significant proportion of patients being cured (or long-term survivors), such as trials for the non-Hodgkins lymphoma disease. The popularly used sample size formula derived under the proportional hazards (PH) model may not be proper to design a survival trial with a cure fraction, because the PH model assumption may be violated. To account for a cure fraction, the PH cure model is widely used in practice, where a PH model is used for survival times of uncured patients and a logistic distribution is used for the probability of patients being cured. In this paper, we develop a sample size formula on the basis of the PH cure model by investigating the asymptotic distributions of the standard weighted log-rank statistics under the null and local alternative hypotheses. The derived sample size formula under the PH cure model is more flexible because it can be used to test the differences in the short-term survival and/or cure fraction. Furthermore, we also investigate as numerical examples the impacts of accrual methods and durations of accrual and follow-up periods on sample size calculation. The results show that ignoring the cure rate in sample size calculation can lead to either underpowered or overpowered studies. We evaluate the performance of the proposed formula by simulation studies and provide an example to illustrate its application with the use of data from a melanoma trial. PMID:22786805

  7. Can structural adjustment work for women farmers.

    PubMed

    Mehra, R

    1991-12-01

    This article discusses the impact of structural adjustment programs (SAPs) on women farmers in developing countries. SAPs aim to improve economic efficiency and promote more rapid economic growth. SAPs are introduced in two phases. The first phase involves short-term loans with the condition that the country adopt monetary restraints and currency devaluation measures. In the second phase, long-term loans are given with the provision that the country deregulate their economy and open up markets. The agricultural sector is affected by SAPs because of their importance in employment, income generation, and export earnings. SAPs result in lower farm commodity prices due to currency devaluations and in removal of subsidies, which results in market-sensitive pricing or higher food prices. The impact of SAPs on agriculture vary between countries. In Morocco and Algeria, agriculture expanded under SAPs. In Indonesia, Bolivia, Costa Rica, and Mexico, the agriculture stagnated or declined. Agricultural growth was slowest in Africa. SAPs were somewhat successful in increasing agricultural exports. Food production grew slowly in many adjusting countries. Blame for failures of SAPs has been placed on government failure to implement reforms properly and overly optimistic assumptions about the timing of productive gains. Little attention has focused on the constraints facing women farmers, who are a large proportion of farmers, particularly in sub-Saharan Africa. This article focuses on the issues of limited access to resources, credit, agricultural extension and information, land ownership, education, and time as constraints to women farmers. Women also must ensure household food security. For SAPs to work effectively, complementary policies must be implemented that reallocate available productive resources and new technologies to women and that deal with women's constraints.

  8. Adjustable-Angle Drill Block

    NASA Technical Reports Server (NTRS)

    Gallimore, F. H.

    1986-01-01

    Adjustable angular drill block accurately transfers hole patterns from mating surfaces not normal to each other. Block applicable to transfer of nonperpendicular holes in mating contoured assemblies in aircraft industry. Also useful in general manufacturing to transfer mating installation holes to irregular and angular surfaces.

  9. Economic Pressures and Family Adjustment.

    ERIC Educational Resources Information Center

    Haccoun, Dorothy Markiewicz; Ledingham, Jane E.

    The relationships between economic stress on the family and child and parental adjustment were examined for a sample of 199 girls and boys in grades one, four, and seven. These associations were examined separately for families in which both parents were present and in which mothers only were at home. Economic stress was associated with boys'…

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

    PubMed Central

    Brancaccio, Mariarita; Coretti, Lorena; Florio, Ermanno; Pezone, Antonio; Calabrò, Viola; Falco, Geppino; Keller, Simona; Lembo, Francesca; Avvedimento, Vittorio Enrico; Chiariotti, Lorenzo

    2016-01-01

    Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene. PMID:27253528

  11. 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

  12. COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

    PubMed

    Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

    2015-07-01

    Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS.

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

    PubMed

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

    2006-07-01

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

  14. Optimization of simultaneous tritium-radiocarbon internal gas proportional counting

    NASA Astrophysics Data System (ADS)

    Bonicalzi, R. M.; Aalseth, C. E.; Day, A. R.; Hoppe, E. W.; Mace, E. K.; Moran, J. J.; Overman, C. T.; Panisko, M. E.; Seifert, A.

    2016-03-01

    Specific environmental applications can benefit from dual tritium and radiocarbon measurements in a single compound. Assuming typical environmental levels, it is often the low tritium activity relative to the higher radiocarbon activity that limits the dual measurement. In this paper, we explore the parameter space for a combined tritium and radiocarbon measurement using a natural methane sample mixed with an argon fill gas in low-background proportional counters of a specific design. We present an optimized methane percentage, detector fill pressure, and analysis energy windows to maximize measurement sensitivity while minimizing count time. The final optimized method uses a 9-atm fill of P35 (35% methane, 65% argon), and a tritium analysis window from 1.5 to 10.3 keV, which stops short of the tritium beta decay endpoint energy of 18.6 keV. This method optimizes tritium-counting efficiency while minimizing radiocarbon beta-decay interference.

  15. The effect of abnormal cell proportion on specimen classifier performance

    NASA Technical Reports Server (NTRS)

    Castleman, K. R.; White, B. S.

    1981-01-01

    An analysis is presented of the results obtained from a cell classifier which is confronted with an abnormal/normal cell ratio which is different from the ratio assumed in the calibration of the classifier. False negative and false positive error rates are determined in advance for classifier operation, along with the necessary sample size in order to validate the predicted distributions. Changes are demonstrated to happen only regarding the false negative rate, where reductions in the abnormal cell rate below the expected rates would cause totally unreliable data. Substantial overproduction of abnormal cells would be quickly noticeable, while production rates beyond, but close to, the expected rates would only require more extensive sampling. Classifier systems for 10% proportions of abnormal cells are concluded to be possible, but difficulties are present with much lower rates

  16. Biologic rationale of esthetic crown lengthening using innovative proportion gauges.

    PubMed

    Fletcher, Paul

    2011-01-01

    Research shows that practitioners tend to underestimate the amount of tooth structure that must be exposed during a crown lengthening procedure. In the anterior portion of the mouth, this can lead to biologic width problems and subsequent cosmetic issues. This paper presents a biologically based, step-by-step approach to periodontal esthetic crown lengthening. Using a series of innovative measuring gauges, the ideal clinical crown length of a tooth as well as the proper occlusogingival placement of the interproximal papilla will be determined based on established, documented tooth proportion relationships. The biologic crown length of the tooth, defined as the distance from the incisal edge to the bone crest, will subsequently be determined as a function of the clinical crown length, with the ultimate goals being adequate tooth structure for the placement of a restorative margin, establishment of a healthy dentogingival complex, and the placement of an esthetically pleasing definitive restoration.

  17. A proportional mortality study of a group of newspaper workers

    PubMed Central

    Greenberg, M.

    1972-01-01

    Greenberg, M. (1972).Brit. J. industr. Med.,29, 15-20. A proportional mortality study of a group of newspaper workers. In investigating an anecdotal report of a high incidence of bladder cancer at a London newspaper printing factory, death certificates for 670 workers relating to the years 1954-66 were studied. While an increased incidence of carcinoma of the urinary organs could not be demonstrated, the total of all malignancies was greater than predicted and carcinoma of the bronchus accounted for much of the excess. Only death by suicide occurred to excess among causes of death other than malignancy. The smoking habits of subjects are not known but if tobacco habit contributed to bronchial carcinoma it had no observable effect on the incidence of chronic bronchitis and ischaemic heart disease in early middle age. It is concluded that a prospective study would be required if occupation is to be implicated as a hazard. PMID:5062168

  18. A Complete Public Archive for the Einstein Imaging Proportional Counter

    NASA Technical Reports Server (NTRS)

    Helfand, David J.

    1996-01-01

    Consistent with our proposal to the Astrophysics Data Program in 1992, we have completed the design, construction, documentation, and distribution of a flexible and complete archive of the data collected by the Einstein Imaging Proportional Counter. Along with software and data delivered to the High Energy Astrophysics Science Archive Research Center at Goddard Space Flight Center, we have compiled and, where appropriate, published catalogs of point sources, soft sources, hard sources, extended sources, and transient flares detected in the database along with extensive analyses of the instrument's backgrounds and other anomalies. We include in this document a brief summary of the archive's functionality, a description of the scientific catalogs and other results, a bibliography of publications supported in whole or in part under this contract, and a list of personnel whose pre- and post-doctoral education consisted in part in participation in this project.

  19. The evolution of human and ape hand proportions.

    PubMed

    Almécija, Sergio; Smaers, Jeroen B; Jungers, William L

    2015-01-01

    Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids.

  20. The evolution of human and ape hand proportions

    PubMed Central

    Almécija, Sergio; Smaers, Jeroen B.; Jungers, William L.

    2015-01-01

    Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids. PMID:26171589