5,059 research outputs found

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

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    PMCID: PMC3711559This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells

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    Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contraction-associated protein expression in myometrial cells and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and further studies confirmed that this was associated with COX-2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP-effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP-effector PDZ-GEF1-2, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX-2 expression and that PGE2 acts through EP-2 to activate MAPK and increase COX-2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function

    Synthesis optimization and charge carrier transfer mechanism in LiLuSiO<sub>4</sub>:Ce, Tm storage phosphor

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    LiLuSiO4:Ce and LiLuSiO4:Ce, Tm show very efficient charge carrier storage properties upon beta irradiation after samples have received treatment in vacuum. They outperform the commercial storage phosphor BaFBr(I):Eu2+ in many aspects. The influence of the synthesis conditions, Ce and Tm concentration, nonstoichiometry and codoping with Ca, Hf, Al and Ge are reported. Based on the results of the synthesis optimization, thermoluminescence (TL) emission and TL excitation spectra a mechanism of charge carrier transfer, storage, and recombination during irradiation and thermal or optical readout is proposed.Accepted Author ManuscriptRST/Fundamental Aspects of Materials and EnergyRST/Luminescence Material

    Survival Analysis with Multivariate adaptive Regression Splines

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    Multivariate adaptive regression splines (MARS) are a useful tool to identify linear and nonlinear effects and interactions between two covariates. In this dissertation a new proposal to model survival type data with MARS is introduced. Martingale and deviance residuals of a Cox PH model are used as response in a common MARS approach to model functional forms of covariate effects as well as possible interactions in a data-driven way. Simulation studies prove that the new method yields a better fit to the data than the traditional Cox PH approach. The analysis of real data of the German Heart Center on survivors of an acute myocardial infarction also documents the good performance of the method

    TM negatively regulates the expression of EMT markers in CRC cells.

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    (A) The expression levels of epithelial and mesenchymal markers (fibronectin, ezrin, and vimentin) as well as COX-2 were analyzed in scrambled control and TM-KD DLD-1 cells via Western blot analysis. GAPDH was used as a loading control. (B) The expression levels of epithelial and mesenchymal markers as well as COX-2 were compared between the vector control- and pcDNA3-topo-TM-transfected HT-29 cells via Western blot analysis. GAPDH was used as a loading control. Mesenchymal markers were up-regulated in TM-KD cells but down-regulated in pcDNA3-topo-TM-transfected cells compared with the corresponding control cells.</p

    Compact RBF meshless methods for photonic crystal modelling

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    Meshless methods based on compact radial basis functions (RBFs) are proposed for modelling photonic crystals (PhCs). When modelling two-dimensional PhCs two generalised eigenvalue problems are formed, one for the transverse-electric (TE) mode and the other for the transverse-magnetic (TM) mode. Conventionally, the Band Diagrams for two-dimensional PhCs are calculated by either the plane wave expansion method (PWEM) or the finite element method (FEM). Here, the eigenvalue equations for the two-dimensional PhCs are solved using RBFs based meshless methods. For the TM mode a meshless local strong form method (RBF collocation) is used, while for the tricker TE mode a meshless local weak form method (RBF Galerkin) is used (so that the discontinuity of the dielectric function epsilon (Porson)(x) can naturally be modelled). The results obtained from the meshless methods are found to be in good agreement with the standard PWEM. Thus, the meshless methods are proved to be a promising scheme for predicting photonic band gap

    Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins.

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    There is concern that cyclooxygenase (COX)-2 inhibitors may promote atherothrombosis by inhibiting vascular formation of prostacyclin (PGI2) and an increased thrombotic risk of COX-2 inhibitors has been reported. It is widely accepted that the prothrombotic effects of COX-2 inhibitors can be explained by the removal of platelet-inhibitory PGI2. Using microarray chip technology, we have previously demonstrated that thrombomodulin (TM) mRNA is upregulated in cultured human coronary artery smooth muscle cells by the stable prostacyclin mimetic iloprost. This study is the first to demonstrate a stimulation of the expression of functionally active thrombomodulin in human smooth muscle cells by prostaglandins, endogenously formed via the COX-2 pathway. Because TM is an important inhibitor of blood coagulation, these findings provide a novel platelet-independent mechanism to explain the prothrombotic effects of COX-2 inhibitors. The full text of this article is available online at http://circres.ahajournals.org

    Probabilistic methods for seasonal forecasting in a changing climate: Cox-type regression models

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    For climate risk management, cumulative distribution functions (CDFs) are an important source of information. They are ideally suited to compare probabilistic forecasts of primary (e.g. rainfall) or secondary data (e.g. crop yields). Summarised as CDFs, such forecasts allow an easy quantitative assessment of possible, alternative actions. Although the degree of uncertainty associated with CDF estimation could influence decisions, such information is rarely provided. Hence, we propose Cox-type regression models (CRMs) as a statistical framework for making inferences on CDFs in climate science. CRMs were designed for modelling probability distributions rather than just mean or median values. This makes the approach appealing for risk assessments where probabilities of extremes are often more informative than central tendency measures. CRMs are semi-parametric approaches originally designed for modelling risks arising from time-to-event data. Here we extend this original concept to other positive variables of interest beyond the time domain. We also provide tools for estimating CDFs and surrounding uncertainty envelopes from empirical data. These statistical techniques intrinsically account for non-stationarities in time series that might be the result of climate change. This feature makes CRMs attractive candidates to investigate the feasibility of developing rigorous global circulation model (GCM)-CRM interfaces for provision of user-relevant forecasts. To demonstrate the applicability of CRMs, we present two examples for El Niño/Southern Oscillation (ENSO)-based forecasts: the onset date of the wet season (Cairns, Australia) and total wet season rainfall (Quixeramobim, Brazil). This study emphasises the methodological aspects of CRMs rather than discussing merits or limitations of the ENSO-based predictor

    GA Landsat 5 TM Analysis Ready Data Collection 3

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    Maintenance and Update Frequency: asNeededStatement: This product is derived from the USGS Landsat Collection 1 archive. The Moderate Resolution Imaging Spectroradiometer (MODIS) MCD43A1 Version 6 Bidirectional Reflectance Distribution Function and Albedo (BRDF/Albedo) Model Parameters dataset was provided by the National Aeronautics and Space Administration (NASA). It was produced daily using 16 days of Terra and Aqua MODIS data at 500 m resolution. The ozone data was provided by Environment Canada. The Aerosol Optical Thickness data was provided by the Commonwealth Scientific and Industrial Research Organisation (CSIRO). The Precipitable Water for Entire Atmosphere data was provided by the National Oceanic and Atmospheric Administration (NOAA) / Earth System Research Laboratory (ESRL) / Physical Sciences Division (PSD). The baseline Digital Surface Model (DSM) data produced from the Shuttle Radar Topography Mission (SRTM) was provided by the National Geospatial-Intelligence Agency (NGA). Level 1 Collection 1 data was provided by the United States Geological Survey (USGS)'s Earth Resources Observation and Science (EROS) Center.&lt;b&gt;BACKGROUND&lt;/b&gt;&lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;The United States Geological Survey's (USGS) Landsat satellite program has been capturing images of the Australian continent for more than 30 years. This data is highly useful for land and coastal mapping studies. &lt;br/&gt;&lt;p&gt;In particular, the light reflected from the Earth’s surface (surface reflectance) is important for monitoring environmental resources – such as agricultural production and mining activities – over time. &lt;br/&gt;&lt;p&gt;We need to make accurate comparisons of imagery acquired at different times, seasons and geographic locations. However, inconsistencies can arise due to variations in atmospheric conditions, sun position, sensor view angle, surface slope and surface aspect. These need to be reduced or removed to ensure the data is consistent and can be compared over time. &lt;br/&gt;&lt;p&gt;&nbsp&lt;/p&gt;&lt;br/&gt;&lt;b&gt;WHAT THIS PRODUCT OFFERS&lt;/b&gt;&lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;GA Landsat 5 TM Analysis Ready Data Collection 3 takes Landsat 5 Thematic Mapper (TM) imagery captured over the Australian continent and corrects for inconsistencies across land and coastal fringes. The result is accurate and standardised surface reflectance data, which is instrumental in identifying and quantifying environmental change. &lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;The TM instrument is an advanced, multispectral scanning, Earth resources sensor which is designed to categorise the Earth's surface. It is particularly useful for agricultural applications and identification of land use. &lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;This product is a single, cohesive Analysis Ready Data (ARD) package, which allows you to analyse surface reflectance data as is, without the need to apply additional corrections. &lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;It contains three sub-products that provide corrections or attribution information:&lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1) GA Landsat 5 TM NBAR Collection 3 &lt;br/&gt;&lt;p&gt;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2) GA Landsat 5 TM NBART Collection 3&lt;br/&gt;&lt;p&gt;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;3) GA Landsat 5 TM OA Collection 3&lt;br/&gt;&lt;p&gt;&lt;br/&gt;&lt;p&gt;The resolution is a 30 m grid based on the USGS Landsat Collection 1 archive

    The dependence of light extraction improvement on optimized surface microstructure for AlGaN-based UVC-LEDs considering TM-polarized emission

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    In order to improve the light extraction of AlGaN-based short wavelength ultraviolet light emitting diodes (DUC-LEDs), a type of microstructure with high aspect ratio is introduced and optimized on the AlN substrate surface. And, particle swarm optimization (PSO) algorithm is used to inverse design of the surface microstructure to maximize the light extraction efficiency (LEE). Considering that the propagation characteristics of TM-polarized light are different from that of TE-polarized light, the optical field distribution and LEE is analyzed for the UVC-LEDs with different TE-polarized component when the optimized surface microstructure is applied. Furthermore, the preparation process tolerance of the high aspect ratio structure is discussed by calculating the LED's LEE when the structural deviation occurs or morphology changes. Simulation results show that, by using the optimized surface microstructure based on parabola cone array, the LEDs' LEE is increased from 4.4% to 8.7% and from 0.4% to 3.7% for TE-polarized and TM-polarized emission, respectively. In addition, it is demonstrated that the light extraction improvement by the surface microstructure has a good tolerance to the structural deviation and morphology. The results are significant for improving light extraction and realizing high efficient short wavelength AlGaN-based UVC-LEDs by designing surface microstructures.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ImPhys/Esmaeil Zadeh grou
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