bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulations of censoring effect in XRF analysis
Authors: Kubala‐Kukuś A. , Pajek M. 
Published: April 2004

AbstractThe quantitative aspects of a use of random left‐censoring as a statistical approach accounting for the detection limit effects in x‐ray fluorescence (XRF) analysis were investigated using the Monte Carlo simulations. More precisely, the performance of the Kaplan–Meier method applied to the estimation of the original concentration distributions from detection limit censored concentration measurements are discussed. The simulations were performed for assumed log‐normal and log‐stable concentration distributions, which are known to model fairly well both concentrations and detection limits for biomedical and environmental samples. In particular, the question of the accuracy of the estimation of the mean value and median for the discussed concentration distributions using the Kaplan–Meier estimator was addressed. It is demonstrated that both the mean value and median of the concentration distribution can be estimated from censored data fairly precisely, typically within 4% for the log‐normal and within 15% for log‐stable models, even for substantial censoring levels (up to 80%). Moreover, the estimation of the median is much more precise than that of the mean value, in particular for stable distributions. Finally, the simulations show that random left‐censoring can be recommended as a standard tool for analysing the detection limit censored concentration measurements of trace elements in XRF analysis. Copyright © 2004 John Wiley & Sons, Ltd.
Random left‐censoring: a statistical approach accounting for detection limits in x‐ray fluorescence analysis
Authors: Pajek M. , Kubala‐Kukuś A. , Banaś D. , Braziewicz J. , Majewska U. 
Published: April 2004

AbstractThe use of x‐ray fluorescence techniques (XRF, TXRF, µXRF) in studies of trace element concentrations is limited by the detection limits (DL) of these methods. In this work we demonstrate that concentration measurements below the DL level, the so‐called ‘non‐detects’, can be included in data analysis by using the statistical concept of ‘censoring’, which is widely used, for instance, in survival analysis. This paper describes the non‐parametric methods of analysis of censored data using the random left‐censoring formalism, which can be used to account for the detection limits in XRF analysis. In particular, the application of the Kaplan–Meier and Nelson–Aalen estimators for the estimation of concentration distributions under censoring is discussed. These approaches are compared with the ‘reconstruction method’ developed earlier in our group to correct XRF data for the effect of detection limits. By using Monte Carlo simulations, the accuracy of the Kaplan–Meier and Nelson–Aalen estimators for censored data is discussed, in particular in the context of the estimation of the mean value and median of a concentration distribution. We demonstrate that for the ‘two‐group’ comparison of left‐censored concentrations, which is a problem of great practical importance, the log‐rank test can be used. The idea of random left censoring is applied to analyse the TXRF detection limit‐censored measurements of the concentrations of trace elements in biomedical samples. Copyright © 2004 John Wiley & Sons, Ltd.
A modular system for XRF and XRD applications consisting of a microfocus X‐ray source and different capillary optics
Authors: Bjeoumikhov A. , Langhoff N. , Rabe J. , Wedell R. 
Published: April 2004

AbstractIn recent years, new components for x‐ray analysis have been developed: capillary optics, microfocus x‐ray tubes and compact detectors, e.g. energy‐dispersive detectors without liquid nitrogen cooling. Microfocus tubes have a relatively low power but their brightness is up to 100 times higher than for normal x‐ray tubes which are used in diffractometry. A combination of these tubes with highly efficient capillary optical elements allows one to obtain parallel or focused beams of high intensity. Combining such a special source with detectors of different kinds, a compact system can be realized which may be successfully used in micro‐XRF, in diffraction and microdiffraction, etc. The system presented is designed in a modular way so that the components may be replaced by each other. Some examples of applications of such systems are reported. Copyright © 2004 John Wiley & Sons, Ltd.
EPMA and µ‐SRXRF analysis and TEM‐based microstructure characterization of a set of Roman glass fragments
Authors: Fredrickx P. , De Ryck I. , Janssens K. , Schryvers D. , Petit J.‐P. , Döcking H. 
Published: April 2004

AbstractA set of Roman glass fragments, excavated at Bliesbruck–Reinheim (French–German border), were analysed by electron probe microanalysis (EPMA) and micro‐synchrotron radiation‐induced x‐ray fluorescence (µ‐SRXRF) in order to determine the major, minor and trace chemical composition. Based on this analysis, five classes of mono‐coloured glass could be discerned. However, one piece of this set was not mono‐coloured, but consisted of a mixture of brown and white opaque glass. This fragment was investigated using EPMA and transmission electron microscopy (TEM) in order to gain a better insight into its microstructure. Both colours proved to contain small crystalline inhomogeneities. Structural information reveals the form in which the detected elements are present and helps to explain the appearance (e.g. colour) of the material. Copyright © 2004 John Wiley & Sons, Ltd.
Planar waveguide‐resonator: a new device for x‐ray optics
Authors: Egorov V. K. , Egorov E. V. 
Published: April 2004

AbstractSystematic investigations of the width dependence on the x‐ray beam propagation mechanism for a narrow extended slit formed by two plane dielectric plates are presented. It is shown that the mechanism of a multiple consecutive total reflection for Cu Kα radiation dominates in a slit width range s ≥ 3 µm. At the same time the manner of Cu Kα radiation propagation for super‐narrow slits s ≤ 0.1 µm is very different from the multiple total reflection mechanism. The x‐ray beam intensity proves to be constant for all this range of magnitude. This gives grounds to expect that the super‐narrow slit area is characterized by a specific type of mechanism of x‐ray beam propagation: waveguide‐resonance. A simple model for the waveguide‐resonance propagation mechanism based on the formation of a uniform x‐ray standing wave interference field in the total space of a narrow extended slit was developed. The design of a new x‐ray optical device, namely a planar x‐ray waveguide‐resonator, is proposed based on the waveguide‐resonance mechanism. Some properties of the composite planar x‐ray waveguide‐resonator are discussed. It is shown that under specific conditions the composite waveguide can demonstrate a partial tunneling effect of the x‐ray beam. The main applications of the new technique are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
A new way of measuring the contribution of scattered photons to x‐ray fluorescence yields in secondary excitation mode
Authors: Kumar Ajay , Mehta D. , Singh Nirmal 
Published: April 2004

AbstractThe characteristic K x‐rays from a secondary exciter in conjunction with an x‐ray tube or a radioisotope as primary source are frequently used for target excitation in x‐ray fluorescence measurements. In this experimental arrangement, the exciting photon spectrum consists of two parts: (i) characteristic K x‐rays of the secondary exciter and (ii) photons from the primary source, which are scattered from the secondary exciter. A new method is proposed for correcting the observed target x‐ray yield due to unwanted excitation by the scattered photons. This method involves measurement of x‐ray yield after replacing the secondary exciter by an equivalent exciter consisting of a low‐Z element foil with a high‐Z element backing. Copyright © 2004 John Wiley & Sons, Ltd.
Semiconductor Peltier‐cooled detectors for x‐ray fluorescence analysis
Authors: Sokolov A. , Loupilov A. , Gostilo V. 
Published: April 2004

AbstractWe discuss recent results obtained in the development of Si(Li), Si p–i–n, CdTe p–i–n and CdZnTe x‐ray detectors with Peltier coolers for fabrication of laboratory and portable XRF analyzers. The characteristics of Si(Li) Peltier‐cooled detectors are close to those of detectors cooled with the liquid nitrogen and remain the most preferred type of detectors for the tasks of x‐ray fluorescence analysis. Considerable success was obtained in the improvement of the characteristics of CdTe p–i–n detectors and CdZnTe detectors with a metal–semiconductor–metal structure, effective in the energy range up to 100 keV. The spectra of all detectors are presented. Copyright © 2004 John Wiley & Sons, Ltd.
Measurements of the surface ionization in multilayered specimens
Authors: Merlet C. , Llovet X. , Salvat F. 
Published: April 2004

AbstractResults from experimental measurements of surface ionization, Φ(0), from multilayered specimens are presented. The studied samples consisted of Cu and C layers of different thicknesses, deposited on single‐element substrates that cover the periodic system, from Be to Bi. The surface ionization was determined by the tracer method, i.e. by measuring the characteristic x‐ray intensity emitted from an ultra‐thin tracer layer deposited on the multilayer structure and, according to Castaing's definition, dividing it by the x‐ray intensity from an equivalent, self‐supporting tracer layer. The considered tracer element was Ni, and measurements were performed for Ni Kα and Ni Lα x‐rays. Experimental results are compared with Monte Carlo simulation results generated by using the general‐purpose simulation package PENELOPE with ionization cross‐sections computed from an optical‐data model. Measured data are also compared with the predictions of an empirical analytical expression for Φ(0), which was derived from systematic Monte Carlo simulations. Copyright © 2004 John Wiley & Sons, Ltd.
P2X7 receptors stimulate AKT phosphorylation in astrocytes
Authors: Jacques‐Silva Maria C , Rodnight Richard , Lenz Guido , Liao Zhongji , Kong Qiongman , Tran Minh , Kang Yuan , Gonzalez Fernando A , Weisman Gary A , Neary Joseph T 
Published: April 2004

Emerging evidence indicates that nucleotide receptors are widely expressed in the nervous system. Here, we present evidence that P2Y and P2X receptors, particularly the P2X7 subtype, are coupled to the phosphoinositide 3‐kinase (PI3K)/Akt pathway in astrocytes.
P2Y and P2X receptor agonists ATP, uridine 5′‐triphosphate (UTP) and 2′,3′‐O‐(4‐benzoyl)‐benzoyl ATP (BzATP) stimulated Akt phosphorylation in primary cultures of rat cortical astrocytes. BzATP induced Akt phosphorylation in a concentration‐ and time‐dependent manner, similar to the effect of BzATP on Akt phosphorylation in 1321N1 astrocytoma cells stably transfected with the rat P2X7 receptor. Activation was maximal at 5 – 10 min and was sustained for 60 min; the EC50 for BzATP was approximately 50 μM. In rat cortical astrocytes, the positive effect of BzATP on Akt phosphorylation was independent of glutamate release.
The effect of BzATP on Akt phosphorylation in rat cortical astrocytes was significantly reduced by the P2X7 receptor antagonist Brilliant Blue G and the P2X receptor antagonist iso‐pyridoxal‐5′‐phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid, but was unaffected by trinitrophenyl‐ATP, oxidized ATP, suramin and reactive blue 2.
Results with specific inhibitors of signal transduction pathways suggest that extracellular and intracellular calcium, PI3K and a Src family kinase are involved in the BzATP‐induced Akt phosphorylation pathway.
In conclusion, our data indicate that stimulation of astrocytic P2X7 receptors, as well as other P2 receptors, leads to Akt activation. Thus, signaling by nucleotide receptors in astrocytes may be important in several cellular downstream effects related to the Akt pathway, such as cell cycle and apoptosis regulation, protein synthesis, differentiation and glucose metabolism.

British Journal of Pharmacology (2004) 141, 1106–1117. doi:10.1038/sj.bjp.0705685
Cannabinoid CB1 receptor‐mediated modulation of evoked dopamine release and of adenylyl cyclase activity in the human neocortex
Authors: Steffens M , Engler C , Zentner J , Feuerstein T J 
Published: April 2004

The present study investigated the binding characteristics of various ligands to cannabinoid CB1 receptors in human neocortex and amygdala. In addition, the functionality of CB1 receptors in the human neocortex was assessed by examining the effects of CB1 receptor ligands on evoked [3H]‐dopamine (DA) release in superfused brain slices and on synaptosomal cAMP accumulation.
Saturation‐binding assays in human neocortical and amygdala synaptosomes using a radiolabelled cannabinoid receptor agonist ([3H]‐CP55.940) revealed pKd values of 8.96 and 8.63, respectively. The numbers of binding sites (Bmax) were 3.99 and 2.67 pmol (mg protein)−1, respectively.
Various cannabinoid receptor ligands inhibited [3H]‐CP55.940 binding with rank order potencies corresponding to those of previous studies in animal tissues.
Electrically evoked [3H]‐DA release from human neocortical slices was inhibited by CP55.940 (IC50 6.76 nM, Imax 65%) and strongly enhanced by the cannabinoid receptor antagonist AM251. However, [3H]‐DA release was not influenced in rat neocortex. In human tissue, the estimated endocannabinoid concentration in the biophase of the release‐modulating CB1 receptors was 1.07 nM, expressed in CP55.940 units.
K+‐evoked [3H]‐DA release in the presence of tetrodotoxin (TTX) was strongly inhibited by CP55.940 in humans, but not in rats.
In human tissue, CP55.940 inhibited forskolin‐stimulated cAMP accumulation (IC50 20.89 nM, Imax 35%). AM251 blocked this effect and per se increased forskolin‐stimulated cAMP accumulation by ∼20%.
In conclusion, cannabinoids modulate [3H]‐DA release and adenylyl cyclase activity in the human neocortex. CB1 receptors are located on dopaminergic nerve terminals and seem to be tonically activated by endocannabinoids.

British Journal of Pharmacology (2004) 141, 1193–1203. doi:10.1038/sj.bjp.0705706
Identification in human airways smooth muscle cells of the prostanoid receptor and signalling pathway through which PGE2 inhibits the release of GM‐CSF
Authors: Clarke Deborah L , Belvisi Maria G , Catley Matthew C , Yacoub Magdi H , Newton Robert , Giembycz Mark A 
Published: April 2004

The prostanoid receptor(s) on human airways smooth muscle (HASM) cells that mediates the inhibitory effect of PGE2 on interleukin (IL)‐1β‐induced granulocyte/macrophage colony‐stimulating factor (GM‐CSF) release has been classified.
IL‐1β evoked the release of GM‐CSF from HASM cells, which was suppressed by PGE2, 16,16‐dimethyl PGE2 (nonselective), misoprostol (EP2/EP3‐selective), ONO‐AE1‐259 and butaprost (both EP2‐selective) with pIC50 values of 8.61, 7.13, 5.64, 8.79 and 5.43, respectively. EP‐receptor agonists that have selectivity for the EP1‐ (17‐phenyl‐ω‐trinor PGE2) and EP3‐receptor (sulprostone) subtypes as well as cicaprost (IP‐selective), PGD2, PGF2α and U‐46619 (TP‐selective) were poorly active or inactive at concentrations up to 10 μM.
AH 6809, a drug that can be used to selectively block EP2‐receptors in HASM cells, antagonised the inhibitory effect of PGE2, 16,16‐dimethyl PGE2 and ONO‐AE1‐259 with apparent pA2 values of 5.85, 6.09 and 6.1 respectively. In contrast, the EP4‐receptor antagonists, AH 23848B and L‐161,982, failed to displace to the right the concentration–response curves that described the inhibition of GM‐CSF release evoked by PGE2 and ONO‐AE1‐259.
Inhibition of GM‐CSF release by PGE2 and 8‐Br‐cAMP was abolished in cells infected with an adenovirus vector encoding an inhibitor protein of cAMP‐dependent protein kinase (PKA) but not by H‐89, a purported small molecule inhibitor of PKA.
We conclude that prostanoid receptors of the EP2‐subtype mediate the inhibitory effect of PGE2 on GM‐CSF release from HASM cells by recruiting a PKA‐dependent pathway. In addition, the data illustrate that caution should be exercised when using H‐89 in studies designed to assess the role of PKA in biological processes.

British Journal of Pharmacology (2004) 141, 1141–1150. doi:10.1038/sj.bjp.0705716
Changes in the vascular β‐adrenoceptor‐activated signalling pathway in 2Kidney‐1Clip hypertensive rats
Authors: Callera Glaucia E , Yeh Ester , Tostes Rita C A , Caperuto Luciana C , Carvalho Carla R O , Bendhack Lusiane M 
Published: April 2004

β‐Adrenoceptor (β‐AR)‐mediated vasodilation, which plays an important physiological role in the regulation of vascular tone, is decreased in two‐kidney, one clip (2K‐1C) renal hypertension. In this study, downstream pathways related to vascular β‐AR activation were evaluated in 2K‐1C rats.
Relaxation responses to isoprenaline, forskolin and 8‐Br‐cAMP were diminished in aortas without endothelium from 2K‐1C when compared to those in normotensive two kidney (2K). Basal adenosine‐3′,5′‐monophosphate (cAMP), as well as isoprenaline‐induced increase in cAMP levels, was not different between 2K and 2K‐1C aortas.
Contractile responses to caffeine, after depletion and reloading of intracellular Ca2+ stores, were greater in 2K‐1C than in 2K. The presence of isoprenaline during the Ca2+‐reloading period abolished the differences between groups by increasing caffeine contraction in 2K without changing this response in 2K‐1C aortas. Inhibition of the sarcolemmal Ca2+ATPase with thapsigargin markedly attenuated isoprenaline vasodilation in both 2K and 2K‐1C and abolished the differences between groups.
Blockade of ATP‐sensitive K+ channels (KATP) channels with glibenclamide significantly decreased isoprenaline vasodilation in 2K‐1C without affecting this response in 2K. Both vascular gene and protein expression of protein kinase A (PKA), as well as phosphoserine‐containing proteins, were increased in 2K‐1C vs 2K rats.
In conclusion, decreased isoprenaline vasodilation in 2K‐1C hypertensive rats is related to impaired modulation of the sarcolemmal Ca2+ATPase activity. Moreover, KATP channels may play a compensatory role on isoprenaline‐induced relaxation in renal hypertension. Both Ca2+ATPase and KATP channel functional alterations, associated with decreased β‐AR vasodilation, are paralleled by an upregulation of protein kinase A (PKA) and phosphoserine proteins expression.

British Journal of Pharmacology (2004) 141, 1151–1158. doi:10.1038/sj.bjp.0705717
Differential regulation of prostaglandin E biosynthesis by interferon‐γ in colonic epithelial cells
Authors: Wright Karen L , Weaver Sean A , Patel Kajal , Coopman Karen , Feeney Mark , Kolios George , Robertson Duncan A F , Ward Stephen G 
Published: April 2004

Cyclooxygenase (COX)‐2 expression and activity in response to pro‐inflammatory cytokines TNFα and IFNγ was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549.
TNFα induced concentration‐ and time‐dependent upregulation of COX‐2 mRNA, protein and prostaglandin (PG)E2 synthesis.
Co‐stimulation of TNFα with IFNγ resulted in reduced COX‐2 mRNA and protein expression.
IFNγ had no effect on the stability of TNFα‐induced COX‐2 mRNA.
TNFα‐induced PGE2 biosynthesis was significantly enhanced by the simultaneous addition of IFNγ and was COX‐2 dependent.
The combination of IFNγ and TNFα induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE2 synthesis.
These results suggest that, in terms of PGE2 biosynthesis, IFNγ plays a negative regulatory role at the level of COX‐2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFNγ in inflammatory diseases.

British Journal of Pharmacology (2004) 141, 1091–1097. doi:10.1038/sj.bjp.0705719
Cerebral uptake of mefloquine enantiomers with and without the P‐gp inhibitor elacridar (GF1210918) in mice
Authors: De Lagerie Sylvie Barraud , Comets Emmanuelle , Gautrand Céline , Fernandez Christine , Auchere Daniel , Singlas Eric , Mentre France , Gimenez François 
Published: April 2004

Mefloquine is a chiral neurotoxic antimalarial agent showing stereoselective brain uptake in humans and rats. It is a substrate and an inhibitor of the efflux protein P‐glycoprotein.
We investigated the stereoselective uptake and efflux of mefloquine in mice, and the consequences of the combination with an efflux protein inhibitor, elacridar (GF120918) on its brain transport.
Racemic mefloquine (25 mg kg−1) was administered intraperitoneally with or without elacridar (10 mg kg−1). Six to seven mice were killed at each of 11 time‐points between 30 min and 168 h after administration. Blood and brain concentrations of mefloquine enantiomers were determined using liquid chromatography.
A three‐compartment model with zero‐order absorption from the injection site was found to best represent the pharmacokinetics of both enantiomers in blood and brain. (−)Mefloquine had a lower blood and brain apparent volume of distribution and a lower efflux clearance from the brain, resulting in a larger brain/blood ratio compared to (+)mefloquine. Elacridar did not modify blood concentrations or the elimination rate from blood for either enantiomers. However, cerebral AUCinf of both enantiomers were increased, with a stronger effect on (+)mefloquine. The efflux clearance from the brain decreased for both enantiomers, with a larger decrease for (+)mefloquine.
After administration of racemic mefloquine in mice, blood and brain pharmacokinetics are stereoselective, (+)mefloquine being excreted from brain more rapidly than its antipode, showing that mefloquine is a substrate of efflux proteins and that mefloquine enantiomers undergo efflux in a stereoselective manner. Moreover, pretreatment with elacridar reduced the brain efflux clearances with a more pronounced effect on (+)mefloquine.

British Journal of Pharmacology (2004) 141, 1214–1222. doi:10.1038/sj.bjp.0705721
Multiple actions of anandamide on neonatal rat cultured sensory neurones
Authors: Evans Rhian M , Scott Roderick H , Ross Ruth A 
Published: April 2004

We have investigated the effects of the endocannabinoid anandamide (AEA) on neuronal excitability and vanilloid TRPV1 receptors in neonatal rat cultured dorsal root ganglion neurones.
Using whole‐cell patch‐clamp electrophysiology, we found that AEA inhibits high‐voltage‐activated Ca2+ currents by 33±9% (five out of eight neurones) in the absence of the CB1 receptor antagonist SR141716A (100 nM) and by 32±6% (seven out of 10 neurones) in the presence of SR141716A.
Fura‐2 fluorescence Ca2+ imaging revealed that AEA produced distinct effects on Ca2+ transients produced by depolarisation evoked by 30 mM KCl. In a population of neurones of larger somal area (372±20 μm2), it significantly enhanced Ca2+ transients (80.26±13.12% at 1 μM), an effect that persists after pertussis toxin pretreatment. In a population of neurones of smaller somal area (279±18 μm2), AEA significantly inhibits Ca2+ transients (30.75±3.54% at 1 μM), an effect that is abolished by PTX pretreatment.
Extracellular application of 100 nM AEA failed to evoke TRPV1 receptor inward currents in seven out of eight neurones that responded to capsaicin (1 μM), with a mean inward current of −0.94±0.21 nA. In contrast, intracellular application of 100 nM AEA elicited robust inward currents in ∼62% of neurones, the mean population response was −0.85±0.21 nA. When AEA was applied to the intracellular environment with capsazepine (1 μM), the mean population inward current was −0.01±0.01 nA. Under control conditions, mean population current fluctuations of −0.09±0.05 nA were observed.

British Journal of Pharmacology (2004) 141, 1223–1233. doi:10.1038/sj.bjp.0705723