bluuebunny/crossref_metadata_2025 huggingface dataset:
Total gaseous mercury emissions from soil in Guiyang, Guizhou, China
Authors: Feng Xinbin , Wang Shaofeng , Qiu Guangle , Hou Yamin , Tang Shunlin
Published: July 2005

Guiyang is located in the Circum‐Pacific Global Mercuriferous Belt, and mercury concentrations in soil in this area are enriched. In situ total gaseous mercury (TGM) exchange fluxes between air and soil surface were intensively measured at four sampling sites in Guiyang from 21 May to 16 June 2003. Overall, net emissions were obtained from all sampling sites. Soil mercury concentration and solar radiation are proved to be the two most important parameters to control mercury emissions from soil. Meanwhile, a rain event can enhance mercury emission rate significantly. A simple model based on the linear correlation between mercury flux and solar radiation was applied to scale up mercury emissions from soil zones with different mercury concentration ranges. It is observed that mercury emission fluxes from soil in Guiyang are one order of magnitude higher than the value used in early models to represent emissions from global mercuriferous belts which is 1.1 ng m−2 h−1. The annual mercury emission from soil in Guiyang is calculated to be 408 kg, which highlights that natural emissions from soil contribute significantly to the elevated TGM concentrations in the ambient air in Guiyang.
Improved estimate of tidal dissipation within Mars from MOLA observations of the shadow of Phobos
Authors: Bills Bruce G. , Neumann Gregory A. , Smith David E. , Zuber Maria T.
Published: July 2005

We report on new observations of the orbital position of Phobos, the innermost natural satellite of Mars, and show that these observations provide an improved estimate of the rate of tidal dissipation within Mars. The observations were made with the Mars Orbiter Laser Altimeter instrument on the Mars Global Surveyor spacecraft. The secular acceleration in along‐track orbital motion is conventionally expressed in terms of a quadratic term in mean orbital longitude, which yields s = (dn/dt)/2 = (136.7 ± 0.6) × 10−5 deg/yr2, where n is the mean motion. The corresponding fractional rate of change in orbital angular velocity is (dn/dt)/n = (6.631 ± 0.029) × 10−9/yr, the highest measured for any natural satellite in the solar system. The energy dissipation rate is (3.34 ± 0.01) MW. Because Phobos is so close to Mars, there are nonnegligible contributions to the tidal evolution from harmonic degrees 2, 3, and 4. However, the elastic tidal Love numbers are observationally constrained only at degree two. The observed acceleration is consistent with that for a homogeneous Maxwell viscoelastic model of Mars with effective viscosity of (8.7 ± 0.6) × 1014 Pa s.
Characterization of aquifer heterogeneity using transient hydraulic tomography
Authors: Zhu Junfeng , Yeh Tian-Chyi J.
Published: July 2005

Hydraulic tomography is a cost‐effective technique for characterizing the heterogeneity of hydraulic parameters in the subsurface. During hydraulic tomography surveys a large number of hydraulic heads (i.e., aquifer responses) are collected from a series of pumping or injection tests in an aquifer. These responses are then used to interpret the spatial distribution of hydraulic parameters of the aquifer using inverse modeling. In this study, we developed an efficient sequential successive linear estimator (SSLE) for interpreting data from transient hydraulic tomography to estimate three‐dimensional hydraulic conductivity and specific storage fields of aquifers. We first explored this estimator for transient hydraulic tomography in a hypothetical one‐dimensional aquifer. Results show that during a pumping test, transient heads are highly correlated with specific storage at early time but with hydraulic conductivity at late time. Therefore reliable estimates of both hydraulic conductivity and specific storage must exploit the head data at both early and late times. Our study also shows that the transient heads are highly correlated over time, implying only infrequent head measurements are needed during the estimation. Applying this sampling strategy to a well‐posed problem, we show that our SSLE can produce accurate estimates of both hydraulic conductivity and specific storage fields. The benefit of hydraulic tomography for ill‐posed problems is then demonstrated. Finally, to affirm the robustness of our SSLE approach, we apply the SSLE approach to a hypothetical three‐dimensional heterogeneous aquifer.
Modeling of acoustic wave dissipation in gas hydrate–bearing sediments
Authors: Guerin Gilles , Goldberg David
Published: July 2005

Recent sonic and seismic data in gas hydrate–bearing sediments have indicated strong waveform attenuation associated with a velocity increase, in apparent contradiction with conventional wave propagation theory. Understanding the reasons for such energy dissipation could help constrain the distribution and the amounts of gas hydrate worldwide from the identification of low amplitudes in seismic surveys. A review of existing models for wave propagation in frozen porous media, all based on Biot's theory, shows that previous formulations fail to predict any significant attenuation with increasing hydrate content. By adding physically based components to these models, such as cementation by elastic shear coupling, friction between the solid phases, and squirt flow, we are able to predict an attenuation increase associated with gas hydrate formation. The results of the model agree well with the sonic logging data recorded in the Mallik 5L‐38 Gas Hydrate Research Well. Cementation between gas hydrate and the sediment grains is responsible for the increase in shear velocity. The primary mode of energy dissipation is found to be friction between gas hydrate and the sediment matrix, combined with an absence of inertial coupling between gas hydrate and the pore fluid. These results predict similar attenuation increase in hydrate‐bearing formations over most of the sonic and seismic frequency range.
PetroGraph: A new software to visualize, model, and present geochemical data in igneous petrology
Authors: Petrelli M. , Poli G. , Perugini D. , Peccerillo A.
Published: July 2005

A new software, PetroGraph, has been developed to visualize, elaborate, and model geochemical data for igneous petrology purposes. The software is able to plot data on several different diagrams, including a large number of classification and “petrotectonic” plots. PetroGraph gives the opportunity to handle large geochemical data sets in a single program without the need of passing from one software to the other as usually happens in petrologic data handling. Along with these basic functions, PetroGraph contains a wide choice of modeling possibilities, from major element mass balance calculations to the most common partial melting and magma evolution models based on trace element and isotopic data. Results and graphs can be exported as vector graphics in publication‐quality form, or they can be copied and pasted within the most common graphics programs for further modifications. All these features make PetroGraph one of the most complete software presently available for igneous petrology research.
Dynamics of 2004–2005 Mt. Etna effusive eruption as inferred from petrologic monitoring
Authors: Corsaro Rosa Anna , Miraglia Lucia
Published: July 2005

From early September to early November, during the 2004–2005 Mt. Etna effusive eruption, petrologic monitoring was enabled by near‐vent sampling of erupting lava and onsite SEM‐EDS capabilities at INGV‐CT. Significant differences in composition and temperature of lava erupted from 2920–2620 m and 2820–2320 m vents, attest to variably evolved shallow magmatic conditions within a geometrically complex storage volume. The petrography and glass compositions of water‐quenched samples indicate that the magma feeding the 2004–2005 activity was likely to have been stored in the shallow plumbing system during the 2000 and 2001 activity, where it experienced volatile loss and extensive crystallization. Both geophysical and petrologic data suggest that this eruption was not triggered by the intrusion of a new dike from depth, but it was more likely that existing shallow magma reservoirs were passively mobilized and erupted in response to edifice deformation.
Impact of the Arctic Oscillation pattern on interannual forest fire variability in Central Siberia
Authors: Balzter Heiko , Gerard France F. , George Charles T. , Rowland Clare S. , Jupp Tim E. , McCallum Ian , Shvidenko Anatoly , Nilsson Sten , Sukhinin Anatoly , Onuchin Alexander , Schmullius Christiane
Published: July 2005

Russia's forests play an important role in the global carbon cycle. Because of their scale and interannual variability, forest fires can change the direction of the net carbon flux over Eurasia. 2002 and 2003 were the first two consecutive years in the atmospheric record in which the carbon content rose by more than 2 ppm per year. Northern Hemisphere fires could be the reason. We show that 2002 and 2003 were the two years with the largest fire extent in Central Siberia since 1996 using new measurements of burned forest area in Central Siberia derived from remote sensing. To quantify the relationship between Siberian forest fires and climate variability, we compare these measurements with time‐series of large‐scale climatic indices for the period 1992–2003. This paper is amongst the first studies that analyse statistical relationships between interannual variability of forest fires in Russia and climate indices. Significant relationships of annual burned forest area with the Arctic Oscillation, summer temperatures, precipitation, and the El Niño index NINO4 were found (p < 0.1). In contrast, we find no significant relation with the El Niño indices NINO1, NINO3 or SOI (p > 0.1). Interannual forest fire variability in Central Siberia could best be explained by a combination of the Arctic Oscillation index and regional summer temperatures (r2 = 0.80).
Ice surfaces in the mesosphere: Absence of dangling bonds in the presence of atomic oxygen
Authors: Boulter James E. , Morgan Christopher G. , Marschall Jochen
Published: July 2005

Ice deposition experiments in the presence of microwave discharge‐dissociated molecular oxygen suggest heterogeneous interactions between dangling OH bonds on the ice surface and atomic oxygen. Ice films deposited on a gold substrate at temperatures of 115, 130, and 140 K from oxygen/water gas mixtures representative of the summertime polar mesosphere exhibit infrared absorption features characteristic of dangling bonds, whereas films grown in the presence of atomic oxygen do not. Dangling bond spectral features are shown to diminish rapidly when the microwave discharge is activated during ice deposition. Similar decreases were not seen when the gas stream was heated or when the ice film was slowly annealed from 130 to 160 K. One interpretation of these results is that atomic oxygen binds to dangling bond sites during ice growth, a phenomenon that may also occur during the formation of ice particles observed just below the cold summertime mesopause.
Chemical effects in 11‐year solar cycle simulations with the Freie Universität Berlin Climate Middle Atmosphere Model with online chemistry (FUB‐CMAM‐CHEM)
Authors: Langematz Ulrike , Grenfell J. Lee , Matthes Katja , Mieth Peter , Kunze Markus , Steil Benedikt , Brühl Christoph
Published: July 2005

The impact of 11‐year solar cycle variations on stratospheric ozone (O3) is studied with the Freie Universität Berlin Climate Middle Atmosphere Model with interactive chemistry (FUB‐CMAM‐CHEM). To consider the effect of variations in charged particle precipitation we included an idealized NOx source in the upper mesosphere representing relativistic electron precipitation (REP). Our results suggest that the NOx source by particles and its transport from the mesosphere to the stratosphere in the polar vortex are important for the solar signal in stratospheric O3. We find a positive dipole O3 signal in the annual mean, peaking at 40–45 km at high latitudes and a negative O3 signal in the tropical lower stratosphere. This is similar to observations, but enhanced due to the idealized NOx source and at a lower altitude compared to the observed minimum. Our results imply that this negative O3 signal arises partly via chemical effects.
Dynamical coupling of the stratosphere and mesosphere in the 2002 Southern Hemisphere major stratospheric sudden warming
Authors: Liu H.‐L. , Roble R. G.
Published: July 2005

NCEP data and a NCAR TIME‐GCM simulation are used to explore the dynamical coupling of the stratosphere and mesosphere during the 2002 Southern Hemisphere major stratospheric sudden warming. The analyses suggest the possibility of feedback interactions between the planetary wave forcing and the mesospheric/stratospheric mean state changes. Multiple strong planetary waves before the warming penetrate into the mesosphere and weaken the polar jet. They alter the wave transmission condition in favor of more upward‐poleward propagation of the wave energy at progressively lower altitudes. The jet reversal and the planetary wave surf zone also descend from the mesosphere down to the stratosphere, making wave breaking more likely at decreasing altitudes with each wave episode. These changes in the wave transmission and breaking conditions in the mesosphere and stratosphere may be critical for the extensive major stratospheric warming.
Primary productivity control of simulated carbon cycle–climate feedbacks
Authors: Matthews H. Damon , Eby Michael , Weaver Andrew J. , Hawkins Barbara J.
Published: July 2005

Positive feedbacks between the terrestrial carbon cycle and climate represent an outstanding area of uncertainty in simulations of future climate change. Coupled climate‐carbon cycle models have simulated widely divergent feedback magnitudes, and attempts to explain model differences have had only limited success. In this study, we demonstrate that the response of vegetation primary productivity to climate changes is a critical controlling factor in determining the strength of simulated carbon cycle‐climate feedbacks. This conclusion sheds new light on coupled climate‐carbon cycle model results, and highlights the need for improved model representation of photosynthesis processes so as to better constrain future projections of climate change.
Seismic reflection evidence for a northeast‐dipping Hayward fault near Fremont, California: Implications for seismic hazard
Authors: Williams Robert A. , Simpson Robert W. , Jachens Robert C. , Stephenson William J. , Odum Jack K. , Ponce David A.
Published: July 2005

A 1.6‐km‐long seismic reflection profile across the creeping trace of the southern Hayward fault near Fremont, California, images the fault to a depth of 650 m. Reflector truncations define a fault dip of about 70 degrees east in the 100 to 650 m depth range that projects upward to the creeping surface trace, and is inconsistent with a nearly vertical fault in this vicinity as previously believed. This fault projects to the Mission seismicity trend located at 4–10 km depth about 2 km east of the surface trace and suggests that the southern end of the fault is as seismically active as the part north of San Leandro. The seismic hazard implication is that the Hayward fault may have a more direct connection at depth with the Calaveras fault, affecting estimates of potential event magnitudes that could occur on the combined fault surfaces, thus affecting hazard assessments for the south San Francisco Bay region.
Explaining and correcting the excessive semiannual variation in the Dst index
Authors: Mursula K. , Karinen A.
Published: July 2005

It is known that the semiannual variation in the Dst index is excessively large compared to all other indices of geomagnetic activity. This has been interpreted in terms of a separate “non‐storm component” which forms roughly one half of the whole semiannual variation in the Dst index. Since this component is not related to storms or the ring current it should be removed from the Dst index. We show how the “non‐storm component” arises from the seasonal variation of the magnetic field at the Dst stations and from the erroneous treatment of the quiet‐time curve during the construction of the index. Moreover, we reconstruct a corrected Dst index which is purified from the non‐storm component and show that then the semiannual variation indeed attains the same level as in other geomagnetic indices. This correction will greatly affect earlier estimates of the physical causes of semiannual variation based on the Dst index. Since the correction will reduce the power at periods even longer than the semiannual period, in particular the annual variation, it has important consequences also on other types of studies based on the Dst index.
Surface wave tomography from microseisms in Southern California
Authors: Sabra Karim G. , Gerstoft Peter , Roux Philippe , Kuperman W. A. , Fehler Michael C.
Published: July 2005

Since it has already been demonstrated that point‐to‐point seismic propagation Green Functions can be extracted from seismic noise, it should be possible to image Earth structure using the ambient noise field. Seismic noise data from 148 broadband seismic stations in Southern California were used to extract the surface wave arrival‐times between all station pairs in the network. The seismic data were then used in a simple, but densely sampled tomographic procedure to estimate the surface wave velocity structure within the frequency range of 0.1–0.2 Hz for a region in Southern California. The result compares favorably with previous estimates obtained using more conventional and elaborate inversion procedures. This demonstrates that coherent noise field between station pairs can be used for seismic imaging purposes.
The magnetic response of the ionosphere to pulsed HF heating
Authors: Papadopoulos K. , Wallace T. , Milikh G. M. , Peter W. , McCarrick M.
Published: July 2005

It shown theoretically and confirmed for the first time experimentally that the magnetic response of the lower auroral ionosphere to pulsed ionospheric HF heating depends critically on the parameter T/Th, where T is the pulse duration and Th is the time required for the electron temperature to reach its steady state value. Theoretical analysis shows that the strength and pulse shape of the near‐zone magnetic field on the ground depends not only on the traditional quasi‐static near‐field term, but also on a term which depends on the derivative of the current (i.e., the impulse response of the ionosphere). Results from newly‐conducted experiments using the HAARP transmitter in Gakona, Alaska are presented that verify our model, and it is shown that for T ≤ Th the magnetic flux on the ground due to the impulse response is 10–15 dB larger than the flux due to the quasi‐static term.
Seismic effects of viscous Biot‐coupling: Finite difference simulations on micro‐scale
Authors: Saenger E. H. , Shapiro S. A. , Keehm Y.
Published: July 2005

This paper is concerned with numerical considerations of viscous fluid effects on wave propagation in porous media. We apply a displacement‐stress rotated staggered finite‐difference (FD) grid technique to solve the elastodynamic wave equation. An accurate approximation of a Newtonian fluid is implemented in this technique by using a generalized Maxwell body. With this approach we consider the velocity predictions of the Biot theory for elastic waves in different digital rock samples. To distinguish between the low and the high frequency range we estimate the effective permeabilities by a flow simulation. Our numerical results indicate that the viscous Biot‐coupling is visible in the numerical experiments. Moreover, the influences of other solid‐fluid interactions (e.g., Squirt flow) are also discussed.
Large latitudinal gradients and temporal heterogeneity in aerosol black carbon and its mass mixing ratio over southern and northern oceans observed during a trans‐continental cruise experiment
Authors: Moorthy K. Krishna , Satheesh S. K. , Babu S. Suresh , Saha Auromeet
Published: July 2005

Extensive, and collocated measurements of the mass concentrations (MB) of aerosol black carbon (BC) and (MT) of composite aerosols were made over the Arabian Sea, tropical Indian Ocean and the Southern Ocean during a trans‐continental cruise experiment. Our investigations show that MB remains extremely low (<50 ng m−3) and remarkably steady (in space and time) in the Southern Ocean (20°S to 56°S). In contrast, large latitudinal gradients exist north of ∼20°S; MB increasing exponentially to reach as high as 2000 ng m−3 in the Arabian Sea (∼8°N). Interestingly, the share of BC showed a distinctly different latitudinal variation, with a peak close to the equator and decreasing on either side. Large fluctuations were seen in MT over Southern Ocean associated with enhanced production of sea‐salt aerosols in response to sea‐surface wind speed. These spatio‐temporal changes in MB and its mixing ratio have important implications to regional and global climate.
Evaluation of electron impact excitation of N2 X 1Σg+(0) into the N2+ X 2Σg+(v), A 2Πu(v), and B 2Σu+(v) states
Authors: Shemansky Donald E. , Liu Xianming
Published: July 2005

Published experimental integrated electric dipole photoionization oscillator strengths (fij) have been applied to the determination of absolute electron impact excitation cross sections of the N2 X 1Σg+(0) state into the N2+ X 2Σg+(v), A 2Πu(v), and B 2Σu+(v) states. The required relative electron impact cross section shape functions from threshold to energy values, limited by the imposition of relativistic effects at the high end, are established in this work by extracting accurate analytic functions from a critical review of extensive published experimental results. The cross sections examined here are important benchmarks used in establishing absolute values for critical rate processes in aeronomy. The determination of the absolute cross sections using the derived fij is accomplished through the physical relationship to a modified Born approximation analytic function that defines the electron impact shape functions. The zero order term of the analytic function is established in value relative to the remaining terms through shape analysis of the experimental electron impact results. The value of fij fixes the absolute value of the zero order term, determining the cross sections over the entire electron impact energy range. It is argued that this methodology is the most accurate approach at this time because of the existence of the intrinsically more accurate photometrically dermined fij. The critical quantities in atmospheric process applications are the branching ratios of excitation into the N2+ X 2Σg+, A 2Πu, and B 2Σu+ states. The N2+ (X 2Σg+, A 2Πu, B 2Σu+) partitioning within the total ionization cross section has been a source of disagreement in the literature, in spite of the fact that substantial effort has been expended in establishing acceptably accurate values. The present work establishes accurate cross sections for these states over the entire practical energy range required for research in atmospheric N2 physical chemistry. The accuracy of the results obtained here are verified by consistency with the most reliably established past experimental electron impact cross sections, in agreement with the independently established total N2+ cross section. We provide analytic collision strengths for the vibrational levels of the N2+ X 2Σg+, A 2Πu, and B 2Σu+ states, allowing establishment of rate coefficients for the system, at an estimated error ≤±8%.
New extrapolation method for coronal mass ejection onset time estimation
Authors: Moon Y.‐J. , Cho K.‐S. , Chae Jongchul , Choe G. S. , Kim Y.‐H. , Bong Su‐Chan , Park Y.‐D.
Published: July 2005

The onset time of a coronal mass ejection (CME) is usually extrapolated from its speed in a coronagraph using the constant speed method. In this study, we present a new empirical method for extrapolating the onset times of flare‐associated CMEs. For this we reexamined seven well‐observed CME‐flare events whose initial eruption speeds are estimated to be about a few tens of kilometers per second from LASCO C1 coronagraph or loop displacements seen in SOHO/EIT and TRACE images. In this study, the CME onset time is assumed to be the earliest observable time of eruption from these images. We estimated the onset time differences between the CMEs and the associated flares observed in soft X rays. We then compared them with the onset time differences estimated by the constant speed extrapolation method from LASCO C2 positions. It is noted that there is a certain quadratic relation between the CME speed first observed in the LASCO C2 field of view and the observed CME travel time from near the solar surface to the C2 field of view in units of the travel time estimated by the constant speed method. This empirical relation thus enables us to determine the onset times of CMEs without any assumption in CME kinematics. We have applied the new empirical method to 91 flare‐associated CMEs that were accompanied by type II bursts. The onset time difference for these events as well as the well‐observed events shows that in most cases (about 80%) the CME initiation precedes the onset of the associated flare. This result provides an important clue to the mechanism and relation of CMEs and flares.
The large Thaumasia graben on Mars: Is it a rift?
Authors: Hauber E. , Kronberg P.
Published: July 2005

We investigate the morphology and topography of one of the largest fault‐bounded tectonic structures on Mars, a complex, approximately N‐S trending system of troughs and scarps at the western border of the Thaumasia plateau in the Claritas region (hereinafter referred to as “Thaumasia graben,” or TG). It is located between 15°S and 38°S latitude and at ∼255°E longitude. No detailed investigation of its morphotectonic setting has been performed yet. The region is a complexly fractured area with a number of different fault sets, including simple and complex graben. The TG extends over more than 1000 km along its trend, averaging 100 km in width and 1.6 km in depth. Crustal extension is accommodated by the formation of a system of asymmetric graben, or halfgraben. On the basis of fault orientation and trough depth, the TG can be subdivided in a north‐south direction into three segments. Except for the northernmost segment, the predominant master fault system is located along the eastern flank of the TG, highlighting the overall asymmetric architecture. Fault length segments vary from 50 to 90 km with observable displacements of 1.3–2.2 km. Crustal extension, inferred from gridded MOLA topography across scarp offsets, varies along trend between 0.5 km and ∼4 km, assuming a fault dip of 60°. This is relatively moderate extension if compared to terrestrial continental rifts, but consistent with extension measured across the Tempe Rift on Mars. We find that the Thaumasia graben displays some characteristics which are common to terrestrial continental rifts, whereas other properties are distinctively not rift‐like.
A framework for next‐generation radiation belt models
Authors: O'Brien T. P.
Published: July 2005

The trapped radiation specifications, such as AE‐8 and AP‐8, are based upon a simple and reasonable framework that happens to be insufficient to the modern demands placed upon them. This manuscript outlines an improved framework for the next generation of radiation models. While existing radiation specifications tend to provide mean fluxes on a grid in magnetic coordinates, scientific and engineering users are starting to demand capabilities that are far beyond this simple framework, such as error bars on total mission dose and real‐time data assimilation. One framework that can provide these added capabilities while still remaining fairly simple is the joint probability distribution, described here. The joint distribution can describe the behavior of individual fluxes on a grid in magnetic coordinates while also describing how those fluxes vary together. This covariance is a crucial ingredient for data assimilation and for proper error bars and percentiles on composite quantities like dose or fluence to a shielded device. This manuscript describes the core math of the proposed framework, an approach to building the model from in situ observations and/or numerical simulations, how to use the model to calculate error bars and percentiles on composite quantities, how to use the model in data assimilation, and how to make a first estimate of the dependence of worst case fluences on aggregation time.
Developing skeletal muscle cells express functional muscarinic acetylcholine receptors coupled to different intracellular signaling systems
Authors: Furlan Ingrid , Godinho Rosely Oliveira
Published: July 2005

This study analyzed the expression of muscarinic acetylcholine receptors (mAChRs) in the rat cultured skeletal muscle cells and their coupling to G protein, phospholipase C and adenylyl cyclase (AC).

Our results showed the presence of a homogeneous population of [3H]methyl‐quinuclidinyl benzilate‐binding sites in the membrane fraction from the rat cultured muscle (KD=0.4 nM, Bmax=8.9 fmol mg protein−1). Specific muscarinic binding sites were also detected in denervated diaphragm muscles from adult rats and in myoblasts isolated from newborn rats.

Activation of mAChRs with carbachol induced specific [35S]GTPγS binding to cultured muscle membranes and potentiated the forskolin‐dependent stimulation of AC. These effects were totally inhibited by 0.1–1 μM atropine.

In addition, mAChRs were able to stimulate generation of diacylglycerol (DAG) in response to acetylcholine, carbachol or selective mAChR agonist oxotremorine‐M.

The carbachol‐dependent increase in DAG was inhibited in a concentration‐dependent manner by mAChR antagonists atropine, pirenzepine and 4‐DAMP mustard.

Finally, activation of these receptors was correlated with increased synthesis of acetylcholinesterase, via a PKC‐dependent pathway.

Taken together, these results indicate that expression of mAChRs, coupled to G protein and distinct intracellular signaling systems, is a characteristic of noninnervated skeletal muscle cells and may be responsible for trophic influences of acetylcholine during formation of the neuromuscular synapse.

British Journal of Pharmacology (2005) 146, 389–396. doi:10.1038/sj.bjp.0706329
Effect of clopidogrel on the expression of inflammatory markers in rabbit ischemic coronary artery
Authors: Molero Laura , López‐Farré Antonio , Mateos‐Cáceres Petra J , Fernández‐Sánchez Ruth , Maestro María Luisa , Silva Jacobo , Rodríguez Enrique , Macaya Carlos
Published: July 2005

Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. Platelets may contribute to increase ischemic injury by enhancing the inflammatory response of leukocytes and endothelial myocardial cells. Pharmacological inhibition of platelet activation prevents ischemic complications in patients with coronary diseases. Agents directed against the integrin glycoprotein IIb/IIIa (GP IIb/IIIa) receptor not only inhibit platelet aggregation but also have been demonstrated to limit the inflammatory response in acute coronary syndromes. The question then raised is if the inhibition of platelet activation by other mechanisms than the blockade of GP IIb/IIIa may also exert anti‐inflammatory effects. The aim of the present study was to analyze if clopidogrel may exert anti‐inflammatory effects during the acute phase of myocardial infarction.

A ligature was placed around the left anterior descending coronary artery of New Zealand White rabbits. After 15 min of ischemia, the myocardium was reperfused and the ischemic coronary artery was isolated 24 h after the ischemia. A group of ischemic rabbits was given a single oral dose of clopidogrel (20 mg kg−1) just after the arterial occlusion and the animal was recovered. Sham‐operated animals served as control.

P‐selectin expression was significantly increased in infarcted rabbits with respect to control rabbits. Clopidogrel administration reduced P‐selectin expression with respect to untreated infarcted rabbits. CD40 ligand and tissue factor expression was increased in the ischemic coronary artery and reduced after clopidogrel administration. Clopidogrel also protected endothelial nitric oxide synthase protein expression in the ischemic coronary artery, a protein that has been found downregulated under inflammatory conditions.

In conclusion, inhibition of platelet activation by clopidogrel exerted anti‐inflammatory effects on the ischemic coronary artery.

British Journal of Pharmacology (2005) 146, 419–424. doi:10.1038/sj.bjp.0706340
Comparison of the biological activities of anagrelide and its major metabolites in haematopoietic cell cultures
Authors: Wang Guosu , Franklin Richard , Hong Ying , Erusalimsky Jorge D
Published: July 2005

The platelet‐lowering drug anagrelide inhibits bone marrow megakaryocytopoiesis by an unknown mechanism. Recently, it was found that anagrelide is bio‐transformed in humans into two major metabolites (6,7‐dichloro‐3‐hydroxy‐1,5 dihydro‐imidazo[2,1‐b]quinazolin‐2‐one (BCH24426) and 2‐amino‐5,6‐dichloro‐3,4,‐dihydroquinazoline (RL603). Whether these metabolites have biological activities that may underlie the mode of action of the parent drug is presently unclear. To clarify this question here we have compared the activities of anagrelide, BCH24426 and RL603 on the growth and differentiation of CD34+ haematopoietic progenitor cells in liquid culture and on the migration of differentiated megakaryocytes.

Incubation with either anagrelide, BCH24426 or RL603 did not affect the early expansion of CD34+ cells stimulated by thrombopoietin. In contrast, both anagrelide and BCH24426 potently inhibited the development of megakaryocytes (IC50±s.e.m.=26±4 and 44±6 nM, respectively), whereas RL603 showed no significant effect.

Anagrelide and BCH24426 did not affect erythroid or myelomonocytic differentiation stimulated by erythropoietin or granulocyte–macrophage colony‐stimulating factor, demonstrating the selectivity of these compounds against the megakaryocytic lineage.

Neither anagrelide nor its metabolites showed a significant effect on the migratory response of megakaryocytes towards stromal cell‐derived factor‐1α.

Although BCH24426 was shown to be considerably more potent than anagrelide as an inhibitor of phosphodiesterase type III (PDEIII) (IC50=0.9 vs 36 nM) this activity did not correlate with the potency of inhibition of megakaryocyte development. Furthermore, other PDEIII inhibitors of widely differing potency were shown to have negligible effects on megakaryocytopoiesis.

Taken together our results demonstrate that anagrelide and BCH24426 target a cellular event involved specifically in the megakaryocyte differentiation programme, which is independent of PDEIII inhibition.

British Journal of Pharmacology (2005) 146, 324–332. doi:10.1038/sj.bjp.0706341
Ethyl caffeate suppresses NF‐κB activation and its downstream inflammatory mediators, iNOS, COX‐2, and PGE2in vitro or in mouse skin
Authors: Chiang Yi‐Ming , Lo Chiu‐Ping , Chen Yi‐Ping , Wang Sheng‐Yang , Yang Ning‐Sun , Kuo Yueh‐Hsiung , Shyur Lie‐Fen
Published: July 2005

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti‐inflammatory functions and mechanism(s) of ethyl caffeate.

Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)‐induced nitric oxide (NO) production (IC50=5.5 μg ml−1), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages.

Transient gene expression assays using human cox‐2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox‐2 transcriptional activity in 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐treated MCF‐7 cells.

Immunohistochemical studies of mouse skin demonstrated that TPA‐induced COX‐2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti‐inflammatory drug.

The phosphorylation and degradation of inhibitor κB (IκB) and the translocation of nuclear transcription factor‐κB (NF‐κB) into the nucleus, as well as the activation of mitogen‐activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF‐κB activation by impairing the binding of NF‐κB to its cis‐acting element. These results suggest that ethyl caffeate suppresses iNOS and COX‐2 expressions partly through the inhibition of the NF‐κB·DNA complex formation.

Structure–activity relationship analyses suggested that the catechol moiety and α,β‐unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF‐κB·DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti‐inflammatory and therapeutic properties of ethyl caffeate.

British Journal of Pharmacology (2005) 146, 352–363. doi:10.1038/sj.bjp.0706343
A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor‐induced tumour angiogenesis and heparanase activity
Authors: Takahashi Hidenori , Ebihara Satoru , Okazaki Tatsuma , Asada Masanori , Sasaki Hidetada , Yamaya Mutsuo
Published: July 2005

Disseminated intravascular coagulation (DIC) is the most common complication of solid tumours. In this study, the effectiveness of three polysaccharide anticoagulants (PSAs), at therapeutic doses, at inhibiting solid tumour growth was investigated.

Mice with tumour xenografts were subcutaneously injected with either unfractionated heparin (UFH; 200 units kg−1 day−1), dalteparin (75 units kg−1 day−1) or danaparoid (50 units kg−1 day−1). At these concentrations, these PSAs are equieffective at inhibiting blood coagulation activated factor X. In mice with Lewis lung carcinoma (LLC) tumours dalteparin and, to a lesser extent, UFH inhibited both tumour growth and angiogenesis, whereas danaparoid did not. In contrast, in mice with KLN205 tumours, all the PSAs inhibited tumour growth and angiogenesis.

All the PSAs significantly inhibited proliferation, migration of endothelial cells and vessel formation in matrigel plugs containing vascular endothelial growth factor (VEGF) and there were no significant differences between these effects of the PSAs. The PSAs had no effect on endothelial cell tubular formation in vitro.

Although all the PSAs inhibited VEGF production in KLN205 tumours in vivo and cells in vitro, in LLC tumours and cells only UFH and dalteparin inhibited VEGF production, whereas danaparoid did not.

In both LLC and KLN205 tumours in vivo, heparanase activity was inhibited by UFH and dalteparin, but not by danaparoid.

Hence, UFH and dalteparin may be more effective than danaparoid at inhibiting cancer progression in DIC patients with solid tumours, due at least in part to their ability to suppress VEGF and heparanase in tumours.

British Journal of Pharmacology (2005) 146, 333–343. doi:10.1038/sj.bjp.0706344
Endogenous opioid mechanisms partially mediate P2X3/P2X2/3‐related antinociception in rat models of inflammatory and chemogenic pain but not neuropathic pain
Authors: McGaraughty Steve , Honore Prisca , Wismer Carol T , Mikusa Joseph , Zhu Chang Z , McDonald Heath A , Bianchi Bruce , Faltynek Connie R , Jarvis Michael F
Published: July 2005

P2X3/P2X2/3 receptors have emerged as important components of nociception. However, there is limited information regarding the neurochemical systems that are affected by antagonism of the P2X3/P2X2/3 receptor and that ultimately contribute to the ensuing antinociception. In order to determine if the endogenous opioid system is involved in this antinociception, naloxone was administered just prior to the injection of a selective P2X3/P2X2/3 receptor antagonist, A‐317491, in rat models of neuropathic, chemogenic, and inflammatory pain.

Naloxone (1–10 mg kg−1, i.p.), dose‐dependently reduced the antinociceptive effects of A‐317491 (1–300 μmol kg−1, s.c.) in the CFA model of thermal hyperalgesia and the formalin model of chemogenic pain (2nd phase), but not in the L5–L6 spinal nerve ligation model of neuropathic allodynia. In comparison experiments, the same doses of naloxone blocked or attenuated the actions of morphine (2 or 8 mg kg−1, s.c.) in each of these behavioral models.

Injection of a peripheral opioid antagonist, naloxone methiodide (10 mg kg−1, i.p.), did not affect A‐317491‐induced antinociception in the CFA and formalin assays, suggesting that the opioid component of this antinociception occurred within the CNS. Furthermore, this utilization of the central opioid system could be initiated by antagonism of spinal P2X3/P2X2/3 receptors since the antinociceptive actions of intrathecally delivered A‐317491 (30 nmol) in the formalin model were reduced by both intrathecally (10–50 nmol) and systemically (10 mg kg−1, i.p.) administered naloxone.

This utilization of the opioid system was not specific to A‐317491 since suramin‐, a nonselective P2X receptor antagonist, induced antinociception was also attenuated by naloxone.

In in vitro studies, A‐317491 (3–100 μM) did not produce any agonist response at δ opioid receptors expressed in NG108‐15 cells. A‐317491 had been previously shown to be inactive at the κ and μ opioid receptors. Furthermore, naloxone, at concentrations up to 1 mM, did not compete for [3H] A‐317491 binding in 1321N1 cells expressing human P2X3 receptors.

Taken together, these results indicate that antagonism of spinal P2X3/P2X2/3 receptors results in an indirect activation of the opioid system to alleviate inflammatory hyperalgesia and chemogenic nociception.

British Journal of Pharmacology (2005) 146, 180–188. doi:10.1038/sj.bjp.0706346
Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia
Authors: Newson Penny , Lynch‐Frame Ann , Roach Rebecca , Bennett Sarah , Carr Vaughan , Chahl Loris A
Published: July 2005

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin‐sensitive primary afferent neurons might be abnormal in schizophrenia.

This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned.

The mean body weight of capsaicin‐treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control.

Capsaicin‐treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol.

Coronal brain sections of capsaicin‐treated rats had smaller cross‐sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex.

It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia.

British Journal of Pharmacology (2005) 146, 408–418. doi:10.1038/sj.bjp.0706349
Interactions of metoclopramide and ergotamine with human 5‐HT3A receptors and human 5‐HT reuptake carriers
Authors: Walkembach Jan , Brüss Michael , Urban Bernd W , Barann Martin
Published: July 2005

The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5‐HT3A receptors and 5‐HT reuptake carriers, stably expressed in HEK‐293 cells, were studied with patch‐clamp‐ and ([3H]5‐HT)‐uptake techniques.

At clinical concentrations, metoclopramide inhibited peak and integrated currents through h5‐HT3A receptors concentration‐dependently (IC50=0.064 and 0.076 μM, respectively) when it was applied in equilibrium (60 s before and during 5‐HT (30 μM) exposure). The onset and offset time constants of metoclopramide action were 1.3 and 2.1 s, respectively. The potency of metoclopramide when exclusively applied during the agonist pulse decreased more than 200‐fold (IC50=19.0 μM, peak current suppression).

Metoclopramide (0.10 μM) did not alter the EC50 of 5‐HT‐induced peak currents. In contrast to the lack of competitive interaction between metoclopramide and 5‐HT in this functional assay, metoclopramide inhibited specific [3H]GR65630 binding to human h5‐HT3A receptors in a surmountable manner. This seeming discrepancy between functional studies and radioligand binding experiments may be accounted for by (1) the slow kinetics of inhibition of peak currents by metoclopramide compared with the fast onset and offset kinetics of 5‐HT‐induced currents and (2) the low efficacy of metoclopramide in inhibiting radioligand binding (e.g. only 20% binding inhibition compared to 79% peak current suppression by 200 nM metoclopramide).

At low concentrations (1–10 nM), ergotamine had no effect on 5‐HT (30 μM)‐induced peak currents. Above clinical concentrations, ergotamine (>3 μM) inhibited them.

When both drugs were applied together (0.10 μM metoclopramide+0.001 to 0.01 μM ergotamine), an inhibition of both, peak and integrated current responses was observed.

Neither metoclopramide (30 μM) nor ergotamine (30 μM) had an effect on the 5‐HT reuptake carrier as they did not alter the citalopram‐sensitive [3H]5‐HT uptake.

British Journal of Pharmacology (2005) 146, 543–552. doi:10.1038/sj.bjp.0706351
Expression and immunolocalization of aquaporin‐7 in rat gastrointestinal tract
Authors: Laforenza Umberto , Gastaldi Giulia , Grazioli Monica , Cova Emanuela , Tritto Simona , Faelli Alide , Calamita Giuseppe , Ventura Ulderico
Published: July 2005

Background information. In the gastrointestinal tract of mammals, water can either be secreted with digestive juices or absorbed by the small and large intestine. Transcellular water movement can be mediated by the transmembrane protein family of AQPs (aquaporins), as has also been recently identified in the gastrointestinal tract. However, the localization, expression and functioning of AQPs in the gastrointestinal tract have not been completely characterized. For the present study, we investigated: (1) the expression of AQP7 in some portions of rat gastrointestinal tract by semiquantitative reverse transcriptase—PCR and by immunoblotting and (2) the cellular and subcellular localization of AQP7 by immunohistochemistry.

Results. AQP7 mRNA and proteins were highly expressed in the small intestine, weakly in the caecum, colon and rectum and were absent in the stomach. Immunoblotting analysis using rat gastrointestinal tract membrane fractions showed two major bands corresponding to a molecular mass of approx. 34 and 40 kDa for the AQP7 protein. No bands were observed when the anti‐AQP7 antibody was preadsorbed with the immunizing peptide. Immunohistochemistry revealed strong AQP7 labelling in the surface epithelial cells of duodenum, jejunum, ileum, caecum, colon and rectum, whereas weak or no labelling was observed in the crypt cells. The labelling was manifest particularly in the apical membrane but intracellular staining was also observed.

Conclusions. The results indicate that AQP7 is present in the small and large intestine. The higher expression of AQP7 protein at the apical pole of the superficial epithelial cells suggests its involvement in rapid fluid movement through the villus epithelium.