bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetospheric and auroral activity during the 18 April 2002 sawtooth event
Authors: Henderson M. G. , Reeves G. D. , Skoug R. , Thomsen M. F. , Denton M. H. , Mende S. B. , Immel T. J. , Brandt P. C. , Singer H. J.
Published: January 2006

We examine the 18 April 2002 sawtooth event. We find that the strong magnetic field dipolarizations observed in association with each tooth are not global in occurrence but are rather confined to the nightside. In addition, we find that the flux increases are not globally dispersionless. Instead, each tooth is associated with a nonglobal, but wider‐than‐usual, dispersionless injection region that is consistent with the high Kp versions of the standard injection boundary model (which places the entire nightside segment of geosynchronous orbit tailward of the injection boundary for values of Kp above about 5). We also find evidence that at least one of the teeth was likely triggered by a pressure pulse. The auroral distribution shows a repeatable evolution in which a wide double‐oval configuration gradually thins. Following this, a localized substorm‐like brightening in the dusk to midnight sector occurs on the lower branch of the double oval which subsequently expands rapidly poleward and azimuthally. A new expanded double oval configuration emerges from this expansion phase activity and the cycle repeats itself for the duration of the sawtooth event. The observations presented give considerable support to the contention that sawtooth events are actually sequences of quasi‐periodic substorms. We suggest that sawtooth events can be viewed as a magnetospheric mode similar to Steady Magnetospheric Convection intervals (SMCs) except that for sawtooth events, the flow of energy from the solar wind into the magnetosphere becomes too large to dissipate without the periodic occurrence of substorms. We further suggest that the quasi‐periodicity arises because the magnetosphere may only become susceptible to external or internal triggering after it has been driven beyond a stability threshold. This hypothesis can account for the existence of more potential external triggers (in the interplanetary magnetic field or solar wind) than teeth in that the magnetosphere may be selectively responsive to them.
Subglacial sediments as a control on the onset and location of two Siple Coast ice streams, West Antarctica
Authors: Peters Leo E. , Anandakrishnan Sridhar , Alley Richard B. , Winberry J. Paul , Voigt Donald E. , Smith Andrew M. , Morse David L.
Published: January 2006

Laterally continuous subglacial sediments are a necessary component for ice streaming in the modern onset regions of the ice streams draining the Siple Coast of West Antarctica on the basis of new seismic data combined with previous results. We present geophysical results from seismic reflection and refraction experiments in the upper reaches of ice streams C and D that highlight continuous sedimentary basins within and upstream of the current onset regions of both ice streams, with streaming ice overlying these sedimentary packages. The subglacial environment changes from no‐sediment to discontinuous‐sediment to continuous‐sediment cover along a longitudinal profile from the ice sheet to tributary C1B. Along this same profile, we observe a speedup of ice flow and then full development of the ice stream tributary. Ice stream D flows above a thick sedimentary package with an uppermost low‐seismic‐velocity zone indicative of soft till, and the upglacier and lateral extensions of ice stream D are tightly constrained by the extent of continuous sediments. The inland termination of these sediments suggests that future migration of high‐velocity, low‐shear‐stress ice flow in these regions appears unlikely.
Crustal thickness variations in the Aegean region and implications for the extension of continental crust
Authors: Zhu Lupei , Mitchell Brian J. , Akyol Nihal , Cemen Ibrahim , Kekovali Kivanc
Published: January 2006

We installed 5 broadband and 45 short‐period temporary seismic stations, distributed partly as a dense, 100‐km‐long, N‐S linear array and partly as a regional network, throughout the Menderes Massif of western Turkey in order to study crust‐upper mantle structure and seismicity. In this study, we have combined teleseismic waveform data from these stations with data from several permanent seismic stations to determine crustal thickness variations in the Aegean region. Receiver function studies at seven broadband stations, using the H‐κ stacking method, have yielded crustal thicknesses and Vp/Vs ratios over a broad region of the Aegean. A more detailed crustal image was obtained in the central Menderes Massif, where we applied common conversion point stacking to receiver functions obtained from the N‐S linear array. The results show a general trend of westward crustal thinning from 36 km in central Anatolia to 28–30 km in the central Menderes Massif to 25 km beneath the Aegean Sea. The results also indicate that crustal thinning in the Aegean is not uniform in the N‐S extensional direction. The crust is thinner in the central Menderes Massif (28–30 km of crustal thicknesses) and the Cycladic Massif (25–26 km) than in surrounding regions where crustal thicknesses are 32–34 km. The long‐lived elevated Moho under the metamorphic core complexes suggests that the lower crust in the Aegean region is at least 3 times more viscous than that in the Basin and Range Province, where the Moho is much flatter.
Satellite‐based climatology of Mediterranean cloud systems and their association with large‐scale circulation
Authors: Chaboureau Jean‐Pierre , Claud Chantal
Published: January 2006

The variability of Mediterranean cloud systems is investigated using 8.5 years (from January 1987 to June 1995) of TIROS‐N Operational Vertical Sounder (TOVS) observations acquired aboard the National Oceanic and Atmospheric Administration (NOAA) series of operational polar satellites. Cloud systems and troughs are automatically detected with the retrievals of the cloud top pressure (CTP) and the temperature of lower stratosphere (TLS). Observed cloud systems have a typical size of few hundred kilometres with a larger occurrence between March and October. A threefold cloud system typology reveals the presence of an upper‐level anomaly for about 30% of the cloud systems in winter, 26% in spring and 7% in autumn (but 23% in October). During summer, in contrast, the forcing is very likely local, and according to the composite analysis, weakly related to upper‐level anomaly. During the cold seasons (15 October to 15 April), more cloud systems are found during negative North Atlantic Oscillation (NAO) phase when the north Atlantic storm track takes its southernmost position. Consistently, more systems are observed during the Greenland Anticyclone and the Atlantic Ridge regimes, compared to the Zonal and Blocking regimes. Finally, severe precipitation events over the Alpine region are associated with a warm TLS anomaly upstream the cloud system, showing once more the impact of the upper levels on the weather over this area.
In‐flight calibration and performance of the Mars Exploration Rover Panoramic Camera (Pancam) instruments
Authors: Bell J. F. , Joseph J. , Sohl‐Dickstein J. N. , Arneson H. M. , Johnson M. J. , Lemmon M. T. , Savransky D.
Published: January 2006

The Mars Exploration Rover Panoramic Camera (MER/Pancam) instruments have acquired more than 60,000 high‐resolution, multispectral, stereoscopic images of soil, rocks, and sky at the Gusev crater and Meridiani Planum landing sites since January 2004. These images, combined with other MER data sets, have enabled new discoveries about the composition, mineralogy, and geologic/geochemical evolution of both sites. One key to the success of Pancam in contributing to the overall success of MER has been the development of a calibration pipeline that can quickly remove instrumental artifacts and generate both absolute radiance and relative reflectance images with high accuracy and precision in order to influence tactical rover driving and in situ sampling decisions. This paper describes in detail the methods, assumptions, and models/algorithms in the calibration pipeline developed for Pancam images, based on new measurements and refinements performed primarily from flight data acquired on Mars. Major calibration steps include modeling and removal of detector bias signal, active and readout region dark current, electronic “shutter smear,” and pixel‐to‐pixel responsivity (flatfield) variations. Pancam images are calibrated to radiance (W/m2/nm/sr) using refined preflight‐derived calibration coefficients, or radiance factor (I/F) using near‐in‐time measurements of the Pancam calibration target and a model of aeolian dust deposition on the target as a function of time. We are able to verify that the absolute radiance calibration of most Pancam images is accurate to within about 10% or less and that the filter‐to‐filter and pixel‐to‐pixel precision of the calibrated relative reflectance data (both based on measurements of the Pancam calibration target) are typically about 3% and 1% or less, respectively. Examples are also presented of scientific applications made possible by the high fidelity of the calibrated Pancam data. These include 11‐color visible to near‐IR spectral analysis, calculation of “true color” and chromaticity values, and generation of “super resolution” image data products. This work represents a follow‐on and enhancement to the Pancam preflight calibration process described by Bell et al. (2003).
Crater gradation in Gusev crater and Meridiani Planum, Mars
Authors: Grant J. A. , Arvidson R. E. , Crumpler L. S. , Golombek M. P. , Hahn B. , Haldemann A. F. C. , Li R. , Soderblom L. A. , Squyres S. W. , Wright S. P. , Watters W. A.
Published: January 2006

The Mars Exploration Rovers investigated numerous craters in Gusev crater and Meridiani Planum during the first ∼400 sols of their missions. Craters vary in size and preservation state but are mostly due to secondary impacts at Gusev and primary impacts at Meridiani. Craters at both locations are modified primarily by eolian erosion and infilling and lack evidence for modification by aqueous processes. Effects of gradation on crater form are dependent on size, local lithology, slopes, and availability of mobile sediments. At Gusev, impacts into basaltic rubble create shallow craters and ejecta composed of resistant rocks. Ejecta initially experience eolian stripping, which becomes weathering‐limited as lags develop on ejecta surfaces and sediments are trapped within craters. Subsequent eolian gradation depends on the slow production of fines by weathering and impacts and is accompanied by minor mass wasting. At Meridiani the sulfate‐rich bedrock is more susceptible to eolian erosion, and exposed crater rims, walls, and ejecta are eroded, while lower interiors and low‐relief surfaces are increasingly infilled and buried by mostly basaltic sediments. Eolian processes outpace early mass wasting, often produce meters of erosion, and mantle some surfaces. Some small craters were likely completely eroded/buried. Craters >100 m in diameter on the Hesperian‐aged floor of Gusev are generally more pristine than on the Amazonian‐aged Meridiani plains. This conclusion contradicts interpretations from orbital views, which do not readily distinguish crater gradation state at Meridiani and reveal apparently subdued crater forms at Gusev that may suggest more gradation than has occurred.
Characterization and petrologic interpretation of olivine‐rich basalts at Gusev Crater, Mars
Authors: McSween H. Y. , Wyatt M. B , Gellert R. , Bell J. F. , Morris R. V. , Herkenhoff K. E. , Crumpler L. S. , Milam K. A. , Stockstill K. R. , Tornabene L. L. , Arvidson R. E. , Bartlett P. , Blaney D. , Cabrol N. A. , Christensen P. R. , Clark B. C. , Crisp J. A. , Des Marais D. J. , Economou T. , Farmer J. D. , Farrand W. , Ghosh A. , Golombek M. , Gorevan S. , Greeley R. , Hamilton V. E. , Johnson J. R. , Joliff B. L. , Klingelhöfer G. , Knudson A. T. , McLennan S. , Ming D. , Moersch J. E. , Rieder R. , Ruff S. W. , Schröder C. , de Souza P. A. , Squyres S. W. , Wänke H. , Wang A. , Yen A. , Zipfel J.
Published: January 2006

Rocks on the floor of Gusev crater are basalts of uniform composition and mineralogy. Olivine, the only mineral to have been identified or inferred from data by all instruments on the Spirit rover, is especially abundant in these rocks. These picritic basalts are similar in many respects to certain Martian meteorites (olivine‐phyric shergottites). The olivine megacrysts in both have intermediate compositions, with modal abundances ranging up to 20–30%. Associated minerals in both include low‐calcium and high‐calcium pyroxenes, plagioclase of intermediate composition, iron‐titanium‐chromium oxides, and phosphate. These rocks also share minor element trends, reflected in their nickel‐magnesium and chromium‐magnesium ratios. Gusev basalts and shergottites appear to have formed from primitive magmas produced by melting an undepleted mantle at depth and erupted without significant fractionation. However, apparent differences between Gusev rocks and shergottites in their ages, plagioclase abundances, and volatile contents preclude direct correlation. Orbital determinations of global olivine distribution and compositions by thermal emission spectroscopy suggest that olivine‐rich rocks may be widespread. Because weathering under acidic conditions preferentially attacks olivine and disguises such rocks beneath alteration rinds, picritic basalts formed from primitive magmas may even be a common component of the Martian crust formed during ancient and recent times.
Gusev crater: Wind‐related features and processes observed by the Mars Exploration Rover Spirit
Authors: Greeley Ronald , Arvidson R. E. , Barlett P. W. , Blaney Diana , Cabrol N. A. , Christensen P. R. , Fergason R. L. , Golombek M. P. , Landis G. A. , Lemmon M. T. , McLennan S. M. , Maki J. N. , Michaels Timothy , Moersch J. E. , Neakrase L. D. V. , Rafkin S. C. R. , Richter Lutz , Squyres S. W. , de Souza P. A. , Sullivan R. J. , Thompson S. D. , Whelley P. L.
Published: January 2006

Wind‐related features observed by the rover Spirit in Gusev crater, Mars, include patches of soil on the surface, some of which are organized into bed forms. Windblown grains include dust (inferred to be <3 μm in diameter), sands (up to a few hundred μm in diameter), and granules (>2 mm in diameter). Microscopic Imager data show the sands and granules to be rounded and relatively spherical, typical of grains transported long distances by the wind. The interior of bed forms exposed by rover operations suggests the infiltration of dust among the grains, indicating that these sands are not currently experiencing saltation. Orientations of 1520 features (such as bed forms and ventifacts) along Spirit's traverse from the landing site (the Columbia Memorial Station) to West Spur in the Columbia Hills suggest primary formative winds from the north‐northwest, which correlate with measurements of features seen in orbiter images and is consistent with afternoon winds predicted by atmospheric models. A secondary wind from the southeast is also suggested, which correlates with predictions for nighttime/early morning winds. Wind abrasion is indicated by ventifacts in the form of facets and grooves cut into rocks, the orientations of which also indicate prevailing winds from the north‐northwest. Orientations of many aeolian features in the West Spur area, however, have more scatter than elsewhere along the traverse, which is attributed to the influence of local topography on the patterns of wind. Active dust devils observed on the floor of Gusev from the Columbia Hills demonstrate that dust is currently mobile. Sequential images of some dust devils show movement as rapid as 3.8 m/s, consistent with wind velocities predicted by atmospheric models for the afternoon, when most of the dust devils were observed. Sands accumulated on the rover deck in the same period suggest that some sands in the Columbia Hills experience active saltation. “Two‐toned” rocks having a light band coating at their bases are considered to represent partial burial by soils and subsequent exposure, while “perched” rocks could represent materials lowered onto other rocks by deflation of supporting soils. Measurements of the heights of the light bands and the perched rocks range from <1 cm to 27 cm, indicating local deflation by as much as 27 cm.
Spectral variability among rocks in visible and near‐infrared multispectral Pancam data collected at Gusev crater: Examinations using spectral mixture analysis and related techniques
Authors: Farrand W. H. , Bell J. F. , Johnson J. R. , Squyres S. W. , Soderblom J. , Ming D. W.
Published: January 2006

Visible and near‐infrared (VNIR) multispectral observations of rocks made by the Mars Exploration Rover Spirit's Panoramic camera (Pancam) have been analyzed using a spectral mixture analysis (SMA) methodology. Scenes have been examined from the Gusev crater plains into the Columbia Hills. Most scenes on the plains and in the Columbia Hills could be modeled as three end‐member mixtures of a bright material, rock, and shade. Scenes of rocks disturbed by the rover's Rock Abrasion Tool (RAT) required additional end‐members. In the Columbia Hills, there were a number of scenes in which additional rock end‐members were required. The SMA methodology identified relatively dust‐free areas on undisturbed rock surfaces as well as spectrally unique areas on RAT abraded rocks. Spectral parameters from these areas were examined, and six spectral classes were identified. These classes are named after a type rock or area and are Adirondack, Lower West Spur, Clovis, Wishstone, Peace, and Watchtower. These classes are discriminable based, primarily, on near‐infrared (NIR) spectral parameters. Clovis and Watchtower class rocks appear more oxidized than Wishstone class rocks and Adirondack basalts based on their having higher 535 nm band depths. Comparison of the spectral parameters of these Gusev crater rocks to parameters of glass‐dominated basaltic tuffs indicates correspondence between measurements of Clovis and Watchtower classes but divergence for the Wishstone class rocks, which appear to have a higher fraction of crystalline ferrous iron‐bearing phases. Despite a high sulfur content, the rock Peace has NIR properties resembling plains basalts.
Overview of the Spirit Mars Exploration Rover Mission to Gusev Crater: Landing site to Backstay Rock in the Columbia Hills
Authors: Arvidson R. E. , Squyres S. W. , Anderson R. C. , Bell J. F. , Blaney D. , Brückner J. , Cabrol N. A. , Calvin W. M. , Carr M. H. , Christensen P. R. , Clark B. C. , Crumpler L. , Des Marais D. J. , de Souza P. A. , d'Uston C. , Economou T. , Farmer J. , Farrand W. H. , Folkner W. , Golombek M. , Gorevan S. , Grant J. A. , Greeley R. , Grotzinger J. , Guinness E. , Hahn B. C. , Haskin L. , Herkenhoff K. E. , Hurowitz J. A. , Hviid S. , Johnson J. R. , Klingelhöfer G. , Knoll A. H. , Landis G. , Leff C. , Lemmon M. , Li R. , Madsen M. B. , Malin M. C. , McLennan S. M. , McSween H. Y. , Ming D. W. , Moersch J. , Morris R. V. , Parker T. , Rice J. W. , Richter L. , Rieder R. , Rodionov D. S. , Schröder C. , Sims M. , Smith M. , Smith P. , Soderblom L. A. , Sullivan R. , Thompson S. D. , Tosca N. J. , Wang A. , Wänke H. , Ward J. , Wdowiak T. , Wolff M. , Yen A.
Published: January 2006

Spirit landed on the floor of Gusev Crater and conducted initial operations on soil‐covered, rock‐strewn cratered plains underlain by olivine‐bearing basalts. Plains surface rocks are covered by wind‐blown dust and show evidence for surface enrichment of soluble species as vein and void‐filling materials and coatings. The surface enrichment is the result of a minor amount of transport and deposition by aqueous processes. Layered granular deposits were discovered in the Columbia Hills, with outcrops that tend to dip conformably with the topography. The granular rocks are interpreted to be volcanic ash and/or impact ejecta deposits that have been modified by aqueous fluids during and/or after emplacement. Soils consist of basaltic deposits that are weakly cohesive, relatively poorly sorted, and covered by a veneer of wind‐blown dust. The soils have been homogenized by wind transport over at least the several kilometer length scale traversed by the rover. Mobilization of soluble species has occurred within at least two soil deposits examined. The presence of monolayers of coarse sand on wind‐blown bedforms, together with even spacing of granule‐sized surface clasts, suggests that some of the soil surfaces encountered by Spirit have not been modified by wind for some time. On the other hand, dust deposits on the surface and rover deck have changed during the course of the mission. Detection of dust devils, monitoring of the dust opacity and lower boundary layer, and coordinated experiments with orbiters provided new insights into atmosphere‐surface dynamics.
Vertical and latitudinal structure of the migrating diurnal tide in the Martian atmosphere: Numerical investigations
Authors: Takahashi Y. O. , Fujiwara H. , Fukunishi H.
Published: January 2006

We investigate the vertical and latitudinal structure of the migrating diurnal tide in a low dust condition (dust optical depth of 0.3 at 0.67 μm) in the Martian atmosphere by using a general circulation model (GCM) and a linear response model (LRM). The migrating diurnal tide simulated in our Mars GCM well represents general characteristics of the migrating diurnal tide which have been reported in previous observational and GCM studies. The GCM simulation shows that the vertical wavelength of the migrating diurnal tide in the low latitude region at equinox is ∼45 km which is larger than that of the major propagating mode predicted from the classical tidal theory (∼25–35 km). The Hough function decomposition and the numerical experiments using the LRM reveal that the large vertical wavelength of the migrating diurnal tide is caused by the effects of the zonal mean vorticity . It is suggested that the vertical wavelength of the migrating diurnal tide increases through the changes of the effects of the planetary rotation in the presence of non‐zero zonal mean vorticity . Such a strong dependence of the vertical wavelength of the migrating diurnal tide on is not observed in the Earth's atmosphere. The Martian radius, about the half of the Earth's radius, would be one of the important factors to cause more effective in the Martian atmosphere than that in the Earth's atmosphere.
Effect of vegetation–water table feedbacks on the stability and resilience of plant ecosystems
Authors: Ridolfi Luca , D'Odorico Paolo , Laio Francesco
Published: January 2006

The interaction of vegetation with the groundwater is one of the key mechanisms affecting the dynamics of wetland plant ecosystems. The main feature of these interactions is the feedback between the downward shift of the water table caused by riparian vegetation and the emergence of soil aeration conditions favorable to plant establishment, growth, and survival. We develop a conceptual framework to explain how vegetation–water table feedbacks may lead to the emergence of multiple stable states in the dynamics of wetland forests and riparian ecosystems. This framework is used to investigate the sensitivity of these ecosystems to vegetation disturbances and changes in water table depth. As a result of these feedbacks, such ecosystems are prone to catastrophic shifts to an unvegetated state. Because of their competitive advantage, water‐tolerant and shallow‐rooted species can replace the original vegetation, contributing to the occurrence of vegetation succession in riparian zones and to the existence of alternative vegetation states between areas with shallow and deep water tables.
Heterotrimeric G‐proteins: a short history
Authors: Milligan Graeme , Kostenis Evi
Published: January 2006

Some 865 genes in man encode G‐protein‐coupled receptors (GPCRs). The heterotrimeric guanine nucleotide‐binding proteins (G‐proteins) function to transduce signals from this vast panoply of receptors to effector systems including ion channels and enzymes that alter the rate of production, release or degradation of intracellular second messengers. However, it was not until the 1970s that the existence of such transducing proteins was even seriously suggested. Combinations of bacterial toxins that mediate their effects via covalent modification of the α‐subunit of certain G‐proteins and mutant cell lines that fail to generate cyclic AMP in response to agonists because they either fail to express or express a malfunctional G‐protein allowed their identification and purification. Subsequent to initial cloning efforts, cloning by homology has defined the human G‐proteins to derive from 35 genes, 16 encoding α‐subunits, five β and 14 γ. All function as guanine nucleotide exchange on–off switches and are mechanistically similar to other proteins that are enzymic GTPases. Although not readily accepted initially, it is now well established that β/γ complexes mediate as least as many functions as the α‐subunits. The generation of chimeras between different α‐subunits defined the role of different sections of the primary/secondary sequence and crystal structures and cocrystals with interacting proteins have given detailed understanding of their molecular structure and basis of function. Finally, further modifications of such chimeras have generated a range of G‐protein α‐subunits with greater promiscuity to interact across GPCR classes and initiated the use of such modified G‐proteins in drug discovery programmes.

British Journal of Pharmacology (2006) 147, S46–S55. doi:10.1038/sj.bjp.0706405
Histamine and its receptors
Authors: Parsons Mike E , Ganellin C Robin
Published: January 2006

This article reviews the development of our knowledge of the actions of histamine which have taken place during the course of the 20th century. Histamine has been shown to have a key physiological role in the control of gastric acid secretion and a pathophysiological role in a range of allergic disorders. The synthesis of, and pharmacological studies on, selective agonists and antagonists has established the existence of four types of histamine receptor and histamine receptor antagonists have found very important therapeutic applications. Thus, in the 1940s, H1‐receptor antagonists (‘the antihistamines’) yielded and still provide valuable treatment for allergic conditions such as hay fever and rhinitis. In the late 1970s and 1980s, H2‐receptor antagonists (in the discovery of which the two authors were personally involved) revolutionised the treatment of peptic ulcer and other gastric acid‐related diseases. The H3‐receptor antagonists, although available since 1987, have been slower to find a therapeutic role. However, the discovery of nonimidazole derivatives such as brain‐penetrating H3antagonists has provided drugs that are in early‐phase clinical trials, possibly for application in obesity, and a variety of central nervous system disorders, such as memory, learning deficits and epilepsy. Finally, the most recently (1999) discovered H4receptor promises the potential to provide drugs acting on the immunological system with possible applications in asthma and inflammation.

British Journal of Pharmacology(2006)147, S127–S135. doi:10.1038/sj.bjp.0706440
Molecular targets underlying general anaesthesia
Authors: Franks Nicholas P
Published: January 2006

The discovery of general anaesthesia, over 150 years ago, revolutionised medicine. The ability to render a patient unconscious and insensible to pain made modern surgery possible and general anaesthetics have become both indispensible as well as one of the most widely used class of drugs. Their extraordinary chemical diversity, ranging from simple chemically inert gases to complex barbiturates, has baffled pharmacologists, and ideas about how they might work have been equally diverse. Until relatively recently, thinking was dominated by the notion that anaesthetics acted ‘nonspecifically’ by dissolving in the lipid bilayer portions of nerve membranes. While this simple idea could account for the chemical diversity of general anaesthetics, it has proven to be false and it is now generally accepted that anaesthetics act by binding directly to sensitive target proteins. For certain intravenous anaesthetics, such as propofol and etomidate, the target has been identified as the GABAA receptor, with particular subunits playing a crucial role. For the less potent inhalational agents, the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, I will describe the work that led up to the identification of the GABAA receptor as the key target for etomidate and propofol and contrast this with current progress that has been made in identifying the relevant targets for other anaesthetics, particularly the inhalational agents.

British Journal of Pharmacology (2006) 147, S72–S81. doi:10.1038/sj.bjp.0706441
The discovery of nitric oxide and its role in vascular biology
Authors: Moncada S , Higgs E A
Published: January 2006

Nitric oxide (NO) is a relative newcomer to pharmacology, as the paper which initiated the field was published only 25 years ago. Nevertheless its impact is such that to date more than 31,000 papers have been published with NO in the title and more than 65,000 refer to it in some way. The identification of NO with endothelium‐derived relaxing factor and the discovery of its synthesis from L‐arginine led to the realisation that the L‐arginine: NO pathway is widespread and plays a variety of physiological roles. These include the maintenance of vascular tone, neurotransmitter function in both the central and peripheral nervous systems, and mediation of cellular defence. In addition, NO interacts with mitochondrial systems to regulate cell respiration and to augment the generation of reactive oxygen species, thus triggering mechanisms of cell survival or death. This review will focus on the role of NO in the cardiovascular system where, in addition to maintaining a vasodilator tone, it inhibits platelet aggregation and adhesion and modulates smooth muscle cell proliferation. NO has been implicated in a number of cardiovascular diseases and virtually every risk factor for these appears to be associated with a reduction in endothelial generation of NO. Reduced basal NO synthesis or action leads to vasoconstriction, elevated blood pressure and thrombus formation. By contrast, overproduction of NO leads to vasodilatation, hypotension, vascular leakage, and disruption of cell metabolism. Appropriate pharmacological or molecular biological manipulation of the generation of NO will doubtless prove beneficial in such conditions.

British Journal of Pharmacology (2006) 147, S193–S201. doi:10.1038/sj.bjp.0706458
Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness
Authors: Youdim Moussa B H , Bakhle Y S
Published: January 2006

A few years after the foundation of the British Pharmacological Society, monoamine oxidase (MAO) was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamine neurotransmitters, noradrenaline, adrenaline and dopamine (and, later, 5‐hydroxytryptamine, as well). Within the next decade, the therapeutic value of inhibitors of MAO in the treatment of depressive illness was established. Although this first clinical use exposed serious side effects, pharmacological interest in, and investigation of, MAO continued, resulting in the characterization of two isoforms, MAO‐A and ‐B, and isoform‐selective inhibitors. Selective inhibitors of MAO‐B have found a therapeutic role in the treatment of Parkinson's disease and further developments have provided reversible inhibitors of MAO‐A, which offer antidepressant activity without the serious side effects of the earlier inhibitors. Clinical observation and subsequent pharmacological analysis have also generated the concept of neuroprotection, reflecting the possibility of slowing, halting and maybe reversing, neurodegeneration in Parkinson's or Alzheimer's diseases. Increased levels of oxidative stress in the brain may be critical for the initiation and progress of neurodegeneration and selective inhibition of brain MAO could contribute importantly to lowering such stress. There are complex interactions between free iron levels in brain and MAO, which may have practical outcomes for depressive disorders. These aspects of MAO and its inhibition and some indication of how this important area of pharmacology and therapeutics might develop in the future are summarized in this review.

British Journal of Pharmacology (2006) 147, S287–S296. doi:10.1038/sj.bjp.0706464
Dopamine: the rewarding years
Authors: Marsden Charles A
Published: January 2006

Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present‐day position as a major neurotransmitter in the brain. This neurotransmitter is involved in the control of movement and Parkinson's disease, the neurobiology and symptoms of schizophrenia and attention deficit hyperactivity disorder. It is also considered an essential element in the brain reward system and in the action of many drugs of abuse. This evolution reflects the ability of several famous names in neuropharmacology, neurology and psychiatry to apply new techniques to ask and answer the right questions. There is now excellent knowledge about the metabolism of dopamine, dopamine receptor systems and the structural organisation of dopamine pathways in the brain. Less is known about the function of the different receptors and how the various dopamine pathways are organised to produce normal behaviour, which exhibits disruption in the disease states mentioned. In particular, we have very limited information as to why and how the dopamine system dies or becomes abnormal in Parkinson's disease or a neurodevelopmental disorder such as schizophrenia. Dopamine neurones account for less than 1% of the total neuronal population of the brain, but have a profound effect on function. The future challenge is to understand how dopamine is involved in the integration of information to produce a relevant response rather than to study dopamine in isolation from other transmission systems. This integrated approach should lead to greater understanding and improved treatment of diseases involving dopamine.

British Journal of Pharmacology (2006) 147, S136–S144. doi:10.1038/sj.bjp.0706473
Phosphodiesterase inhibitors
Authors: Boswell‐Smith Victoria , Spina Domenico , Page Clive P
Published: January 2006

Phosphodiesterases are a diverse family of enzymes that hydrolyse cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messengers cAMP and cGMP, and hence cell function. Theophylline and papaverine have historically been used therapeutically and are known to be weak inhibitors of PDE, but to what extent this contributed toward their clinical efficacy was poorly defined. However, the discovery of 11 isoenzyme families and our increased understanding of their function at the cell and molecular level provides an impetus for the development of isoenzyme selective inhibitors for the treatment of various diseases. This review focuses on the development of PDE3 inhibitors for congestive heart failure, PDE4 inhibitors for inflammatory airways disease and most successfully, PDE5 inhibitors for erectile dysfunction

British Journal of Pharmacology (2006) 147, S252–S257. doi:10.1038/sj.bjp.0706495
A novel bipartite phospholipid‐binding module in the neurofibromatosis type 1 protein
Authors: D'angelo Igor , Welti Stefan , Bonneau Fabien , Scheffzek Klaus
Published: January 2006

Neurofibromatosis type 1 (NF1) is a common tumour predisposition syndrome associated with numerous clinical complications. Mutations in the tumour suppressor gene NF1 are responsible for disease pathogenesis. This gene encodes the 320 kDa protein neurofibromin, the only clearly defined function of which is to act as a Ras‐specific GTPase‐activating protein (RasGAP). Here we report the structural discovery of a novel module in neurofibromin, composed of a Sec14p homologous segment and a previously undetected pleckstrin homology (PH)‐like domain of potentially novel function. We show phospholipid binding by this bipartite module and identify residues that are involved in this activity; we also show that the PH‐like domain is not sufficient for lipid binding. The unique architecture of the domain interface points to a model of how the PH‐like domain may regulate binding of a ligand by the Sec14 module.
Skin human papillomavirus type 38 alters p53 functions by accumulation of ΔNp73
Authors: Accardi Rosita , Dong Wen , Smet Anouk , Cui Rutao , Hautefeuille Agnes , Gabet Anne‐Sophie , Sylla Bakary S , Gissmann Lutz , Hainaut Pierre , Tommasino Massimo
Published: January 2006

The E6 and E7 of the cutaneous human papillomavirus (HPV) type 38 immortalize primary human keratinocytes, an event normally associated with the inactivation of pathways controlled by the tumour suppressor p53. Here, we show for the first time that HPV38 alters p53 functions. Expression of HPV38 E6 and E7 in human keratinocytes or in the skin of transgenic mice induces stabilization of wild‐type p53. This selectively activates the transcription of ΔNp73, an isoform of the p53‐related protein p73, which in turn inhibits the capacity of p53 to induce the transcription of genes involved in growth suppression and apoptosis. ΔNp73 downregulation by an antisense oligonucleotide leads to transcriptional re‐activation of p53‐regulated genes and apoptosis. Our findings illustrate a novel mechanism of the alteration of p53 function that is mediated by a cutaneous HPV type and support the role of HPV38 and ΔNp73 in human carcinogenesis.
Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non‐overlapping functions in inner ear development
Authors: Fiolka Katharina , Hertzano Ronna , Vassen Lothar , Zeng Hui , Hermesh Orit , Avraham Karen B , Dührsen Ulrich , Möröy Tarik
Published: January 2006

Gfi1 is a transcriptional repressor essential for haematopoiesis and inner ear development. It shares with its paralogue Gfi1b an amino‐terminal SNAG repressor domain and six carboxy‐terminal zinc‐finger motifs, but differs from Gfi1b in sequences separating these domains. Here, we describe two knock‐in mouse models, in which the N‐terminal SNAG repressor domain was mutated or in which the Gfi1 coding region was replaced by Gfi1b. Mouse mutants without an intact SNAG domain show the full phenotype of Gfi1 null mice. However, Gfi1:Gfi1b knock‐in mice show almost normal pre‐T‐cell and neutrophil development, but lack properly formed inner ear hair cells. Hence, our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis but, surprisingly, not in inner ear hair cell development, demonstrating that Gfi1 and Gfi1b have equivalent and domain‐dependent, cell type‐specific functions.
Nonlinear modeling of start-up phase pressure spectra from optically smoothed induced spatial incoherence laser imprint
Authors: Keskinen M. J. , Schmitt A.
Published: January 2006

The spectrum of early time pressure perturbations, due to optically smoothed induced spatial incoherence (ISI) laser imprint, is computed for a planar target using a forced, dissipative model. The time-dependent ISI laser deposition is computed using a time-dependent electromagnetic full-wave Maxwell code. It is found that the pressure spectrum evolves into a power law in which spectral power is transferred from large to smaller scales through a nonlinear cascade process. The model results are compared with experimental observations.
The rutile TiO2 (110) surface: Obtaining converged structural properties from first-principles calculations
Authors: Hameeuw K. J. , Cantele G. , Ninno D. , Trani F. , Iadonisi G.
Published: January 2006

We investigate the effects of constraining the motion of atoms in finite slabs used to simulate the rutile TiO2 (110) surface in first-principles calculations. We show that an appropriate choice of fixing atoms in a slab eliminates spurious effects due to the finite size of the slabs, leading to a considerable improvement in the simulation of the (110) surface. The method thus allows for a systematic improvement in convergence in calculating both geometrical and electronic properties. The advantages of this approach are illustrated by presenting the first theoretical results on the displacement of the surface atoms in agreement with experiment.
Flexible simple point-charge water model with improved liquid-state properties
Authors: Wu Yujie , Tepper Harald L. , Voth Gregory A.
Published: January 2006

In order to introduce flexibility into the simple point-charge (SPC) water model, the impact of the intramolecular degrees of freedom on liquid properties was systematically studied in this work as a function of many possible parameter sets. It was found that the diffusion constant is extremely sensitive to the equilibrium bond length and that this effect is mainly due to the strength of intermolecular hydrogen bonds. The static dielectric constant was found to be very sensitive to the equilibrium bond angle via the distribution of intermolecular angles in the liquid: A larger bond angle will increase the angle formed by two molecular dipoles, which is particularly significant for the first solvation shell. This result is in agreement with the work of Höchtl et al. [J. Chem. Phys. 109, 4927 (1998)]. A new flexible simple point-charge water model was derived by optimizing bulk diffusion and dielectric constants to the experimental values via the equilibrium bond length and angle. Due to the large sensitivities, the parametrization only slightly perturbs the molecular geometry of the base SPC model. Extensive comparisons of thermodynamic, structural, and kinetic properties indicate that the new model is much improved over the standard SPC model and its overall performance is comparable to or even better than the extended SPC model.
Testing statistical significance of multivariate time series analysis techniques for epileptic seizure prediction
Authors: Schelter Björn , Winterhalder Matthias , Maiwald Thomas , Brandt Armin , Schad Ariane , Schulze-Bonhage Andreas , Timmer Jens
Published: January 2006

Nonlinear time series analysis techniques have been proposed to detect changes in the electroencephalography dynamics prior to epileptic seizures. Their applicability in practice to predict seizure onsets is hampered by the present lack of generally accepted standards to assess their performance. We propose an analytic approach to judge the prediction performance of multivariate seizure prediction methods. Statistical tests are introduced to assess patient individual results, taking into account that prediction methods are applied to multiple time series and several seizures. Their performance is illustrated utilizing a bivariate seizure prediction method based on synchronization theory.
Reaction dynamics of Ca(4s3dD21)+CH4→CaH(XΣ+2)+CH3: Reaction pathway and energy disposal for the CaH product
Authors: Chen Li , Hsiao Ming-Kai , Chang Ya-Lan , Lin King-Chuen
Published: January 2006

The reaction pathway for Ca(4s3dD21)+CH4→CaH(XΣ+2)+CH3 has been investigated by using a pump-probe technique in combination with potential-energy surface (PES) calculations. The nascent product distributions of CaH have been characterized with Boltzmann rotational temperatures of 1013±102 and 834±70K for the v=0 and 1 levels, respectively, and a Boltzmann vibrational temperature of 1313±173K. The rotational and vibrational energy partitions in CaH have been estimated to be 461±45 and 252±15cm−1, respectively. According to the PES calculations, the pathway favors an insertion mechanism. Ca(3D21) approaches CH4 along an attractive potential surface in a C2v (or Cs) symmetry and then the collision complex undergoes nonadiabatic transition to the reactive ground-state surface. An Arrhenius plot shows a potential-energy requirement of 2695±149cm−1, which accounts for the endothermicity of 2930cm−1 for the reaction scheme. The Ca–C bond distance in the transition state structure is short enough to allow for tight orbital overlap between CaH and CH3. The strong coupling between the moieties renders the energy transfer sufficient from CaH into the CH3 radical. As compared to the Ca(4P11) reaction, the dissociation lifetime of the intermediate complex with less excess energy is prolonged so as to cause much less vibrational energy disposal into CaH.
Simulating rare events in equilibrium or nonequilibrium stochastic systems
Authors: Allen Rosalind J. , Frenkel Daan , ten Wolde Pieter Rein
Published: January 2006

We present three algorithms for calculating rate constants and sampling transition paths for rare events in simulations with stochastic dynamics. The methods do not require a priori knowledge of the phase-space density and are suitable for equilibrium or nonequilibrium systems in stationary state. All the methods use a series of interfaces in phase space, between the initial and final states, to generate transition paths as chains of connected partial paths, in a ratchetlike manner. No assumptions are made about the distribution of paths at the interfaces. The three methods differ in the way that the transition path ensemble is generated. We apply the algorithms to kinetic Monte Carlo simulations of a genetic switch and to Langevin dynamics simulations of intermittently driven polymer translocation through a pore. We find that the three methods are all of comparable efficiency, and that all the methods are much more efficient than brute-force simulation.
Wetting behavior of low-index cubic SiC surfaces
Authors: Catellani Alessandra , Cicero Giancarlo , Galli Giulia
Published: January 2006

We report on the interaction of water molecules with polar and nonpolar stoichiometric surfaces of cubic silicon carbide, as described by ab initio molecular dynamics at finite temperature. Our calculations show that, irrespective of coverage, in the gas phase water spontaneously dissociates on both polar Si-terminated (001) and nonpolar (110) surfaces, following similar mechanisms. The specific geometric arrangement of atoms on the outermost surface layer is responsible for water orientation and coordination and thus plays a major role in determining surface reactivity. This is found to be the case also for water on a computer-generated amorphous-SiC surface. In addition, from a macroscopic standpoint, the ability of the two crystalline surfaces with different polarities to induce water dissociation can be related to the similarities of their ionization potentials.
Asymmetric bridging of interconnected pores by encased semiflexible macromolecules
Authors: Cifra P.
Published: January 2006

An increase of chain rigidity of macromolecule encased in interconnected cavities leads to bridging conformational transition in which polymer molecule at certain conditions spans the cavities. This is a similar phenomenon to that described for flexible chains on increase of confinement. Chain stiffness introduces, however, a delicate effect of interplay between confinement, chain stiffness, and concentration that leads to a breakup of symmetric bridging conformation to a striking asymmetric conformation even in the symmetric system of cavities. We provide the first data on this transition with complex translocation landscape and offer a tentative explanation.