bluuebunny/crossref_metadata_2025 huggingface dataset:
Brucellaisolated in humans and animals in Latin America from 1968 to 2006
Authors: LUCERO N. E. , AYALA S. M. , ESCOBAR G. I. , JACOB N. R.
Published: June 2007

We report a retrospective analysis of 1933Brucellastrains isolated from humans and animals in Latin American countries between 1968 and 1991 and in Argentina between 1994 and 2006. During the first period 50% of strains were from humans, mainly from Argentina, Mexico and Peru but, whileB. suiswas the main cause of infection in Argentina,B. melitensiswas responsible for most infections in the other countries. In Argentina in the later years,B. melitensisandB. suiswere observed more frequently than in the first period while isolation ofB. abortusdecreased. Of 145B. melitensishuman isolates, eight gave susceptibility patterns to dyes and penicillin and two wereB. melitensisbiovar 3, which has never been reported in animals. Forty-six percent ofB. suisisolated were resistant to dyes which is an atypical feature in this species.
Some notes on the PARC 700 Dependency Bank
Authors: BY TOMAS
Published: June 2007

The PARC 700 dependency bank is a potentially very useful resource for parser evaluation that has, so to speak, a high barrier to entry, because of tokenisation that is quite different from the source of the data, the Penn Treebank, and because there is no representation of word order, producing an uncertainty factor of some 15%. There is also a small, but perhaps not insignificant, number of errors. When using the dependency bank for evaluation, it seems likely that these things will cause inflated counts for mismatches, so to obtain more accurate measurements, it is desirable to eliminate them. The work reported here consists of an automatic conversion of the dependency bank into a Prolog representation where the word order is explicit, as well as graphical representations of the dependency trees for all 700 sentences, automatically generated from the Prolog data. As a side effect of the transformation, errors were detected and corrected. It is hoped that this work will lead to more widespread use of the PARC 700 dependency bank for parser evaluation.
Testing the universality of biology: a review
Authors: Chela-Flores J.
Published: June 2007

We discuss whether it is possible to test the universality of biology, a quest that is of paramount relevance for one of its most recent branches, namely astrobiology. We review this topic in terms of the relative roles played on the Earth biota by contingency and evolutionary convergence. Following the seminal contribution of Darwin, it is reasonable to assume that all forms of life known to us so far are not only terrestrial, but are descendants of a common ancestor that evolved on this planet at the end of a process of chemical evolution. We also raise the related question of whether the molecular events that were precursors to the origin of life on Earth are bound to occur elsewhere in the Universe, wherever the environmental conditions are similar to the terrestrial ones. We refer to ‘cosmic convergence’ as the possible occurrence elsewhere in the Universe of Earth-like environmental conditions. We argue that cosmic convergence is already suggested by observational data. The set of hypotheses for addressing the question of the universality of biology can be tested by future experiments that are feasible with current technology. We focus on landing on Europa and the broader implications of selecting the specific example of the right landing location. We have previously discussed the corresponding miniaturized equipment that is already in existence. The significance of these crucial points needs to be put into a wider scientific perspective, which is one of the main objectives of this review.
Pension nondiscrimination rules and the incentive to cross subsidize employees
Authors: BRADY PETER J.
Published: June 2007

Among the requirements a pension plan must meet to qualify for tax benefits are the nondiscrimination rules. Nondiscrimination rules are designed to ensure that pension benefits do not disproportionately accrue to highly compensated employees. But the rules are also complex and increase administrative and compliance costs associated with offering a pension plan. Recent pension reform proposals would simplify nondiscrimination rules, reducing administrative and compliance costs and potentially leading to more employers offering pension benefits. However, there are concerns that any loosening of the rules could lead to a drop in participation by low-wage workers. This paper examines the economic incentive that nondiscrimination rules provide to employers to cross subsidize employees; that is, the incentive to increase pension benefits (and total compensation) paid to low-paid workers for the express purpose of enabling high-paid workers to receive a higher proportion of compensation in the form of pension benefits. The study calculates the incentives faced by a hypothetical firm, and then illustrates how those incentives change when assumptions about employee contribution behavior, employee compensation, and employer-matching formulas are allowed to vary. Results show that only firms with a relatively low ratio of low-paid workers to high-paid workers would have an economic incentive under a standard 401(k) plan to cross subsidize employees. Although this incentive may exist in a large number of firms, these firms likely employ only a small portion of the workforce. This is ultimately an empirical question, however, and examining data on the distribution of earnings within pension plans, as well as determining if firms find nondiscrimination rules binding, would be a useful extension of this research.
What can the life-cycle model tell us about 401(k) contributions and participation?
Authors: LOVE DAVID A.
Published: June 2007

This paper solves and simulates a stochastic life-cycle model of an economy with 401(k) plans. We use the model to establish a benchmark for patterns of contributions and participation and show how these patterns depend on such features as employer matching, vesting policies, and the ability to make early withdrawals. Consistent with empirical studies, the model predicts relatively low participation rates among younger workers and shows that these rates tend to rise with more generous matching, lower vesting periods, and improved liquidity.
Magnetic field rotation analysis and the applications
Authors: Shen C. , Li X. , Dunlop M. , Shi Q. Q. , Liu Z. X. , Lucek E. , Chen Z. Q.
Published: June 2007

An analysis technique, termed MRA (magnetic rotation analysis), has been designed to probe three‐dimensional magnetic field topology. It is based on estimating the gradient tensor of four‐point measurements of the magnetic field which have been taken by the Cluster mission. The method first constructs the symmetrical magnetic rotation tensor and in general terms deduces the rotation rate of magnetic field along one arbitrary direction. In particular, the maximum, medium, and minimum magnetic rotation rates along corresponding characteristic directions of a magnetic structure can be obtained. The value of the curvature of a magnetic field line, for example, is given by the magnetic rotation rate along the magnetic unit vector and its corresponding radius of curvature is readily obtained. MRA has been applied here to analyze the geometrical structure of two distinct magnetospheric structures, i.e., the tail current sheet and the tail flux rope. The normal of the current sheet is the direction at which the magnetic field has the largest rotation rate. The half thickness of the one‐dimensional neutral sheet can also be determined from the reciprocal of the maximum magnetic rotation rate. The advantage of the MRA method is that not only it can determine the orientation but also the internal geometrical configuration and spatial scale of the magnetic structures. A key feature of the MRA method is that it provides the detailed picture of the magnetic rotation point by point through any crossing of the current sheet. As a result, the thickness of the neutral sheet (NS) can be explicitly demonstrated to vary with time, as indicated in one case study, where the NS becomes thicker after the onset of a substorm. MRA has also been applied here to analyze the detailed features of magnetic field variations inside of a flux rope. The principal axis of the flux rope is the direction at which the magnetic field rotates at the least rate. The magnetic scale of the flux rope can also be determined (about 1RE in the case chosen). It is also found that there are both frontside‐backside and dawn‐dusk asymmetries for the flux rope under study.
Sensitivity of the Earth’s magnetosphere to solar wind activity: Three‐dimensional macroparticle model
Authors: Baraka S. , Ben‐Jaffel L.
Published: June 2007

A new approach is proposed to study the sensitivity of the Earth’s magnetosphere to the variability of the solar wind bulk velocity. The study was carried out using a three‐dimensional electromagnetic particle‐in‐cell code, with the microphysics interaction processes described by Maxwell and Lorentz equations, respectively, for the fields and particles. Starting with a solar wind with zero interplanetary magnetic field (IMF) impinging upon a magnetized Earth, the formation of the magnetospheric cavity and its elongation around the planet were modeled over time until a steady state structure of a magnetosphere was attained. The IMF was then added as a steady southward magnetic field. An impulsive disturbance was applied to the system by changing the bulk velocity of the solar wind to simulate a decrease in the solar wind dynamic pressure, followed by its recovery, for both zero and southward IMF. In response to an imposed drop in the solar wind drift velocity, a gap (air pocket) in the incoming solar wind plasma appeared moving toward Earth. The orientation of the cusps was highly affected by the depression of the solar wind for all orientation of IMF. The magnetotail lobes flared out with zero IMF due to the “air pocket” effect. With the nonzero IMF, as soon as the gap hit the initial shock of the steady magnetosphere, a reconnection between the Earth’s magnetic field and the IMF was noticed at the dayside magnetopause. During the expansion phase of the system, the outer boundary of the dayside magnetopause broke up in the absence of the IMF, yet it sustained its bullet shape when a southward IMF was included. The expansion/contraction of the magnetopause nose is almost linear in the absence of the IMF but evolves nonlinearly with a southward IMF. The system recovered its initial state on the dayside soon after the impulsive disturbance was beyond Earth for both cases of zero and nonzero IMF. Comparison with existing observations from Cluster and Interball‐1 seems to confirm many of our simulation results.
Numerical modeling of a gravity wave packet ducted by the thermal structure of the atmosphere
Authors: Yu Yonghui , Hickey Michael P.
Published: June 2007

A time‐dependent and fully nonlinear numerical model is employed to solve the Navier‐Stokes equations in two spatial dimensions and to describe the propagation of a Gaussian gravity wave packet generated in the troposphere. A Fourier spectral analysis is used to analyze the frequency power spectra of the wave packet, which propagates through and dwells within several thermal ducting regions. The frequency power spectra of the wave packet are derived at several discrete altitudes, which allow us to determine the evolution of the packet. This spectral analysis also clearly reveals the existence of a stratospheric duct, a mesospheric and lower thermospheric duct, and a duct lying between the tropopause and the lower thermosphere. In addition, we determine the spatially localized wave kinetic energy density and the horizontally averaged, time‐resolved, normalized vertical velocity. Examination of these diagnostic variables allows us to better understand the process of wave ducting and the vertical transport of wave energy among multiple thermal ducts. The spectral analysis allows us to unambiguously identify the ducted wave modes. These results compare favorably with those derived from a full‐wave model.
Three‐dimensional MHD simulation of CMEs in three‐dimensional background solar wind with the self‐consistent structure on the source surface as input: Numerical simulation of the January 1997 Sun‐Earth connection event
Authors: Shen Fang , Feng Xueshang , Wu S. T. , Xiang Changqing
Published: June 2007

A three‐dimensional time‐dependent, numerical magnetohydrodynamic (MHD) model is used to investigate the propagation of coronal mass ejections (CMEs) in the nonhomogenous background solar wind flow. On the basis of the observations of the solar magnetic field and K‐coronal brightness, the self‐consistent structure on the source surface of 2.5 Rs is established with the help of MHD equations. Using the self‐consistent source surface structures as initial‐boundary conditions, we develop a three‐dimensional MHD regional combination numerical model code to obtain the background solar wind from the source surface of 2.5 Rs to the Earth’s orbit (215 Rs) and beyond. This model considers solar rotation and volumetric heating. Time‐dependent variations of the pressure and velocity configured from a CME model at the inner boundary are applied to generate transient structures. The dynamical interaction of a CME with the background solar wind flow between 2.5 and 215 Rs (1 AU) is then investigated. We have chosen the well‐defined halo‐CME event of 6–12 January 1997 as a test case. Because detailed observations of this disturbance at 1 AU (by WIND spacecraft) are available, this event gives us an excellent opportunity to verify our MHD methodology and to learn about the physical processes of the Sun‐Earth connection. In this study, we find that this three‐dimensional MHD model, with the self‐consistent structures on the source surface as input, provides a relatively satisfactory comparison with the WIND spacecraft observations.
Rayleigh wave tomography beneath intraplate volcanic ridges in the South Pacific
Authors: Weeraratne Dayanthie S. , Forsyth Donald W. , Yang Yingjie , Webb Spahr C.
Published: June 2007

We test models for the origin of intraplate volcanic ridges and gravity lineations on young seafloor west of the East Pacific Rise using Rayleigh wave dispersion measured in the Gravity Lineations and Intraplate Melting Petrology and Seismic Expedition (GLIMPSE) seismic experiment. The excellent azimuthal distribution of teleseismic sources recorded over a 12‐month period provides resolution of phase velocities at periods up to 100 s. The average phase velocities for the study area reveal a pronounced low‐velocity zone reaching a minimum shear velocity of ∼3.95 km/s. The negative velocity gradient defining the base of the lithosphere, observed at 40 ± 15 km, abruptly reverses at 70 km depth. The underlying positive gradient changes slope at ∼125 km. We attribute these changes in gradient to the onset of incipient partial melting of upwelling mantle in the presence of water at 125 km, followed by increased melt production at 70 km that leads to dehydration of the residual matrix and migration of melt to the surface spreading center. Rayleigh wave tomography shows that there are anomalously low shear velocities extending to at least 50 km depth beneath the Sojourn Ridge and the Hotu Matua volcanic complex, with relatively high velocities between these volcanic chains. These observations are not consistent with passive models for the origin of the volcanic ridges involving lithospheric extension or thermoelastic cracking. Dynamic models invoking flow in the asthenosphere in the form of small‐scale convection or viscous fingering instabilities may explain the observed pattern of seismic velocity anomalies.
Does eddy subduction matter in the northeast Atlantic Ocean?
Authors: Gebbie Geoffrey
Published: June 2007

Mesoscale eddies are an important contributor to subduction in the Gulf Stream region and the Antarctic Circumpolar Current, but is eddy subduction also important in the relatively quiescent interior of the world's subtropical gyres? Observations from the Subduction Experiment of the northeast Atlantic do not have the spatial resolution necessary to calculate eddy subduction and answer this question. Regional numerical models can diagnose subduction, but their representativeness is unknown. Furthermore, water mass budgets in an open‐ocean domain show that the simulated properties of subducted water directly depend upon uncertain open‐boundary conditions and surface fluxes. To remedy these problems, a state estimate of the ocean circulation is formed by constraining an eddy‐permitting general circulation model to observations by adjusting the model parameters within their uncertainty. The resulting estimate is self‐consistent with the equations of motion and has the necessary resolution for diagnosing subduction. In the northeast Atlantic during 1991–1993, the time‐variable circulation contributes less than 1 Sv of net subduction, while the total subduction is 4 Sv. Eddy volume fluxes of 40 m/yr in the North Equatorial Current and the Azores Current, however, are significant and rival the subduction by Ekman pumping locally. Furthermore, a state estimate at 1/6° resolution has 2–3 Sv more subduction in the density bands centered around σ = 24.0 kg/m3 and σ = 26.0 kg/m3 than a 2° state estimate. This result implies that the inability to accurately simulate mesoscale phenomena and surface fluxes in climate models would lead to an accumulation of errors in water mass properties over 10–20 years, even in the interior of the subtropical gyre.
Continental‐scale multiobservation calibration and assessment of Colorado State University Unified Land Model by application of Moderate Resolution Imaging Spectroradiometer (MODIS) surface albedo
Authors: Matsui Toshihisa , Beltrán‐Przekurat Adriana , Pielke Roger A. , Niyogi Dev , Coughenour Michael B.
Published: June 2007

This study attempts to establish the first continental‐scale multiobservation calibration and assessment of a land surface model (LSM) over the conterminous United States by using the Colorado State University Unified Land Model (CSU ULM) within the NASA GSFC's Land Information System and the Parameter Estimation (PEST) model. This study aims to calibrate the vegetation and soil optical parameters in different landcover classes by comparing model‐predicted surface albedo and those derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) (including black‐ and white‐sky albedo for visible and near‐infrared band). The sum of squared deviations (Ψ) between model‐ and MODIS‐derived albedo is iteratively reduced via the Gauss‐Marquardt‐Levenberg (GML) algorithm. The first calibration process (1) reduced Ψ by about 80% for noncalibrated as well as calibrated seasons and years, (2) revealed the functional biases related to diffuse‐radiation upscattering parameters in two‐stream canopy radiation scheme (which was fixed before the second calibration), and (3) shows that the parameter related to the leaf angle distribution function could not be tuned. The second calibration was implemented from the lessons learned from the first calibration, and results in the more realistic convergence of the parameters. After calibration, the summertime surface energy budget simulated by offline ULM changed significantly over the less vegetated regions; for example, net shortwave radiation and available energy increased by more than 40 W m−2 and radiative temperature increased by more than 1.6 K in the postcalibrated experiment.
Pseudoreciprocity in a disturbed nonisotropic medium and its application to radio wave propagation
Authors: Coleman C. J.
Published: June 2007

Reciprocity is an important result of electromagnetism that breaks down in the case of a nonisotropic media. For such media, however, there exist pseudoreciprocity results for which the pseudoreciprocal fields have different, but related, permittivity and permeability tensors. It is shown that these results can be readily extended to take account of disturbances in the medium of one of the pseudoreciprocal fields. These extensions are used to develop algorithms for radio wave propagation and, in particular, algorithms for the study of propagation through disturbed nonisotropic media. The ionosphere is an example of such a medium, and the algorithms are demonstrated through their application to the study of radio wave propagation through a traveling ionospheric disturbance.
Plant rooting strategies in water‐limited ecosystems
Authors: Collins D. B. G. , Bras R. L.
Published: June 2007

Root depth and distribution are vital components of a plant's strategy for growth and survival in water‐limited ecosystems and play significant roles in hydrologic and biogeochemical cycling. Knowledge of root profiles is invaluable in measuring and predicting ecosystem dynamics, yet data on root profiles are difficult to obtain. We developed an ecohydrological model of environmental forcing, soil moisture dynamics, and transpiration to explore dependencies of optimal rooting on edaphic, climatic, and physiological factors in water‐limited ecosystems. The analysis considers individual plants with fixed biomass. Results of the optimization approach are consistent with profiles observed in nature. Optimal rooting was progressively deeper, moving from clay to loam, silt and then sand, and in wetter and cooler environments. Climates with the majority of the rainfall in winter produced deeper roots than if the rain fell in summer. Long and infrequent storms also favored deeper rooting. Plants that exhibit water stress at slight soil moisture deficiencies consistently showed deeper optimal root profiles. Silt generated the greatest sensitivity to differences in climatic and physiological parameters. The depth of rooting is governed by the depth to which water infiltrates, as influenced by soil properties and the timing and magnitude of water input and evaporative demand. These results provide a mechanistic illustration of the diversity of rooting strategies in nature.
Flood basalts from Mt. Capitole in the central Kerguelen Archipelago: Insights into the growth of the archipelago and source components contributing to plume‐related volcanism
Authors: Xu Guangping , Frey Frederick A. , Weis Dominique , Scoates James S. , Giret André
Published: June 2007

The Kerguelen Archipelago, constructed on the submarine Northern Kerguelen Plateau, is attributed to Cenozoic volcanism arising from the Kerguelen hot spot. Geochemical studies of 325 to 1000 m thick lava sections of the ∼30 to 25 Ma flood basalt forming the bulk of the archipelago show a temporal change from older tholeiitic basalt to younger slightly alkalic basalt. This compositional transition is expressed in a 630 m lava section at Mt. Capitole where the lava sequence is lowermost tholeiitic basalt overlain by slightly alkalic basalt overlain by plagioclase‐rich cumulates that are mixtures of plagioclase‐phyric basalt and more evolved magmas. During growth of the archipelago, magma supply from the hot spot was variable and at times sufficiently low to enable extensive crystal fractionation; e.g., at Mt. Capitole and nearby Mt. Tourmente only 10 of 120 lava flows have >6 wt% MgO. On the basis of this study and previous isotopic data for the ∼34 Ma submarine lavas erupted on the Northern Kerguelen Plateau, other flood basalt sections in the Kerguelen Archipelago, and younger lavas erupted in the archipelago and at Heard Island, there is significant Sr, Nd, Hf, and Pb isotopic heterogeneity that can be explained by two stages of mixing. The first mixing event, best shown by the submarine lavas, is between components that are related to Indian Ocean mid‐ocean ridge basalt (MORB) and the Kerguelen hot spot. From ∼34 Ma to <1 Ma, on average the proportion of the MORB‐related component decreased. Subsequently, a second mixing process involved addition of a component with relatively high 87Sr/86Sr (>0.7060) and low 143Nd/144Nd (<0.5125) and 176Hf/177Hf (<0.2827) and nonradiogenic Pb isotope ratios (<17.9 for 206Pb/204Pb). We infer that this component was lower continental crust.
First in‐situ observations of strong ionospheric perturbations generated by a powerful VLF ground‐based transmitter
Authors: Parrot M. , Sauvaud J. A. , Berthelier J. J. , Lebreton J. P.
Published: June 2007

This paper is related to observations by the satellite DEMETER of strong ionospheric perturbations close to the VLF transmitter NWC in Australia (L = 1.41). Electrostatic waves from HF to ELF ranges are generated and strong turbulence appears. Fluctuations of electron and ion densities are observed as well as increase of temperature. The perturbations are located to the geographic North of the transmitter and cover an area of ∼500,000 km2 which is centred at the altitude of the satellite (700 km) around the magnetic field line at L = 1.41. The phenomenon is due to the electron and ion heating induced by the powerful transmitter VLF wave. This perturbation is in addition to the already known precipitation of energetic particles which interact with the VLF wave through a cyclotron resonance mechanism. The particle precipitation zone is located south of the transmitter at a slightly larger L‐shell value (1.9).
Impact of ocean color on the maintenance of the Pacific Cold Tongue
Authors: Anderson W. G. , Gnanadesikan A. , Hallberg R. , Dunne J. , Samuels B. L.
Published: June 2007

The impact of the penetration length scale of shortwave radiation into the surface ocean is investigated with a fully coupled ocean, atmosphere, land and ice model. Oceanic shortwave radiation penetration is assumed to depend on the chlorophyll concentration. As chlorophyll concentrations increase the distribution of shortwave heating becomes shallower. This change in heat distribution impacts mixed‐layer depth. This study shows that removing all chlorophyll from the ocean results in a system that tends strongly towards an El Niño state—suggesting that chlorophyll is implicated in maintenance of the Pacific cold tongue. The regions most responsible for this response are located off‐equator and correspond to the oligotrophic gyres. Results from a suite of surface chlorophyll perturbation experiments suggest a potential positive feedback between chlorophyll concentration and a non‐local coupled response in the fully coupled ocean‐atmosphere system.
An analysis of the scale heights in the lower topside ionosphere based on the Arecibo incoherent scatter radar measurements
Authors: Liu Libo , Le Huijun , Wan Weixing , Sulzer Mike P. , Lei Jiuhou , Zhang Man‐Lian
Published: June 2007

We statistically analyze the ionospheric scale heights in the lower topside ionosphere based on the electron density (Ne) and temperature profiles observed from the incoherent scatter radar (ISR) at Arecibo (293.2°E, 18.3°N), Puerto Rico. In this study, a database containing the Arecibo ISR observations from 1966 to 2002 has been used in order to investigate the diurnal and seasonal variations and solar activity dependences of the vertical scale height (VSH), which is deduced from the electron concentration profiles defined as the value of −dh/d(ln(Ne)), and the effective scale height (Hm), which is defined as the scale height in the Chapman‐α function to approximate the Ne profiles. As a measure of the slope of the height profiles of the topside electron density, the derived VSH and Hm show marked diurnal and seasonal variations and solar activity dependences. Their features are discussed in terms of thermal structures in the lower topside ionosphere. We also investigate the quantitative relationships between Hm, VSH, and plasma scale height (Hp) over Arecibo. The similarities and differences in these scale heights are discussed. Results suggest that both the contributions from topside temperature structure and diffusion processes can also greatly control VSH and Hm through changing the profile shape.
Peripheral and central H1 histamine receptor occupancy by levocetirizine, a non‐sedating antihistamine; a time course study in the guinea pig
Authors: Gupta A , Gillard M , Christophe B , Chatelain P , Massingham R , Hammarlund‐Udenaes M
Published: June 2007

Background and purpose:

The H1 receptor occupancy (H1RO) in brain is an indicator of central side effects of antihistamines. Here, we determined the kinetics of central and peripheral H1RO by levocetirizine in relation to its brain and plasma concentration, and investigated the role of the blood‐brain barrier in any delay in brain H1RO.

Experimental approach:

Concentration‐time profiles in plasma and brain were obtained after 0.1 and 1 mg kg−1 oral doses of levocetirizine in guinea pigs. H1RO in brain was measured ex vivo using [3H]‐mepyramine and, in the periphery, by measuring the degree of inhibition of histamine‐induced contractions of isolated guinea pig ileum.

Key results:

The concentration‐time profile of levocetirizine indicated lower levels (partition coefficient, Kp=0.06‐0.08), higher tmax (2‐4 h vs 1‐1.5 h) and longer terminal half‐life (4‐5.6 h vs 2.1‐2.8 h) in brain than plasma. The H1RO at 0.1 and 1 mg kg−1 were 75% and 97%, respectively, at 1 hr in the periphery and, in the brain, were <20% and 28‐67% respectively, at all time points studied. Brain H1RO vs plasma concentrations profile showed a delay, but not when compared to brain concentrations.

Conclusions and Implications:

This study demonstrates an effective peripheral antihistamine effect of levocetirizine without central adverse effects at the dose close to human therapeutic dose. The slow increase in H1RO in the brain with time was caused by slow blood‐brain barrier transport of levocetirizine. This demonstrates the importance of measuring time course of brain H1RO in relation to brain concentrations of drugs.

British Journal of Pharmacology (2007) 151, 1129–1136; doi:10.1038/sj.bjp.0707318
The adenosine A1receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure
Authors: Kalk P , Eggert B , Relle K , Godes M , Heiden S , Sharkovska Y , Fischer Y , Ziegler D , Bielenberg G‐W , Hocher B
Published: June 2007

Background and purpose:

Myocardial fibrosis is an unwanted effect associated with chronic renal failure. The adenosine system is involved in cardiac and renal function. Therefore, we investigated the novel selective adenosine A1receptor antagonist SLV320 focusing on its potential in preventing cardiomyopathy in rats with 5/6 nephrectomy.

Experimental approach:

Male Sprague‐Dawley rats were allocated to 4 groups of 12 rats each: 5/6 nephrectomy (5/6 NX), 5/6 NX plus SLV320 (10 mg kg−1 d−1mixed with food), sham and sham plus SLV320. Study duration was 12 weeks, blood pressure was assessed repeatedly. At study end kidney function was assessed, blood samples and hearts were taken for histology/immunohistochemistry. Pharmacological properties of SLV320 were assessed using receptor binding and enzyme assays and in vivo.

Key results:

SLV320 is a selective and potent adenosine A1antagonistin vitro(Ki=1 nM) with a selectivity factor of at least 200 versus other adenosine receptor subtypes. Functional A1antagonism was demonstratedin vivo. In rats with 5/6 NX SLV320 significantly decreased albuminuria by about 50%, but did not alter glomerular filtration rate (GFR). SLV320 normalized cardiac collagen I+III contents in 5/6 NX rats. SLV320 prevented nephrectomy‐dependent rise in plasma levels of creatinine kinase (CK), ALT and AST. Blood pressure did not differ between study groups.

Conclusion:

SLV320 suppresses cardiac fibrosis and attenuates albuminuria without affecting blood pressure in rats with 5/6 nephrectomy, indicating that selective A1receptor antagonists may be beneficial in uraemic cardiomyopathy.

British Journal of Pharmacology(2007)151, 1025–1032; doi:10.1038/sj.bjp.0707319
Virodhamine and CP55,940 modulate cAMP production and IL‐8 release in human bronchial epithelial cells
Authors: Gkoumassi E , Dekkers B G J , Dröge M J , Elzinga C R S , Schmidt M , Meurs H , Zaagsma J , Nelemans S A
Published: June 2007

Background and purpose:

We investigated expression of cannabinoid receptors and the effects of the endogenous cannabinoid virodhamine and the synthetic agonist CP55,940 on cAMP accumulation and interleukin‐8 (IL‐8) release in human bronchial epithelial cells.

Experimental approach:

Human bronchial epithelial (16HBE14o−) cells were used. Total mRNA was isolated and cannabinoid receptor mRNAs were detected by RT‐PCR. Expression of CB1and CB2receptor proteins was detected with Western blotting using receptor‐specific antibodies. cAMP accumulation was measured by competitive radioligand binding assay. IL‐8 release was measured by ELISA.

Key results:

CB1and CB2receptor mRNAs and proteins were found. Both agonists concentration‐dependently decreased forskolin‐induced cAMP accumulation. This effect was inhibited by the CB2receptor antagonist SR144528, and was sensitive toPertussistoxin (PTX), suggesting the involvement of CB2receptors and Gi/o‐proteins. Cell pretreatment with PTX unmasked a stimulatory component, which was blocked by the CB1receptor antagonist SR141716A. CB2receptor‐mediated inhibition of cAMP production by virodhamine and CP55,940 was paralleled by inhibition of tumor necrosis factor‐α (TNF‐α) induced IL‐8 release. This inhibition was insensitive to SR141716A. In the absence of agonist, SR144528 by itself reduced TNF‐α induced IL‐8 release.

Conclusions and implications:

Our results show for the first time that 16HBE14o−cells respond to virodhamine and CP55,940. CB1and CB2receptor subtypes mediated activation and inhibition of adenylyl cyclase, respectively. Stimulation of the dominant CB2receptor signalling pathway diminished cAMP accumulation and TNF‐α‐induced IL‐8 release. These observations may imply that cannabinoids exert anti‐inflammatory properties in airways by modulating cytokine release.

British Journal of Pharmacology(2007)151, 1041–1048; doi:10.1038/sj.bjp.0707320
The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L‐29) on pain behaviour in rodent models of neuropathy
Authors: Wallace V C J , Segerdahl A R , Lambert D M , Vandevoorde S , Blackbeard J , Pheby T , Hasnie F , Rice A S C
Published: June 2007

Background and Purpose:

Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB1) receptor‐mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L‐29), which via inhibition of fatty acid amide hydrolase (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side effects.

Experimental Approach:

Thein vivoanalysis of the effect of L‐29 on measures of pain behaviour in three rat models of neuropathic pain.

Key Results:

Systemically administered L‐29 (10 mg kg−1) reduced hypersensitivity to mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral (ddC)‐associated hypersensitivity and a model of varicella zoster virus (VZV)‐associated hypersensitivity. The effects of L‐29 were comparable to those of gabapentin (50 mg kg−1). The CB1receptor antagonist SR141716a (1 mg kg−1) and the CB2receptor antagonist SR144528 (1 mg kg−1) reduced the effect of L‐29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The peroxisome proliferator‐activated receptor‐α antagonist, MK‐886 (1 mg kg−1), partially attenuated the effect of L‐29 on hypersensitivity in the PSNI model. L‐29 (10 mg kg−1) significantly attenuated thigmotactic behaviour in the open field arena without effect on locomotor activity.

Conclusions and Implications:

L‐29 produces analgesia in a range of neuropathic pain models. This presents L‐29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation.

British Journal of Pharmacology(2007)151, 1117–1128; doi:10.1038/sj.bjp.0707326
The second extracellular loop of α2A‐adrenoceptors contributes to the binding of yohimbine analogues
Authors: Laurila J M M , Xhaard H , Ruuskanen J O , Rantanen M J M , Karlsson H K , Johnson M S , Scheinin M
Published: June 2007

Background and purpose:

Rodent α2A‐adrenoceptors bind the classical α2‐antagonists yohimbine and rauwolscine with lower affinity than the human α2A‐adrenoceptor. A serine‐cysteine difference in the fifth transmembrane helix (TM; position 5.43) partially explains this, but all determinants of the interspecies binding selectivity are not known. Molecular models of α2A‐adrenoceptors suggest that the second extracellular loop (XL2) folds above the binding cavity and may participate in antagonist binding.

Experimental approach:

Amino acids facing the binding cavity were identified using molecular models: side chains of residues 5.43 in TM5 and xl2.49 and xl2.51 in XL2 differ between the mouse and human receptors. Reciprocal mutations were made in mouse and human α2A‐adrenoceptors at positions 5.43, xl2.49 and xl2.51, and tested with a set of thirteen chemically diverse ligands in competition binding assays.

Key results:

Reciprocal effects on the binding of yohimbine and rauwolscine in human and mouse α2A‐adrenoceptors were observed for mutations at 5.43, xl2.49 and xl2.51. The binding profile of RS‐79948‐197 was reversed only by the XL2 substitutions.

Conclusions and implications:

Positions 5.43, xl2.49 and xl2.51 are major determinants of the species preference for yohimbine and rauwolscine of the human versus mouse α2A‐adrenoceptors. Residues at positions xl2.49 and xl2.51 determine the binding preference of RS‐79948‐197 for the human α2A‐adrenoceptor. Thus, XL2 is involved in determining the species preferences of α2A‐adrenoceptors of human and mouse for some antagonists.

British Journal of Pharmacology (2007) 151, 1293–1304; doi:10.1038/sj.bjp.0707330
An intelligent filter control system using fuzzy logic for APS insertion device beamlines
Authors: Shu Deming , Minich Jim , Haeffner Dean , Brite Christa , Nian Tom , Dejus Roger , Kuzay Tuncer
Published: June 2007

A modular filter has been designed for the white-beam undulator/wiggler beamlines at the Advanced Photon Source. For a typical hard x-ray application, the filter assembly consists of four filter banks, and each bank has five beam apertures. Therefore a maximum of 625 filter combinations is mechanically possible. To prevent any mistaken setup, which could either damage the filter itself or downstream optical components, a programmable logic controller (PLC) based protection system has been designed. Fuzzy logic was used in this system to limit the memory size and improve the system performance. Ten different storage-ring beam currents and ten insertion-device gap setups have been chosen to cover a large dynamic operation range. Aspects of the system fuzzy logic design as well as an example of the calculated results for the control database are presented in this paper.
Using metallic filters in APS undulator beamlines
Authors: Wang Zhibi , Kuzay Tuncer M.
Published: June 2007

Metallic filters are needed by APS users in their beamlines. Two general areas of use for the white-beam metallic filters are: (1) to attenuate the x-ray beam to reduce the thermal load during routine operations and (2) to attenuate the x-ray beam during alignment and for special testing of optics at low power. Metallic filters are important for users who will be working primarily in the high energy x-ray range because unwanted lower energy photons are absorbed through the metallic filters. Notwithstanding their high thermal conductivity, the metals, in general, absorb x-rays significantly near surface layers and hence can attain very large temperatures causing structural deformations and/or damage. Thermomechanical behavior and failure prediction need to be done carefully. In this paper, particulars of metallic filters are discussed and generalized analytical solutions are offered to help users of metallic filters determine their applicability for x-ray beamlines
Internally shielded beam transport and support system (abstract)
Authors: Schildkamp W. , Brewer H.
Published: June 2007

Due to environmental concerns, the Advanced Photon Source has a policy that disallows any exposed lead within the facility. This creates a real problem for the beam transport system, not so much for the pipe but for the flexible coupling (bellows) sections. A complete internally shielded x-ray transport system, consisting of long transport lines joined by flexible coupling sections, has been designed for CARS sector 14 to operate either at high vacuum or as a helium flight tube. It can effectively shield against air scattering of wiggler or undulator white beam with proper placement of apertures, collimators, and masks for direct beam control. The system makes use of male- and female-style fittings that create a labyrinth allowing for continuous shielding through the flexible coupling sections. These parts are precision machined from a ternary hypereutectic lead alloy (cast under 15 inches of head pressure to assure a pinhole-free casting) then pressed into either end (rotatable vacuum flanges) of the bellows assembly. The transport pipe itself consists of a four part construction using a stepped transition ring (Z-ring) to connect an inner tube to the vacuum flange and also to a protective and supportive outer tube. The inner tube is wrapped with 1/16″ pure lead sheet to a predetermined thickness following the shape of the stepped transition ring for continuous shielding. This design has been prototyped and radiation tested.
Design analysis of a composite L5-20 slit for x-ray beamlines at the Advanced Photon Source
Authors: Nian H.L. Thomas , Kuzay Tuncer M. , Shu D. , Benson C.
Published: June 2007

White-beam slits are precision high heat load devices used on beamlines of the Advanced Photon Source (APS) to trim and shape the incoming x-ray beam before the beam is transmitted to other optical components. At the APS, the insertion devices that generate the x-ray beams are very powerful. For example, the heat flux associated with an x-ray beam generated by undulator A will be on the order of 220 W/mm2 at the L5-20 slit location (about 27.5 m away from the insertion device) at normal incidence. The total power is about 6 kW. Optical slits with micron-level precision are very difficult to design under such heat flux and total power considerations. A novel two-metal composite slit has been designed to meet the diverse thermal, structural, and precision requirements. A commercial code, ANSYS, has been used as the finite element source for the analysis of the optimized design for the set.
End-field design and tuning methods for insertion devices
Authors: Gottschalk S. C. , Robinson K. E. , Vasserman I. , Dejus R. , Moog E. R.
Published: June 2007

The magnetic field distribution, gap-dependent steering, and integrated magnetic multipole moments of insertion devices installed in synchrotron radiation sources have stringent requirements for yielding high brightness without adversely perturbing the electron orbit. Correct termination of the ends of the device yields a large number of full-field poles and helps achieve gap-independent steering. End-field tuning methods used for the Advanced Photon Source insertion devices are reviewed. Techniques include magnet strength reduction, reduced height poles, magnetic shims, and pole shaping. Measurements show that two-imensional finite element analysis is a useful tool for predicting general field shape and trajectories. However, experimental entrance steering of different devices with identical end configurations shows variance, necessitating empirical fine tuning of each device.
A high-efficiency positive (negative) surface ionization source for radioactive ion beam (abstract)a)
Authors: Alton G. D. , Mills G. D.
Published: June 2007

A versatile, new concept, spherical-geometry, positive (negative) surface-ionization source has been designed and fabricated which will have the capability of generating both positive- and negative-ion beams without mechanical changes to the source. The source utilizes a highly permeable, high-work-function Ir ionizer (φ≡5.29 eV) for ionizing highly electropositive atoms/molecules; while for negative-surface ionization, the work function is lowered to φ≡1.43 eV by continually feeding cesium vapor through the ionizer matrix. The use of this technique for negative ion beam generation has the potential of overcoming the chronic poisoning effects experienced with LaB6 while enhancing considerably the efficiency for negative surface ionization of atoms and molecules with intermediate electron affinities. The flexibility of operation in either mode makes it especially attractive for radioactive ion beam applications and, therefore, the source will be used as a complementary replacement for the high-temperature electron impact ionization sources presently in use at the Holifield radioactive beam facility. The design features and operational principles of the source will be described in this report.
Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites
Authors: Cyrklaff Marek , Kudryashev Mikhail , Leis Andrew , Leonard Kevin , Baumeister Wolfgang , Menard Robert , Meissner Markus , Frischknecht Friedrich
Published: June 2007

Microtubules are dynamic cytoskeletal structures important for cell division, polarity, and motility and are therefore major targets for anticancer and antiparasite drugs. In the invasive forms of apicomplexan parasites, which are highly polarized and often motile cells, exceptionally stable subpellicular microtubules determine the shape of the parasite, and serve as tracks for vesicle transport. We used cryoelectron tomography to image cytoplasmic structures in three dimensions within intact, rapidly frozen Plasmodium sporozoites. This approach revealed microtubule walls that are extended at the luminal side by an additional 3 nm compared to microtubules of mammalian cells. Fourier analysis revealed an 8-nm longitudinal periodicity of the luminal constituent, suggesting the presence of a molecule interacting with tubulin dimers. In silico generation and analysis of microtubule models confirmed this unexpected topology. Microtubules from extracted sporozoites and Toxoplasma gondii tachyzoites showed a similar density distribution, suggesting that the putative protein is conserved among Apicomplexa and serves to stabilize microtubules.