bluuebunny/crossref_metadata_2025 huggingface dataset:
The cannabinomimetic arachidonyl‐2‐chloroethylamide (ACEA) acts on capsaicin‐sensitive TRPV1 receptors but not cannabinoid receptors in rat joints
Authors: Baker Chris L , McDougall Jason J
Published: August 2004

The vasoactive effects of the synthetic cannabinoid (CB) arachidonyl‐2‐chloroethylamide (ACEA) was tested in the knee joints of urethane‐anaesthetised rats. Experiments were also performed to determine whether these vasomotor responses could be blocked by the selective CB1 receptor antagonists AM251 (N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide) (10−9 mol) and AM281 (1‐(2,4‐dichlorophenyl)‐5‐(4‐iodophenyl)‐4‐methyl‐N‐4‐morpholinyl‐1H‐pyrazole‐3‐carboxamide) (10−8 mol), as well as the selective CB2 receptor antagonist AM630 (6‐iodo‐2‐methyl‐1‐[2‐4(morpholinyl)ethyl]‐[1H‐indol‐3‐yl](4‐methoxyphenyl)methanone) (10−8 mol).

Peripheral application of ACEA (10−14–10−9 mol) onto the exposed surface of the knee joint capsule caused a dose‐dependent increase in synovial blood flow. The dilator action of the CB occurred within 1 min after drug administration and rapidly returned to control levels shortly thereafter. The maximal vasodilator effect of ACEA corresponded to a 30% increase in articular perfusion compared to control levels.

The hyperaemic action of ACEA was not significantly altered by coadministration of AM251, AM281 or AM630 (P>0.05; two‐way ANOVA).

The transient receptor potential channel vanilloid receptor 1 (TRPV1) antagonist capsazepine (10−6 mol) significantly reduced the vasodilator effect of ACEA on joint blood vessels (P=0.002). Furthermore, destruction of unmyelinated and thinly myelinated joint sensory nerves by capsaicin (8‐methyl‐N‐vanillyl‐6‐nonenamide) treatment also attenuated ACEA responses (P<0.0005).

These data clearly demonstrate a vasodilator effect of the cannabinomimetic ACEA on knee joint perfusion. Rather than a classic CB receptor pathway, ACEA exerts its vasomotor influence by acting via TRPV1 receptors located on the terminal branches of capsaicin‐sensitive afferent nerves innervating the joint.

British Journal of Pharmacology (2004) 142, 1361–1367. doi:10.1038/sj.bjp.0705902
A compensated heat-pulse calorimeter for low temperatures
Authors: Wilhelm H. , Lühmann T. , Rus T. , Steglich F.
Published: August 2004

We describe a technique for measuring heat capacities (Cmin≈1 μJ/K at 0.1 K) of small solid samples at low temperatures (0.03 K<T<6 K) and in high magnetic fields (B<12 T). In this compensated heat-pulse technique the thermal losses are compensated through a background heating. A detailed analysis of the heat flow takes the heat input and losses into account. Test measurements on tin and YbRh2(Si0.95Ge0.05)2 showed that the heat capacity can be determined with high precision in a fast and accurate way. This technique provides a versatile calorimeter for a wide range of heat capacities which achieves its main performance if several sample platforms are mounted and one sample is measured while the other may cool down.
Wave cutoff method to measure absolute electron density in cold plasma
Authors: Kim Jung-Hyung , Choi Sang-Chul , Shin Yong-Hyeon , Chung Kwang-Hwa
Published: August 2004

A method for precise measurements of absolute electron density in plasma using wave cutoff is described. This method of measurement uses a network analyzer with radiating and detecting antenna A microwave signal of 10 kHZ–3 GHz frequency is introduced into the plasma from a radiating port of the network analyzer and propagates in the plasma. The transmitted wave is monitored at a distance from a radiating antenna using an antenna connected to the receiving port of the network analyzer. The transmitted wave decays rapidly at a cutoff plasma frequency, which is a direct measure of the absolute electron density. This cutoff method is free of many difficulties often encountered with a Langmuir probe, such as thin film deposition and plasma potential fluctuation. The cutoff probe can also measure the spatial distribution of the electron density. The measurement technique is analyzed theoretically and experimentally, demonstrated in density measurements of an inductively coupled radio-frequency plasma, and is compared with the double probe and a plasma oscillation methods.
Multiparameter segmented scan multichannel scaling system
Authors: Kumar S. V. K. , Anathakrishnan T. S. , Krishnakumar E. , Ashoka V. S. , Kataria S. K.
Published: August 2004

A PC based data acquisition cum control system has been developed using a general purpose interface bus (GPIB/IEEE-488/IEC-625) plug in card and GPIB interfaceable NIM electronics for use in experiments on absorption spectroscopy studies of molecules using laser-induced fluorescence (LIF), resonance multiphoton ionization (REMPI), electron impact ionization and dissociative attachment from the ground state as well as from excited states, to name a few examples. Unlike commercially available multichannel scalers, this system can handle several parameters as the acquisition parameter (e.g., dye laser) is scanned over the desired wavelength in preselected segments saving precious data acquisition time. This system has been tested on laser excited dissociative electron attachment experiments.
Design of a 250 eV cryogenic ignition capsule for the National Ignition Facility
Authors: Strobel George L. , Haan Steven W. , Munro David H. , Dittrich Thomas R.
Published: August 2004

Optimized performance of a capsule intended to produce ignition on the National Ignition Facility [J. A. Paisner, J. D. Boyes, S. A. Kumpan, W. H. Lowdermilk, and M. S. Sorem, Laser Focus World 30, 75 (1994)] is presented. Performance is optimized, for a 250 eV isotropic drive on a beryllium(copper) ablator, by varying the ablator outside radius, ablator thickness, the concentration of copper dopant in the ablator, and the fuel thickness, while keeping the absorbed energy fixed. Dopant concentration is constrained to be uniform in the ablator. The drive shock timing is adjusted to produce a low entropy implosion for each set of dimensions. The absorbed energy is kept fixed at 190 kJ, which results in the ablator outside radius remaining practically constant, about 0.137 cm. For capsule geometry near that resulting in optimal implosion yield, the absorbed energy depends only slightly on the ablator or fuel thickness. The parameter space of capsule dimensions was searched for central vapor densities of 0.3 and 0.5 mg/cc. Despite the detailed optimization, it is found that the capsule is notably more unstable than comparable capsules with a graded dopant in the ablator, as reported in previous literature.
Convective transport in the scrape-off-layer by nonthermalized spinning blobs
Authors: Myra J. R. , D’Ippolito D. A. , Krasheninnikov S. I. , Yu G. Q.
Published: August 2004

In this paper, two-dimensional blob models of convective transport in the scrape-off-layer (SOL) are generalized to include the internal temperature profile of the blob. This generalization provides a mechanism for blob internal spin and enables consideration of SOL energy transport. Solutions with aligned density and temperature contours satisfy the resulting “hot blob” equations and are considered here. It is shown that spin increases blob coherence, prevents the formation of extended radial streamers or fingers, reduces the radial convection velocity due to mixing and mitigation of the curvature-induced charge polarization, and provides a new mechanism for poloidal motion of the blob. Additionally, spinning blobs are shown to survive as coherent objects in the presence of weak externally sheared flows, and have blob speeds that depend on the sign of the spin relative to the external sheared flow. The work provides strong motivation for investigating the physics of parallel disconnected blobs, and the relationship of spin and disconnection physics to edge localized mode propagation and the density limit.
Transient growth and minimal defects: Two possible initial paths of transition to turbulence in plane shear flows
Authors: Biau Damien , Bottaro Alessandro
Published: August 2004

Two possible initial paths of transition to turbulence in simple wall-bounded shear flows are examined by looking at the development in space of infinitesimal disturbances. The first is the—by-now-classical—transient growth scenario which may have an important role in the bypass transition of flows for which traditional eigenmode analysis predicts asymptotic stability. It is studied by means of a simplified parabolic model justified by the underlying physics of the problem; results for optimal disturbances and maximum transient growth are found in excellent agreement with computations based on the full Orr–Sommerfeld/Squire equations. The second path starts with the exponential amplification, in nominally subcritical conditions, of modal disturbances superposed to base flows mildly distorted compared to their idealized counterparts. Such mean flow distortions might arise from the presence of unwanted external forcing related, for example, to the experimental environment. A technique is described that is capable of providing the worst case distortion of fixed norm for any ideal base flow, i.e., that base flow modification capable of maximizing the amplification rate of a given instability mode. Both initial paths considered here provide feasible initial conditions for the transition process, and it is likely that in most practical situations algebraic and exponential growth mechanisms are concurrently at play in destabilizing plane shear flows.
Free stream turbulence induced disturbances in boundary layers with wall suction
Authors: Yoshioka Shuya , Fransson Jens H. M. , Alfredsson P. Henrik
Published: August 2004

An experimental investigation of free stream turbulence (FST) induced disturbances in asymptotic suction boundary layers (ASBL) has been performed. In the present study four different suction rates are used and the highest is 0.40% of the free stream velocity, together with three different FST levels (Tu=1.6, 2.0, and 2.3%). A turbulence generating grid of the active type is used and offers the possibility to vary the Tu-level while the scales of the turbulence remain almost constant. It is known that FST induces elongated disturbances consisting of high and low velocity regions, usually denoted streaky structures, into the boundary layer. The experiments show that wall suction suppresses the disturbance growth and may significantly delay or inhibit the break-down to turbulence. Two-point correlation measurements in the spanwise direction show that the averaged streak spacing decreases with increasing FST-level, whereas the spanwise scale in the ASBL is more or less constant if scaled with the free stream velocity and viscosity. This is in contrast to what is observed in a Blasius boundary layer where streaks develop and adapt their spanwise scale close to the boundary layer thickness.
Linear stability of radial displacements in porous media: Influence of velocity-induced dispersion and concentration-dependent diffusion
Authors: Riaz A. , Pankiewitz C. , Meiburg E.
Published: August 2004

A parametric study is conducted in order to investigate the influence of (a) velocity dependent dispersion, and (b) concentration-dependent diffusion on the stability of miscible porous media displacements in the radial geometry. Numerical solutions for the base concentration profile demonstrate that velocity induced dispersion dominates for short times and large Péclet numbers. For large times, the growth rates approach those obtained when only molecular diffusion is taken into account. Concentration-dependent diffusion coefficients are seen to modify the mobility profiles of the base flow, and to shift the eigenfunctions into more or less viscous environments. This results in a destabilization for nearly all Péclet values and mobility ratios.
On the equilibrium states predicted by second moment models in rotating, stably stratified homogeneous shear flow
Authors: Ji Minsuk , Durbin Paul A.
Published: August 2004

The structural equilibrium behavior of the general linear second-moment closure model in a stably stratified, spanwise rotating homogeneous shear flow is considered with the aid of bifurcation analysis. A closed form equilibrium solution for the anisotropy tensor aij, dispersion tensor Kij, dimensionless scalar variance θ2̄/k(S/Sθ)2, and the ratio of mean to turbulent time scale ε/Sk is found. The variable of particular interest to bifurcation analysis, ε/Sk is shown as a function of the parameters characterizing the body forces: Ω/S (the ratio of the rotation rate to the mean shear rate) for rotation and Rig (the gradient Richardson number) for buoyancy; it determines the bifurcation surface in the ε/Sk−Ω/S−Rig space. It is shown, with the use of the closed form solution, that the Isotropization of Production model does not have a real and stable equilibrium solution when rotational and buoyant forces of certain magnitudes are simultaneously imposed on the flow. When this occurs, time integration of the turbulence model results in a diverging solution. A new set of scalar model coefficients that is consistent with experimental data, predicts turbulence decay past the critical gradient Richardson number Rigcr=0.25, and ensures the existence of stable, real solutions for all combinations of rotation and buoyancy is proposed.
Self-focusing of electromagnetic beams in collisional plasmas with nonlinear absorption
Authors: Sharma Ashutosh , Verma M. P. , Sodha M. S.
Published: August 2004

In this paper the formalism of self-focusing of electromagnetic waves is extended to include nonlinear absorption by the medium. A complex eikonal has been employed, which does not need any approximation about the relative magnitudes of the real and imaginary parts of the dielectric constant or their dependence on the irradiance of the beam. The specific case of collisional plasmas has been considered as an application of the theory. It is seen that the nonlinearity in absorption tends to cancel the effect of divergence on account of diffraction. The dependence of the beam width and attenuation on distance of propagation has been illustrated for specific cases. The relevance of the investigation to radio wave propagation has also been pointed out.
Experimental study of velocity filtered joint density function for large eddy simulation
Authors: Wang Danhong , Tong Chenning , Pope Stephen B.
Published: August 2004

The velocity filtered joint density function (VFJDF) used in large eddy simulation and the structure of the subgrid-scale (SGS) velocity are studied experimentally. Measurements are made in the fully developed region of an axisymmetric turbulent jet (with jet Reynolds number UjDj/ν=40 000) using an array consisting of three X-wire probes. Filtering in the cross-stream and streamwise directions is realized by using the array and by invoking Taylor’s hypothesis, respectively. On the jet centerline the means of the VFJDF conditional on the SGS turbulent kinetic energy are found to be close to joint normal when the SGS energy is small compared to its mean but has a uniform portion when the SGS energy is large. The latter distribution has not been observed previously and suggests that the SGS velocity contains approximately linear structures and is under local rapid distortion. The results at off-centerline positions are also consistent with the existence of linear structures. Further analyses show that the SGS velocity field with large SGS energy is in nonequilibrium (SGS production exceeds dissipation) and that the degree of nonequilibrium largely determines the shape of the VFJDF. The conditional energy dissipation has moderate dependence on the SGS velocity as expected due to their scale separation. However, the off-diagonal component of the conditional dissipation tensor is non-negligible when the SGS energy is large, at least for the Reynolds number studied. The present study suggests that the different structures and the local rapid distortion observed are important for SGS modeling. The results also suggest that the eddy-viscosity-type models for the SGS stress generally cannot give qualitatively correct predictions for SGS turbulence under local rapid distortion.
Effect of a temperature difference between the cylinders on the Taylor–Couette bifurcation in a gas
Authors: Handa Masato , Doi Toshiyuki
Published: August 2004

A gas in a time-independent state between rotating coaxial circular cylinders with different temperatures is considered. The effect of the temperature difference on the Taylor–Couette bifurcation in the continuum limit is studied on the basis of the fluid-dynamic-type equations and their boundary conditions derived from the Boltzmann system. The behavior of the bifurcation point for a wide range of temperature differences is presented, and the mechanism of the shift of the bifurcation point owing to a small temperature difference is clarified analytically. The effect of the temperature difference on the bifurcation cannot be explained correctly by the guess by the analogy with the Bénard problem.
On the dynamics of self-sustained one-dimensional detonations: A numerical study in the shock-attached frame
Authors: Kasimov Aslan R. , Stewart D. Scott
Published: August 2004

In this work we investigate the dynamics of self-sustained detonation waves that have an embedded information boundary such that the dynamics is influenced only by a finite region adjacent to the lead shock. We introduce the boundary of such a domain, which is shown to be the separatrix of the forward characteristic lines, as a generalization of the concept of a sonic locus to unsteady detonations. The concept plays a fundamental role both in steady detonations and in theories of much more frequently observed unsteady detonations. The definition has a precise mathematical form from which its relationship to known theories of detonation stability and nonlinear dynamics can be clearly identified. With a new numerical algorithm for integration of reactive Euler equations in a shock-attached frame, that we have also developed, we demonstrate the main properties of the unsteady sonic locus, such as its role as an information boundary. In addition, we introduce the so-called “nonreflecting” boundary condition at the far end of the computational domain in order to minimize the influence of the spurious reflected waves.
Measurement of solar cell ac parameters using the time domain technique
Authors: Deshmukh M. P. , Kumar R. Anil , Nagaraju J.
Published: August 2004

The instrumentation to measure solar cell ac parameters [cell capacitance (CP) and cell resistance (RP)] using the time domain technique is developed. The cell capacitance (CP) and series resistance (r) are calculated using open circuit voltage decay (OCVD) technique. It is calibrated with the help of an electrical network with passive components similar to ac equivalent circuit of a solar cell consisting of precision resistors and capacitors. The maximum error observed in the measurement of resistor and capacitor value is ±3.5%. The cell resistance (RP) is calculated from I–V characteristics of solar cell. The data obtained in time domain technique is compared with the impedance spectroscopy technique data measured on same solar cell and it is found that the deviation in cell capacitance and resistance are within ±8%.
Design and operation of a retarding field energy analyzer with variable focusing for space-charge-dominated electron beams
Authors: Cui Y. , Zou Y. , Valfells A. , Reiser M. , Walter M. , Haber I. , Kishek R. A. , Bernal S. , O’Shea P. G.
Published: August 2004

A retarding electrostatic field energy analyzer for low-energy beams has been designed, simulated, and tested with electron beams of several keV, in which space-charge effects play an important role. A cylindrical focusing electrode is used to overcome the beam expansion inside the device due to space-charge forces, beam emittance, etc. The cylindrical focusing voltage is independently adjustable to provide proper focusing strength. Single particle simulation and theoretical error analysis using beam envelopes show that this energy analyzer can get very high resolution for low-energy beams (up to 10 keV), which was found to be in good agreement with experimental results. The measured beam energy spectrum is both temporally and spatially resolved. In addition, a computer-controlled automatic system is developed and significantly improves the speed and efficiency of the data acquisition and processing. The measured beam energy spreads, are in remarkably good agreement with the intrinsic limits set by the effects of nonadiabatic acceleration in the electron gun and that of Coulomb collisions, as predicted by theory.
High sensitivity optical microscope for single molecule spectroscopy studies
Authors: Malengo Gabriele , Milani Roberto , Cannone Fabio , Krol Silke , Diaspro Alberto , Chirico Giuseppe
Published: August 2004

We describe the setup and apply two algorithms for fast imaging in a sample raster scanning two photon microscope. Imaging can be performed at a rate of 1–100 lines per second with a closed loop piezo actuator, and the detection is performed via avalanche photodiodes. This allows to investigate single molecule emission with 50 ms time resolution. In a slow scanning algorithm we have implemented fluorescence fluctuation analysis by computing the photon counting histogram (PCH) on each pixel of the image. In a fast-scan acquistion method the image acquistion rate is 5 lines per second on a large field of view and high resolution(50 nm scanning step, 100×100 μm2 field of view) and ≅100 lines per second on smaller field of views with optically limited resolution (200 nm scanning step, 20×20 μm2 field of view). This figure, which is lower than the typical value for normal confocal scanning imaging (≅500 lines per second), allows nevertheless to perform imaging studies of extended samples in reasonable times for intracellular kinetics and interactions. With this setup and by means of the PCH analysis we are able to discriminate between local concentration and molecular brightness on extended samples also at the level of the single molecule.
Conducting atomic force microscopy for nanoscale tunnel barrier characterization
Authors: Lang K. M. , Hite D. A. , Simmonds R. W. , McDermott R. , Pappas D. P. , Martinis John M.
Published: August 2004

Increasing demands on nanometer-scale properties of oxide tunnel barriers necessitate a consistent means to assess them on these length scales. Conducting atomic force microscopy (CAFM) is a promising technique both for understanding connections between nanoscale tunnel barrier characteristics and macroscopic device performance as well as for rapid qualitative evaluation of new fabrication methods and materials. Here we report CAFM characterization of aluminum oxide (AlOx) barriers to be used in Josephson-junction qubits, with a particular emphasis on developing reproducible imaging conditions and appropriate interpretation. We find that control of the imaging force is a critical factor for reproducibility. We imaged the same sample on the same day with the same cantilever varying only the imaging force between scans. Statistical properties compiled from the resulting current maps varied approximately exponentially with imaging force, with typical currents increasing by two orders of magnitude for only a factor of 5 increase in imaging force. Given appropriate control of the imaging force, scan to scan variation of the current recorded at the same location was approximately ±0.5〈I〉, which establishes a criterion for statistical reproducibility of CAFM measurements. We further find that the appropriate interpretation for CAFM (under most imaging conditions), is as a probe of local propensity for insulator breakdown. Samples stored in air for weeks before study showed current features with oxidation times of order minutes. This indicates that these features were created by the scanning of the tip, and thus represent local pinhole susceptible regions. We finally present results for several AlOx samples showing that under appropriate imaging conditions significant sample to sample variation is observed, thus demonstrating the potential of this technique to qualitatively assess and facilitate under standing of potential qubit tunnel barrier devices.
The existence problem for dynamics of dissipative systems in quantum probability
Authors: Jorgensen Palle E. T.
Published: August 2004

Motivated by existence problems for dissipative systems arising naturally in lattice models from quantum statistical mechanics, we consider the following C*-algebraic setting: A given Hermitian dissipative mapping δ is densely defined in a unital C*-algebra A. The identity element in A is also in the domain of δ. Completely dissipative maps δ are defined by the requirement that the induced maps, (aij)→(δ(aij)), are dissipative on the n-by-n complex matrices over A for all n. We establish the existence of different types of maximal extensions of completely dissipative maps. If the enveloping von Neumann algebra of A is injective, we show the existence of an extension of δ which is the infinitesimal generator of a quantum dynamical semigroup of completely positive maps in the von Neumann algebra. If δ is a given well-behaved *-derivation, then we show that each of the maps ±δ is completely dissipative.
Contactless technique for thermal conductivity measurement at very low temperature
Authors: Hao H.-Y. , Neumann M. , Enss C. , Fleischmann A.
Published: August 2004

We present a low-temperature thermal conductivity measurement, which requires no electrical wire in contact with the sample. The temperature gradient in the sample is generated via optical heating and detected by two magnetization thermometers with inductively coupled dc-SQUID readouts. The parasitic heat leak and power dissipation of the setup can be arranged to be below 10−15 W. Therefore this contact-free method is well-suited for measuring samples with very small thermal conductiviy at low temperature. We present results for BK7 glass and a-SiO2 down to 5.3 mK.
Extremal covariant quantum operations and positive operator valued measures
Authors: D’Ariano Giacomo Mauro
Published: August 2004

We consider the convex sets of QO’s (quantum operations) and POVM’s (positive operator valued measures) which are covariant under a general finite-dimensional unitary representation of a group. We derive necessary and sufficient conditions for extremality, and give general bounds for ranks of the extremal POVM’s and QO’s. Results are illustrated on the basis of simple examples.
Calculation of the transport properties of carbon dioxide. III. Volume viscosity, depolarized Rayleigh scattering, and nuclear spin relaxation
Authors: Bock Steffen , Bich Eckard , Vogel Eckhard , Dickinson Alan S. , Vesovic Velisa
Published: August 2004

Transport properties of pure carbon dioxide have been calculated from the intermolecular potential using the classical trajectory method. Results are reported in the dilute-gas limit for volume viscosity, depolarized Rayleigh scattering, and nuclear spin relaxation for temperatures ranging from 200 to 1000 K. Three recent carbon dioxide potential energy hypersurfaces have been investigated. Calculated values for the rotational collision number for all three intermolecular surfaces are consistent with the measurements and indicate that the temperature dependence of the Brau-Jonkman correlation is not applicable for carbon dioxide. The results for the depolarized Rayleigh scattering cross section and the nuclear spin relaxation cross section show that calculated values for the generally more successful potentials differ from the observations by 9% at about 290 K, although agreement is obtained for nuclear spin relaxation at about 400 K.
Spatial mode structures of electrostatic drift waves in a collisional cylindrical helicon plasma
Authors: Schröder Christiane , Grulke Olaf , Klinger Thomas , Naulin Volker
Published: August 2004

In a cylindrical helicon plasma, mode structures of coherent drift waves are studied in the poloidal plane, the plane perpendicular to the ambient magnetic field. The mode structures rotate with a constant angular velocity in the direction of the electron diamagnetic drift and show significant radial bending. The experimental observations are compared with numerical solutions of a linear nonlocal cylindrical model for drift waves [Ellis et al., Plasma Phys. 22, 113 (1980)]. In the numerical model, a transition to bended mode structures is found if the plasma collisionality is increased. This finding proves that the experimentally observed bended mode structures are the result of high electron collisionality.
Hybrid continuum-atomistic simulation of singular corner flow
Authors: Nie Xiaobo , Chen Shiyi , Robbins Mark O.
Published: August 2004

A hybrid numerical method is used to study cavity flow driven by a moving wall. Continuum equations with no-slip boundary conditions predict singular stresses at the corners between moving and static walls. Molecular dynamics simulations are used to resolve these singular regions, and the flow field in the remainder of the cavity is obtained from the Navier-Stokes (NS) equations. This hybrid solution agrees well with fully atomistic simulations on small systems, and allows calculations to be accelerated by orders of magnitude in larger systems. Fully continuum and hybrid solutions for the stress and velocity also agree over most of the cavity. Both yield a shear stress that scales as the inverse of the distance from the corner over almost two orders of magnitude. However, in the hybrid solution, this divergence is cut off within a distance S from the corners. In the limit of low wall velocities U, S is a few molecular diameters and corresponds to the length over which slip occurs. By comparing the hybrid solution to NS solutions, we show that the slip cannot be quantitatively described by the Navier slip condition. At higher U, non-Newtonian behavior near the corner causes S to rise linearly with U.
Transport coefficients in relativistic collisionless plasmas
Authors: Bendib-Kalache K. , Bendib A. , Matthieussent G.
Published: August 2004

The computation of the relativistic transport coefficients in collisionless plasmas is presented. The stationary relativistic Vlasov equation is analytically solved for perturbed plasmas with respect to the global equilibrium defined by the Maxwell–Boltzmann–Jüttner distribution function. The explicit expression of the distribution function is derived and the generalized collisionless transport coefficients are deduced for arbitrary plasma temperature. It is found that the relativistic effects tend to increase the value of the transport coefficients. In particular, in ultrarelativistic regimes the temperature anisotropy reaches its maximum value.
Synthetic antibodies from a four-amino-acid code: A dominant role for tyrosine in antigen recognition
Authors: Fellouse Frederic A. , Wiesmann Christian , Sidhu Sachdev S.
Published: August 2004

Antigen-binding fragments (Fabs) with synthetic antigen-binding sites were isolated from phage-displayed libraries with restricted complementarity-determining region (CDR) diversity. Libraries were constructed such that solvent-accessible CDR positions were randomized with a degenerate codon that encoded for only four amino acids (tyrosine, alanine, aspartate, and serine). Nonetheless, high-affinity Fabs (
K
d
= 2–10 nM) were isolated against human vascular endothelial growth factor (hVEGF), and the crystal structures were determined for two distinct Fab-hVEGF complexes. The structures revealed that antigen recognition was mediated primarily by tyrosine side chains, which accounted for 71% of the Fab surface area that became buried upon binding to hVEGF. In contrast, aspartate residues within the CDRs were almost entirely excluded from the binding interface. Alanine and serine residues did not make many direct contacts with antigen, but they allowed for space and conformational flexibility and thus played an auxiliary role in facilitating productive contacts between tyrosine and antigen. Tyrosine side chains were capable of mediating most of the contacts necessary for high-affinity antigen recognition, and, thus, it seems likely that the overabundance of tyrosine in natural antigen-binding sites is a consequence of the side chain being particularly well suited for making productive contacts with antigen. The findings shed light on the basic principles governing the evolution of natural immune repertoires and should also aid the development of improved synthetic antibody libraries.
Imaging of single-molecule translocation through nuclear pore complexes
Authors: Yang Weidong , Gelles Jeff , Musser Siegfried M.
Published: August 2004

Nuclear pore complexes (NPCs) mediate bidirectional transport of proteins, RNAs, and ribonucleoprotein complexes across the double-membrane nuclear envelope.
In vitro
studies with purified transport cofactors have revealed a general scheme of cofactor-dependent transport energetically driven by the G protein Ran. However, the size and complexity of NPCs have made it difficult to clearly define the loci and kinetics of the cofactor–NPC interactions required for transport. We now report the use of single-molecule fluorescence microscopy to directly monitor a model protein substrate undergoing transport through NPCs in permeabilized cells. This substrate, NLS-2xGFP, interacts with NPCs for an average of 10 ± 1 ms during transport. However, because the maximum nuclear accumulation rate of NLS-2xGFP was measured to be at least ≈10
3
molecules per NPC per s, NPCs must be capable of transporting at least ≈10 substrate molecules simultaneously. Molecular tracking reveals that substrate molecules spend most of their transit time randomly moving in the central pore of the NPC and that the rate-limiting step is escape from the central pore.
Structural origins of constitutive activation in rhodopsin: Role of the K296/E113 salt bridge
Authors: Kim Jong-Myoung , Altenbach Christian , Kono Masahiro , Oprian Daniel D. , Hubbell Wayne L. , Khorana H. Gobind
Published: August 2004

The intramolecular interactions that stabilize the inactive conformation of rhodopsin are of primary importance in elucidating the mechanism of activation of this and other G protein-coupled receptors. In the present study, site-directed spin labeling is used to explore the role of a buried salt bridge between the protonated Schiff base at K296 in TM7 and its counterion at E113 in TM3. Spin-label sensors are placed at positions in the cytoplasmic surface of rhodopsin to monitor changes in the structure of the helix bundle caused by point mutations that disrupt the salt bridge. The single point mutations E113Q, G90D, and A292E, which were previously reported to cause constitutive activation of the apoprotein opsin, are found to cause profound movements of both TM3 and TM6 in the dark state, the latter of which is similar to that caused by light activation. The mutant M257Y, which constitutively activates opsin but does not disrupt the salt bridge, is shown to cause related but distinguishable structural changes. The double mutants E113Q/M257Y and G90D/M257Y produce strong activation of the receptor in the dark state. In the E113Q/M257Y mutant investigated with spin labeling, the movement of TM6 and other changes are exaggerated relative to either E113Q or M257Y alone. Collectively, the results provide structural evidence that the salt bridge is a key constraint maintaining the resting state of the receptor, and that the disruption of the salt bridge is the cause, rather than a consequence, of the TM6 motion that occurs upon activation.
Vaccination with genetically engineered allergens prevents progression of allergic disease
Authors: Niederberger V. , Horak F. , Vrtala S. , Spitzauer S. , Krauth M.-T. , Valent P. , Reisinger J. , Pelzmann M. , Hayek B. , Kronqvist M. , Gafvelin G. , Grönlund H. , Purohit A. , Suck R. , Fiebig H. , Cromwell O. , Pauli G. , van Hage-Hamsten M. , Valenta R.
Published: August 2004

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (
n
= 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.
Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines
Authors: Hohlfeld Reinhard , Wekerle Hartmut
Published: August 2004

Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of multiple sclerosis (MS), and thus are logical targets for therapy. Indeed, several immunomodulatory agents, including IFN-β1b, IFN-β1a, glatiramer acetate, and mitoxantrone, have had beneficial clinical effects in different forms of MS. However, because the available treatments are only partially effective, MS therapy needs to be further improved. Selective (antigen-specific) immunotherapies are especially appealing because in theory they combine maximal efficacy with minimal side effects. Indeed, several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. For example, autoreactive T cells can be selectively targeted by means of antigen, T cell receptor, or activation markers. However, experimental autoimmune encephalomyelitis is far from being a perfect approximation of MS because MS is more heterogeneous and the target antigen(s) is (are) not known. Further advances in MS therapy will depend on our growing understanding of the pathogenesis of this still incurable disease.
Granulocyte-macrophage colony-stimulating factor-induced arteriogenesis reduces energy failure in hemodynamic stroke
Authors: Schneeloch Edda , Mies Günter , Busch Hans-Jörg , Buschmann Ivo R. , Hossmann Konstantin-Alexander
Published: August 2004

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a powerful arteriogenic factor in the hypoperfused rat brain. To test the pathophysiological relevance of this response, the influence of GM-CSF on brain energy state was investigated in a model of hemodynamic stroke. Sprague-Dawley rats were submitted to three-vessel (bilateral vertebral and unilateral common carotid artery) occlusion (3-VO) to induce unilaterally accentuated brain hypoperfusion. One week later, hemodynamic stroke was induced by additional lowering of arterial blood pressure. Experiments were terminated by
in situ
freezing of the brain. ATP was measured in cryostat sections by using a bioluminescence method. The use of 3-VO, in combination with 15 min of hypotension of 50, 40, or 30 mmHg, did not produce disturbances of energy metabolism, however, focal areas of ATP depletion were unilaterally detected after 3-VO, in combination with 15 min of hypotension of 20 mmHg. Treating such animals with GM-CSF (40 μg·kg
-1
·d
-1
) during the 1-week interval between 3-VO and induced hypotension significantly reduced the hemispheric volume of energy depletion from 48.8 ± 44.2% (untreated group,
n
= 10) to 15.8 ± 17.4% (treated group,
n
= 8,
P
= 0.033). GM-CSF-induced arteriogenesis is another approach to protect the brain against ischemic injury.
Cotranslational integration and initial sorting at the endoplasmic reticulum translocon of proteins destined for the inner nuclear membrane
Authors: Saksena Suraj , Shao Yuanlong , Braunagel Sharon C. , Summers Max D. , Johnson Arthur E.
Published: August 2004

The current diffusion-retention model for protein trafficking to the inner nuclear membrane (INM) proposes that INM proteins diffuse laterally from the membrane of the endoplasmic reticulum into the INM and are then retained in the INM by binding to nuclear proteins or DNA. Because some data indicate that the sorting of baculovirus envelope proteins to the INM is protein-mediated, we have examined the early stages of INM protein integration and sorting by using photocrosslinking. Both viral and host INM-directed proteins were integrated cotranslationally through the endoplasmic reticulum translocon, and their nonrandom photocrosslinking to two translocon proteins, Sec61α and translocating chain-associated membrane protein (TRAM), revealed that the first transmembrane sequence (TMS) of each viral and host INM-directed protein occupied a very similar location within the translocon. Because few TMSs of non-INM-directed membrane proteins photocrosslink to TRAM, it seems that the INM-directed TMSs occupy different sites within the translocon than do non-INM-directed TMSs. The distinct proximities of translocon components to INM-directed TMSs strongly suggest that such TMSs are recognized and initially sorted within the translocon. Taken together, these data indicate that membrane protein sorting to the INM is an active process involving specific nonnuclear proteins.
A gain-of-function mutation of
Fgfr2c
demonstrates the roles of this receptor variant in osteogenesis
Authors: Eswarakumar Veraragavan P. , Horowitz Mark C. , Locklin Rachel , Morriss-Kay Gillian M. , Lonai Peter
Published: August 2004

The
b
and
c
variants of fibroblast growth factor receptor 2
(FGFR2)
differ in sequence, binding specificity, and localization.
Fgfr2b
, expressed in epithelia, is required for limb outgrowth and branching morphogenesis, whereas the mesenchymal
Fgfr2c
variant is required by the osteocyte lineage for normal skeletogenesis. Gain-of-function mutations in human FGFR2c are associated with craniosynostosis syndromes. To confirm and extend this evidence, we introduced a Cys342Tyr replacement into
Fgfr2c
to create a gain-of-function mutation equivalent to a mutation in human Crouzon and Pfeiffer syndromes.

Fgfr2c
C342Y/

+
heterozygote mice are viable and fertile with shortened face, protruding eyes, premature fusion of cranial sutures, and enhanced
Spp1
expression in the calvaria. Homozygous mutants display multiple joint fusions, cleft palate, and trachea and lung defects, and die shortly after birth. They show enhanced
Cbfa1
/
Runx2
expression without significant change in chondrocyte-specific
Ihh, PTHrP, Sox9, Col2a
, or
Col10a
gene expression. Histomorphometric analysis and bone marrow stromal cell culture showed a significant increase of osteoblast progenitors with no change in osteoclastogenic cells. Chondrocyte proliferation was decreased in the skull base at embryonic day 14.5 but not later. These results suggest that long-term aspects of the mutant phenotype, including craniosynostosis, are related to the
Fgfr2c
regulation of the osteoblast lineage. The effect on early chondrocyte proliferation but not gene expression suggests cooperation of
Fgfr2c
with
Fgfr3
in the formation of the cartilage model for endochondral bone.
The
Caenorhabditis elegans
F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome
Authors: Jäger Sibylle , Schwartz Hillel T. , Horvitz H. Robert , Conradt Barbara
Published: August 2004

The
Caenorhabditis elegans
F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that
sel-10
is the same gene as
egl-41
, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of
sel-10
also have masculinizing activity, indicating that
sel-10
functions to promote female development. Genetically,
sel-10
acts upstream of the genes
fem-1
,
fem-2
, and
fem-3
and downstream of
her-1
and probably
tra-2
. When expressed in mammalian cells, SEL-10 protein coimmunoprecipitates with FEM-1, FEM-2, and FEM-3, which are required for masculinization, and FEM-1 and FEM-3 are targeted by SEL-10 for proteasomal degradation. We propose that SEL-10-mediated proteolysis of FEM-1 and FEM-3 is required for normal hermaphrodite development.
Economic value of tropical forest to coffee production
Authors: Ricketts Taylor H. , Daily Gretchen C. , Ehrlich Paul R. , Michener Charles D.
Published: August 2004

Can economic forces be harnessed for biodiversity conservation? The answer hinges on characterizing the value of nature, a tricky business from biophysical, socioeconomic, and ethical perspectives. Although the societal benefits of native ecosystems are clearly immense, they remain largely unquantified for all but a few services. Here, we estimate the value of tropical forest in supplying pollination services to agriculture. We focus on coffee because it is one of the world's most valuable export commodities and is grown in many of the world's most biodiverse regions. Using pollination experiments along replicated distance gradients, we found that forest-based pollinators increased coffee yields by 20% within ≈1 km of forest. Pollination also improved coffee quality near forest by reducing the frequency of “peaberries” (i.e., small misshapen seeds) by 27%. During 2000–2003, pollination services from two forest fragments (46 and 111 hectares) translated into ≈$60,000 (U.S.) per year for one Costa Rican farm. This value is commensurate with expected revenues from competing land uses and far exceeds current conservation incentive payments. Conservation investments in human-dominated landscapes can therefore yield double benefits: for biodiversity and agriculture.
Social networks and aggressive behaviour in Chinese children
Authors: Xu Yiyuan , Farver Jo Ann M. , Schwartz David , Chang Lei
Published: August 2004

This exploratory study investigated Mainland Chinese children’s social networks and peer group affiliations with a particular emphasis on their aggressive behaviour. The participants were 294 elementary school students in Tianjin, P. R. China (mean age 11.5 years; 161 boys). Social network analysis identified relatively large and gender-specific peer groups. Although different measures were used, the pattern of homophily characteristic of Western aggressive children was partially supported. This finding may be due to the large size of the peer groups. The results showed that some aggressive children formed friendships with nonaggressive children. Moreover, for the aggressive children who were group members, the number of within-group friendships moderated the relation between aggression and overall peer preference. In addition, despite the moderating effect of within-group friendship, the relation between aggression and peer preference remained significantly negative even at the highest levels of friendship. Aggressive children who were isolated from all peer groups had higher hyperactivity ratings and were less liked by peers than were aggressive children who were group members. These findings illustrate how culture may be an influence on patterns of peer group affiliation.