bluuebunny/crossref_metadata_2025 huggingface dataset:
FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues
Authors: Bulgakov Oleg V. , Eggenschwiler Jonathan T. , Hong Dong-Hyun , Anderson Kathryn V. , Li Tiansen
Published: April 2004

Sonic hedgehog (SHH) is a secreted morphogen that regulates the patterning and growth of many tissues in the developing mouse embryo, including the central nervous system (CNS). We show that a member of the FK506-binding protein family, FKBP8, is an essential antagonist of SHH signaling in CNS development. Loss of FKBP8 causes ectopic and ligand-independent activation of the Shh pathway, leading to expansion of ventral cell fates in the posterior neural tube and suppression of eye development. Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development.
Reduction rate of neptunium(V) in heterogeneous solution with magnetite
Authors: Nakata K. , Nagasaki S. , Tanaka S. , Sakamoto Y. , Tanaka T. , Ogawa H.
Published: April 2004

The sorption kinetics of neptunium on magnetite was investigated under both aerobic and anaerobic conditions in 0.1mol L-1NaNO3at pH=5.7 to 5.9. It was found that the sorption of neptunium on magnetite reaches an equilibrium in 1h under aerobic conditions, while it takes 10h or more to reach the equilibrium under anaerobic conditions. The difference in sorption kinetics between aerobic and anaerobic conditions took place because sorption kinetics under the anaerobic condition involved the reduction of Np(V) to Np(IV), confirmed by an extraction technique using 0.5mol L-1TTA in xylene and 2.0mol L-1HNO3solution. The reduction rate of Np(V) by Fe(II) in magnetite was calculated in solution with magnetite. It was found that Np(V) was reduced 1000 or more times faster in solution with magnetite than the Np(V) reduction by Fe(II) ions in homogeneous solution. It was revealed that the reduction of Np(V) in solution with magnetite took place on the surface of magnetite.
Preparation of U(VI) and Th(IV) alpha-sources from sea and fresh water samples by combining coprecipitation, solvent extraction and electrodeposition procedures
Authors: Zarki R. , Elyahyaoui A. , Chiadli A.
Published: April 2004

A simple method combining coprecipitation, solvent extraction and electrodeposition for determining uranium and thorium in sea water and fresh water samples is developed. It offers a considerable saving in time, minimising chemical treatment and costs. The analytical procedure consists of enrichment of U and Th by coprecipitation with iron(III) hydroxides and subsequent extraction by diethylether solution and electrodeposition of each actinide in the extracting organic phase in which it was separated.

The dependence of the coprecipitation, the extraction-electrodeposition and the overall yields of the above mentioned elements is examined in relation to the initial aqueous solution acidity and various amounts of iron carrier. At an initial pH between 6 and 10, quantitative coprecipitation of U and Th requires use of an Fe(III) quantity which depends on the acidity of these solutions. This quantity varies, under explored conditions, between 10 and 110mg/L. At a starting pH of 11, this coprecipitation becomes almost independent of Fe(III) amounts.

The proposed procedure was used to analyse the content of U and Th isotopes in water samples. Recoveries of 60%-93% are obtained for uranium and 63%-86% for thorium. Good resolutions (37-56.5keV) are also achieved under optimum conditions. These resolutions allow to make accurate determination of U and Th isotopes in various water samples.
Adaptive output tracking for a class of non‐linear time‐delay systems
Authors: Pepe P.
Published: April 2004

In this paper the output tracking control problem for a class of non‐linear time delay systems with some unknown constant parameters is addressed. Such a problem is solved in the case that the non‐linear time‐delay system has full delay relative degree and stable internal dynamics. It is supposed moreover that the output and its time derivatives until n−1, where n is the length of the state vector (euclidean part), do not depend explicitly on the unknown parameters. This work is the first step towards the application of the methodologies of adaptive control for non‐linear delayless systems, based on tools of differential geometry, to non‐linear time‐delay systems too. Copyright © 2004 John Wiley & Sons, Ltd.
Clinical spectrum of myelophthisis in cancer patients
Authors: Makoni Stephen N. , Laber Damian A.
Published: April 2004

Myelophthisis is a form of bone marrow failure due to replacement of hematopoietic tissue by abnormal tissue, most commonly metastatic carcinomas. This results in extramedullary hematopoiesis, typically in the spleen leading to premature release of hematopoietic cells into the circulation. Peripheral blood findings may include nucleated red blood cells, tear drop forms, giant platelets, and immature leukocytes. This is called a leukoerythroblastic picture. The first case demonstrates acute myelophthisis as a presentation of pancreatic cancer. The second case is of extramedullary hematopoiesis as a manifestation of widely metastatic melanoma. The presence of a leukoerythroblastic peripheral blood picture should serve as a valuable clue about a possible underlying malignancy. This late presentation of advanced cancer may now be rarely seen because of early diagnosis and more effective therapies. Am. J. Hematol. 76:92–93, 2004. © 2004 Wiley‐Liss, Inc.
Effect of red cell exchange transfusion on plasma levels of inflammatory mediators in sickle cell patients with acute chest syndrome
Authors: Liem Robert I. , O'Gorman Maurice R. , Brown Deborah L.
Published: April 2004

Red cell exchange transfusion is the recommended therapy for patients with sickle cell disease (SCD) who have severe, progressive acute chest syndrome (ACS). A double‐volume red cell exchange transfusion decreases the percentage of hemoglobin S (Hgb S) containing red blood cells to less than 20%, improving vascular perfusion. We speculated that reduction of pro‐inflammatory mediators might also contribute to the therapeutic effect of an exchange transfusion. We measured white blood cell count (WBC), absolute neutrophil count (ANC), platelet concentration as well as plasma levels of interleukin‐1α (IL‐1α), interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), interleukin‐8 (IL‐8), and soluble vascular cell adhesion molecule‐1 (sVCAM‐1) in 8 sickle cell patients with 9 episodes of ACS who received a manual, double‐volume exchange transfusion. Six patients with SCD seen during a routine clinic visit were used as controls. The mean number of hospitalization days was 6, with an average of 2 days in the intensive care unit. All patients recovered without complication. Sickle cell patients with ACS had a higher WBC and ANC at baseline but lower sVCAM‐1 levels compared to controls. TNF‐α, IL‐1α, IL‐1β, and IL‐8 levels were not significantly different from controls. WBC, ANC, platelet, and sVCAM‐1 measurements were significantly decreased immediately post‐exchange in patients with ACS; however, this effect was not persistent as levels trended towards pre‐exchange values by 24 hr post‐exchange. Due to wide inter‐individual variability, a consistent pattern was not seen for TNF‐α, IL‐1α, IL‐1β, or IL‐8. We conclude that in sickle cell patients with ACS, a manual, double‐volume exchange transfusion lowers WBC, ANC, platelets, and sVCAM‐1 levels, but the effect is short‐lived. Am. J. Hematol. 76:19–25, 2004. © 2004 Wiley‐Liss, Inc.
Parenteral iron therapy options
Authors: Silverstein Scott B. , Rodgers George M.
Published: April 2004

Parenteral iron therapy is occasionally necessary for patients intolerant or unresponsive to oral iron therapy, for receiving recombinant erythropoietin therapy, or for use in treating functional iron deficiency. There are now three parenteral iron products available: iron dextran, ferric gluconate, and iron sucrose. We summarize the advantages and disadvantages of each product, including risk of anaphylaxis and hypersensitivity, dosage regimens, and costs. The increased availability of multiple parenteral iron preparations should decrease the need to use red cell transfusions in patients with iron‐deficiency anemia. Am. J. Hematol. 76:74–78, 2004. © 2004 Wiley‐Liss, Inc.
Genetic heterogeneity in Usher syndrome
Authors: Keats Bronya J.B. , Savas Sevtap
Published: April 2004

Mutations in seven different genes have been associated with Usher syndrome, and an additional four loci have been mapped. The identified genes encode myosin VIIa, harmonin (a PDZ‐domain protein), cadherin 23, protocadherin 15, sans (a scaffold‐like protein), usherin and clarin. Three clinical types of Usher syndrome have been described: USH1 patients have severe to profound congenital hearing loss, vestibular dysfunction, and retinal degeneration beginning in childhood, those with USH2 have moderate to severe congenital hearing loss, normal vestibular function, and later onset of retinitis pigmentosa, and USH3 patients have progressive hearing loss, which distinguishes them from the other two types. The shaker‐1, waltzer, Ames waltzer, and Jackson shaker mice provide murine models for four of the genetic forms of Usher syndrome. Ongoing studies are enabling early diagnosis of Usher syndrome in children who present with hearing loss, thus providing time to prepare for the onset of visual loss. © 2004 Wiley‐Liss, Inc.
Disomy of distal Xq in males: Case report and overview
Authors: Novelli Antonio , Bernardini Laura , Salpietro Damiano Carmelo , Briuglia Silvana , Merlino Maria Valeria , Mingarelli Rita , Dallapiccola Bruno
Published: April 2004

A 46,XYq 8‐year‐old male was referred for microcephaly, growth, and mental retardation, hypotonia, genital hypoplasia, and dysmorphisms. FISH analysis showed that the rearranged Y chromosome originated from an unbalanced translocation of Xq27.3‐qter onto the deleted Yq11.22. Analysis of reported patients with disomy of region distal to Xq26 suggests that this rare anomaly, associated with failure to dosage compensate X‐linked genes that are normally inactivated, when present in two copies, is causing a quite distinct phenotype. This imbalance is the aberrant by product of the recombinogenic pairing of the distal pseudoautosomal Xq–Yq region at male meiosis. © 2004 Wiley‐Liss, Inc.
Functional Porous Coordination Polymers
Authors: Kitagawa Susumu , Kitaura Ryo , Noro Shin‐ichiro
Published: April 2004

The chemistry of the coordination polymers has in recent years advanced extensively, affording various architectures, which are constructed from a variety of molecular building blocks with different interactions between them. The next challenge is the chemical and physical functionalization of these architectures, through the porous properties of the frameworks. This review concentrates on three aspects of coordination polymers: 1) the use of crystal engineering to construct porous frameworks from connectors and linkers (“nanospace engineering”), 2) characterizing and cataloging the porous properties by functions for storage, exchange, separation, etc., and 3) the next generation of porous functions based on dynamic crystal transformations caused by guest molecules or physical stimuli. Our aim is to present the state of the art chemistry and physics of and in the micropores of porous coordination polymers.
Rectorite/thermoplastic polyurethane nanocomposites: Preparation, characterization, and properties
Authors: Ma Xiaoyan , Lu Haijun , Liang Guozheng , Yan Hongxia
Published: April 2004

A newly developed kind of layered clay, rectorite (REC), has been used to yield intercalated or exfoliated thermoplastic polyurethane rubber (TPUR) nanocomposites by melt‐processing intercalation. Because of the swollen layered structure of REC, similar to that of montmorillonite, organic rectorites (OREC) can also be obtained through ion‐exchange reaction with two different quaternary ammonium salts (QAS1, QAS2) and benzidine (QAS3). The microstructure and dispersibility of OREC layers in TPUR matrix were examined by X‐ray diffraction and transmission electron microscopy, which revealed not only that the composites with lower amounts of clay are intercalation or part exfoliation nanocomposites, but also that the mechanical properties of the composites were substantially enhanced. The maximum ultimate tensile strength for TPUR/OREC nanocomposites appeared at 2 wt % OREC loading. With increasing OREC contents, the tear strength of the composites increased significantly. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 608–614, 2004
Effect of thermal conductivity and heat transfer on crystallization, structure, and morphology of polypropylene containing different fillers
Authors: Radhakrishnan S. , Sonawane Pradip , Pawaskar N.
Published: April 2004

The crystallization behavior, structure, and morphology developed was investigated for polypropylene containing different fillers such as silica, calcium carbonate, talc, mica, graphite, etc. by using compression‐molded samples prepared at several cooling rates. It was observed that the crystallinity obtained for any given composition depended on the thermal conductivity of the filler and the PP composite containing it as well as the cooling rate to which it was subjected. These composites exhibited skin‐core type of morphology and the skin layer thickness was found to depend not only on the cooling rate but also on the type of filler, its thermal conductivity, etc. These various experimental findings were discussed in light of the phenomenological model described in our earlier work, which correlates thermal conductivity and degree of crystallinity for various compositions of PP containing additives. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 615–623, 2004
Crystallization kinetics of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/clay nanocomposites
Authors: Chen G. X. , Hao G. J. , Guo T. Y. , Song M. D. , Zhang B. H.
Published: April 2004

The preparation and properties of nanocomposites, consisting of a poly(3‐Hydroxybutyrate‐co‐3‐hydroxyvalerate) and an organophilic clay are described. The effect of organophilic clay on the crystallization behavior of (PHBV) was studied. A differential scanning calorimeter (DSC) was used to monitor the energy of the crystallization process from the melt. During the crystallization process from the melt, the organophilic clay led to an increase in crystallization temperature (Tc) of PHBV compared with that for plain PHBV. During isothermal crystallization, dependence of the relative degree of crystallization on time was described by the Avrami equation. The addition of organophilic clay caused an increase in the overall crystallization rate of PHBV, but did not influence the mechanism of nucleation, and growth of the PHBV crystals and the increase caused by a small quantity of clay is move effective than that large one. The equilibrium melting temperature of PHBV was determined as 186°C. Analysis of kinetic data according to nucleation theories showed that the increase in crystallization rate of PHBV in the composite is due to the decrease in surface energy of the extremity surface. The mechanical test shows that the tensile strength of hybrid increased to 35.6 MPa, which is about 32% higher than that of the original PHBV with the incorporation of 3 wt % clay, and the tensile modulus was also increased. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 655–661, 2004
Development of an integrated automation system with a magnetic bead‐mediated nucleic acid purification device for genetic analysis and gene manipulation
Authors: Akutsu Jun‐ichi , Tojo Yuriko , Segawa Osamu , Obata Kimimichi , Okochi Mina , Tajima Hideji , Yohda Masafumi
Published: April 2004

We have developed an integrated automation system for genetic analysis and gene manipulation. The system, SX‐8G Plus, is equipped with an 8‐nozzle dispensing unit, a thermal cycler, a cooled reagent reservoir, four tip storage racks, four microplate platforms, buffer reservoirs, an agarose gel electrophoresis unit, a power supply, a pump for exchanging electrophoresis buffer, and a CCD camera. Automation of nucleic acid extraction and purification, the most difficult step in automating genetic analysis and gene manipulation, was realized using magnetic beads with Magtration Technology, which we have previously developed for automating the handling of paramagnetic beads. Using this system, we could perform the automated separation and purification of DNA fragments by agarose gel electrophoresis starting from sample loading. The system would enable the automation of almost all procedures in genetic analysis and gene manipulation. © 2004 Wiley Periodicals, Inc.
Chemoarchitectonic subdivisions of the songbird septum and a comparative overview of septum chemical anatomy in jawed vertebrates
Authors: Goodson James L. , Evans Andrew K. , Lindberg Laura
Published: April 2004

Available data demonstrate that the avian septal region shares a number of social behavior functions and neurochemical features in common with mammals. However, the structural and functional subdivisions of the avian septum remain largely unexplored. In order to delineate chemoarchitectural zones of the avian septum, we prepared a large dataset of double‐, triple‐, and quadruple‐labeled material in a variety of songbird species (finches and waxbills of the family Estrildidae and a limited number of emberizid sparrows) using antibodies against 10 neuropeptides and enzymes. Ten septal zones were identified that were placed into lateral, medial, caudocentral, and septohippocampal divisions, with the lateral and medial divisions each containing multiple zones. The distributions of numerous immunoreactive substances in the lateral septum closely match those of mammals (i.e., distributions of met‐enkephalin, vasotocin, galanin, calcitonin gene‐related peptide, tyrosine hydroxylase, vasoactive intestinal polypeptide, substance P, corticotropin‐releasing factor, and neuropeptide Y), enabling detailed comparisons with numerous chemoarchitectonic zones of the mammalian lateral septum. Our septohippocampal and caudocentral divisions are topographically comparable to the mammalian septohippocampal and septofimbrial nuclei, respectively, although additional data will be required to establish homology. The present data also demonstrate the presence of a medial septal nucleus that is histochemically comparable to the medial septum of mammals. The avian medial septum is clearly defined by peptidergic markers and choline acetyltransferase immunoreactivity. These findings should provide a useful framework for functional and comparative studies, as they suggest that many features of the septum are highly conserved across vertebrate taxa. J. Comp. Neurol. 473:293–314, 2004. © 2004 Wiley‐Liss, Inc.
Axon diameters and intradural trajectories of the dural innervation in the rat
Authors: Strassman Andrew M. , Weissner Wendi , Williams Molly , Ali Saad , Levy Dan
Published: April 2004

Neurophysiological studies have characterized the sensory responses of primary afferent nociceptors that innervate the intracranial dura. The present study used anatomical methods to examine in greater detail the axonal trajectories within the dura, as well as the axonal size distribution of the dural innervation. Immunostaining for CGRP in dural wholemounts revealed a network of fibers extending across the entire dura, with an especially dense plexus running along the borders of the transverse and superior sagittal sinuses. The plexus along the caudal border of the transverse sinus partially overlapped the dural area that shows the greatest density of mast cells. Visualization of axon bundles by DiI application in formalin‐fixed tissue revealed two separate systems of fibers in the dura that could be distinguished by the orientation of their trajectories: one that runs parallel to the middle meningeal artery (MMA), and another with a more or less orthogonal orientation that runs rostromedially from the transverse sinus across the MMA. Axons traversed large distances across the dura, but the majority of the branching and arborization was usually concentrated in the distal part of the trajectory. In separate animals, measurement of myelinated axon diameters with electron microscopy showed that approximately one‐third of the myelinated axons in the nerves supplying the dura (nervus spinosus and tentorial nerves) could be classified as A‐beta, since they were comparable in size to the majority of axons in the trochlear nerve and the upper end of the size range in the trigeminal nerve (i.e., >5 μm). J. Comp. Neurol. 473:364–376, 2004. © 2004 Wiley‐Liss, Inc.
Full f particle simulation method for solution of transient edge phenomena
Authors: Heikkinen J. A. , Janhunen J. S. , Kiviniemi T. P. , Kåll P.
Published: April 2004

An electrostatic gyrokinetic guiding‐centre particle code is described where electrons and ions are simultaneously followed in the edge region. Full f technique is used for particle sampling and loading to allow efficient treatment of strong time variation in the collisional edge bulk plasma. Both the gyrokinetic ion polarization term and the implicit electron term in the quasi‐neutrality condition are determined based on the full‐f sampling for both electrons and ions. Issues relevant for the SOL modeling like recycling, heat source, and boundary conditions for plasma/wall interaction are discussed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Energy transport modelling including ergodic effects
Authors: McTaggart N. , Bonnin X. , Runov A. , Schneider R. , Zagorski R.
Published: April 2004

The effect of ergodization (either by additional coils like in TEXTOR‐DED or by intrinsic plasma effects like in W7‐X) defines the need for transport models being able to describe this properly. A prerequisite for this is the concept of local magnetic coordinates allowing a correct discretization with minimized numerical errors. For these coordinates the full respective metric tensor has to be known.

To study the energy transport in complex edge geometries (in particular for W7‐X) we use a finite difference discretization of the transport equations on a custom‐tailored grid in local magnetic coordinates. This grid is generated by field line tracing to guarantee an exact discretization of the dominant parallel transport (this also minimizes the numerical diffusion problem). The perpendicular fluxes are interpolated on cross‐sectional planes (toroidal cuts), where a quasi‐isotropic problem is solved by a constrained Delaunay triangulation (preserving magnetic surfaces where they exist), and discretization. All terms involving toroidal terms are discretized by finite differences. The first tests for W7X and NCSX were successfully performed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Particle transport and density gradient scale lengths in the edge pedestal
Authors: Stacey W. M.
Published: April 2004

A new flux‐gradient relation for the ion particle flux in the edge pedestal is derived from continuity and momentum balance, taking into account atomic physics, and cast in the form of a generalized ‘diffusion‐pinch’ transport relation. This flux‐gradient relation is used to derive a new expression for a first‐principles calculation of the ion density gradient scale length. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Space‐Charge Limited Current from Plasma‐Facing Material Surface
Authors: Takamura S. , Ohno N. , Ye M. Y. , Kuwabara T.
Published: April 2004

We have derived an exact theoretical expression for the space‐charge limited current from the solid surfaces adjacent to plasmas that is applicable for an arbitrary sheath voltage. Our expression shows that the spacecharge limited current tends to saturate with the sheath voltage. This new formula is evaluated by 1‐D Particle in Cell (PIC) simulation and experiment, and is in a good agreement with the simulation and experimental results. We have also obtained an analytical equation fitted to the new formula based on conventional Child‐Langmuir formula by taking into account a more sophisticated dependence of the electrode potential and the plasma density through the effect of Debye shielding and a sheath expansion due to increased voltage across the sheath. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Particle Simulation Study of Dust Particle Dynamics in Sheaths
Authors: Smirnov R. , Tomita Y. , Takizuka T. , Takayama A. , Chutov Yu.
Published: April 2004

Dynamics of dust particles in a divertor plasma is simulated using numerical solutions of dust momentum and charging equations in an electrostatic sheath and an ionizing presheath, where an electrostatic force and a drag force due to absorption of plasma ions are taken into account. Spatial distributions of plasma parameters in a divertor are obtained with particle simulations including ionization by electron‐impact. We found that the critical dust radius exists. Dust particles with a larger radius than this critical one are incapable to come off a divertor plate because the ion drag force is stronger compared to the electrostatic force. Control of the plate potential can suppress the dust motion from the plate. The radii of heavy dust particles are classified with respect to equilibrium positions. Considering dust particles started at the plate with radii smaller than the critical one, two types of dust motion were found. Dust particles with the first type of motion come back to the plate before approaching their equilibrium positions. The second type of motion is presented by smaller dust particles which oscillate around their equilibrium positions. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theoretical Study of the Effect of the Dynamic Ergodic Divertor on MARFE Onset
Authors: Kelly F. A. , Tokar M. Z.
Published: April 2004

The effect of the TEXTOR Dynamic Ergodic Divertor (DED) on the formation of Multi‐facetted Asymmetric Radiation From the Edge (MARFE) is investigated. The thermal instability analysis accounts for the poloidal inhomogeneity of the background plasma equilibrium due to the Shafranov shift of the magnetic surfaces and the localized effect of the DED on edge transport and recycling; the influxes of working gas and impurity neutrals determined by plasma‐wall interaction; and the non‐coronal character of the impurity radiation, which depends on the perpendicular transport of impurity neutrals and radiant ion species. The model results in a Sturm‐Liouville eigenvalue equation for the poloidal dependence of perturbations. Numerical results for both carbonized and boronized TEXTOR walls are compared for the poloidally symmetric transport case and for various assumptions regarding poloidally inhomogeneous DED transport and conclude that the DED will decrease the MARFE onset density. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Turbulence in the Divertor Region of Tokamak Edge Plasma
Authors: Umansky M. V. , Rognlien T. D. , Xu X. Q. , Cohen R. H. , Nevins W. M.
Published: April 2004

Results of recent modeling of tokamak edge plasma with the turbulence code BOUT are presented. In previous studies with BOUT, the background profiles of plasma density and temperature were set as flux surface functions. However, in the divertor region of a tokamak, the temperature is typically lower and density is higher than those at the mid‐plane. To account for this in the present study, a poloidal variation of background plasma density and temperature is included to provide a more realistic model. For poloidally uniform profiles of the background plasma, the calculated turbulence amplitude peaks near outer mid‐plane, while in the divertor region the amplitude is small. However, present simulations show that as the background plasma profiles become more poloidally non‐uniform, the amplitude of density fluctuations, ñi, starts peaking in the divertor. It is found that in the divertor region the amplitude of ni fluctuations grows approximately linearly with the local density of the background plasma, ni0, while the amplitudes of Te and ϕ fluctuations are positively correlated with the local electron temperature, Te0. Correlation analysis shows that plasma turbulence above and below the x‐point is largerly uncorrelated. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Self‐consistent simulation of turbulence and transport in tokamak edge plasmas
Authors: Rognlien T. D. , Umansky M. V. , Xu X. Q. , Cohen R. H.
Published: April 2004

The status of coupling the fluid 3D turbulence code BOUT and the fluid plasma/neutral 2D transport code UEDGE is reported, where both codes simulate the edge region of diverted tokamaks from several cm inside the magnetic separatrix to the far scrape‐off layer (SOL), thereby including the magnetic X‐point. Because the characteristic time scale of the turbulence is short (∼10−5 − 10−4 s) and the profile evolution time scale can be long (∼10−2 − 10−1 s owing to recycling), an iterative scheme is used that relaxes the turbulent fluxes passed from BOUT to UEDGE and the profiles from UEDGE to BOUT over many coupling steps. Each code is run on its own characteristic time scale, yielding a statistically averaged steady state. For this initial study, the ion and neutral densities and parallel velocities are evolved, while the temperature profiles are stationary. Here the turbulence code is run in the electrostatic approximation. For this example of self‐consistent coupling with strong L‐mode‐like turbulence, the ion flux to the main‐chamber exceeds that to the divertor plates. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Multi‐fluid code simulations including anomalous non‐diffusive transport of plasma and impurities in the tokamak SOL
Authors: Pigarov A. Yu. , Krasheninnikov S. I. , Rognlien T. D. , West W. P. , LaBombard B. , Lipschultz B. , Maingi R. , Soukhanovskii V.
Published: April 2004

Fast intermittent transport has been observed in the scrape‐off layer (SOL) of major tokamaks including Alcator C‐Mod, DIII‐D, and NSTX. This kind of transport is not diffusive but rather convective. It strongly increases plasma flux to the chamber walls and enhances the recycling of neutral particles in the main chamber. We discuss the anomalous cross‐field convection (ACFC) model for impurity and main plasma ions and its relation to intermittent transport events, i.e. plasma density blobs and holes in the SOL. Along with plasma diffusivity coefficients, our transport model introduces time‐independent anomalous convective velocities across the confining magnetic field. In the discharge modeling, diffusivity coefficients and ACFC velocity profiles are adjusted to match a set of representative experimental data. We use this model in the edge plasma physics code UEDGE to simulate the multi‐fluid two‐dimensional transport for these three tokamaks. We present simulation results suggesting the dominance of anomalous convection in the far SOL transport. These results are consistent with the hypothesis that the chamber wall is an important source of impurities and that different impurity charge states have different magnitude and sign of their anomalous radial convective velocities. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Influence of Impurities and Gas‐Puff on MARFE Evolution in TEXTOR Tokamak
Authors: Zagórski R. , Gerhauser H. , Sergienko G.
Published: April 2004

The 2D multifluid code TECXY is used to study the evolution of so‐called Marfes, thermal instabilities which arise locally in the front of the bumper limiter of the TEXTOR tokamak. The physical model is based on Braginskij‐like equations and incorporates drift motions and currents in a fully self‐consistent way. The radial electric field in the transition layer inside the separatrix is derived from the global ambipolarity condition. We model the bumper region by assuming high additional recombination losses inside this region and a suitably chosen profile for the recycled neutrals penetrating from the bumper surface into the adjacent plasma. A parameter study has been carried out to investigate the influence of impurities and of localized gas‐puffing on the Marfe evolution. Results of numerical simulations are compared with experimental measurements. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos
Authors: Lincoln Joy , Alfieri Christina M. , Yutzey Katherine E.
Published: April 2004

Abnormalities in valvuloseptal development significantly contribute to congenital heart defects, yet the underlying causes are complex and poorly understood. Early cardiac regulatory genes are differentially expressed during valvuloseptal development, consistent with novel functions during heart chamber formation in chicken and mouse embryos. Distinct valve cell lineages were identified in the leaflets, chordae tendineae, and myotendinous junctions with the papillary muscles based on restricted expression of extracellular matrix molecules. Specific cell types within these structures demonstrate characteristics of chondrogenesis and tendon development, identified byscleraxis, type II collagen, and tenascin expression. In chicken embryos, valve remodeling and maturation accompanies a decrease in mitotic index indicated by reduced bromodeoxyuridine incorporation. Analysis ofTie2‐cre× ROSA26R mice demonstrates that mature valve structures, including the atrioventricular and outflow tract semilunar valve leaflets, chordae tendineae, and the fibrous continuity that connects the septal leaflets of mitral and tricuspid valves, arise from endothelial cells of the endocardial cushions. Together, these studies provide novel insights into the origins and cell lineage diversity of mature valve structures in the developing vertebrate heart. Developmental Dynamics 230:239–250, 2004. © 2004 Wiley‐Liss, Inc.
Construction and analysis of a subtracted library and microarray of cDNAs expressed specifically in chicken heart progenitor cells
Authors: Afrakhte Mozhgan , Schultheiss Thomas M.
Published: April 2004

A subtracted library was constructed of genes expressed specifically in the chick precardiac mesoendoderm. The subtracted library was obtained by hybridization of nucleic acids derived from a starting tester library of stage 4–7 chick precardiac mesoendoderm and a starting driver library of stage 2 area pellucida. Approximately 11,000 clones from the resulting subtracted library were printed onto a microarray. Screening of the microarray with probes derived from cardiac and noncardiac tissues, followed by in situ hybridization during chick embryo development, has identified multiple cardiac‐specific genes, including several that have not been characterized previously. The microarray will be useful for future attempts to identify additional novel cardiac‐specific genes, as well as to characterize patterns of gene expression during heart differentiation. Developmental Dynamics 230:290–298, 2004. © 2004 Wiley‐Liss, Inc.
Phase‐shifts in shear stress as an explanation for the maintenance of pool–riffle sequences
Authors: Wilkinson Scott N. , Keller Robert J. , Rutherfurd Ian D.
Published: April 2004

The stability of the pool–rifﬂe sequence is one of the most fundamental features of alluvial streams. For several decades, the process of velocity, or shear stress, reversal has been proposed as an explanation for an increase in the amplitude of pool–rifﬂe sequence bars during high ﬂows, offsetting gradual scour of rifﬂes and deposition in pools during low ﬂows. Despite several attempts, reversal has rarely been recorded in ﬁeld measurements. We propose that, instead of being reversed, maxima and minima in shear stress are phase‐shifted with respect to the pool–rifﬂe sequence bedform proﬁle, so that maximum shear stress occurs upstream of rifﬂe crests at high ﬂow, and downstream at low ﬂow. Such phase‐shifts produce gradients of shear stress that explain rifﬂe deposition, and pool scour, at high ﬂow, in accord with sediment continuity. The proposal is supported by results of a one‐dimensional hydraulic model applied to the surveyed bathymetry of a pool–rifﬂe sequence in a straight reach of a gravel‐bed river. In the sequence studied, the upstream phase‐shift in shear stress at high ﬂow was associated with variations in channel width, with width minima occurring upstream of rifﬂe crests, approximately coincident with shear stress maxima, and width maxima occurring downstream of rifﬂe crests. Assuming that the width variation is itself the result of ﬂow deﬂection by rifﬂe crests at low ﬂow, and associated bank‐toe scour downstream, low and high ﬂow can be seen to have complementary roles in maintaining alluvial pool–rifﬂe sequences. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of α‐tocopherol and N‐acetylcysteine on benzoyl peroxide toxicity in human keratinocytes
Authors: Bellei Elisa , Rota Cristina , Bergamini Stefania , Manfredini Paolo , Albertazzi Alberto , Tomasi Aldo , Iannone Anna
Published: April 2004

Benzoyl peroxide is a free‐radical generating compound widely used in the polymer industry and also in pharmaceuticals as antimicrobial agent to treat acne. However, benzoyl peroxide causes irritation and contact dermatitis in about 1% of patients. Concern over the use of this compound is motivated by the demonstration that it can also act as skin tumor promoter in mice. In addition, benzoyl peroxide induces DNA strand breaks in many cells, including keratinocytes. Benzoyl peroxide toxicity is presumably mediated by the formation of reactive free radicals and by the consumption of intracellular antioxidants.

In this work we investigated the effect of both the lipophilic antioxidant α‐tocopherol and the hydrophilic thiol donor N‐acetylcysteine (NAC) in human keratinocyte line HaCaT exposed to benzoyl peroxide. A protective effect against benzoyl peroxide cytotoxicity was achieved when cells were grown on a α‐tocopherol layer. On the contrary, the addition of α‐tocopherol dissolved in ethanol had a pro‐oxidant effect, leading to an enhancement of benzoyl peroxide toxicity. Cytotoxicity was also reduced adding NAC to the culture medium; the presence of both NAC and α‐tocopherol exerts a synergis‐ tic cytoprotection. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:107–114, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20008
Benzene metabolism in human lung cell lines BEAS‐2B and A549 and cells overexpressing CYP2F1
Authors: Sheets Patrick L. , Yost Garold S. , Carlson Gary P.
Published: April 2004

Benzene is an occupational and environmental toxicant. The main human health concern associated with benzene exposure is leukemia. The toxic effects of benzene are dependent on its metabolism by the cytochrome P450 enzyme system. The cytochrome P450 enzymes CYP2E1 and CYP2F2 are the major contributors to the bioactivation of benzene in rats and mice. Although benzene metabolism has been shown to occur with mouse and human lung microsomal preparations, little is known about the ability of human CYP2F to metabolize benzene or the lung cell types that might activate this toxicant. Our studies compared bronchiolar derived (BEAS‐2B) and alveolar derived (A549) human cell lines for benzene metabolizing ability by evaluating the roles of CYP2E1 and CYP2F1. BEAS‐2B cells that overexpressed CYP2F1 and recombinant CYP2F1 were also evaluated. BEAS‐2B cells overexpressing the enzyme CYP2F1 produced 47.4 ± 14.7 pmols hydroxylated metabolite/106 cells/45 min. The use of the CYP2E1‐selective inhibitor diethyldithiocarbamate and the CYP2F2‐selective inhibitor 5‐phenyl‐1‐pentyne demonstrated that both CYP2E1 and CYP2F1 are important in benzene metabolism in the BEAS‐2B and A549 human lung cell lines. The recombinant expressed human CYP2F1 enzyme had a Km value of 3.83 μM and a Vmax value of 0.01 pmol/pmol P450 enzyme/min demonstrating a reasonably efficient catalysis of benzene metabolism (Vmax/Km = 2.6). Thus, these studies have demonstrated in human lung cell lines that benzene is bioactivated by two lung‐expressed P450 enzymes. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:92–99, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20010
Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: Role of aminoguanidine
Authors: Abd El‐Gawad Hanan M. , El‐Sawalhi Maha M.
Published: April 2004

Doxorubicin (DOX) is a potent antitumor antibiotic drug known to cause severe cardiac toxicity. Moreover, its adverse effects were found to be extended to the cerebral tissue. Several mechanisms for this toxicity have been ascribed. Currently, one of the most accepted mechanisms is through free radicals; however, the exact role of nitric oxide (NO) is still unclear. Accordingly, a NO‐synthase inhibitor with some antioxidant property, aminoguanidine (AG), was selected to examine its potential protective effect against DOX‐induced toxicity. Male Wistar albino rats (150–200 g) were allocated into a normal control group, DOX‐induced toxicity group, and DOX + AG‐treated group. DOX was injected i.p. at a dose of 10 mg/kg divided into four equal injections over a period of 2 weeks. AG was injected i.p. at a dose of 100 mg/kg 1 h before each DOX injection. The animals were sacrificed 24 h after the last DOX injection and the following parameters were measured: serum lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities, cardiac and cerebral contents of malondialdehyde (MDA), conjugated diene (CD), glutathione (GSH), NO, and cytosolic calcium, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSHPX) activities. Cardiotoxicity was manifested by a marked increase in serum LDH and CPK in addition to the sharp increase in MDA reaching eightfolds the basal level. This was accompanied by significant increase in CD, NO, cytosolic calcium, SOD, and GSHPX content/activity by 69, 85, 76, 125, and 41% respectively as compared to normal control. On the other hand, GSH was significantly depressed. In brain, only significant increase in MDA and GSHPX and decrease in GSH were obtained but to a lesser extent than the cardiac tissue. AG treatment failed to prevent the excessive release of cardiac enzymes; however, it alleviated the adverse effects of DOX in heart. AG administration resulted in marked decrease in the elevated levels of MDA, NO, SOD, and GSHPX, however, MDA level was still pathological. The altered parameters in brain were restored by AG. It is concluded that, AG could not provide complete protection against DOX‐induced toxicity. Therefore, it is recommended that, maintenance of the endogenous antioxidant, GSH, and regulation of calcium homeostasis must be considered, rather than NO formation, to guard against DOX‐induced toxicity. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:69–77, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20013
1‐Benzyl‐1,2,3,4‐tetrahydroisoquinoline, a Parkinsonism‐inducing endogenous toxin, increases α‐synuclein expression and causes nuclear damage in human dopaminergic cells
Authors: Shavali Shaik , Carlson Edward C. , Swinscoe John C. , Ebadi Manuchair
Published: April 2004

1‐Benzyl‐1,2,3,4‐tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is known to cause parkinsonism in rodents and nonhuman primates. The levels of 1BnTIQ in cerebrospinal fluid of patients with Parkinson's disease (PD) were reported to be three times higher than those in control subjects. In the present study, we have evaluated the effects of 1BnTIQ on α‐synuclein (α‐syn) expression together with biochemical and morphological changes in human dopaminergic SH‐SY5Y cells in culture. 1BnTIQ at lower concentrations (1–50 μM) increased α‐syn protein expression in a time‐ and dose‐dependent manner in these cells. There was also up‐regulation of α‐syn mRNA by 1BnTIQ. Inhibition of complex I by rotenone and depletion of glutathione by L‐buthionine sulfoxamine also correlated with an increase in α‐syn expression, suggesting that oxidative stress may cause an increase in α‐syn levels in dopaminergic cells. Furthermore, 1BnTIQ significantly depleted glutathione levels. 1BnTIQ at higher concentrations (500 μM) increased reactive oxygen species levels, decreased ATP levels, and caused nuclear damage in the cells. The 1BnTIQ‐induced α‐syn up‐regulation was inhibited by cotreatment with the antioxidants selegiline, coenzyme Q10, and N‐acetylcystein and the caspase inhibitor DEVD‐CHO. Taken together, these results suggest that α‐syn up‐regulation and oxidative stress are contributing factors in 1BnTIQ‐induced neurotoxicity in dopaminergic neurons in PD. © 2004 Wiley‐Liss, Inc.
Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery
Authors: Mikami Yuji , Okano Hideyuki , Sakaguchi Masanori , Nakamura Masaya , Shimazaki Takuya , Okano Hirotaka James , Kawakami Yutaka , Toyama Yoshiaki , Toda Masahiro
Published: April 2004

We report a treatment for spinal cord injury involving implantation of dendritic cells (DCs), which act as antigen‐presenting cells in the immune system. The novel mechanisms underlying this treatment produce functional recovery. Among the immune cells tested, DCs showed the strongest activity inducing proliferation and survival of neural stem/progenitor cells (NSPCs) in vitro. Furthermore, in DC‐implanted adult mice, endogenous NSPCs in the injured spinal cord were activated for mitotic de novo neurogenesis. These DCs produced neurotrophin‐3 and activated endogenous microglia in the injured spinal cord. Behavioral analysis revealed the locomotor functions of DC‐implanted mice to have recovered significantly as compared to those of control mice. Our results suggest that DC‐implantation exerts trophic effects, including activation of endogenous NSPCs, leading to repair of the injured adult spinal cord. © 2004 Wiley‐Liss, Inc.
In search of authenticity: Now more than ever, soft skills are needed
Authors: Bunker Kerry , Wakefield Michael
Published: April 2004

In an environment where organizations and their people are experiencing greater and faster change—often highly disruptive change—it's crucial that more emphasis be placed on identifying and developing executives who possess emotional intelligence skills in addition to the more traditional leadership competencies. Among other things, today's leaders need to manage the dynamic tension between a sense of urgency and realistic patience and between optimism and realism and openness.
Impact of dopamine transporter SPECT using 123I‐Ioflupane on diagnosis and management of patients with clinically uncertain parkinsonian syndromes
Authors: Catafau Ana M. , Tolosa Eduardo
Published: April 2004

Imaging with 123I‐Ioflupane single‐photon emission computed tomography (SPECT) is a marker of nigrostriatal neuronal integrity, allowing differentiation of parkinsonism with loss of dopaminergic terminals (presynaptic Parkinson syndrome [PS]) from parkinsonism without nigrostriatal degeneration. This study assessed SPECT imaging in 118 patients with clinically uncertain parkinsonian syndromes (CUPS). In 36% of patients with presynaptic PS and 54% with nonpresynaptic PS, imaging results were not consistent with the initial diagnosis. After imaging, diagnosis was changed in 52% of patients. All patients with a final diagnosis of presynaptic PS had an abnormal image, whereas 94% of patients with nonpresynaptic PS had a normal scan. Imaging increased confidence in diagnosis, leading to changes in clinical management in 72% of patients. Consequently, visual assessment of 123I‐Ioflupane SPECT may have a significant impact on the clinical management of CUPS patients. © 2004 Movement Disorder Society