bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of Lamotrigine in Children in the Absence of other Antiepileptic Drugs
Authors: Chen Chao , Casale Eugene J. , Duncan Benjamin , Culverhouse Elizabeth H. , Gilman Jamie
Published: April 2004

We evaluated the pharmacokinetics of lamotrigine in 12 children with epilepsy who were receiving no other antiepileptic drugs. Each patient received a single oral dose of lamotrigine 2 mg/kg. Plasma concentrations of the drug were measured up to 48 hours after dosing. Pharmacokinetic parameters were calculated using noncompartmental methods. After rapid absorption, the lamotrigine concentration declined monoexponentially. Oral clearance was 0.64 ± 0.26 ml/min/kg. The apparent volume of distribution was 1.50 ± 0.51 L/kg. Weight‐normalized clearance and volume were higher in children than in adults. The mean half‐life was 32 hours, similar to that in adults. Should similar plasma lamotrigine concentrations in adults and children be desirable, children will likely require higher weight‐normalized doses at the same dosing frequency.
Reversible Akinetic Mutism Possibly Induced by Baclofen
Authors: Rubin Devon I. , So Elson L.
Published: April 2004

A 76‐year‐old man developed akinetic mutism after 3 days of receiving low‐dosage baclofen. Electroencephalography showed a diffusely slow background with intermittent generalized sharp wave discharges. The condition resolved after discontinuing baclofen. To our knowledge, this is the first reported case of baclofen‐induced akinetic mutism in a patient with normal renal function. The pathophysiology of this condition is unknown, but it may result from selective binding of the drug to the γ‐aminobutyric acid‐B receptors located in the frontal lobes or thalamic nuclei, interrupting the thalamocortical limbic pathways.
Aligning and Reorienting Carbon Nanotubes with Nematic Liquid Crystals
Authors: Dierking I. , Scalia G. , Morales P. , LeClere D.
Published: April 2004

Exploiting the self‐assembling properties of liquid crystals, large‐scale spontaneous alignment of single‐ and multi‐walled carbon nanotubes induced by elastic interactions with the nematic LC matrix is demonstrated (see Figure). Collective reorientation processes of the liquid crystal are further used to reversibly manipulate the alignment direction of the dispersed nanotubes, as evidenced by conductivity measurements.
Development of the trabecular structure within the ulnar medial coronoid process of young dogs
Authors: Wolschrijn Claudia F. , Weijs Win A.
Published: April 2004

This study describes the timing of development of the trabecular structure of the ulnar medial coronoid process (MCP) in the dog. The right MCPs of nine healthy golden retrievers, aged 4 to 24 weeks, without signs of secondary joint disease were dissected and scanned with microcomputed tomography (micro‐CT) at a voxel size of 34 μm to determine histomorphometric parameters. Bone volume fraction and mean trabecular separation show a reciprocal pattern in time, reflecting an initial high bone density (and low trabecular separation), and then a sharp drop in density at 8–10 weeks, followed by a gradual increase to high values at 24 weeks. With a similar bone volume fraction as in young bone, the older bone shows thicker trabeculae and a more plate‐like structure. This is reflected in the much smaller number of trabeculae and the lower surface/volume ratio at higher age. An anisotropic structure of the trabeculae with an orientation in the direction of the proximodistal axis of the ulna is already present at 6 weeks after birth. This primary alignment was perpendicular to the humeroulnar articular surface, matching the direction of the compressive forces applied to the MCP by the humeral trochlea. The secondary alignment appeared at 13 weeks after birth and was directed along the craniocaudal axis of the MCP, toward the attachment of the anular ligament. In comparison with data from long bones and vertebrae, the findings of a high bone volume fraction and a well‐defined trabecular alignment at a very early age are remarkable. The high bone volume fraction is possibly a remnant of the fetal trabecular structure, as dogs are relatively immature at birth compared to other animals. Soon after the start of steady locomotion, the trabecular structure changes into a more mature‐like structure. The early trabecular alignment is possibly a reflection of the early load‐bearing function of the MCP in the elbow joint. Anat Rec Part A 278A:514–519, 2004. © 2004 Wiley‐Liss, Inc.
Noninvasive analyses of polyunsaturated fatty acids in human oral mucosa in vivo by Fourier‐transform infrared spectroscopy
Authors: Yoshida Satoshi , Yoshida Hiroshi
Published: April 2004

The aim of this study was to develop a noninvasive method to observe polyunsaturated fatty acids (PUFAs) behavior in the human body using Fourier transform infrared spectroscopy. For the noninvasive measurement of human oral mucosa, we have used infrared spectroscopy with a suitable attachment for an in vivo attenuated total reflectance system. The fatty acid contents in the tissues were determined by gas‐chromatography mass‐spectrometry after methylation. The alkene C‐H stretching vibrations of unsaturated fatty acids in dietary oils showed infrared absorption bands with various peak positions and intensities at around 3010 cm‐1 depending on the extent of unsaturation and their species. The diurnal fluctuation of the alkene peak position of oral mucosa suggested that the contents of PUFAs were increased gradually in the early afternoon, and these data were supported by the direct determination of fatty acid species in oral mucosa where the relative increase of arachidonic and docosahexaenoic acids was observed in the early afternoon. This diurnal change of alkene peak position resembled the pattern of a “lipid factor” change calculated with the factor analysis applied to the overall infrared spectrum. We could monitor the diurnal fluctuations of PUFA contents of human oral mucosa noninvasively using a reagent‐free infrared analysis system. The measurement of alkene and methylene infrared bands may provide a useful tool for detecting changes in PUFA balance in the human body. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Numerical simulation of the forest impact on aquifers
Authors: Leontiev A. , Huacasi W. , Herskovits J. , Mota Soares C. M.
Published: April 2004

Here we propose a numerical method for the computer simulation of forest impact on aquifers. With this phenomenon we understand changes in the level of groundwater table beneath the areas recovered by trees. The mathematical model of the forest impact includes a boundary value problem with free and contact boundary conditions. Considering this free‐contact boundary problem as a shape optimization problem we perform boundary elements discretization. Assuming the state and free boundary variables as independents, we treat the discretized problem as a non‐linear mathematical program and apply interior point algorithm to solve it. Numerical results for an illustrative 2D test problem are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of coupled seepage and stress fields in rock mass around the Xiaowan arch dam
Authors: Junrui Chai , Yanqing Wu , Shouyi Li
Published: April 2004

The Xiaowan arch dam, with a maximum height of 292 m, is located across the Lancangjiang River in Yunnan Province of China, and once completed will be the highest arch dam in China. Because of the high water head and the arch action, it is necessary to analyse the interaction between seepage and stress fields in rock mass around the Xiaowan arch dam. Numerical solution of coupled seepage and stress fields in rock mass around the Xiaowan arch dam is analysed by means of the multi‐level fracture network model and the finite element method. It can be shown from the computation results that storage of the reservoir makes the seepage field change much, and makes the effective vertical stress in rock foundation near the dam and the tensile stress in the abutment rock mass increase, and that the coupled action between seepage and stress fields should be taken into account. Copyright © 2004 John Wiley & Sons, Ltd.
Egfl7, a novel epidermal growth factor‐domain gene expressed in endothelial cells
Authors: Fitch Michael J. , Campagnolo Luisa , Kuhnert Frank , Stuhlmann Heidi
Published: April 2004

We report the cloning and characterization of a novel epidermal growth factor (EGF) domain gene that was identified in a retroviral gene entrapment screen and is expressed in endothelial cells. This gene encodes a protein of 278 amino acids with an amino‐terminal signal peptide and two centrally located EGF‐like domains. We have named this novel gene in accordance with the guidelines of the Mouse Genome Informatics group Egfl7, for EGF‐like domain 7. Egfl7 mRNA is expressed in highly vascularized adult tissues such as the lung, heart, uterus, and ovary. In addition, Egfl7 is expressed early during mouse embryogenesis and in undifferentiated murine embryonic stem cells. The analysis of Egfl7 expression in embryonic day 9.5 embryos by in situ hybridization indicates that Egfl7 is expressed in vascular structures in both the embryo proper and the yolk sac and at sites of mesodermal precursors of angioblasts. Within the cell, EGFL7 protein is localized to the endoplasmic reticulum and Golgi apparatus, suggesting that the protein is targeted for secretion. Indeed, recombinant EGFL7 is readily detectable in the supernatant media of transiently transfected HEK293 cells. We also report the identification of an Egfl7 paralog, Egfl8, and show that EGFL8 protein shares similar domains and molecular weight with EGFL7. Developmental Dynamics 230:316–324, 2004. © 2004 Wiley‐Liss, Inc.
Environmental issues related to end‐of‐life options of plastics containing brominated flame retardants
Authors: Tange Lein , Drohmann Dieter
Published: April 2004

Bromine is used as the building block for some of the most effective flame retarding agents available to the plastics industry today. They are used to protect against the risk of accidental fires in a wide range of Electrical and Electronic Equipment (EEE). Brominated flame retardants (BFRs), as all flame retardants, act to decrease the risk of fire by increasing the fire resistance of the materials in which they are applied. There is a perception that BFRs affect adversely the end‐of‐life management of plastics through formation of Polybrominated Dibenzo Dioxins and Dibenzo Furans (PBDD/F). In fact, there exists a wide range of data and practical experience demonstrating that the end‐of‐life management of plastics containing BFRs is fully compliant with legislation setting the strictest limit values for PBDD/F and is fully compatible with an integrated waste management concept. Copyright © 2004 John Wiley & Sons, Ltd.
Numerical determination of 3D temperature fields in steel joints
Authors: Franssen Jean‐Marc
Published: April 2004

A numerical study was undertaken to investigate the temperature field in steel joints and to compare the temperatures in the joints with the temperatures of the adjacent steel members on the hypothesis that the thermal protection is the same on the joint and in the members.

Very brief information is given on the numerical model, supplemented with parametric studies made in order to determine the required level of discretization in the time and in the space domain. A simplified assumption for representing the thermal insulation is also discussed and validated.

Different numerical analyses are performed, with a variation of the following parameters: (i) type of joints, from very simple to more complex configurations, with welds and/or bolts, all of them representing joints between elements located in the same plane; (ii) unprotected joints or protected by one sprayed material; (iii) ISO, hydrocarbon or one natural fire scenario.

The fact that the thermal attack from the fire might be less severe because the joints are usually located in the corner of the compartment is not taken into account. Copyright © 2004 John Wiley & Sons, Ltd.
Advanced analysis of 3D steel framework exposed to compartment fire
Authors: Liew J. Y. Richard , Ma K. Y.
Published: April 2004

This paper describes the use of advanced analysis that accounts for both material and geometric nonlinearity to assess the performance of steel structures exposed to a natural compartment fire. The advanced analysis is developed based on inelastic beam‐column theory which can capture the ultimate strength behaviour of members for global analysis of large structures in fire. The heat transfer is computed using a refined finite element mesh. Compartment fire is simulated in accordance with the latest Eurocode prEN 1991‐1‐2. Performance‐based assessments are carried out on multi‐storey space frames subjected to a natural compartment fire. The computed results are compared with those from the conventional approach based on ISO standard fire curve and the advantage of the advanced analysis is highlighted. The effect of fire load and ventilation on the structural response of the frames is studied and the worst‐case fire scenarios are identified. The design implications on the requirement of fire protection are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Analytical method for the behaviour of a reinforced concrete flexural member at elevated temperatures
Authors: Kang Suk‐Won , Hong Sung‐Gul
Published: April 2004

An analytical method is proposed for the thermal behaviour of a reinforced concrete flexural member subjected to fire. The analysis procedure can be subdivided into two different steps; sectional analysis and member solution. A segmentation scheme is employed in the analysis for a section. It implicates uniform sectional properties and temperature distribution through the longitudinal axis of the member. The mechanical changes at the segmented section such as strain changes and corresponding stresses due to temperature increase are integrated into the member behaviour at the member solution step. According to the analysis results, there exist very severe nonlinear strain changes with the depth measured from the fire‐exposed surface, which are caused by a nonlinear temperature distribution at the section. Self‐equilibrating stresses are manifested during heating just to let the section remain plane after deformation. Copyright © 2004 John Wiley & Sons, Ltd.
Restraint of fire‐exposed concrete floor systems
Authors: Lim Linus , Buchanan Andrew H. , Moss Peter J.
Published: April 2004

This paper describes the numerical analyses of restrained concrete floor slabs exposed to fire. The analyses of the slabs were carried out with the SAFIR finite element program considering a 200 mm thick slab, spanning 5 m between two end supports. The slabs were exposed to the ISO standard fire for up to 4 h and were analysed with pinned and rotationally restrained supports. Different heights of the line of thrust at the supports and different levels of axial restraint were also investigated. The analyses show that fully restrained pin‐supported slabs can survive the 4 h ISO fire without collapse if the position of the line of thrust is located near the soffit of the slab. If the position of the line of thrust is located much above the soffit of the slab, the slabs will rapidly undergo large deformations and sag into a catenary, imposing axial tensile forces at the supports. The analyses have shown that even if the line of thrust is located close to the soffit, the slab can still deform into a catenary if there is insufficient horizontal axial restraint. In this study, rotationally restrained slabs experience much smaller vertical deflections than pin‐supported slabs when exposed to fires. Rotationally restrained slabs with low levels of horizontal restraint do not collapse, due to the beneficial effects of moment redistribution. However, high levels of horizontal restraint can be detrimental, causing slabs to collapse at advanced stages of the fire. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of support conditions on the fire behaviour of steel and composite beams
Authors: Moss Peter J. , Buchanan Andrew H. , Seputro Jenny , Wastney Clayton , Welsh Richard
Published: April 2004

The fire behaviour of a structural steel beam or a steel and concrete composite beam in a fire compartment depends on many factors including the nature of the supports at the ends of the beam.

This paper describes a detailed analytical investigation into the effects of support conditions on the fire performance of steel and composite steel‐concrete beams exposed to linearly increasing temperature with time, as well as to standard and parametric fires.

The support conditions include simply supported, fully fixed, and a range of intermediate cases, providing varying levels of axial and flexural restraint. In each case, a comparison of the deflected shape with the evolving internal forces shows unusual but predictable behaviour, strongly dependent on the stress–strain relationship of the steel. In addition to the standard support conditions, a spring was used to simulate the effect of axial restraint provided by adjacent spans of a multi‐span beam. This case showed that the spring stiffness had a very considerable influence on the behaviour of the beam and the time to failure under an increasing fire temperature.

This paper gives new insight into the structural performance of steel and composite beams, observed in recent fires such as the eight storey steel frame at Cardington. There are major implications for structural designers. Copyright © 2004 John Wiley & Sons, Ltd.
Key events in the structural response of a composite steel frame structure in fire
Authors: Usmani A. S. , Lamont S.
Published: April 2004

The structural design of composite steel frame buildings in fire has traditionally been based on single element behaviour, under standard fire conditions. This approach is widely recognized as unsatisfactory and there is a general consensus that it leads to excessive fire protection being applied to the steel members based on grossly inaccurate assumptions about whole structure behaviour in fire. A great deal of research has been carried out to understand the mechanics of whole structure behaviour in fire. This paper presents a summary of this research by computational analysis of a small but realistic steel‐frame composite structure with mainly unprotected beams and fully fire‐protected columns.

The main purpose of this paper is to highlight a number of key events that define the response of the steel frame structure in fire. Some of these events can be observed in real fire tests (such as Cardington), however, others have only been discovered by careful analysis of the output data from computational analyses supported by fundamental theoretical analysis. For instance, an event has been discovered entirely from computational modelling of the above‐mentioned small structure with no similar events observed in experiments or reported in the literature. This particular event involves a sudden and sharp increase in deflection of the whole floor at particular steel temperatures during the fire. If this event occurred in a real structure, it might cause an overload of the floor because of the dynamic effect of this instability (unaccounted for in the static analysis performed here) leading to compartment breach or collapse.

All these events will be presented in order of appearance as the compartment fire progresses and the member temperatures increase. The reason for the occurrence of each event will be discussed supported by simple analysis of the relevant structural mechanics and brief discussion of design implications. Copyright © 2004 John Wiley & Sons, Ltd.
Examples of fire engineering design for steel members, using a standard curve versus a new parametric curve
Authors: Barnett C. R. , Clifton G. C.
Published: April 2004

This paper presents examples of the differences that can occur when a standard time‐temperature curve and a parametric time‐temperature curve are used to determine temperatures likely to be reached by uninsulated and insulated steel members during a fire. For low and moderate structural fire severity situations, determination of the adequacy of a steel member by comparing the temperature reached in a ‘design fire’ with the limiting temperature based on the member heat sink characteristics, extent of insulation and utilization factor is becoming increasingly common fire engineering design practice. For this it is important to have an accurate and widely applicable parametric fire model as is practicable.

The standard time‐temperature curve used in the examples is the ISO 834 curve. The two parametric time‐temperature curves used in the paper are the Eurocode parametric curve and a recently developed one termed the ‘BFD curve’. The latter has been found to fit the results of a wide range of actual fire tests more closely than do existing parametric curves and is mathematically simpler in form.

The shape of the BFD curve and the parameters used to define it bear a strong relationship to both the pyrolysis coefficient (R/Avhv0.5) and the opening factor, F02. The curve also models the development of fire without the need for time shifts. It uses a single and relatively simple equation to generate the temperature of both the growth and decay phases of a fire in a building and only three factors are required to derive the curve. These factors are (i) the maximum gas temperature, (ii) the time at which this maximum temperature occurs, and (iii) a shape constant for the curve. If desired, the shape constant can be different on the growth and the decay sides to model a very wide range of natural fire conditions and test results.

This paper presents an overview of the background to the BFD curve. It then illustrates its use in a simple fire engineering design application, where the adequacy of a steel beam is checked using the Eurocode parametric curve and the BFD curve to represent the fire. Copyright © 2004 John Wiley & Sons, Ltd.
Improvement of MEAs for Direct‐Methanol Fuel Cells by Tuned Layer Preparation and Coating Technology
Authors: Lindermeir A. , Rosenthal G. , Kunz U. , Hoffmann U.
Published: April 2004

Large scale production of membrane electrode assemblies (MEAs) for fuel cells requires a fabrication technology, which is not only based on electrochemical phenomena but also takes into account aspects of materials processing and conversion. For the fabrication of MEAs for DMFC a production sequence consisting of wet ball‐milling, wet spray coating and calendering was developed at the ICVT Clausthal. This has a proven ability for the preparation of diffusion backings and catalyst layers with high reproducibility. To improve MEA performance, investigations concerning the influence of layer fabrication and composition are made with respect to the resulting morphology of the structures. Intermediates and MEAs are evaluated by conductivity measurements, determination of permeability values and current density‐voltage characteristics supported by SEM and optical microscopy.
Recent Advances to the Development of Low‐Temperature Solid Oxide Fuel Cells
Authors: Xia C. , Lang Y. , Meng G.
Published: April 2004

While existing solid oxide fuel cell (SOFC) technology has demonstrated much higher energy efficiency with minimal pollutant emission than the conventional technologies, the costs of the current SOFC systems are still prohibitive for broad commercialization. To be economically competitive, both the cost of materials and the cost of fabrication must be dramatically reduced. One effective approach to cost reduction is to reduce the operating temperature; many cell components, including interconnect, heat exchangers, and other structural or balance‐of‐plant components, can be fabricated from much less expensive materials when the operating temperature is sufficiently low. However, the interfacial polarization resistances increase rapidly as the operating temperature is reduced. This paper will address the critical issues in creating electrodes and interfaces of minimal polarization resistance in order to minimize internal electrochemical losses at low temperatures. In particular, design, fabrication, and characterization of composite electrodes consisting of silver and bismuth oxide will be discussed. Another approach to cost reduction is to reduce the cost of fabrication. Dense electrolyte films supported on porous anodes fabricated by screen‐printing and dry press will be presented.
The Influence of Mass Transfer on a Porous Fuel Cell Electrode
Authors: Sun Y.‐P. , Scott K.
Published: April 2004

A one‐dimensional model for a porous fuel cell electrode using a liquid electrolyte with dissolved reactant is presented. The model consists of a Poisson, second‐order ordinary differential equation, describing the effect of the electric field and a one‐dimensional; Fickian diffusion, second‐order ordinary differential equation describing the concentration variation associated with diffusion. The model accounts for mass transport and heterogeneous electrochemical reaction. The solution of this model is by the approximate Adomian polynomial method and is used to determine lateral distributions of concentration, overpotential and current density and overall cell polarisation. The model is used to simulate the effects of important system and operating parameters, i.e. local diffusion rates, and mass transport coefficients and electrode polarisation behaviour.
The Status and Prospects of Key Materials for the Proton Exchange Membrane Fuel Cell at the Dalian Institute of Chemical Physics
Authors: Yu H. , Yi B.
Published: April 2004

The development of key materials for proton exchange membrane fuel cells including electrocatalysts, electrodes, proton exchange membranes and bipolar plates in DICP are introduced in this paper. The basic fundamentals and the most recent progress in the key materials have been discussed. The preparation methods of electrocatalysts have been reviewed. Characteristics of various electrode preparation methods are also introduced. A new electrode design and prospective manufacturing methods are indicated. The disadvantages of the present exchange membrane are presented. The results of proton exchange membrane degradation mechanisms are given. Studies of the Nafion/PTFE membrane, blending membrane and PBI membrane are reviewed. Developmental trends of the membrane in both the medium and long term are previewed. Different bipolar plates are compared.
Ethanol and Acetaldehyde Adsorption on a Carbon‐Supported Pt Catalyst: A Comparative DEMS Study
Authors: Wang H. , Jusys Z. , Behm R.J.
Published: April 2004

The adsorption of ethanol and acetaldehyde on carbon Vulcan supported Pt fuel cell catalyst and the electrochemical desorption of the adsorption products were studied, using electrochemical measurements and differential electrochemical mass spectrosmetry (DEMS), under continuous flow conditions. Faradaic current adsorption transients at different constant adsorption potentials, which also include CO adsorption for comparison, show pronounced effects of the adsorption potential and the nature of the reactant molecule. Acetaldehyde adsorption is much faster than ethanol adsorption at all potentials. Pronounced Had induced blocking effects for ethanol adsorption are observed at very cathodic adsorption potentials, < 0.16 V, while for acetaldehyde adsorption this effect is much less significant. Comparison of the adsorption charge for CO adsorption with the H‐upd charge allows differentiation between H‐displacement and double‐layer charging effects. Continuous bulk oxidation is observed for both reactants at potentials > 0.31 V; for acetaldehyde adsorption, increasing bulk reduction is found at low potentials. Based on the electron yield per CO2 molecule formed and on the similarity with the CO stripping characteristics the dominant stable adsorbate is CO, coadsorbed with smaller amounts of (partly oxidized) hydrocarbon decomposition fragments, which are also oxidized at higher potentials (> 0.85 V) and which can be reductively desorbed as methane or, to a very small extent, as ethane. The presence of small amounts of adsorbed C2 species and the oxidative dissociation of these species in the main CO oxidation potential range is clearly demonstrated by increased methane desorption after a potential shift to 0.85 V. The data demonstrate that the Pt/Vulcan catalyst is very reactive for C‐C bond breaking upon adsorption of these reactants.
Early stages of oligodendrocyte development in the embryonic murine spinal cord proceed normally in the absence of Hoxa2
Authors: Nicolay Danette J. , Doucette J. Ronald , Nazarali Adil J.
Published: April 2004

Recent discoveries have enhanced our knowledge of the transcriptional control of oligodendrocyte (OG) development. In particular, the transcription factors (TFs) Olig2, Pax6, and Nkx2.2 have been shown to be important in the specification and/or maturation of the OG lineage. Although numerous other TFs are expressed by OGs, little is known regarding their role(s) in oligodendrogenesis. One such TF is the homeobox gene Hoxa2, which was recently shown to be expressed by O4+ pro‐oligodendrocytes. The objectives of this study were to examine the expression of Hoxa2 during the early stages of OG development, as well as to determine whether Hoxa2 is required for specification and/or early maturation of OGs. Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxa2 was expressed throughout oligodendrogenesis, diminishing only with the acquisition of a myelinating phenotype. Serial transverse spinal cord sections from embryonic days 12.5, 14.25, 16, and 18 Hoxa2+/+, Hoxa2+/−, and Hoxa2−/− mice were subjected to single and double immunohistochemical analysis in order to examine Hoxa2, Olig2, Nkx2.2, and Pax6 expression profiles. Results obtained from Hoxa2+/+ and Hoxa2+/− mice suggested that Hoxa2 was expressed by migratory oligodendroglial cells. In addition, comparison of spinal cord sections obtained from Hoxa2+/+, Hoxa2+/−, and Hoxa2−/− mice suggested that specification and early maturation of OGs proceeded normally in the absence of Hoxa2, since there were no obvious alterations in the expression patterns of Olig2, Nkx2.2, and/or Pax6. Hence, although Hoxa2 is expressed throughout OG development, it does not appear to be critical for early stages of oligodendrogenesis in the murine spinal cord. © 2004 Wiley‐Liss, Inc.
Olfactory ensheathing cell grafts have minimal influence on regeneration at the dorsal root entry zone following rhizotomy
Authors: Riddell John S. , Enriquez‐Denton Manuel , Toft Andrew , Fairless Richard , Barnett Susan C.
Published: April 2004

The effectiveness of grafts of olfactory ensheathing cells (OECs) as a means of promoting functional reconnection of regenerating primary afferent fibers was investigated following dorsal root injury. Adult rats were subjected to dorsal root section and reanastomosis and at the same operation a suspension of purified OECs was injected at the dorsal root entry zone and/or into the sectioned dorsal root. Regeneration of dorsal root fibers was then assessed after a survival period ranging from 1 to 6 months. In 11 animals, electrophysiology was used to look for evidence of functional reconnection of regenerating dorsal root fibers. However, electrical stimulation of lesioned dorsal roots failed to evoke detectable cord dorsum or field potentials within the spinal cord of any of the animals examined, indicating that reconnection of regenerating fibers with spinal cord neurones had not occurred. In a further 11 rats, immunocytochemical labeling and biotin dextran tracing of afferent fibers in the lesioned roots was used to determine whether regenerating fibers were able to grow into the spinal cord in the presence of an OEC graft. Although a few afferent fibers could be seen to extend for a limited distance into the spinal cord, similar minimal in‐growth was seen in control animals that had not been injected with OECs. We therefore conclude that OEC grafts are of little or no advantage in promoting the in‐growth of regenerating afferent fibers at the dorsal root entry zone following rhizotomy. © 2004 Wiley‐Liss, Inc.
Specific characteristic of radial glia in the human fetal telencephalon
Authors: Zecevic Nada
Published: April 2004

Phenotypic characteristics of cells in the developing human telencephalic wall were analyzed using electron microscopy and immunocytochemistry with various glial and neuronal cell markers. The results suggest that multiple defined cell types emerge in the neocortical proliferative zones and are differentially regulated during embryonic development. At 5–6 weeks gestation, three major cell types are observed. Most proliferating ventricular zone (VZ) cells are labeled with radial glial (RG) markers such as vimentin, glial fibrillary acidic protein (GFAP), and glutamate astrocyte‐specific transporter (GLAST) antibodies. A subpopulation of these RG cells also express the neuronal markers β III‐tubulin, MAP‐2, and phosphorylated neurofilament SMI‐31, in addition to the stem cell marker nestin, indicating their multipotential capacity. In addition, the presence of VZ cells that immunoreact only with neuronal markers indicates the emergence of restricted neuronal progenitors. The number of multipotential progenitors in the VZ gradually decreases, whereas the number of more restricted progenitors increases systematically during the 3‐month course of human corticogenesis. These results suggest that multipotential progenitors coexist with restricted neuronal progenitors and RG cells during initial corticogenesis in the human telencephalon. Since the multipotential VZ cells disappear during the major wave of neocortical neurogenesis, the RG and restricted neuronal progenitors appear to serve as the main sources of cortical neurons. Thus, the diversification of cells in human VZ and overlying subventricular zone (SVZ) begins earlier and is more pronounced than in rodents. © 2004 Wiley‐Liss, Inc.
Interleukin‐10 attenuates production of HSV‐induced inflammatory mediators by human microglia
Authors: Marques Cristina P. , Hu Shuxian , Sheng Wen , Cheeran Maxim C‐J. , Cox Diana , Lokensgard James R.
Published: April 2004

Infection of the central nervous system (CNS) with herpes simplex virus (HSV)‐1 initiates a rapidly progressive, necrotizing, and fatal encephalitis in humans. Even with the advent of antiviral therapy, effective treatments for HSV‐1 brain infection are limited because the cause of the resulting neuropathogenesis is not completely understood. We previously reported that human microglial cells, while nonproductively infected, respond to HSV‐1 by producing robust amounts of pro‐inflammatory mediators, such as tumor necrosis factor(TNF), interleukin (IL)‐1β, CCL5 (RANTES), and CXCL10 (IP‐10). Although initiation of immune responses by glial cells is an important protective mechanism in the CNS, unrestrained inflammatory responses may result in irreparable brain damage. To elucidate the potential immunomodulatory role of anti‐inflammatory cytokines, we investigated the effects of IL‐4, IL‐10, and transforming growth factor (TGF)‐β on microglial cell cytokine and chemokine production in response to HSV‐1. Results from these studies demonstrated a consistent IL‐10‐mediated suppression of TNF‐α (60% ± 2%), IL‐1β (68% ± 3%), CCL5 (62 ± 4%), but not CXCL10 production by HSV‐1‐infected microglial cells. This inhibition was associated with decreased HSV‐1‐induced activation of NF‐κB. These results suggest that IL‐10 has the ability to regulate microglial cell production of immune mediators and thereby, dampen the pro‐inflammatory response to HSV‐1. © 2004 Wiley‐Liss, Inc.
Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human livers
Authors: Roskams Tania A. , Theise Neil D. , Balabaud Charles , Bhagat Govind , Bhathal Prithi S. , Bioulac-Sage Paulette , Brunt Elizabeth M. , Crawford James M. , Crosby Heather A. , Desmet Valeer , Finegold Milton J. , Geller Stephen A. , Gouw Annette S.H. , Hytiroglou Prodromos , Knisely A. S. , Kojiro Masamichi , Lefkowitch Jay H. , Nakanuma Yasuni , Olynyk John K. , Park Young Nyun , Portmann Bernard , Saxena Romil , Scheuer Peter J. , Strain Alastair J. , Thung Swan N. , Wanless Ian R. , West Brian A.
Published: April 2004

The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field. (Hepatology 2004; 39:1739-1745.)
Heterosynaptic metaplastic regulation of synaptic efficacy in CA1 pyramidal neurons of rat hippocampus
Authors: Le Ray Didier , Fernández De Sevilla David , Belén Porto Ana , Fuenzalida Marco , Buño Washington
Published: April 2004

The induction threshold, and the magnitude and direction of changes in synaptic plasticity may depend on the previous history of neuronal activity. This phenomenon, termed “metaplasticity,” could play an important role in integration processes by coordinating the modulation of synapses. Although metaplasticity has been analyzed extensively, its underlying cellular mechanisms remain largely unknown. Using in vitro electrophysiological and computer simulation approaches, we investigated the contribution of the slow Ca2+‐dependent afterhyperpolarization (sAHP) in the metaplastic control of the induction of long‐term potentiation (LTP) at convergent CA3‐CA1 pyramidal neuron synapses. We report that classical conditioning protocols may lead to the simultaneous induction of a sustained homosynaptic LTP and a potentiation of the sAHP that endured ≈1 h. The sAHP potentiation dramatically altered the spike responses of the CA1 pyramidal neuron. Of particular interest was the reduction of the CA1 neuron excitability and, consequently, of the capacity of a nonpotentiated synaptic input to elicit spikes while the sAHP was potentiated. This reduction in excitability temporarily prevented nonpotentiated synaptic inputs to exhibit an LTP induced by presynaptic tetanization. This metaplasticity was strongly resistant to increases in the magnitude of synaptic tetanization protocols. We propose that this heterosynaptic metaplasticity, mediated by intrinsic cellular mechanisms, triggered by brief periods of activity, and relying on changes of a slow Ca2+‐activated K+ current, may contribute to adjusting the efficacy of synaptic connections and shaping network behavior to regulate integration processes. © 2004 Wiley‐Liss, Inc.
Biocompatibility and biodegradation of a bone composite containing tricalcium phosphate and genipin crosslinked gelatin
Authors: Yao Chun‐Hsu , Liu Bai‐Shuan , Hsu Shan‐Hui , Chen Yueh‐Sheng , Tsai Chin‐Chuan
Published: April 2004

A biodegradable composite (GGT) containing tricalcium phosphate ceramic particles and genipin crosslinked gelatin was developed for use as a bone substitute. The objective of this study was to assess the biocompatibility and the osteoconductivity of the GGT composite on new bone formation in vitro. Additionally, biodegradation and biocompatibility of the GGT composite in animals were investigated. Results of the GGT composites cocultured with osteoblasts showed that the concentration of genipin used as a crosslinking agent should be <0.5 wt % to avoid cytotoxicity. For in vivo degradation studies, we found that when the concentration of genipin in the composite <0.5 wt % was not enough to fully crosslink the gelatin, it results in a rapid degradation of the gelatin–genipin mixture. However, we also found that the foreign body capsule surrounding the GGT composite containing 1.0 wt % of the genipin was much thicker than that in the other three groups, that is, the composites containing 0.05, 0.1, and 0.5 wt % of the genipin. We therefore concluded that the ideal concentration of genipin used in the GGT was 0.5 wt %. Finally, we examined the organ culture units, which were maintained in cultured medium for 5 weeks. Morphology of tissue was observed and the quantitative evaluation of the regenerated bone was determined. We found that the GGT composites containing 0.5 wt % of the genipin had an excellent biocompatibility and could produce osteoconduction for the regenerating bone tissues. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 709–717, 2004
New regular embeddings of n‐cubes Qn
Authors: Kwon Young Soo
Published: April 2004

We investigate highly symmetrical embeddings of the n‐dimensional cube Qn into orientable compact surfaces which we call regular embeddings of Qn. We derive some general results and construct some new families of regular embeddings of Qn. In particular, for n = 1, 2,3(mod 4), we classify the regular embeddings of Qn which can be expressed as balanced Cayley maps. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 297–312, 2004
Im Schatten Schwarzer Löcher: Theoretische Astrophysik
Authors: de Vries Andreas
Published: April 2004

Schwarze Löcher werden im Rahmen der Allgemeinen Relativitätstheorie als Singularitäten beschrieben. Sie krümmen die Raumzeit in ihrer Umgebung so stark, dass Licht in einem bestimmten Abstand auf Kreis‐ oder Ellipsenbahnen um die Singularität herumläuft. Insofern werfen Schwarze Löcher vor einem hellen Hintergrund einen Schatten. Mit großen Teleskopen könnten diese zukünftig eventuell nachgewiesen werden und Informationen über die einzigen Eigenschaften Schwarzer Löcher liefern: Masse, Ladung und Rotation.
Atomkühlung mit Lichtresonatoren
Authors: Rempe Gerhard
Published: April 2004

Alle bisherigen Verfahren zur Kühlung eines atomaren Gases funktionieren grundsätzlich nicht bei Molekülen. Eine Gruppe am Max‐Planck‐Institut für Quantenoptik in Garching hat kürzlich eine neue Methode entwickelt, mit der sich einzelne Atome zwischen zwei Spiegeln abbremsen lassen. Diese ist auch auf Moleküle anwendbar [1].
Wann uns Quantenteilchen klassisch erscheinen
Authors: Arndt Markus
Published: April 2004

Atome und Moleküle weisen ebenso Welleneigenschaften auf wie beispielsweise Licht. Eine Eigenschaft, die mit wachsender Teilchengröße zunehmend schwerer zu beweisen ist. Eine Forschergruppe an der Universität Wien demonstrierte jüngst, wie auch die thermische Lichtemission von Molekülen den Wellencharakter unbeobachtbar macht [1].
Wie lang ist ein Meter?
Authors: Heering Peter
Published: April 2004

Längeneinheiten gehören vermutlich zu den ältesten Maßen, das heute so geläufige Meter wurde aber erst Ende des 18. Jahrhunderts geschaffen. Seine genaue Bestimmung stellt auch heute noch eine Herausforderung an die Messtechnik dar.
Perspektive täuscht
Authors: Schlichting H. Joachim
Published: April 2004

Die perspektivische Verkürzung täuscht bekanntlich Konvergenzen vor, wo keine sind. In größeren Entfernungen, in denen das binokulare räumliche Sehen nicht mehr funktioniert, ist die perspektivische Täuschung ein wesentliches Element der räumlichen Wahrnehmung. Der Dom Santa Maria del Fiore in Florenz bietet hierfür ein besonders beeindruckendes Beispiel. Mit diesem Beitrag beginnen wir eine Serie über Alltägliches und auf den zweiten Blick Verblüffendes.
Has the yo‐yo stopped? An assessment of human protein‐coding gene number
Authors: Southan Christopher
Published: April 2004

Since the identification of ∼ 25 000 proteins from the draft human genome assembly in 2001, estimates of the total have oscillated between 30 000 and 70 000. The recently announced genome closure has not generated a consensus gene count despite this being a key parameter for many areas of biology including drug target discovery and characterization of the human proteome. Contrary to earlier predictions of constitutive under‐detection for eukaryotic genes, the latest model organism updates have produced minor increases in the worm but fly and yeast gene numbers have decreased. The postdraft, precompletion interval has produced large increases in human transcript coverage, continuous improvements in genome assembly and refinements in automated genomic annotation. Notably these enhancements have resulted in an Ensembl human protein‐coding gene number of 22 184, a decrease of 1862 since the first release. Longitudinal database surveys indicate that redundancy‐reduced human mRNA and protein collections are flattening out at ∼ 28 000, although Ensembl maps ∼ 20 000 known sequences. Observations suggest high‐throughput cloning projects are predominantly extending known genes or sampling new splice forms and novel protein discovery has slowed to a trickle. The hypothesis that substantial numbers of short proteins remain experimentally and computationally undetected in mammalian genomes is neither supported by sequence data nor by the extensive homology between mouse and human proteins. Aggregating the independent annotations for complete transcripts from seven completed human chromosomes extrapolates to ∼ 25 000 genes. The inclusion of partial putative genes would increase this to above 30 000 but recent data suggest these represent predominantly nonprotein‐coding transcripts. Mass spectrometry‐based proteomics has already verified more than 10% of human genes but has not identified significant numbers of unpredicted proteins. The available data are thus converging to a basal protein‐coding gene number well below 30 000, which could even be as low as 25 000.
Differential protein composition of bovine whey: A comparison of whey from healthy animals and from those with clinical mastitis
Authors: Hogarth Caroline J. , Fitzpatrick Julie L. , Nolan Andrea M. , Young Fiona J. , Pitt Andrew , Eckersall P. David
Published: April 2004

During clinical mastitis in dairy cows, the quantity of milk produced decreases and the composition of the milk is altered. As the severity of inflammation associated with the disease increases, the chemical composition of milk approaches that of blood as a consequence of increased permeability of the blood mammary barrier, or de novo intramammary synthesis, as has been suggested for mammary associated serum amyloid A3. A better understanding of these events may provide new approaches for the diagnosis and treatment of mastitis. The objective of this study was to document the changes in the protein composition of milk during clinical mastitis using a proteomic approach, with the objective of identifying new diagnostic markers of mastitis. Whey from dairy cows with clinical mastitis was compared to whey from healthy animals by two‐dimensional gel electrophoresis (2‐DE) with colloidal Coomassie staining and matrix‐assisted desorption/ionization mass spectrometry. Increases in the concentrations of proteins of blood serum origin, including serotransferrin and albumin, were identified in mastitic whey compared to normal whey, while concentrations of the major whey proteins α‐lactalbumin and β‐lactoglobulin were reduced in mastitic whey. Mass spectrometry subsequently confirmed the location of albumin, α‐lactalbumin and β‐lactoglobulin on the 2‐DE gels at Mr/pI of 69 294/5.8, 14 200/4.5 and 19 883/4.9 respectively.
Prediction of disulfide‐bonded cysteines in proteomes with a hidden neural network
Authors: Martelli Pier Luigi , Fariselli Piero , Casadio Rita
Published: April 2004

A hidden neural network‐based method is used to predict the bonding state of cysteines starting from the residue sequence of the protein chain. The method scores as high as 89% and 86% per cysteine residue and per protein, respectively, and in this overcomes other predictors of the same category. We then explore the efficacy of our predictor in computing the disulfide content of the whole proteome of Escherichia coli (K12 and O157), Aeropirum pernix, Thermotoga maritima, and Homo sapiens. We find that the percentage of extracellular disulfide containing proteins is higher than that of intracellular one, and that the human proteome is by far the one with the highest content of sulfur‐sulfur linkages in proteins.