bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathology of Rett syndrome
Authors: Armstrong Dawna Duncan
Published: October 2002

Rett Syndrome is unlike any other pediatric neurologic disease, and its clinical‐pathologic correlation can not be defined with standard histology techniques. Based on hypotheses suggested by careful clinical observations, the nervous system of the Rett child has been explored utilizing morphometry, golgi preparations, computerized tomography, magnetic resonance imaging, chemistry, immunocytochemistry, autoradiography, and molecular biologic techniques. From these many perspectives we conclude that Rett syndrome is not a typical degenerative disorder, storage disorder, nor the result of gross malformation, infectious or neoplastic processes. There remain regions of the brain that have not been studied in detail but the available data suggest that the neuropathology of Rett syndrome can be summarized as follows: the Rett brain is small for theageand theheightof the patient; it does not become progressively smaller over three to four decades; it has small dendritic trees in pyramidal neurons of layers III and V in selected lobes (frontal, motor, and temporal); it has small neurons with an increased neuronal packing density; it has an immature expression of microtubular protein‐2 and cyclooxygenase; it exhibits a changing pattern of neurotransmitter receptors with an apparent reduction in many neurotransmitters, possibly contributing to some symptomatology. A mutation inMecp2causes this unique disorder of brain development. Neuronal mosaicism for normal and mutatedMecp2produces a consistent phenotype in the classic female patient and a small brain with some preserved islands of function, but with an inability to support hand use and speech. This paper summarizes our current observations about neuropathology of Rett syndrome. MRDD Research Reviews 2002;8:72–76. © 2002 Wiley‐Liss, Inc.
Two‐dimensional spatially‐selective RF excitation pulses in echo‐planar imaging
Authors: Rieseberg Susanne , Frahm Jens , Finsterbusch Jürgen
Published: October 2002

Two‐dimensional spatially‐selective RF (2DRF) excitation pulses were developed for single‐shot echo‐planar imaging (EPI) with reduced field of view (FOV) in the phase‐encoding direction. The decreased number of k‐space lines significantly shortens the length of the EPI echo train. Thus, both gradient‐echo and spin‐echo 2DRF‐EPI images of the human brain at 2.0 T exhibit markedly reduced susceptibility artifacts in regions close to major air cavities. Based on a blipped‐planar trajectory, implementation of a typical 2DRF pulse resulted in a 26‐ms pulse duration, a 5‐mm section thickness, a 40‐mm FOV along the phase‐encoding direction, and a 200‐mm distance of the unavoidable side excitations from the center of the FOV. For the above conditions and at 2 × 2 mm2 resolution, 2DRF‐EPI yielded an echo train length of only 21 ms, as opposed to 102 ms for conventional EPI. This gain in time may be used to achieve higher spatial resolution. For example, spin‐echo 2DRF‐EPI of a 40‐mm FOV at 1 × 1 mm2 resolution led to an echo train of 66 ms. Although the current implementation still lacks user‐friendliness, 2DRF pulses are likely to become a useful addition to the arsenal of advanced MRI tools. Magn Reson Med 47:1186–1193, 2002. © 2002 Wiley‐Liss, Inc.
MRI of the lungs using hyperpolarized noble gases
Authors: Möller Harald E. , Chen X. Josette , Saam Brian , Hagspiel Klaus D. , Johnson G. Allan , Altes Talissa A. , de Lange Eduard E. , Kauczor Hans‐Ulrich
Published: October 2002

The nuclear spin polarization of the noble gas isotopes3He and129Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments. Magn Reson Med 47:1029–1051, 2002. © 2002 Wiley‐Liss, Inc.
Phase coherent averaging in magnetic resonance spectroscopy using interleaved navigator scans: Compensation of motion artifacts and magnetic field instabilities
Authors: Thiel Thorsten , Czisch Michael , Elbel Gregor K. , Hennig Juergen
Published: October 2002

The quality of spectra in 1H magnetic resonance spectroscopy (MRS) is strongly affected by temporal signal instabilities during the acquisition. One reason for these instabilities are hardware imperfections, e.g., drifts of the main magnetic field in superconducting magnets. This is of special concern in high‐field systems where the specification of the field stability is close to the spectral linewidth. A second major potential source of artifacts, particularly in clinical MRS, is patient motion. Using standard acquisition schemes of phase‐cycled averaging of the individual acquisitions, long‐term effects (field drifts) as well as changes on a shorter time scale (motion) can severely reduce spectral quality. The new technique for volume‐selective MRS presented here is based on the additional interleaved acquisition of a navigator signal during the recovery time of the metabolite acquisition. It corrects for temporal signal instabilities by means of a deconvolution of the metabolite and the navigator signal. This leads to phase‐corrected individual metabolite scans and upon summation to a phase‐coherent averaging scheme. The interleaved navigator acquisition does not require any user interaction or supervision, while sequence efficiency is maintained. Magn Reson Med 47:1077–1082, 2002. © 2002 Wiley‐Liss, Inc.
Volume tracking cardiac 31P spectroscopy
Authors: Kozerke Sebastian , Schär Michael , Lamb Hildo J. , Boesiger Peter
Published: October 2002

The limited reliability and accuracy of cardiac spectroscopy have been partly attributed to effects from respiratory motion. In this work, we developed a prospective volume tracking method for respiratory motion compensation based on multiple navigator echoes and demonstrated its application in cardiac 31P spectroscopy. The sequence consists of two 2D selective excitation pulses preceding the spectroscopic experiment to sample respiratory motion components. The navigator information is evaluated in real‐time to calculate the shift of the heart from respiration. Based on the displacement information, the spectroscopic volume and/or grid position is prospectively corrected to track the volume of interest. The method was validated with a moving compartment phantom simulating in vivo respiratory motion. With volume tracking, no signal contamination was apparent. Spectra obtained in 14 healthy volunteers were evaluated using time‐domain fitting procedures. The fitting accuracy improved consistently with volume tracking compared to data from non‐navigated reference acquisitions. Compared to other gating approaches available for spectroscopy, the current technique does not degrade the scan efficiency, thus allowing effective use of scan time. Magn Reson Med 48:380–384, 2002. © 2002 Wiley‐Liss, Inc.
Gastrointestinal transit times in mice and humans measured with 27Al and 19F nuclear magnetic resonance
Authors: Schwarz Roman , Kaspar Armin , Seelig Joachim , Künnecke Basil
Published: October 2002

Gastric emptying and gastrointestinal (GI) transit times in mice and humans were monitored noninvasively by using 27Al and 19F nuclear magnetic resonance (NMR). Al3+ bound to ion‐exchange resin and perfluorononane were administered orally as selective and specific markers for the stomach and the entire GI tract, respectively. 27Al‐ and 19F‐MR spectroscopy (MRS) was employed to follow quantitatively boli of the mixed markers in awake, fed mice over a period of 48 hr. The selectivity of the markers was confirmed by whole‐body 1H‐, 27Al‐, and 19F‐MRI of anesthetized mice. Gastric emptying in humans was also monitored with 27Al‐MRS of aluminum‐loaded ion exchange resin. GI transit was assessed by 19F projection imaging of pharmaceutical capsules tagged with perfluorononane. Quantitative analysis of the MR data revealed that gastric emptying in humans proceeded linearly, whereas in mice an exponential decay was observed. This difference is explained by the respective feeding patterns of humans and mice. Humans usually achieve nearly complete gastric emptying before each meal. In contrast, very short delays between successive food intakes in small animals result in successive dilution of the stomach contents. For stomach emptying in mice the exponential decay constant was 74 min, whereas the half‐time of the linear gastric emptying in humans was 30 min. Magn Reson Med 48:255–261, 2002. © 2002 Wiley‐Liss, Inc.
In vivo GABA+ measurement at 1.5T using a PRESS‐localized double quantum filter
Authors: McLean M.A. , Busza A.L. , Wald L.L. , Simister R.J. , Barker G.J. , Williams S.R.
Published: October 2002

A point‐resolved spectroscopy (PRESS)‐localized double quantum filter was implemented on a 1.5T clinical scanner for the estimation of γ‐amino butyric acid (GABA) concentrations in vivo. Several calibrations were found to be necessary for consistent results to be obtained. The apparent filter yield was approximately 38%; filter strength was sufficient to reduce the singlet metabolite peaks in vivo to below the level of the noise. Metabolite‐nulled experiments were performed, which confirmed that significant overlap occurred between macromolecule signals and the GABA resonance at 3.1 ppm. Although the multiplet arm at 2.9 ppm was confirmed to be relatively free of contamination with macromolecules, some contribution from these and from peptides is likely to remain; therefore, the term GABA+ is used. GABA+ concentrations were estimated relative to creatine (Cr) at the same echo time (TE) in a group of controls, studied on two occasions. The GABA+ concentration in 35‐ml regions of interest (ROIs) in the occipital lobe was found to be 1.4 ± 0.2 mM, with scan‐rescan repeatability of 38%. Magn Reson Med 48:233–241, 2002. © 2002 Wiley‐Liss, Inc.
Impact of initial muscle length on force deficit following lengthening contractions in mammalian skeletal muscle
Authors: Gosselin Luc E. , Burton Harold
Published: October 2002

The purpose of this study was to determine whether initial muscle length influenced the extent of isometric force deficit following 20 in vitro lengthening contractions of the soleus muscle from Fischer 344 rats. Force deficit was evaluated following one of five protocols: (1) lengthening contractions from optimal muscle length (Lo) to 120% Lo; (2) lengthening contractions from 80% Lo to Lo; (3) lengthening contractions from Lo to 120% Lo but with a stimulation frequency that elicited the same force as protocol 2; (4) 20 isometric contractions at Lo; (5) 20 stretches ± 20% Lo in inactive muscle. Following lengthening contractions, extent of force deficit significantly differed between protocols 1, 2, and 3 (P < 0.05). Maximal isometric force (Po) was decreased by ∼32%, ∼8%, and ∼15% in protocols 1, 2, and 3, respectively. In contrast, neither isometric contractions nor passive stretching (protocols 4 and 5) resulted in any reduction in Po. Irrespective of muscle length, the extent of force deficit was highly correlated (R = −0.774, P < 0.001) with peak force during active lengthening. Thus, the magnitude of isometric force deficit following lengthening contractions is influenced by both initial muscle length and peak force development. These findings have important practical implications for both exercise conditioning and rehabilitation, which are discussed. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Molecular analysis of the superoxide dismutase 1 gene in Spanish patients with sporadic or familial amyotrophic lateral sclerosis
Authors: García‐Redondo A. , Bustos F. , Juan Y Seva B. , Del Hoyo P. , Jiménez S. , Campos Y. , Martín M. A. , Rubio J.C. , Cañadillas F. , Arenas J. , Esteban J.
Published: October 2002

We performed a genetic analysis of the Cu/Zn superoxide dismutase gene (SOD1) in Spanish patients with sporadic or familial amyotrophic lateral sclerosis (ALS). We found mutations in 2 of 11 families (18%) with ALS. In addition, 1 of the 87 sporadic ALS patients studied harbored a mutation in the same gene. We identified G37R in exon 2 of the SOD1 gene in 1 family. Another patient, with sporadic ALS, showed a novel N65S in exon 3. In addition, we found a novel I112M in exon 4 in another family. Our data highlight the genetic heterogeneity of patients with ALS harboring mutations in the SOD1 gene and confirm that families with autosomal dominant inheritance of the trait, regardless of their ethnic background, are more likely to carry mutations in such a gene. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 274–278, 2002
Effect of moderate dehydration on torque, electromyography, and mechanomyography
Authors: Evetovich Tammy K. , Boyd Joseph C. , Drake Shawn M. , Eschbach Lawrence C. , Magal Meir , Soukup Jeffrey T. , Webster Michael J. , Whitehead Malcolm T. , Weir Joseph P.
Published: October 2002

The purpose of the present investigation was to test the hypotheses that the mechanomyographic (MMG) signal would be affected by hydration status due to changes in the intra‐ and extracellular fluid content (which could affect the degree of fluid turbulence), changes in the filtering properties of the tissues between the MMG sensor and muscle, and changes in torque production that may accompany dehydration. Ten subjects (age 22.5 ± 1.6 years) were tested for maximal isometric (MVC), submaximal isometric (25, 50, and 75%MVC), and maximal concentric isokinetic muscle strength of the biceps brachii in either a euhydrated or dehydrated state while the electromyographic (EMG) and MMG signals were recorded. Separate three‐way and two‐way ANOVAs indicated no change in torque, EMG amplitude, EMG mean power frequency (MPF), MMG amplitude, and MMG MPF with dehydration. The lack of dehydration effect suggests that MMG may be more reflective of the intrinsic contractile processes of a muscle fiber (torque production) or the motor control mechanisms (reflected by the EMG) than the tissues and fluids surrounding the muscle fiber. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 225–231, 2002
Identification of non‐linear stress–strain–time relationship of soils using genetic algorithm
Authors: Feng Xia‐Ting , Li Shaojun , Liao Hongjian , Yang Chengxiang
Published: October 2002

Recognition of non‐linear constitutive rock/soil model from experimental results is often multi‐modal in the large parameter space. A genetic evolution algorithm is thus proposed for its recognition, including that of structure of the model and coefficients in the model. The structure of the model can be firstly determined according to mechanical mechanism if the mechanism is clearly understood or searched by using evolutionary algorithm. The coefficients to be determined are then searched in global optional space. With the new evolutionary algorithm, the non‐linear stress–strain–time constitutive law to describe strain softening behaviours of diatomaceous soil under consolidated and undrained state was recognized by learning stress–strain–time behaviour of an intact sample under consolidated pressure of σc=0.1 MPa and strain velocity ofa=0.175%/min. This model gave reasonable prediction for diatomaceous soils under varying consolidated pressures (0.1–3.5 MPa) and strain velocities (0.0044–1.75%/min). It indicates that the methodology proposed in this paper is robust enough and strongly attractive for recognition of non‐linear constitutive model of soil and rock materials. Copyright © 2002 John Wiley & Sons, Ltd.
On the availability of R out of N repairable systems
Authors: Frostig Esther , Levikson Benny
Published: October 2002

An R out of N repairable system consisting of N components and operates if at least R components are functioning. Repairable means that failed components are repaired, and upon repair completion they are as good as new. We derive formulas for the expected up‐time, expected down‐time, and the availability of the system, using Markov renewal processes. We assume that either the repair times of the components are generally distributed and the components' lifetimes are exponential or vice versa. The analysis is done for systems with either cold or warm stand‐by. Numerical examples are given for several life time and repair time distributions. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 483–498, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10025
Evidence for species differences in the pattern of androgen receptor distribution in relation to species differences in an androgen‐dependent behavior
Authors: Shaw Brian K. , Kennedy Grace G.
Published: October 2002

Chickens (Gallus gallus domesticus) and Japanese quail (Coturnix japonica), two closely related gallinaceous bird species, exhibit a form of vocalization—crowing—which differs between the species in two components: its temporal acoustic pattern and its accompanying postural motor pattern. Previous work utilizing the quail‐chick chimera technique demonstrated that the species‐specific characteristics of the two crow components are determined by distinct brain structures: the midbrain confers the acoustic pattern, and the caudal hindbrain confers the postural pattern. Crowing is induced by androgens, acting directly on androgen receptors. As a strategy for identifying candidate neurons in the midbrain and caudal hindbrain that could be involved in crow production, we performed immunocytochemistry for androgen receptors in these brain regions in both species. We also investigated midbrain‐to‐hindbrain vocal‐motor projections. In the midbrain, both species showed prominent androgen receptor immunoreactivity in the nucleus intercollicularis, as had been reported in previous studies. In the caudal hindbrain, we discovered characteristic species differences in the pattern of androgen receptor distribution. Chickens, but not quail, showed strong immunoreactivity in the tracheosyringeal division of the hypoglossal nucleus, whereas quail, but not chickens, possessed strong immunoreactivity in a region of the ventrolateral medulla. Some of these differences in hindbrain androgen receptor distribution may be related to the species differences in the postural component of crowing behavior. The results of the present study imply that the spatial distribution of receptor proteins can vary even between closely related species. Such variation in receptor distribution could underlie the evolution of species differences in behavior. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 203–220, 2002
Presynaptic adenosine A1 receptors regulate retinohypothalamic neurotransmission in the hamster suprachiasmatic nucleus
Authors: Hallworth Richard , Cato Matthew , Colbert Costa , Rea Michael A.
Published: October 2002

Adenosine has been implicated as a modulator of retinohypothalamic neurotransmission in the suprachiasmatic nucleus (SCN), the seat of the light‐entrainable circadian clock in mammals. Intracellular recordings were made from SCN neurons in slices of hamster hypothalamus using the in situ whole‐cell patch clamp method. A monosynaptic, glutamatergic, excitatory postsynaptic current (EPSC) was evoked by stimulation of the optic nerve. The EPSC was blocked by bath application of the adenosine A1 receptor agonist cyclohexyladenosine (CHA) in a dose‐dependent manner with a half‐maximal concentration of 1.7 μM. The block of EPSC amplitude by CHA was antagonized by concurrent application of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX). The adenosine A2A receptor agonist CGS21680 was ineffective in attenuating the EPSC at concentrations up to 50 μM. Trains of four consecutive stimuli at 25 ms intervals usually depressed the EPSC amplitude. However, after application of CHA, consecutive responses displayed facilitation of EPSC amplitude. The induction of facilitation by CHA suggested a presynaptic mechanism of action. After application of CHA, the frequency of spontaneous EPSCs declined substantially, while their amplitude distribution was unchanged or slightly reduced, again suggesting a mainly presynaptic site of action for CHA. Application of glutamate by brief pressure ejection evoked a long‐lasting inward current that was unaffected by CHA at concentrations sufficient to reduce the evoked EPSC amplitude substantially (1 to 5 μM), suggesting that postsynaptic glutamate receptor‐gated currents were unaffected by the drug. Taken together, these observations indicate that CHA inhibits optic nerve‐evoked EPSCs in SCN neurons by a predominantly presynaptic mechanism. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 230–240, 2002
On the formulation of closest‐point projection algorithms in elastoplasticity—part I: The variational structure
Authors: Armero F. , Pérez‐Foguet A.
Published: October 2002

We present in this paper the characterization of the variational structure behind the discrete equations defining the closest‐point projection approximation in elastoplasticity. Rate‐independent and viscoplastic formulations are considered in the infinitesimal and the finite deformation range, the later in the context of isotropic finite‐strain multiplicative plasticity. Primal variational principles in terms of the stresses and stress‐like hardening variables are presented first, followed by the formulation of dual principles incorporating explicitly the plastic multiplier. Augmented Lagrangian extensions are also presented allowing a complete regularization of the problem in the constrained rate‐independent limit. The variational structure identified in this paper leads to the proper framework for the development of new improved numerical algorithms for the integration of the local constitutive equations of plasticity as it is undertaken in Part II of this work. Copyright © 2001 John Wiley & Sons, Ltd.
Three‐dimensional time‐harmonic Green's functions for a triclinic full‐space using a symbolic computation system
Authors: Dravinski Marijan , Niu Yuqing
Published: October 2002

Time‐harmonic Green's functions for a triclinic anisotropic full‐space are evaluated through the use of a symbolic computation system.This procedure allows evaluation of the Green's functions for the most general anisotropic materials. The proposed computational algorithms are programmed in a MATLAB environment by incorporating symbolic calculations performed using Maple Computer Algebra System. Extensive testing of the numerical results has been performed for both displacement and stress fields. The tests demonstrate the accuracy of the proposed algorithm in evaluating the Green's functions. Copyright © 2001 John Wiley & Sons, Ltd.
Comparison of method of lines and finite difference solutions of 2‐D Navier–Stokes equations for transient laminar pipe flow
Authors: Selçuk Nevin , Tarhan Tanıl , Tanrıkulu Songül
Published: October 2002

Performances of method of lines (MOL) and finite difference method (FDM) were tested from the viewpoints of solution accuracy and central processing unit (CPU) time by applying them to the solution of time‐dependent 2‐D Navier–Stokes equations for transient laminar flow without/with sudden expansion and comparing their results with steady‐state numerical predictions and measurements previously reported in the literature. Predictions of both methods were obtained on the same computer by using the same order of spatial discretization and the same uniform grid distribution. Axial velocity and pressure distribution in pipe flow and steady‐state reattachment lengths in sudden expansion flow on uniform grid distribution predicted by both methods were found to be in excellent agreement. Transient solutions of both methods for pipe flow problem show favourable comparison and are in accordance with expected trends. However, non‐physical oscillations were produced by both methods in the transient solution of sudden expansion pipe flow. MOL was demonstrated to yield non‐oscillatory solutions for recirculating flows when intelligent higher‐order discretization scheme is utilized for convective terms. MOL was found to be superior to FDM with respect to CPU and set‐up times and its flexibility for incorporation of other conservation equations. Copyright © 2001 John Wiley & Sons, Ltd.
Development of shear locking‐free shell elements using an enhanced assumed strain formulation
Authors: César de Sá José M. A. , Natal Jorge Renato M. , Fontes Valente Robertt A. , Almeida Areias Pedro M.
Published: October 2002

The degenerated approach for shell elements of Ahmad and co‐workers is revisited in this paper. To avoid transverse shear locking effects in four‐node bilinear elements, an alternative formulation based on the enhanced assumed strain (EAS) method of Simo and Rifai is proposed directed towards the transverse shear terms of the strain field. In the first part of the work the analysis of the null transverse shear strain subspace for the degenerated element and also for the selective reduced integration (SRI) and assumed natural strain (ANS) formulations is carried out. Locking effects are then justified by the inability of the null transverse shear strain subspace, implicitly defined by a given finite element, to properly reproduce the required displacement patterns. Illustrating the proposed approach, a remarkably simple single‐element test is described where ANS formulation fails to converge to the correct results, being characterized by the same performance as the degenerated shell element. The adequate enhancement of the null transverse shear strain subspace is provided by the EAS method, enforcing Kirchhoff hypothesis for low thickness values and leading to a framework for the development of shear‐locking‐free shell elements. Numerical linear elastic tests show improved results obtained with the proposed formulation. Copyright © 2001 John Wiley & Sons, Ltd.
Meshfree analysis and design sensitivity analysis for shell structures
Authors: Kim Nam Ho , Choi Kyung Kook , Chen Jiun‐Shyan , Botkin Mark E.
Published: October 2002

A unified design sensitivity analysis method for a meshfree shell structure with respect to size, shape, and configuration design variables is presented in this paper. A shear deformable shell formulation is characterized by a CAD connection, thickness degeneration, meshfree discretization, and nodal integration. Because of a strong connection to the CAD tool, the design variable is selected from the CAD parameters, and a consistent design velocity field is then computed by perturbing the surface geometric matrix. The material derivative concept is utilized in order to obtain a design sensitivity equation in the parametric domain. Numerical examples show the accuracy and efficiency of the proposed design sensitivity analysis method compared to the analytical solution and the finite difference solution. Copyright © 2002 John Wiley & Sons, Ltd.
A contact formulation based on localized Lagrange multipliers: formulation and application to two‐dimensional problems
Authors: Rebel G. , Park K. C. , Felippa C. A.
Published: October 2002

The non‐penetration condition in contact problems is traditionally based on the classical Lagrange multiplier method. This method makes extensive use of modelling details of the contacting bodies for contact enforcement as the contact surface meshes are in general non‐matching. To deal with this problem we introduce a novel element in the Lagrange multiplier approach of contact modelling, namely, a contact frame placed in between contacting bodies. It acts as a medium through which contact forces are transferred without violating equilibrium in the contact domain for discrete contact models. Only nodal information of the contacting bodies is required which makes the proposed contact enforcement generic. The contact frame has its own independent freedoms, which allows the formulation to pass contact patch tests by design. Copyright © 2002 John Wiley & Sons, Ltd.
Numerical modelling of shear bands by element bands
Authors: Wang X. , Chan D. , Morgenstern N.
Published: October 2002

It is presently a concern and challenge to numerically model shear band localization. Many numerical methods have been developed to take into account the strain and displacement discontinuities across a shear band. In this paper, a contact band element method is proposed to model the shear band with a finite thickness under large shear deformation. The shear band elements, alternatively called contact band elements, are continuously updated based on their current configurations to prevent the large distortions of conventional finite elements and maintain realistic shear band configurations. The contact band element method, with a technique for the special shear band element, consists of the schemes to keep the shear band elements in good shapes, handle the band overlapping, kinking and separation problems. A few examples have shown that the contact band element method is a very efficient way to model the shear bands under large shear deformation. Copyright © 2002 John Wiley & Sons, Ltd.
A 3D contact smoothing method using Gregory patches
Authors: Puso Michael Anthony , Laursen Tod A.
Published: October 2002

In this work, a method is developed for smoothing three‐dimensional contact surfaces. The method can be applied to both regular and irregular meshes. The algorithm employs Gregory patches to interpolate finite element nodes and provide tangent plane continuity between adjacent patches. The resulting surface interpolation is used to calculate gaps and contact forces, in a variationally consistent way, such that contact forces due to normal and frictional contact vary smoothly as slave nodes transition from one patch to the next. This eliminates the ‘chatter’ which typically occurs in a standard contact algorithm when a slave node is situated near a master facet edge. The elimination of this chatter provides a significant improvement in convergence behaviour, which is illustrated by a number of numerical examples. Furthermore, smoothed surfaces also provide a more accurate representation of the actual surface, such that resulting stresses and forces can be more accurately computed with coarse meshes in many problems. This fact is also demonstrated by the numerical examples. Published in 2002 by John Wiley & Sons, Ltd.
Adaptive hierarchical enrichment for delamination fracture using a decohesive zone model
Authors: Crisfield M. A. , Alfano G.
Published: October 2002

The paper describes a method for modelling delamination in fibre‐reinforced composite structures with the aid of a decohesive zone model and interface elements. Unless a fine mesh is provided, the resulting load/deflection responses are very non‐smooth and the iterative non‐linear solution procedure may fail. To overcome this problem, the elements around the softening process zone are enriched with hierarchical polynomial functions. The enriched zones change as the analysis proceeds and the cracks propagate. This procedure is implemented using a technique which continually modifies the boundary conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Allelic imbalance analysis of chromosome 16q shows that grade I and grade III invasive ductal breast cancers follow different genetic pathways
Authors: Roylance Rebecca , Gorman Patricia , Hanby Andrew , Tomlinson Ian
Published: October 2002

It remains controversial as to whether low‐ and high‐grade invasive ductal breast cancers are related by progression through grade, or generally follow distinct genetic pathways. It has previously been shown by comparative genomic hybridization (CGH) that the latter is more likely to be correct, based on the high frequency of chromosome 16q deletion in grade I cancers, but not in grade III. This study used microsatellite markers on 16q to confirm the differences between grade I and grade III tumours and to exclude the possibility that grade III tumours generally arise from grade I tumours through a process involving regain of 16q. The concordance between the CGH and microsatellite data is good but imperfect, probably reflecting the different sensitivities and specificities of the two techniques and the varying mechanisms of allele loss in each tumour type. Copyright © 2002 John Wiley & Sons, Ltd.
VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma
Authors: Schraml Peter , Struckmann Kirsten , Hatz Florian , Sonnet Stefan , Kully Charlotte , Gasser Thomas , Sauter Guido , Mihatsch Michael J. , Moch Holger
Published: October 2002

Mutations of the von Hippel‐Lindau (VHL) gene are considered critical for the initiation of clear cell renal cell carcinoma. The VHL protein is involved in regulation of the cell cycle and neo‐vascularization. In this study, the association of VHL mutations with tumour cell proliferation, angiogenesis, and clinical outcome was analysed in 113 clear cell renal cell carcinomas. The degree of angiogenesis and tumour cell proliferation was immunohistochemically determined by counting microvessels (microvessel density, anti‐CD34 antibody) and cells with proliferating activity (Ki‐67 labelling index, MIB‐1 antibody). Forty‐eight different VHL sequence alterations were found in 38 of 113 patients (34%) by direct sequencing. Nineteen VHL mutations were frameshifts and nonsense mutations, predicted to change the open reading frame of VHL. These ‘loss‐of‐function’ mutations correlated with worse prognosis in univariate analysis (p=0.02). Tumour grade, stage, microvessel density, and tumour cell proliferation were not associated with VHL alterations. These findings may indicate that ‘loss‐of‐function’ VHL mutations are involved in the progression of a clear cell renal cell carcinoma subset, whereas regulation of angiogenesis and proliferation of renal carcinoma in vivo is apparently not directly influenced by VHL alterations. Copyright © 2001 John Wiley & Sons, Ltd.
Expression of Bcl‐x, Bcl‐2, Bax, and Bak in endarterectomy and atherectomy specimens
Authors: Saxena A. , McMeekin J. D. , Thomson D. J.
Published: October 2002

The regulation of apoptosis in atherosclerosis is not completely defined. The aim of this study was to determine the expression of Bcl‐2, Bcl‐x, Bax, and Bak in relation to apoptosis in advanced atherosclerotic lesions. In atherectomy (15), endarterectomy (10), and control non‐atherosclerotic segments of renal (2) and of coronary and carotid (5) arteries, the extent of apoptosis was determined using TdT dUTP nick end labelling (TUNEL) and nuclear morphology (karyorrhexis/pyknosis) and expression of apoptosis regulators by immunohistochemistry and western blot analysis on paraffin‐embedded material. In all specimens, the atherosclerotic involvement was advanced: grade V (n=18) and grade VI (n=7). The apoptotic index was high (mean 30%) in advanced lesions compared with controls (<2%) and smooth muscle cells (SMCs) were the predominant cell type undergoing apoptosis. In all TUNEL‐positive apoptotic cells, Bax and Bak were present, while Bcl‐x was absent. Bcl‐2 was absent in a majority of these cells, but occasional TUNEL‐positive cells expressed Bcl‐2. In non‐apoptotic cells, Bcl‐x was present and western blot detected only the long isoform, Bcl‐xL, from the plaques. In conclusion, increased Bax and Bak coupled with lack/paucity of Bcl‐2 and Bcl‐xL are associated with SMC apoptosis in advanced lesions. Bcl‐xL in non‐apoptotic cells appears to contribute to prolonged cell survival. Copyright © 2002 John Wiley & Sons, Ltd.
Macrophages expressing the scavenger receptor CD163: a link between immune alterations of the gut and synovial inflammation in spondyloarthropathy
Authors: Baeten Dominique , Demetter Pieter , Cuvelier Claude A. , Kruithof Elli , Van Damme Nancy , De Vos Martine , Veys Eric M. , De Keyser Filip
Published: October 2002

The objective of this study was to investigate CD163+ macrophages in the synovial membrane of patients with spondyloarthropathy (SpA). Immunohistochemistry was performed on synovium of 17 SpA and 18 rheumatoid arthritis (RA) patients, on colonic biopsies of 16 SpA patients and ten healthy controls, and on paired synovial biopsies of eight SpA patients, before and after anti‐TNFα therapy. Phenotype and cytokine production were analysed by flow cytometry. CD163+ macrophages were increased in the synovial lining and sublining in SpA versus RA, as well as in colonic lamina propria in SpA versus controls. The number of CD163+ macrophages in the synovial sublining correlated with C‐reactive protein levels and erythrocyte sedimentation rate. Paralleling the increase of CD163, HLA‐DR was increased in the synovial lining and sublining of SpA. In contrast, the co‐stimulatory molecules CD80 and CD86 and the dendritic cell markers CD1a and CD83 were scarce in SpA synovium. Flow cytometry indicated that CD163+ macrophages expressed high levels of HLA‐DR and could produce in vitro tumour necrosis factor α (TNFα) but not interleukin‐10 (IL‐10). Finally, anti‐TNFα therapy in vivo induced a decrease of CD163+ macrophages in the synovial lining and sublining. In conclusion, macrophages expressing the scavenger receptor CD163 are increased in synovium and in colonic mucosa in SpA, highlighting the relationship between joint and gut in this disease. The correlation with inflammatory parameters, the expression of HLA‐DR, the production of TNFα but not IL‐10, and the reduction by anti‐TNFα therapy support a role for CD163+ macrophages in the synovial inflammation in SpA. Copyright © 2002 John Wiley & Sons, Ltd.
Involvement of the Fas/FasL pathway in the pathogenesis of germ cell tumours of the adult testis
Authors: Kersemaekers Anne‐Marie F. , van Weeren Pascale C. , Wolter Oosterhuis J. , Looijenga Leendert H. J.
Published: October 2002

Induction of apoptosis by Fas ligand (FasL) of Fas‐containing cells is a known mechanism involved in the eradication of inappropriate cells during normal development. Alterations of the Fas/FasL pathway have been found in various types of cancer, leading to circumvention of attack of the tumour by the immune system. An alternative way to circumvent eradication by induction of apoptosis is through changes in the downstream inhibitors. For example, Fas‐associating phosphatase‐1 (Fap‐1) binds directly to the Fas receptor and results in a block of the downstream signalling. To shed more light on the role of the Fas/FasL pathway in the development of human testicular germ cell tumours of the adult testis, this study investigated the presence of Fas, FasL, Fap‐1, HLA class I and II molecules, CD45 (lymphocyte marker), and CD57 [natural killer (NK) cell marker] by immunohistochemistry on frozen sections of 41 cases of seminomas, non‐seminomas, and spermatocytic seminomas. Every germ cell tumour was positive for Fap‐1 and negative for HLA classes I and II, like their non‐malignant cells of origin. The infiltrating lymphocytes, predominantly present in seminomas, showed consistently positive staining for Fas and CD45, but not for Fap‐1. No Fas was found on NK cells. All seminomas and non‐seminomas (except teratomas), including their precursor stages, carcinoma in situ, intratubular seminoma and intratubular non‐seminoma, showed positive staining for FasL, but not for Fas. Teratoma showed no staining for FasL and was positive for Fas. In contrast, both Fas and FasL were detectable on spermatocytic seminoma. These data indicate a different regulation of the Fas/FasL system in seminoma and spermatocytic seminoma, supporting a separate pathogenesis for these germ cell‐derived tumours. The presence of Fap‐1 in all histological variants of germ cell tumours might be related to the consistently positive staining in cells of the germ lineage. This study indicates that production of FasL by the germ cell tumour cells might be involved in the early development of these types of adult testicular cancer by inducting apoptosis of Fas‐positive, Fap‐1‐negative tumour‐infiltrating lymphocytes. Copyright © 2002 John Wiley & Sons, Ltd.
Value of tissue markers p27kip1, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer
Authors: Vis A. N. , van Rhijn B. W. G. , Noordzij M. A. , Schröder F. H. , van der Kwast Th. H.
Published: October 2002

The pre‐operative prediction of prognostic tumour features in the radical prostatectomy specimen using routine clinicopathological variables remains limited. The present study evaluated the predictive value of the cell‐cycle protein p27kip1, the proliferation marker MIB‐1, and the cell‐adhesion protein CD44s, determined on the diagnostic needle biopsy of asymptomatic men screened for prostate cancer. Of 81 screen‐detected prostate cancers, representative biopsy cores and matched radical prostatectomy specimens were immunohistochemically stained for these tissue markers. Conventional pre‐operative and post‐operative clinicopathological variables were assessed and cancers were divided according to a validated tumour classification model (potentially harmless, clinically significant). Low (<50%) p27kip1 expression, high (≥10%) MIB‐1 expression, and low (<25%) CD44s expression were considered adverse prognostic signs. Binary logistic regression analysis was performed to assess the most valuable predictors of clinically significant disease. An adverse prognostic immunostaining assessment on the biopsy was found in 10 (12.3%), 17 (21.0%), and 25 (30.9%) cases for p27kip1, MIB‐1, and CD44s, respectively. The concordance in tissue marker assessment between the biopsy specimen and matched radical prostatectomy specimens was low for all three. The positive predictive value (PPV) of p27kip1 was 90.0%, remarkably higher than that of MIB‐1 and CD44s (41.2% and 52.0%, respectively), indicating that a low radical prostatectomy p27kip1 score is expected if the biopsy p27kip1 score is low. Logistic regression analysis revealed that biopsy Gleason score (p<0.01) and p27kip1 assessment (p<0.01) remained the only significant predictors of clinically significant disease. All cases with low p27kip1 expression were found to have clinically significant disease after radical prostatectomy. The assessment of p27kip1 in the biopsy specimen might thus assist in distinguishing between potentially aggressive and potentially non‐aggressive disease in prostate cancer screening. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of histological features associated with metastatic potential in thin (<1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group
Authors: Cook Martin G. , Spatz Alain , Bröcker Eva‐Bettina , Ruiter Dirk J.
Published: October 2002

An Erratum has been published for this article in The Journal of Pathology 197(5) 2002, 692.

Contrary to expectations, a small number of thin (<1 mm) melanomas do metastasize. This collaborative study was performed in an attempt to identify the morphological basis of such aggressive behaviour. Regression was expected to be the explanation for the lack of thickness in some cases. Whether a vertical growth phase (VGP) was present in the remainder was carefully assessed. A pilot study had identified two other patterns associated with metastasis in thin melanomas. These were termed ‘junctional expansion nodules’ and ‘melanomatous follicular invasion’. Both were seen in the absence of other dermal invasion. These two patterns were included in the study, which comprised 54 cases and 56 controls, which were thin melanomas which had not metastasized 5 years after excision. Regression was present in 50% of test cases (30.4% in controls, p=0.036) and VGP was present in 59.3% of cases and 48.2% of controls. The thinnest metastasizing melanoma without regression was 0.27 mm. Eight (14.8%) cases, however, had metastasized but showed neither regression nor VGP; seven of these showed a junctional expansion nodule, present in only three controls (p=0.016). Five of these seven also showed melanomatous follicular invasion. One of these five showed this follicular involvement without a junctional nodule. Melanomatous follicular invasion was not seen in the control cases (p=0.012). Mitoses were seen in the VGP of both test and control cases, but high counts (>3 per mm2) were much more common in the metastasizing lesions (p=0.007). These findings support the idea that in most cases, regression and/or a VGP are required for metastasis to occur. However, a small number of thin melanomas without these features, as conventionally described, still metastasize. This implies that VGP may require redefinition and that junctional expansion nodules and melanomatous follicular invasion may be variants of VGP. Copyright © 2002 John Wiley & Sons, Ltd.
Herpesviruses in brain and Alzheimer's disease
Authors: Lin Woan‐Ru , Wozniak Matthew A. , Cooper Robert J. , Wilcock Gordon K. , Itzhaki Ruth F.
Published: October 2002

It has been established, using polymerase chain reaction (PCR), that herpes simplex virus type 1 (HSV1) is present in a high proportion of brains of elderly normal subjects and Alzheimer's disease (AD) patients. It was subsequently discovered that the virus confers a strong risk of AD when in brain of carriers of the type 4 allele of the apolipoprotein E gene (apoE‐ε4). This study has now sought, using PCR, the presence of three other herpesviruses in brain: human herpesvirus 6 (HHV6)—types A and B, herpes simplex virus type 2 (HSV2) and cytomegalovirus (CMV). HHV6 is present in a much higher proportion of the AD than of age‐matched normal brains (70% vs. 40%, p=0.003) and there is extensive overlap with the presence of HSV1 in AD brains, but HHV6, unlike HSV1, is not directly associated in AD with apoE‐ε4. In 59% of the AD patients' brains harbouring HHV6, type B is present while 38% harbour both type A and type B, and 3% type A. HSV2 is present at relatively low frequency in brains of both AD patients and normals (13% and 20%), and CMV at rather higher frequencies in the two groups (36% and 35%); in neither case is the difference between the groups statistically significant. It is suggested that the striking difference in the proportion of elderly brains harbouring HSV1 and HSV2 might reflect the lower proportion of people infected with the latter, or the difference in susceptibility of the frontotemporal regions to the two viruses. In the case of HHV6, it is not possible to exclude its presence as an opportunist, but alternatively, it might enhance the damage caused by HSV1 and apoE‐ε4 in AD; in some viral diseases it is associated with characteristic brain lesions and it also augments the damage caused by certain viruses in cell culture and in animals. Copyright © 2002 John Wiley & Sons, Ltd.