bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of electromechanical events in defining skeletal muscle properties
Authors: Roy Roland R. , Zhong Hui , Hodgson John A. , Grossman Elena J. , Siengthai Boonclaire , Talmadge Robert J. , Edgerton V. Reggie
Published: October 2002

Inactivity of the cat soleus muscle was induced via spinal cord isolation (SI), and the cats were maintained for 4 months. The soleus was electrically stimulated while lengthening (SI‐L) or shortening (SI‐S) during a simulated step cycle or during isometric (SI‐I) contractions. For the SI, SI‐S, SI‐L, and SI‐I groups, the soleus weights were 33, 55, 55, and 64% of the control, respectively, and the maximum tetanic tensions were 15, 30, 36, and 44% of the control, respectively. The specific tension was lower in all SI groups than in the control. Absolute forces at stimulation frequencies of 5–200 Hz were smaller in all SI groups than in the control. The SI‐I group tended to have higher values for all force‐related parameters than the other SI groups. Fatigue resistance was similar among all groups. The isometric twitch time‐to‐peak tension was shorter, and the frequency of the stimulation–tension response was shifted to the right in all SI groups with respect to the control. Maximum shortening velocities were 70, 59, and 73% faster for the SI, SI‐S, and SI‐L groups and similar to the control for the SI‐I group. Inactivity resulted in an increased percentage of faster myosin heavy chains (MHCs) that was blunted in the SI‐I and SI‐L groups but not in the SI‐S group. Pure type I MHC fibers atrophied by 80, 59, 58, and 47% in the SI, SI‐S, SI‐L, and SI‐I groups. The data from the SI group quantify the contribution of activity‐independent factors in maintaining the mechanical and phenotypic properties of the cat soleus. Relative to a fast‐fatigable muscle, these results suggest that only 25% of the slowness (type I MHC) and none of the resistance to fatigue of the soleus muscle are dependent on activity‐related factors. Short, daily bouts of electromechanical activation ameliorated several of these adaptations, with the isometric contractions being the most effective countermeasure. The clinical implications of these findings for rehabilitation strategies are discussed. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26:238–251, 2002
Modelling of elastoplastic damage in concrete due to desiccation shrinkage
Authors: Bourgeois F. , Burlion N. , Shao J. F.
Published: October 2002

We present a numerical modelling of elastoplastic damage due to drying shrinkage of concrete in the framework of mechanics of partially saturated porous media. An elastoplastic model coupled with isotropic damage is first formulated. Two plastic flow mechanisms are involved, controlled by applied stress and suction, respectively. A general concept of net effective stress is used in take into account effects of capillary pressure and material damage on stress‐controlled plastic deformation. Damage evolution depends both on elastic and plastic strains. The model's parameters are determined or chosen from relevant experimental data. Comparisons between numerical simulations and experimental data are presented to show the capacity of model to reproduce mains features of concrete behaviour under mechanical loading and during drying shrinkage of concrete. An example of application concerning drying of a concrete wall is finally presented. The results obtained allow to show potential capacity of proposed model for numerical modelling of complex coupling processes in concrete structures. Copyright © 2002 John Wiley & Sons, Ltd.
Probabilistic analysis of underground pillar stability
Authors: Griffiths D. V. , Fenton Gordon A. , Lemons Carisa B.
Published: October 2002

The majority of geotechnical analyses are deterministic, in that the inherent variability of the materials is not modelled directly, rather some ‘factor of safety’ is applied to results computed using ‘average’ properties. In the present study, the influence of spatially varying strength is assessed via numerical experiments involving the compressive strength and stability of pillars typically used in underground construction and mining operations. The model combines random field theory with an elasto‐plastic finite element algorithm in a Monte‐Carlo framework. It is found that the average strength of the rock is not a good indicator of the overall strength of the pillar. The results of this study enable traditional approaches involving factors of safety to be re‐interpreted as a ‘probability of failure’ in the context of reliability based design. Copyright © 2002 John Wiley & Sons, Ltd.
Preprocessing Steiner problems from VLSI layout
Authors: Uchoa Eduardo , Poggi de Aragão Marcus , Ribeiro Celso C.
Published: October 2002

VLSI layout applications yield instances of the Steiner tree problem over grid graphs with holes, which are considered hard to be solved by current methods. In particular, preprocessing techniques developed for Steiner problems over general graphs are not likely to reduce, significantly, such VLSI instances. We propose a new preprocessing procedure, extending earlier ideas from the literature and improving their application, so as to make them effective for VLSI problems. We report significant reductions within reasonable computational times, obtained with the application of this procedure to 116 instances of the SteinLib. These reductions allowed a branch and cut to solve 28 of 32 open instances of the SteinLib, some with more than 10,000 vertices and 20,000 edges. © 2002 Wiley Periodicals, Inc.
Buckling optimization and antioptimization of composite plates: uncertain loading combinations
Authors: de Faria Alfredo R.
Published: October 2002

The problem of optimal design for elastic buckling loads of composite plates under uncertain loading conditions is considered. It is observed that this is a multicriterion optimization problem whose solution is time consuming. Thus, an alternative minimax formulation is proposed and demonstrated. The buckling load is maximized with respect to the structural parameters and minimized with respect to variations in the load parameters. The mechanical loads applied to the rectangular plates are a combination of normal compression and shear. Moreover, the admissible loading configurations belong to a convex hull which significantly enhances the optimization procedure. The consideration of an uncertainty degree in the mechanical loads leads to optimal designs which are inherently insensitive to perturbations and/or randomness in the applied loads. Copyright © 2001 John Wiley & Sons, Ltd.
Thermo‐elasto‐plastic finite element analysis of quasi‐state processes in Eulerian reference frames
Authors: Shanghvi J. Y. , Michaleris P.
Published: October 2002

An Eulerian finite element formulation for quasi‐state one way coupled thermo‐elasto‐plastic systems is presented. The formulation is suitable for modeling material processes such as welding and laser surfacing. In an Eulerian frame, the solution field of a quasi‐state process becomes steady state for the heat transfer problem and static for the stress problem. A mixed small deformation displacement elasto‐plastic formulation is proposed. The formulation accounts for temperature dependent material properties and exhibits a robust convergence. Streamline upwind Petrov–Galerkin (SUPG) is used to remove spurious oscillations. Smoothing functions are introduced to relax the non‐differentiable evolution equations and allow for the use of gradient (stiffness) solution scheme via the Newton–Raphson method. A 3‐dimensional simulation of a laser surfacing process is presented to exemplify the formulation. Results from the Eulerian formulation are in good agreement with results from the conventional Lagrangian formulation. However, the Eulerian formulation is approximately 15 times faster than the Lagrangian. Copyright © 2001 John Wiley & Sons, Ltd.
Conservation properties of a time FE method—part III: Mechanical systems with holonomic constraints
Authors: Betsch P. , Steinmann P.
Published: October 2002

A Galerkin‐based discretization method for index 3 differential algebraic equations pertaining to finite‐dimensional mechanical systems with holonomic constraints is proposed. In particular, the mixed Galerkin (mG) method is introduced which leads in a natural way to time stepping schemes that inherit major conservation properties of the underlying constrained Hamiltonian system, namely total energy and angular momentum. In addition to that, the constraints on the configuration level and on the velocity/momentum level are fulfilled exactly. The application of the mG method to specific mechanical systems such as the pendulum, rigid body dynamics and the coupled motion of rigid and flexible bodies is presented. Related numerical examples are investigated to evaluate the numerical performance of the mG(1) and mG(2) method. Copyright © 2002 John Wiley & Sons, Ltd.
Low‐frequency assessment of the in situ acoustic absorption of materials in rooms: an inverse problem approach using evolutionary optimization
Authors: Dutilleux Guillaume , Sgard Franck C. , Kristiansen Ulf R.
Published: October 2002

The in situ assessment of the acoustic absorption of materials is often a necessity. The need to cover the whole frequency range of interest for the building engineer has led the authors to an approach involving two frequency‐complementary measurement methods. This paper deals with the part dedicated to low frequencies. The measurement is defined here as a boundary inverse interior problem. A numerical model of the room under investigation, allowing for the computation of the pressure field in the volume, given impedance boundary conditions and a point source, is combined to a global optimization algorithm. The algorithm explores the set of possible boundary conditions in order to minimize the difference between the computed pressure values and the one observed at a few measurement points, leading to the determination of all the boundary conditions at a time. In practice, the finite element method (FEM) or the finite difference method (FDM) is used here to model the room and an Evolution Strategy as the optimization tool. After describing the ES operators, a numerical study is carried out on simulated measurements, both on problem‐ and algorithm‐specific parameters, in the case of an academic two‐dimensional room geometry. The method is then applied to a three‐dimensional room with promising results. Copyright © 2002 John Wiley & Sons, Ltd.
Constitutive modeling of cementitious materials in the framework of chemoplasticity
Authors: Lackner R. , Hellmich Ch. , Mang H. A.
Published: October 2002

In this paper, a multi‐surface plasticity model for chemically reactive media such as shotcrete is described. It consists of the Drucker‐Prager criterion for simulation of compressive failure and the Rankine criterion accounting for brittle material response under tensile loading. The material model is formulated in the principal stress space. The robustness of this formulation and, hence, the applicability of the proposed material model is demonstrated by means of the analysis of the Sieberg tunnel in Lower Austria. Insights into the structural response as well as the level of loading of the tunnel lining are given. Copyright © 2002 John Wiley & Sons, Ltd.
Buoyancy forces and the 2D finite element analysis of flexible offshore pipes and risers
Authors: Yazdchi M. , Crisfield M. A.
Published: October 2002

Many analysts use simple lower‐order beam elements for the non‐linear analysis of curved beam and arch structures. The aim of the present paper is to indicate how one may add the effects of buoyancy, steady‐state current loading and riser top‐tension to such an idealization so that it may be used for the analysis of offshore pipes and risers. The current work is restricted to static two‐dimensional modelling but it paves the way for further work in three dimensions, which will include dynamics. Copyright © 2002 John Wiley & Sons, Ltd
Modelling of failure mode transition in ballistic penetration with a continuum model describing microcracking and flow of pulverized media
Authors: Gailly Benjamin A. , Espinosa Horacio D.
Published: October 2002

An Erratum has been published for this article in International Journal for Numerical Methods in Engineering 2002; 55(4):499–501.

A new continuum model to describe damage, fragmentation and large deformation of pulverized brittle materials is presented. The multiple‐plane‐microcracking (MPM) model, developed by Espinosa, has been modified to track microcracking on 13 orientations under high pressure, high strain rate and high deformation. This model provides the elastic and inelastic response of the material before massive crack coalescence. When pulverization occurs, the constitutive response is modelled by means of a visco‐plastic model for granular material, which is a generalization to three dimensions of the double‐sliding theory augmented by a consolidation mechanism. The initialization of the granular model is governed by a yield surface at the onset of massive crack coalescence. This is accomplished by examining a representative volume element, modelled using the MPM model, in compression‐shear. The main advantage of this approach is to keep a continuum model at all stages of the deformation process and thus avoid the difficulties of crack representation in a discrete finite element code. This model has been implemented in LS‐DYNA and used to examine interface defeat of long rod penetrators by a confined ceramic plate. The numerical simulations are compared to experiments in order to identify failure modes. The model parameters were obtained independently by simulating plate and rod impact experiments. The proposed model captures most of the physical observations as well as failure mode transition, from interface defeat to full penetration, with increasing impact velocity. Copyright © 2002 John Wiley & Sons, Ltd.
A vector level set method and new discontinuity approximations for crack growth by EFG
Authors: Ventura G. , Xu J. X. , Belytschko T.
Published: October 2002

A new vector level set method for modelling propagating cracks in the element‐free Galerkin (EFG) method is presented. With this approach only nodal data are used to describe the crack; no geometrical entity is introduced for the crack trajectory, and no partial differential equations need to be solved to update the level sets. The nodal description is updated as the crack propagates by geometric equations. The advantages of this approach, here introduced and analysed for the two‐dimensional case, are particularly promising in three‐dimensional applications, where the geometrical description and evolution of an arbitrary crack surface in a complex solid is very awkward. In addition, new methods for crack approximations in EFG are introduced, using a jump function accounting for the displacement discontinuity along the crack faces and the Westergard's solution enrichment near the crack tip. These enrichments, being extrinsic, can be limited only to the nodes surrounding the crack and are naturally coupled to the level set crack representation. Copyright © 2002 John Wiley & Sons, Ltd.
Accurate reanalysis of structures by a preconditioned conjugate gradient method
Authors: Kirsch Uri , Kocvara Michal , Zowe Jochem
Published: October 2002

A preconditioned conjugate gradient (PCG) method that is most suitable for reanalysis of structures is developed. The method presented provides accurate results efficiently. It is easy to implement and can be used in a wide range of applications, including non‐linear analysis and eigenvalue problems. It is shown that the PCG method presented and the combined approximations (CA) method developed recently provide theoretically identical results. Consequently, available results from one method can be applied to the other method. Effective solution procedures developed for the CA method can be used for the PCG method, and various criteria and error bounds developed for conjugate gradient methods can be used for the CA method. Numerical examples show that the condition number of the selected preconditioned matrix is much smaller than the condition number of the original matrix. This property explains the fast convergence and accurate results achieved by the method. Copyright © 2002 John Wiley & Sons, Ltd.
A feature‐preserving volumetric technique to merge surface triangulations
Authors: Cebral Juan R. , Camelli Fernando E. , Löhner Rainald
Published: October 2002

Several extensions and improvements to surface merging procedures based on the extraction of iso‐surfaces from a distance map defined on an adaptive background grid are presented. The main objective is to extend the application of these algorithms to surfaces with sharp edges and corners. In order to deal with objects of different length scales, the initial background grids are created using a Delaunay triangulation method and local voxelizations. A point enrichment technique that introduces points into the background grid along detected surface features such as ridges is used to ensure that these features are preserved in the final merged surface. The surface merging methodology is extended to include other Boolean operations between surface triangulations. The iso‐surface extraction algorithms are modified to obtain the correct iso‐surface for multi‐component objects. The procedures are demonstrated with various examples, ranging from simple geometrical entities to complex engineering applications. The present algorithms allow realistic modelling of a large number of complex engineering geometries using overlapping components defined discretely, i.e. via surface triangulations. This capability is very useful for grid generation starting from data originated in measurements or images. Copyright © 2002 John Wiley & Sons, Ltd.
Multi‐scale constitutive modelling of heterogeneous materials with a gradient‐enhanced computational homogenization scheme
Authors: Kouznetsova V. , Geers M. G. D. , Brekelmans W. A. M.
Published: October 2002

A gradient‐enhanced computational homogenization procedure, that allows for the modelling of microstructural size effects, is proposed within a general non‐linear framework. In this approach the macroscopic deformation gradient tensor and its gradient are imposed on a microstructural representative volume element (RVE). This enables us to incorporate the microstructural size and to account for non‐uniform macroscopic deformation fields within the microstructural cell. Every microstructural constituent is modelled as a classical continuum and the RVE problem is formulated in terms of standard equilibrium and boundary conditions. From the solution of the microstructural boundary value problem, the macroscopic stress tensor and the higher‐order stress tensor are derived based on an extension of the Hill–Mandel condition. This automatically delivers the microstructurally based constitutive response of the higher‐order macro continuum and deals with the microstructural size in a natural way. Several examples illustrate the approach, particularly the microstructural size effects. Copyright © 2002 John Wiley & Sons, Ltd.
A multisymplectic variational integrator for the nonlinear Schrödinger equation
Authors: Chen Jing‐Bo , Qin Meng‐Zhao
Published: October 2002

The multisymplectic structure for the nonlinear Schrödinger equation is presented. Based on the multisymplectic structure, we derive a nine‐point variational integrator from the discrete variational principle and a six‐point multisymplectic integrator from the Preissman multisymplectic scheme. We show that the two integrators are essentially equivalent. Therefore, we call it a multisymplectic variational integrator. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 523–536, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10021
EGFR family expression in breast carcinomas. c‐erbB‐2 and c‐erbB‐4 receptors have different effects on survival
Authors: Suo Zhenhe , Risberg Bjørn , Kalsson Mats G. , Willman Kenneth , Tierens Anne , Skovlund Eva , Nesland Jahn M.
Published: October 2002

One hundred patients with breast carcinoma followed for 7–11 years were included in the present study of EGFR family members, using immunohistochemistry and RT‐PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c‐erbB‐2, c‐erbB‐3, and c‐erbB‐4. All the immunoreactive tumours were confirmed positive by RT‐PCR. Tumour size, histological grade, lymph node status, S‐phase fraction, and stage were confirmed to be significantly associated with both disease‐free and cancer‐specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c‐erbB‐2 expression and reduced disease‐free and cancer‐specific survival. c‐erbB‐4 expression was associated with a more favourable outcome. Co‐expression of c‐erbB‐2 and EGFR was associated with a worse prognosis. c‐erbB‐4 expression, however, showed an antagonistic effect on the clinical influence of c‐erbB‐2 expression. In conclusion, c‐erbB‐2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c‐erbB‐4 antagonizes the c‐erbB‐2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c‐erbB‐2 receptor, clarifying the status of c‐erbB‐4 expression may be of significance. Copyright © 2001 John Wiley & Sons, Ltd.
Fractalkine expression in human renal inflammation
Authors: Cockwell Paul , Chakravorty Srabasti J. , Girdlestone John , Savage Caroline O. S.
Published: October 2002

Immune and inflammatory human renal disease is associated with heavy mononuclear cell infiltration. The trafficking of these cells to extravascular sites is directed by local production of chemokines. Fractalkine is the first described cell‐surface anchored chemokine and has potent mononuclear cell‐directed adhesion and chemotactic properties. The purpose of this study was to analyse the expression and distribution of fractalkine in human renal inflammation. In situ hybridization and immunohistochemistry were used to study renal biopsies from 15 patients with predominant glomerular inflammation (vasculitic glomerulonephritis) and 15 with predominant tubular and interstitial inflammation (acute renal allograft rejection). Controls comprised non‐inflammatory glomerulonephritis and normal tissue. Fractalkine mRNA was predominantly expressed in the major compartment, glomerular or tubulointerstitial, affected by disease and with the strongest expression localized to vascular sites local to inflammation. In acute renal allograft rejection, there was increased expression of fractalkine mRNA by tubular epithelial cells. There was no expression of fractalkine by infiltrating leukocytes and there was only sparse expression in control tissue. Fractalkine mRNA expression correlated with infiltrating leukocyte subsets. Immunohistochemistry confirmed this pattern of expression, with serial section co‐localization showing fractalkine expression in areas with macrophage (CD68+) and T cell (CD3+) infiltrates. These expression patterns show that fractalkine is a strong candidate for directing mononuclear cell infiltration in human renal inflammation. Copyright © 2001 John Wiley & Sons, Ltd.
Expression of receptors for advanced glycation end‐products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer
Authors: Kuniyasu Hiroki , Oue Naohide , Wakikawa Atsuko , Shigeishi Hideo , Matsutani Norimasa , Kuraoka Kazuya , Ito Reiko , Yokozaki Hiroshi , Yasui Wataru
Published: October 2002

The receptor for advanced glycation end‐products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. This study investigated the expression of RAGE in gastric carcinomas and its association with invasion and metastasis. Of eight gastric cancer cell lines examined, seven constitutively expressed RAGE messenger ribonucleic acid (mRNA), MKN45 being the exception. RAGE protein expression of MKN28 cells treated with RAGE antisense S‐oligodeoxynucleotide was nine times less than that of sense S‐oligodeoxynucleotide‐treated cells. Growth of cells under RAGE antisense S‐oligodeoxynucleotide treatment was not different from that seen under sense S‐oligodeoxynucleotide treatment in MKN28 (a cell line producing high levels of RAGE) and MKN45 (a non‐RAGE‐expressing cell line). RAGE antisense S‐oligodeoxynucleotide treatment suppressed the invasive activity of RAGE‐positive MKN28 cells, as estimated by in vitro invasion assay. The number of MKN28 cells invading the type IV collagen‐coated membrane under RAGE antisense S‐oligodeoxynucleotide treatment was significantly lower than under RAGE sense S‐oligodeoxynucleotide treatment (p<0.0001). In contrast, antisense and sense S‐oligodeoxynucleotide‐treated RAGE‐negative MKN45 cells showed no difference. A wound‐healing assay showed that no RAGE antisense S‐oligodeoxynucleotide‐treated MKN28 cells migrated into the scraped area, whereas sense S‐oligodeoxynucleotide‐treated cells showed many budding nests in the scraped area. Immunohistochemistry of gastric carcinoma tissue showed that 62 (65%) of the 96 cases examined were RAGE‐positive and that poorly differentiated adenocarcinomas preferentially expressed RAGE protein (38/42, 90%) (p<0.0001). Strong RAGE immunoreactivity was also correlated with depth of invasion and lymph node metastasis (p<0.0001). RAGE‐positive cancer cells tended to be distributed at the invasive front of primary tumours and were detected in all metastatic foci in lymph nodes. In contrast, a major RAGE ligand, amphoterin, was expressed in 82 (85%) of the 96 cases, regardless of histological type and disease progression. RAGE expression appears to be closely associated with invasion and metastasis in gastric cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Angiogenic co‐operation of VEGF and stromal cell TP in endometrial carcinomas
Authors: Sivridis Efthimios , Giatromanolaki Alexandra , Anastasiadis Panagiotis , Georgiou Loukas , Gatter Kevin C. , Harris Adrian L. , Bicknell Roy , Koukourakis Michael I.
Published: October 2002

Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) are important angiogenic enzymes, inducing new blood vessel formation in many human malignancies. In this study, the immunohistochemical expression of the two molecules was analysed in a series of 121 endometrial carcinomas. VEGF was expressed exclusively in cancer cells, while TP expression was shown in cancer cells (TPcc) and in stromal cells (TPsc) of both fibroblastic and myometrial origin. In all cases, enzymatic detection was particularly evident at the invading tumour front. At this site, TPsc, but not VEGF, expression was associated with non‐endometrioid‐type carcinomas, high tumour grade, deep myometrial invasion, and advanced stage. VEGF, but not TP, expression was related to increased angiogenesis (p=0.01). Double stratification of the two factors, however, marked VEGF/TPsc co‐expression as the most potent angiogenic phenotype (p=0.008), suggesting a synergistic function. Survival analysis revealed that VEGF and TPsc, whether expressed alone or in combination, define poor prognosis. In multivariate analysis, however, stage of disease (p<0.0001, t‐ratio 4.4) and VEGF expression (p=0.01, t‐ratio 2.4) were the most important prognostic variables. Furthermore, VEGF expression emerged as the only independent prognostic variable in stage I endometrial carcinomas (p=0.04, t‐ratio 1.9). This was not shown for TP, probably because of its close association with histopathological parameters. In conclusion, VEGF is a major angiogenic factor in endometrial carcinomas and an independent prognostic factor in stage I endometrial disease. TP is not an effective contributor to the angiogenic process, but is associated with aggressive histological features. The two factors, when co‐expressed, play a co‐operative role in the induction of angiogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
A novel bcl‐1/JH breakpoint from a patient affected by mantle cell lymphoma extends the major translocation cluster
Authors: Degan Massimo , Doliana Roberto , Gloghini Annunziata , Di Francia Raffaele , Aldinucci Donatella , Mazzocut‐Zecchin Linda , Colombatti Alfonso , Attadia Vincenza , Carbone Antonino , Gattei Valter
Published: October 2002

Mantle cell lymphoma (MCL) is a B‐lymphocytic malignancy frequently associated with the presence of the t(11;14) chromosomal translocation. By using a polymerase chain reaction (PCR) strategy to detect breakpoints within the major translocation cluster (MTC), an unexpectedly large product (about 1.1 kb by using first‐round bcl‐1/JH primers) has been identified in one out of 16 patients harbouring the t(11;14) translocation. Sequence analysis of the atypical PCR product, re‐amplified and cloned with second‐round primers, revealed a 459 bp portion corresponding exactly to the 3′‐end segment of the MTC, followed by a sequence of 433 bp that lacked homology with any previously known sequence. PCR experiments using DNA from healthy donors identified that fragment as an extension of MTC fused, through a N‐region of seven nucleotides, to the JH4 region of IgH gene. A computer‐based search of the novel MTC portion aimed at detecting potential recombination motifs revealed the presence of several 4‐bp sequences (5′‐CCAG‐3′ or its complement 5′‐CTGG‐3′), one of them within seven nucleotides from the putative breakpoint, known to play a role in non‐homologous recombination events at the Ig loci. The recognition of this novel breakpoint may have important implications for the diagnosis and detection of minimal residual disease in t(11;14)‐positive lymphomas. Copyright © 2002 John Wiley & Sons, Ltd.
Frequent genomic imbalances in chromosomes 17, 19, and 22q in peripheral nerve sheath tumours detected by comparative genomic hybridization analysis
Authors: Koga Takamasa , Iwasaki Hiroshi , Ishiguro Masako , Matsuzaki Akio , Kikuchi Masahiro
Published: October 2002

Comparative genomic hybridization (CGH) was used to detect changes in relative chromosome copy number in 50 cases of peripheral nerve sheath tumour (PNSTs), including nine malignant peripheral nerve sheath tumours (MPNSTs), 27 neurofibromas (with three plexiform neurofibromas) and 14 schwannomas. Chromosome imbalances were frequently detected in benign as well as malignant PNSTs. In both NF1‐associated and sporadic MPNSTs, the number of gains was higher than the number of losses, suggesting proto‐oncogene activation during MPNST progression. NF1‐asociated MPNSTs exhibited gains of chromosomes 17q and X (2/4 cases each), where as sporadic MPNSTs showed gains of chromosome 4q (3/5 cases). On the other hand, in benign neurofibromas and schwannomas, the number of losses was higher than the number of gains, suggesting a predominant role of tumour suppressor genes in tumourigenesis. Both sporadic and NF1‐associated neurofibromas exhibited losses at chromosome 22q in more than 50% of cases. These chromosomal regions may contain common chromosomal abnormalities characteristic of both types of neurofibromas. In NF1‐associated neurofibromas, most frequent losses were found in chromosomes 17 [17p11.2–p13 in nine cases (60%); 17q24–25 in 6 cases (40%)] and 19 [19p13.2 in eight cases (53%); 19q13.2–qter in eight cases (53%)], whereas in sporadic neurofibromas and schwannomas losses of chromosomes 17 and 19 were detected in less than 50% of cases. Since this 17p11.2–p13 region is known to contain the tumour suppressor gene TP53, patients with NF1 may be at high risk of malignant neoplasms including MPNSTs. Gains were more frequently detected in plexiform neurofibromas (2/3 cases) than other benign tumours, suggesting proto‐oncogene activation in tumourigenesis of plexiform neurofibroma. The significance of the losses of chromosome 19 in these cases is not clear at present, but in NF1‐associated neurofibromas, the presence of some as yet unknown tumour suppressor genes on chromosome 19 cannot be ruled out. Copyright © 2002 John Wiley & Sons, Ltd.
Mast cells in the pathogenesis of chronic back pain: a hypothesis
Authors: Freemont Anthony J. , Jeziorska Maria , Hoyland Judith A. , Rooney Paul , Kumar Shant
Published: October 2002

The pathophysiology of chronic low back pain is poorly understood, mainly because it is difficult to study experimentally or objectively. Recently it has been found that there is a relationship between neovascularization and innervation of the usually avascular and aneural intervertebral disc at the sites of discogenic pain. These data, together with the recognized involvement of mast cells in tissue repair, in the induction of angiogenesis, and in the production of and response to neurotrophic stimuli such as nerve growth factor, has suggested the hypothesis that mast cells may have a causative role in chronic low back pain. If so, the mast cell may represent an attractive therapeutic target. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of Epstein–Barr virus genome within thymic epithelial tumours in Taiwanese patients by nested PCR, PCR in situ hybridization, and RNA in situ hybridization
Authors: Chen Paul Chih‐Hsueh , Pan Chin‐Chen , Yang An‐Hang , Wang Liang‐Shun , Chiang Hung
Published: October 2002

Epstein–Barr virus (EBV) is known to be associated with a variety of tumours, including Burkitt's lymphoma, nasopharyngeal carcinoma, and some carcinomas of other organs with similar lymphoepithelioma‐like features. The association between EBV and thymic epithelial tumours is inconclusive, as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. This study examined 78 thymomas and 21 thymic carcinomas in Taiwanese patients, to detect the viral genome at both DNA and RNA levels. The tissue blocks were first screened by nested polymerase chain reaction (PCR) targeting on the first tandem internal repeats. The positive cases were further submitted for viral localization by in situ PCR insitu hybridization (ISH) and Epstein–Barr‐encoded RNA‐1 (EBER‐1) ISH. None of the thymomas showed a detectable EBV genome. Eight thymic carcinomas were positive for EBV by nested PCR, of which six displayed nuclear signals within the tumour cells by in situ PCR ISH and/or RNA ISH, one displayed signals within the lymphocytes, and one showed no discernible in situ signals. Most of them exhibited a lymphoepithelioma‐like morphology. These results show that nested PCR is a sensitive method for screening the EBV genome in thymic epithelial tumours. In situ PCR ISH is reliable for localization of the virus, in addition to EBER‐1 RNA ISH. Thymomas are not related to EBV, even in this endemic area. Thymic carcinomas, especially the lymphoepithelioma‐like thymic carcinomas, are more often associated with the virus. Copyright © 2002 John Wiley & Sons, Ltd.
Pancreatic stem cells
Authors: Bonner‐Weir Susan , Sharma Arun
Published: October 2002

β‐cell replacement therapy via islet transplantation has had renewed interest, due to the recent improved success. In order to make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin‐producing cells must be readily available. The recent conceptual revolution of the presence of adult pluripotent stem cells in bone marrow and in most, if not all, organs suggests that adult stem cells may be a potential source of insulin‐producing cells. Pancreatic stem/progenitor cells or markers for these cells have been sought in both islets and ducts. There is considerable evidence that such cells exist and several candidate cells have been reported. However, no clearly identifiable adult pancreatic stem cell has been found as yet. The putative pancreatic stem cells will be the focus of this review. Copyright © 2002 John Wiley & Sons, Ltd.
Diagnosis of chronic atrophic gastritis by morphometric image analysis. A new method to overcome the confounding effect of the inflammatory infiltrate
Authors: Staibano Stefania , Rocco Alba , Mezza Ernesto , De Rosa Gaetano , Budillon Gabriele , Nardone Gerardo
Published: October 2002

The risk of gastric cancer increases with the severity of gastric mucosal atrophy. Atrophy is a ‘loss of properly specialized glands’. These glands may be substituted by metaplastic cells and by interstitial fibrosis, or displaced by an inflammatory infiltrate. Agreement among pathologists for the diagnosis of atrophy is poor (κcoefficient < 0.4), probably because inflammatory infiltrate can confound the identification of gland loss. The aim of this study was to evaluate interstitial fibrosis by image analysis, and thereby overcoming the confounding effect of the inflammatory infiltrate. Gastric biopsies of 40 controls (20 children and 20 adults) and 111 patients with chronic atrophic gastritis were examined. Patients underwent another biopsy a year later. Gastric sections were examined by conventional histology (updated Sydney system) and image analysis to detect collagen and non‐collagen fibres. There were no significant intra‐ or inter‐operator differences in the evaluation by image analysis of fibre content in either controls or patients. In both controls and patients, the mean percentage of collagen fibres was lower in the gastric body (9%) than in the antrum (10%). In the antrum it was 14%, 17% and 20% in patients with mild, moderate and severe atrophy, respectively. A year later, histology showed that the grade of atrophy had decreased in 42%, probably due to the regression of inflammation, and increased in 10% of cases, but interstitial fibrosis (expressed as collagen fibre content) was practically unchanged. The use of image analysis of gastric biopsies appears to be a reliable method with which to measure interstitial fibrosis, even in the presence of an inflammatory infiltrate. This study highlights the difference between ‘real gastric atrophy’, where glands are replaced by collagen fibres, and ‘apparent gastric atrophy’, where glands are displaced by an inflammatory infiltrate. Copyright © 2002 John Wiley & Sons, Ltd.
Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non‐invasive prenatal diagnosis
Authors: Campagnoli Cesare , Roberts Irene A. G. , Kumar Sailesh , Choolani Mahesh , Bennett Phillip R. , Letsky Elizabeth , Fisk Nicholas M.
Published: October 2002

Objectives

Selective amplification of rare fetal cells in maternal blood is a potential strategy for non‐invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones.

Methods

Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co‐cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co‐cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X‐Y fluorescence in situ hybridisation (FISH)

Results

The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU‐GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU‐e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8‐fold, range 174.0–968.0 vs 71.9‐fold, range 41.1–192.0; p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2‐fold (range 128.0–2915.0) expansion of fetal cells.

Conclusion

Selective expansion of first trimester fetal haemopoietic progenitors may be useful for amplifying fetal cells from maternal blood. Copyright © 2002 John Wiley & Sons, Ltd.
Uniparental disomy in fetuses diagnosed with balanced Robertsonian translocations: risk estimate
Authors: Silverstein Shira , Lerer Israela , Sagi Michal , Frumkin Ayala , Ben‐Neriah Ziva , Abeliovich Dvorah
Published: October 2002

Forty‐two fetuses with non‐homologous Robertsonian translocations were analyzed for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q) had maternal isodisomy of chromosome 14. In a summary of the published data (including the present study), 315 cases were analyzed for UPD after prenatal diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD, giving a risk estimate of 0.65% (CI 0.2–2.3). This risk justifies the recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian translocations, with the emphasis on the chromosomes known to contain imprinted genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of Robertsonian translocation carriers with normal karyotype. Based on the risk for UPD in fetuses with Robertsonian translocation we suggest to test these fetuses for UPD and to do so on amniocytes rather than chorionic villi when the risk for unbalanced karyotype is ∼1%, comparable to the risk for UPD. Copyright © 2002 John Wiley & Sons, Ltd.
First trimester screening with free β‐hCG, PAPP‐A and nuchal translucency in pregnancies conceived with assisted reproduction
Authors: Orlandi Francesco , Rossi Cinzia , Allegra A. , Krantz David , Hallahan Terrence , Orlandi Emanuela , Macri James
Published: October 2002

Objective

To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on free beta‐human chorionic gonadotrophin (β‐hCG), pregnancy‐associated plasma protein A (PAPP‐A) and nuchal translucency (NT).

Methods

First trimester maternal dried whole blood specimens from 74 singleton pregnancies (32 by IVF and 42 by ICSI) and 30 twin pregnancies (16 by IVF and 14 by ICSI) in which conception was achieved with assisted reproduction techniques were matched with five controls resulting in 370 singleton controls and 150 twin controls. NT was measured using the Fetal Medicine Foundation protocol. Free β‐hCG, PAPP‐A and NT levels were compared between the IVF and control groups and between the ICSI and control groups using the Mann‐Whitney U test.

Results

In singleton pregnancies, the only significant difference was a 21% (95% CI: −35%–−7%) reduction in PAPP‐A in IVF cases. In twin pregnancies, the only significant difference was a 12% (95% CI: −34%–−3%) reduction in NT in IVF cases. In singleton pregnancies, the false‐positive rate for Down syndrome screening was 1.4% and 1.9% greater for the IVF and ICSI groups, respectively, compared to controls for a general screening population.

Conclusions

Patients undergoing assisted reproduction techniques should be counseled about the possibility of increased false‐positive rates. Larger studies are needed to confirm this observation and to develop appropriate adjustment factors to reduce false‐positive rates. Copyright © 2002 John Wiley & Sons, Ltd.
Thermosensitive and hydrolysis‐sensitive poly(organophosphazenes)
Authors: Lee Bae Hoon , Lee Young Moo , Sohn Youn Soo , Song Soo‐Chang
Published: October 2002

The lower critical solution temperature (LCST) properties and hydrolytic behaviour of thermosensitive biodegradable polyphosphazenes with monomethoxy‐poly(ethylene glycol), glycine ethyl ester and depsipeptide ethyl esters substituents have been studied. All the polymers synthesized show LCST properties. The LCSTs of the polymers are affected by the composition of the polymers and increase with the degradation of the polymers in aqueous solution. The higher content of depsipeptide ethyl esters in the polymers accelerates the LCST change and the degradation of the polymers in aqueous solution. Most polymers synthesized have half‐lives of less than 10 days in neutral solution.

© 2002 Society of Chemical Industry
Blends of natural rubber and polyurethane latices studied by1H wideline and13C MAS solid‐state NMR
Authors: Ricardo Nágila M P S , Lahtinen Mika , Price Colin , Heatley Frank
Published: October 2002

1H wideline and13C magic‐angle spinning NMR have been used to study the morphology and dynamics of latex‐cast and solution‐cast film blends of natural rubber (NR) and a polyurethane (PU) based on poly(ϵ‐caprolactone) diol and isophorone di‐isocyanate.1HT1andT1ρrelaxation times have been measured, and the extent of interpenetration of the NR and PU constituents has been monitored using the Goldman–Shen technique. The NMR spectra and relaxation properties indicated that the NR and PI constituents largely occupy separated domains on a distance scale of >10 nm. The Goldman–Shen experiments indicated that there was slightly greater contact between NR and PU in the solution‐cast samples than in the latex‐cast. The tensile properties of the films have been measured. The tensile strength and initial Young's modulus pass through a maximum at a PU content of about 50 wt%.

© 2002 Society of Chemical Industry
Gelation of a new hydrogel system ofatactic‐poly(vinyl alcohol)/NaCl/H2O
Authors: Dai Lixing , Ukai Kohshuke , Shaheen Sharif Mohammad , Yamaura Kazuo
Published: October 2002

a‐PVA/NaCl/H2O hydrogels have been prepared by gelation of aqueousatactic‐poly(vinyl alcohol) (a‐PVA) solutions in the presence of NaCl. The gelling temperature, melting temperature and the preservation of water of the hydrogels have been measured. The effect of the addition of NaCl to the hydrogels on gelling temperature and melting temperature is marked when the NaCl concentration is over a certain value. High NaCl concentration favours high‐melting‐point hydrogels. When the NaCl concentration is high enough (such as 11%), high‐melting‐point and white turbid opaquea‐PVA/NaCl/H2O hydrogels can be prepared, regardless of the PVA concentration. Similarly, the low gelling temperature ofa‐PVA/NaCl/H2O solutions comes from low NaCl concentration, while high gelling temperature ranges from 50 to 70 °C when the NaCl concentration is 11%. In appearance, the types of syneresis ofa‐PVA/NaCl/H2O are χ‐type or a mixture of χ‐ andn‐types; water release of the hydrogels is slowed down by the addition of NaCl.

© 2002 Society of Chemical Industry
Molecular selectivity of tyrosine‐imprinted polymers prepared by seed swelling and suspension polymerization
Authors: Zhang Liyong , Cheng Guoxiang , Fu Cong
Published: October 2002

Tyrosine‐imprinted microspheres have been prepared in an aqueous system by seed swelling and suspension polymerization, using trimethylolpropane trimethacrylate (TRIM), acrylamide (AM) as well as methacrylic acid (MAA), linear polystyrene and toluene as crosslinker, functional monomers, seeds and porogens, respectively. The size distribution proved to be greatly influenced by the ratio of water:TRIM (W/T) and the concentration of dispersant. When W/T was 46:1 (v/v), 4.6% (by mass) of poly(vinyl alcohol) (PVA) was used as dispersant, the molar ratios of tyrosine, MAA, AM and TRIM were 1:8:8:17, the polymer beads had the better size monodispersity, and the average size was 135 µm, while the sizes of the pores on the beads surfaces ranged from 1.25 µm to 9.0 µm. The adsorption behaviour and molecular selectivity of the beads were analysed using liquid chromatography; the results showed that the adsorption behaviour of the beads followed the rule of Langmuir, and the value of saturated absorption was 0.197 mmol g−1. The tyrosine‐imprinted polymers exhibited an inherent selectivity for tyrosine; when phenylalanine was used as the competing molecule the separation factor α was up to 1.91. However, the control polymers did not have this special molecule‐selection capability, and the relative separation factor β was about 1.82 compared with the imprinted polymers.

© 2002 Society of Chemical Industry