bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimum design of stochastically excited non‐linear dynamic systems without geometric constraints
Authors: Oblak M. M. , Lesnika A. S. , Butinar B. J.
Published: October 2002

This paper presents an efficient procedure for min–max dynamic response optimization of stochastically excited non‐linear systems with multiple time‐delayed inputs. This procedure employs a stochastic linearization technique to overcome system non‐linearity and an auto‐covariance analysis technique to represent the original stochastic mechanical model in a suitable form for optimization. Special attention is given to the sensitivity analysis, due to the complex nature of the problem. Therefore, exact expressions are obtained in a simple form for the evaluation of the required gradients, which greatly improve the stability and efficiency of the optimization algorithm. The numerical results and performance are presented by means of solving two min–max dynamic response optimization problems. Copyright © 2002 John Wiley & Sons, Ltd.
A finite point method for compressible flow
Authors: Löhner Rainald , Sacco Carlos , Oñate Eugenio , Idelsohn Sergio
Published: October 2002

A weighted least squares finite point method for compressible flow is formulated. Starting from a global cloud of points, local clouds are constructed using a Delaunay technique with a series of tests for the quality of the resulting approximations. The approximation factors for the gradient and the Laplacian of the resulting local clouds are used to derive an edge‐based solver that works with approximate Riemann solvers. The results obtained show accuracy comparable to equivalent mesh‐based finite volume or finite element techniques, making the present finite point method competitive. Copyright © 2001 John Wiley & Sons, Ltd.
High‐order finite volume schemes for the advection–diffusion equation
Authors: Hernández J. A.
Published: October 2002

A high‐order finite volume method based on piecewise interpolant polynomials is proposed to discretize spatially the one‐dimensional and two‐dimensional advection–diffusion equation. Evolution equations for the mean values of each control volume are integrated in time by a classical fourth‐order Runge–Kutta. Since our work focuses on the behaviour of the spatial discretization, the time step is chosen small enough to neglect the time integration error.

Two‐dimensional interpolants are built by means of one‐dimensional interpolants. It is shown that when the degree of the one‐dimensional interpolant q is odd, the proper selection of a fixed stencil gives rise to centred schemes of order q+1. In order not to lose precision due to the change of stencil near boundaries, the degree of the interpolants close to boundaries is raised to q+1. Four test cases with small values of diffusion are integrated with high‐order methods. It is shown that the spatial discretization of the advection–diffusion equation with periodic boundary conditions leads to normal discretization matrices, and asymptotic stability must be assured to bound the spatial discretization error. Once the asymptotic stability is assured by means of the spectra of the discretization matrix, the spatial error is of the order of the truncation error. However, it is shown that the discretization of the advection–diffusion equation with arbitrary boundary conditions gives rise to non‐normal matrices. If asymptotic stability is assured, the spatial order of steady solutions is of the order of the truncation error. But, for transient processes, the order of the spatial error is determined by both the truncation error and the norm of the exponential matrix of the spatial discretization. The use of the pseudospectra of the discretization matrix is proposed as a valuable tool to analyse the transient error of the numerical solution. Copyright © 2001 John Wiley & Sons, Ltd.
A new class of Cn interpolations and its application to the finite element method
Authors: Hashemolhosseini H. , Sadati N. , Farzin M.
Published: October 2002

A new class of Cn continuous interpolations is presented. These interpolations consist of two or more Lagrangian interpolations blended by pseudo Hermitian interpolation. Using this class of interpolations a new Cn family of displacement type elements is developed. The properties of this new family of elements such as their precision and their superconvergent points are discussed. Some solutions to the corner elements problem and implication of different boundary conditions are proposed. Using this new kind of element, several examples of deflection of elastic beams and plates are treated, the results of which are encouraging. Copyright © 2001 John Wiley & Sons, Ltd.
Three‐dimensional finite element solution of gas‐assisted injection moulding
Authors: Ilinca F. , Hétu J.‐F.
Published: October 2002

This paper presents a finite element algorithm for solving gas‐assisted injection moulding problems. The filling material is considered incompressible and has temperature and shear rate dependent viscosity. The solution of the three‐dimensional (3D) equations modelling the momentum, mass and energy conservation is coupled with two front‐tracking equations, which are solved for the polymer/air and gas/polymer interfaces. The performances of the proposed procedure are quantified by solving the gas‐assisted injection problem on a thin plate with a flow channel. Solutions are shown for different polymer/gas ratios injected. The effect of the melt temperature, gas pressure and gas injection delay, on the solution behaviour is also investigated. The approach is then applied to a thick 3D part. Published in 2001 by John Wiley & Sons, Ltd.
The extended finite element method (XFEM) for solidification problems
Authors: Chessa Jack , Smolinski Patrick , Belytschko Ted
Published: October 2002

An enriched finite element method for the multi‐dimensional Stefan problems is presented. In this method the standard finite element basis is enriched with a discontinuity in the derivative of the temperature normal to the interface. The approximation can then represent the phase interface and the associated discontinuity in the temperature gradient within an element. The phase interface can be evolved without re‐meshing or the use of artificial heat capacity techniques. The interface is described by a level set function that is updated by a stabilized finite element scheme. Several examples are solved by the proposed method to demonstrate the accuracy and robustness of the method. Copyright © 2001 John Wiley & Sons, Ltd.
A BEM‐based genetic algorithm for identification of polarization curves in cathodic protection systems
Authors: Miltiadou Panayiotis , Wrobel Luiz C.
Published: October 2002

The purpose of this work is to apply an inverse boundary element formulation in order to develop efficient algorithms for identification of polarization curves in a cathodic protection system. The problem is to minimize an objective function measuring the difference between observed and BEM‐predicted surface potentials. The numerical formulation is based on the application of genetic algorithms, which are robust search techniques emulating the natural process of evolution as a means of progressing towards an optimum solution.

Examples of application are included in the paper for different types of polarization curves in finite and infinite electrolytes. The accuracy and efficiency of the numerical results are verified by comparison with standard conjugate gradient techniques. As a result of this research, the genetic algorithm approach is shown to be more robust, independent of the position of the sensors and of initial guesses, and will be further developed for three‐dimensional applications. Copyright © 2002 John Wiley & Sons, Ltd.
Flexible multibody dynamics based on a non‐linear Euler–Bernoulli kinematics
Authors: Boyer F. , Glandais N. , Khalil W.
Published: October 2002

This paper presents a new dynamic model of a multi‐beam system in the floating‐frame approach. The proposed solution can be used to model light flexible manipulators in fast dynamic conditions or large space structures undergoing moderate but finite deformations. The model is based on the non‐linear Euler–Bernoulli kinematics proposed in J. Mech. Mach. Theory 1999; 34:205. From this ‘exact’ kinematics we develop two approximate models. The first one is a linear model with respect to the deformation parameters, the second is a quadratic one. These two models capture the dynamic stiffening, and are consistent in the sense that they contain all the terms up to their maximal order with respect to the energy conservation. These two models are tested by simulation and compared with the standard floating frame model based on linear elastic kinematics and with the finite element codes of Reference [23] (Module d'analyse de mécanismes flexibles MECANO: Manuel d'utilisation. LTAS report, University of Liege, Belgium, 1988). Copyright © 2002 John Wiley & Sons, Ltd.
The partition of unity quadrature in meshless methods
Authors: Carpinteri A. , Ferro G. , Ventura G.
Published: October 2002

In dealing with mesh‐free formulations a major problem is connected to the computation of the quadratures appearing in the variational principle related to the differential boundary value problem. These integrals require, in the standard approach, the introduction of background quadrature subcells which somehow make these methods not ‘truly meshless’. In this paper a new general method for computing definite integrals over arbitrary bounded domains is proposed, and it is applied in particular to the evaluation of the discrete weak form of the equilibrium equations in the framework of an augmented Lagrangian element‐free formulation. The approach is based on splitting the integrals over the entire domain into the sum of integrals over weight function supports without modifying in any way the variational principle or requiring background quadrature cells. The accuracy and computational cost of the technique compared to standard Gauss subcells quadrature are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
A consistent geometrically non‐linear approach for delamination
Authors: Wells G. N. , de Borst R. , Sluys L. J.
Published: October 2002

A new model is presented for the simulation of delamination in laminated composite materials. A key feature is that the material structure and the finite element mesh are uncoupled. The displacement discontinuities that arise during the delamination process are described mathematically using discontinuous functions. This leads naturally to a set of coupled equations for the continuous and the discontinuous parts of the response. Discontinuities can pass through solid finite elements arbitrarily, with the displacement jump continuous across element boundaries. The performance of the model is demonstrated for several problems of delamination and geometric instability. Copyright © 2002 John Wiley & Sons, Ltd.
High‐order artificial boundary conditions for ideal axisymmetric irrotational flow around 3D obstacles
Authors: Zheng Chunxiong , Han Houde
Published: October 2002

In this paper the numerical solution for ideal irrotational incompressible flow around axisymmetric 3D obstacles is discussed with the artificial boundary method. By introducing an artificial boundary, we divide the exterior unbounded domain into a bounded part and an unbounded part. After setting up a proper artificial boundary condition, we get an approximate reduced problem defined on the bounded part. Both non‐local and local artificial boundary conditions are designed. Numerical experiment is also presented, and its result demonstrates the effectiveness of these artificial boundary conditions. Copyright © 2002 John Wiley & Sons, Ltd.
A hybrid extended finite element/level set method for modeling phase transformations
Authors: Ji H. , Chopp D. , Dolbow J. E.
Published: October 2002

A hybrid numerical method for modelling the evolution of sharp phase interfaces on fixed grids is presented. We focus attention on two‐dimensional solidification problems, where the temperature field evolves according to classical heat conduction in two subdomains separated by a moving freezing front. The enrichment strategies of the eXtended Finite Element Method (X‐FEM) are employed to represent the jump in the temperature gradient that governs the velocity of the phase boundary. A new approach with the X‐FEM is suggested for this class of problems whereby the partition of unity is constructed with C1(Ω) polynomials and enriched with a C0(Ω) function. This approach leads to jumps in temperature gradient occurring only at the phase boundary, and is shown to significantly improve estimates for the front velocity. Temporal derivatives of the temperature field in the vicinity of the phase front are obtained with a projection that employs discontinuous enrichment. In conjunction with a finer finite difference grid, the Level Set method is used to represent the evolution of the phase interface. An iterative procedure is adopted to satisfy the constraints on the temperature field on the phase boundary. The robustness and utility of the method is demonstrated with several benchmark problems of phase transformation. Copyright © 2002 John Wiley & Sons, Ltd.
Numerical solution of thermal convection problems using the multidomain boundary element method
Authors: Florez W. F. , Power H. , Chejne F.
Published: October 2002

The multidomain dual reciprocity method (MD‐DRM) has been effectively applied to the solution of two‐dimensional thermal convection problems where the momentum and energy equations govern the motion of a viscous fluid. In the proposed boundary integral method the domain integrals are transformed into equivalent boundary integrals by the dual reciprocity approach applied in a subdomain basis. On each subregion or domain element the integral representation formulas for the velocity and temperature are applied and discretised using linear continuous boundary elements, and the equations from adjacent subregions are matched by additional continuity conditions. Some examples showing the accuracy, the efficiency and flexibility of the proposed method are presented. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 469–489, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10016
Robust hyperplane synthesis for sliding mode control systems via sensitivity minimization
Authors: Tam Hei Ka , Ho Daniel W.C. , Lam James
Published: October 2002

A robust hyperplane computation scheme for sliding mode control systems is proposed in this paper. A novel sensitivity index for the sliding eigenvalues with respect to perturbations in the system matrix, the input matrix and the hyperplane matrix is derived in the first instance. The robust hyperplane design problem is then formulated as an optimization task in which the proposed sensitivity index is accordingly minimized. Gradient information of the objective function is established which permits optimization to be proceeded effectively. A numerical example with statistical testing is employed to illustrate the design technique. Copyright © 2002 John Wiley & Sons, Ltd.
Review of polystyrene diffusion studies in latex particles by small‐angle neutron scattering
Authors: Kim S. D. , Klein A. , Sperling L. H.
Published: October 2002

This paper reviews small‐angle neutron scattering (SANS) and some results from direct nonradiative energy transfer (DET), for the observation of the diffusion coefficients of polystyrene chains at latex interfaces. To compare SANS with DET, doubly labeled polystyrene with deuterium and fluorescence groups were synthesized, showing that while SANS and DET produce comparable data in terms of diffusion coefficients, both results differ in detail, each having their own advantages. Chain confinement, ionic end groups, and short branch effects on interdiffusion were studied. Large polymer chains confined in small particles have non‐Gaussian shapes that store rubber elastic energy. Rapid, non‐diffusion relaxation is inhibited because the density would be required to become less than normal. Hence confinement effects on the diffusion rate are not significant. Using the DET method, ionic end‐groups were found to increase the early‐time apparent interdiffusion coefficients during film formation. The early‐time apparent diffusion coefficients of polystyrene with varying end‐groups were found to increase as follows:

The higher apparent diffusion coefficients of the chains with ionic groups are presumably due to a surface segregation of the end‐groups caused by the polar, aqueous environment during latex synthesis.

The interdiffusion behavior of sulfite‐ended polystyrene (Mn ≅ 300 000 g/mol) with H‐ends, one sulfite end, and two sulfite ends were compared via SANS and DET. The diffusion coefficients of polystyrene with one or two sulfite end groups were five times and ten times lower than that of polystyrene, respectively. The ionic end group effects on the reduced diffusion coefficients are interpreted as the competition between enhancement by the surface segregation of end groups and reduction by end group aggregation. Noting that sulfate end groups diffused faster, while sulfite end groups diffused slower, the effect is complex, and not yet fully resolved.

Diffusion coefficients of polystyrene with branches were studied by DET. Short branches work to decrease the Tg and hence increase the diffusion coefficients. However, after the experimental temperature, T, is converted to a normalized temperature, T‐Tg, the diffusion coefficients are found to be almost independent upon the number of branches and the length of branches. The branch length ranged from one‐carbon to 40 carbons. Side chains of entanglement molecular weight or longer may be required to significantly reduce the diffusion coefficient. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation into the surface relief grating mechanism via XPS in new azobenzene based optical material
Authors: Sharma Lakshmi , Matsuoka Toshio , Kimura Tatsumi , Matsuda Hiro
Published: October 2002

Research into azobenzene and its compounds focuses on the molecules ability to cis‐trans isomerize, this photoisomerization enables surface relief gratings (SRGs) to be formed on the azobenzene functionalized polymer films. SRG allows information to be written and then erased, an essential requirement of most modern electrical products. The interest into SRG photofabrication is thus rapidly increasing and is emerging at the forefront of photonic and nanotechnology research. The surface relief grating mechanism, however, is not fully understood, a photoplasticization process is postulated, which is thought to occur via the azo‐chromophores photoisomerization, so encouraging polymer chain migration to the surface. In comparison, suggestions have shown the SRG process does not involve a change in the film surface profile but in the local refractive index. Currently, no research has yet established the surface relief grating mechanism, this paper sets out to determine the mechanism and investigate those theories already postulated by observing the thin film surfaces prior to and after SRG using X‐ray photoelectron spectroscopy (XPS). By identifying the surface components, greater insight and understanding of the SRG mechanism can be achieved.

In this paper, poly(4‐(N‐(2‐methacryloyloxyethyl)‐N‐ethylamino)‐4′‐nitroazobenzene)90‐co‐(methylmethacrylate)10 50 : 50 PMMA blend was exposed to SRGs. Using XPS the surface composition was determined prior to and after SRG. Following SRG, the spectra for O 1s, N 1s and C 1s using XPS expressed a change in the components at the surface. This is most evident in the N 1s spectra, with PMMA not containing nitrogen, the N 1s becomes the determining factor. The nitrogen absence combined with a significant increase in the carbon and oxygen peak intensity concludes the azobenzene lies not on the surface but, in fact, within the bulk after SRG. The initial light irradiation process must be a consideration. However, on X‐ray analysis the sample showed the same spectra as the one prior to SRG. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of synaptic vesicle protein 2 (SV2) in neuroendocrine tumours of the gastrointestinal tract and pancreas
Authors: Jakobsen Anne‐Marie , Ahlman Håkan , Wängberg Bo , Kölby Lars , Bengtsson Malin , Nilsson Ola
Published: October 2002

Identification of neuroendocrine differentiation in tumours has important implications for prognosis and therapy. The aim of the present study was to evaluate monoclonal antibodies against synaptic vesicle protein 2 (SV2) as histopathological markers for neuroendocrine differentiation intumours of the gastroinestinal tract and pancreas. Paraffin blocks from 211 gastrointestinal tumours were examined by immunocytochemistry, using a monoclonal antibody against SV2. Virtually all endocrine tumours of the gastrointestinal tract (11/11 gastric, 53/53 ileal, 16/21 appendiceal, and 22/22 rectal) and pancreas (24/24) were positively labelled. SV2 labelling was also demonstrated in gastrointestinal pacemaker cell tumours (8/8), while adenocarcinomas of the gastrointestinal tract and pancreas were negative, with the exception of occasional adenocarcinomas demonstrating weak SV2 labelling (stomach 1/22, rectum 1/29, and pancreas 0/21). Western blotting of tumour biopsies confirmed expression of SV2 in endocrine tumours of the gastrointestinal tract and pancreas. No relationship was observed between SV2 expression in tumours and hormone production or malignant potential. In conclusion, SV2 is expressed in neuroendocrine tumours of the gastrointestinal tract and pancreas, but not in non‐endocrine tumours. The SV2 monoclonal antibody can therefore be used as a general marker for neuroendocrine differentiation in gastrointestinal and pancreatic tumours. Copyright © 2001 John Wiley & Sons, Ltd.
Cyclooxygenase‐2 expression during carcinogenesis in the human stomach
Authors: van Rees Bastiaan P. , Saukkonen Kirsi , Ristimäki Ari , Polkowski Wojciech , Tytgat Guido N. J. , Drillenburg Paul , Johan A. Offerhaus G.
Published: October 2002

The prolonged use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with a reduced risk of gastric cancer. The best‐known target of these drugs is cyclooxygenase (COX); the COX‐2 isoform is frequently up‐regulated in gastric adenocarcinomas. Using the post‐gastrectomy stomach as a model, the expression of COX‐2 mRNA and protein has been investigated during tumour progression in the human stomach. COX‐2 expression was comparable in gastric stump carcinomas and conventional gastric carcinomas and localized primarily to the cytoplasm of the neoplastic cells. COX‐2 mRNA was elevated in biopsies containing intestinal metaplasia, as determined by reverse transcriptase polymerase chain reaction (RT‐PCR). COX‐2 immunopositivity became more frequent during progression from reactive epithelium to high‐grade dysplasia, both in the epithelial and in the stromal cell compartment. Co‐localization of COX‐2‐positive stromal cells was seen with CD68, α‐smooth muscle actin (α‐SMA), vimentin, and HLA‐DR, but an as yet unidentified subpopulation of stromal cells remained. Co‐localization with the macrophage marker CD68 was only observed in a minority of COX‐2‐positive cells. These data show that COX‐2 expression is a relatively early event during carcinogenesis in the stomach. COX‐2 expression increases during tumour progression in the stomach, suggesting a role for COX‐2 expression in gastric tumourigenesis. Copyright © 2001 John Wiley & Sons, Ltd.
VEGF and bFGF are highly expressed in intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia
Authors: Lappi‐Blanco Elisa , Soini Ylermi , Kinnula Vuokko , Pääkkö Paavo
Published: October 2002

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP) are fibrous pulmonary disorders in which new fibromyxoid connective tissue is formed in distal air spaces. In BOOP this tissue is susceptible to even complete reversal, but in UIP it participates in the remodelling of the interstitium. Our previous study showed that in BOOP this newly formed intraluminal tissue is more capillarized than in UIP. This paper studies the immunohistochemical expression of vascular endothelial growth factor (VEGF) and its receptors Flt‐1 and Flk‐1, and basic fibroblast growth factor (bFGF) in BOOP and UIP. It was hypothesized that there would be a difference in the expression of these angiogenic growth factors paralleling the difference in their capillarization. The results show that both VEGF and bFGF are widely expressed in BOOP and in UIP. It was shown with two different VEGF antibodies that its expression was more pronounced in the intraluminal fibromyxoid lesions in BOOP than in UIP (p<0.001 and 0.004, respectively). Similarly, bFGF also showed stronger espression in BOOP than in UIP (p<0.02) in these areas. The expression of Flt‐1 and Flk‐1 was in agreement with the expression of VEGF. It is concluded that the growth factors VEGF and bFGF may have an important role in the pathogenesis of BOOP and UIP; furthermore, their expression correlates with the angiogenic activity of the newly formed intraluminal fibromyxoid connective tissue in BOOP. Angiogenesis mediated by these growth factors may be one reason for the reversal of intraluminal fibromyxoid connective tissue in BOOP and for its good clinical outcome. Copyright © 2001 John Wiley & Sons, Ltd.
Multiple molecular alterations of FHIT in betel‐associated oral carcinoma
Authors: Chang Kuo‐Wei , Kao Shou‐Yen , Tzeng Reuo‐Jar , Liu Chung‐Ji , Cheng Ann‐Joy , Yang Shun‐Chun , Wong Yong‐Kie , Lin Shu‐Chun
Published: October 2002

To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5–9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of theinformative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT‐PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre‐invasive lesions, and 5% of the non‐cancerous match tissue.An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. Astatistically significant association was found between aberrant transcription of the FHIT geneand an abnormal level of Fhit immunoreactivity. The results indicated that alteration ofFHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Does MSI‐low exist?
Authors: Tomlinson Ian , Halford Sarah , Aaltonen Lauri , Hawkins Nicholas , Ward Robyn
Published: October 2002

Microsatellite instability is a well‐recognised phenomenon. Ten to 15% of sporadic colorectal cancers with a high level of MSI form a well defined group with distinct clinicopathological features. The set of tumours with low level of microsatellite instability (MSI‐low), though widely referred to, is not a clearly defined group. The definitions of MSI‐low have varied among groups and between different studies from the same group. Some studies have found associations between the MSI‐L phenotype and molecular features, notably a higher frequency of K‐ras mutations, and, possibly, methylation of methylguanine methyltransferase. Two recent independent studies, however, showed respectively that 68% and 79%, non‐MSI‐H cancers showed some MSI and could therefore be classed nominally as MSI‐L. There was no evidence for a qualitatively discrete MSI‐L group, but quantitative differences in the level of MSI were found. Copyright © 2002 John Wiley & Sons, Ltd.
Deregulated Bag‐1 protein expression in human oral squamous cell carcinomas and lymph node metastases
Authors: Hague Angela , Packham Graham , Huntley Suzanne , Shefford Kathryn , Eveson John W.
Published: October 2002

Bag‐1 is an anti‐apoptotic protein that promotes metastasis in some tumour cell types. To determine whether Bag‐1 expression is altered in 64 oral squamous cell carcinomas, tumour samples were compared with 17 samples of normal oral epithelium. Normal oral epithelia had pronounced nuclear staining in the basal and maturation layers and weak cytoplasmic staining that was most pronounced in the basal and suprabasal layers. Oral squamous cell carcinomas demonstrated a tendency for reduced nuclear staining intensity (p=0.036). Cytoplasmic staining intensity was not significantly different between tumour and normal tissue. However, many tumours were observed to have less of a difference between nuclear staining intensity and cytoplasmic staining intensity than normal oral epithelium. Furthermore, in lymph node metastases, cytoplasmic Bag‐1 staining was stronger in 8/13 cases than in corresponding primary tumours (p=0.021). Western blotting using nine oral primary carcinoma cell lines and four normal keratinocyte cultures showed that the isoforms Bag‐1S, Bag‐1M, and Bag‐1L were expressed in normal and malignant oral epithelial cells. Bag‐1L unique sequences were shown to adopt an exclusively nuclear, and predominantly nucleolar, localization by use of transiently transfected N‐terminal Bag‐1L‐EGFP. However, levels of Bag‐1L in carcinoma cells did not differ significantly from those of normal keratinocytes. Therefore the reduced nuclear staining observed in oral squamous cell carcinomas compared with normal epithelium may reflect changes in the localization of Bag‐1 isoforms, rather than decreased expression of Bag‐1L. Alterations in the relative proportions of Bag‐1S, Bag‐1M, and Bag‐1L were detected in 6/9 oral carcinoma cell lines; 5/9 oral carcinoma cell lines had a significantly greater proportion of Bag‐1M than normal keratinocytes and in another cell line, Bag‐1L was significantly underrepresented. Overall, the results suggest that Bag‐1 deregulation plays a role in oral carcinogenesis at two different stages: during primary carcinoma development and during lymph node metastasis. Copyright © 2002 John Wiley & Sons, Ltd.
Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation
Authors: Sylvester Paul A. , Wong Newton A. C. S. , Myerscough Neil , Warren Bryan F. , Corfield Anthony P. , Thomas Michael G. , Durdey Paul
Published: October 2002

Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long‐term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety. Ileoanal pouch biopsies from a cohort of patients and normal ileal and colonic controls were subjected to histological, biochemical, histochemical, and immunohistochemical mucin analysis. Mucin sulphation and sialic acid O‐acetylation were studied as parameters of colonic phenotypic change. Fifty‐one patients, 16 ileal, and 22 colonic controls were studied. Seventy percent of biopsies retained villous mucosal architecture, with no cases of dysplasia detected. Ileoanal pouch mucosal sulphation and sialic acid O‐acetylation did not reach colonic levels, thus indicating limited evidence for a more colonic phenotype. The data from this study suggest that colonic phenotypic change within the ileoanal reservoir is incomplete, with no cases of dysplasia detected. The degree of phenotypic change is less than in previous studies, which may support, butnot prove, our hypothesis that there may be a process of reversion to an ileal type mucosa in the ileoanal reservoir with time. Copyright © 2002 John Wiley & Sons, Ltd.
Short‐term rhythmic proliferation of human breast cancer cell lines: surface effects and fractal growth patterns
Authors: Sedivy Roland , Thurner Stefan , Budinsky Alexandra C. , Köstler Wolfgang J. , Zielinski Christoph C.
Published: October 2002

Kinetic studies of cell proliferation rates shed light on the growth dynamics of cancer. Most such studies are based on measurements of cell numbers that were evaluated in time intervals of about 12 h. Studies of the initial tumour growth with short measuring intervals are rare. This study was therefore designed with 1 h measuring intervals over a 24 h period. Human breast cancer cell lines (ZR‐75‐1, SK‐BR‐3, MCF‐7) and a benign cell line (HBL‐100) were used to study the hourly thymidine uptake as a measure of cells in synthesis. In parallel experiments, the same cell lines were also exposed to tumour necrosis factor alpha (TNF‐α) to explore the effect of an apoptosis‐inducing substance on initial tumour growth kinetics. In time‐evolution plots, there was an oscillation of the labelling index of thymidine uptake for all investigated cell lines, with and without TNF‐α. Based on the results obtained, a mathematical model was developed mimicking the real experiment. To describe the system dynamically a cellular automaton model was studied. The growth kinetics revealed by the simulation were in accordance with our experimental data. Two‐ and three‐dimensional growth simulations of this computer model yielded objects morphologically similar to real images of human breast cancer. Almost identical fractal dimensions of the virtual and real tumours further supported this visual similarity. The cellular automata models could, therefore, be seen as a bridge towards realistic in vivo scenarios. From a clinical point of view, the results obtained may be applicable not only to primary tumours, but even to tumour cell microfoci and small metastases, which are a major concern in early metastasizing tumours such as breast cancer. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c‐erbB2
Authors: Bartošová Mária , Parkkila Seppo , Pohlodek Kamil , Karttunen Tuomo J. , Galbavý Štefan , Mucha Vojtech , Harris Adrian L. , Pastorek Jaromír , Pastoreková Silvia
Published: October 2002

CA IX is a tumour‐associated carbonic anhydrase with proposed roles in pH modulation and intercellular communication. Its distribution was examined in normal, benign and malignant breast tissues and compared with expression of breast tumour markers including oestrogen receptor, c‐erbB2, c‐erbB3 and CD44. Tissue specimens were analysed using immunohistochemistry and/or reverse transcriptase–polymerase chain reaction (RT‐PCR). CA IX was detected by IHC in 12/26 (46%) malignant tissues, 4/36 (11%) benign lesions, but not in 10 normal breasts. Staining was mostly confined to plasma membranes of abnormal epithelial cells, but in five cases was found in adjacent stroma. Semi‐quantitative RT‐PCR detected CA9 mRNA in 25/39 (64%) malignant tumours, 11/33 (33%) benign lesions, but in none of three normal breasts. Comparative RT‐PCR analysis of malignant tissues revealed a relationship between CA9 positivity and c‐erbB2 overexpression (p=0.05). Moreover, CA9‐positive specimens displayed a significantly higher median level of c‐erbB2 than CA9‐negative ones (p=0.02). No significant association was found with the other markers. The results of this study support the possible importance of CA IX for breast carcinogenesis and suggest its potential use as a breast tumour marker. Copyright © 2002 John Wiley & Sons, Ltd.
Tenascin‐C is a useful marker for disease activity in myocarditis
Authors: Imanaka‐Yoshida Kyoko , Hiroe Michiaki , Yasutomi Yasuhiro , Toyozaki Tetsuya , Tsuchiya Takuro , Noda Naomi , Maki Toshiki , Nishikawa Toshio , Sakakura Teruyo , Yoshida Toshimichi
Published: October 2002

Tenascin‐C (TNC) is an extracellular matrix protein which appears at active sites of tissue remodelling during embryogenesis or cancer invasion. In normal heart, TNC is only present during the early stages of development but reappears in pathological states. This study examined the diagnostic value of TNC for assessing disease activity of myocarditis. Expression of TNC was examined in myosin‐induced autoimmune myocarditis mouse models. Sequential changes in amount, localization and the producing cells were analysed by reverse transcriptase–polymerase chain reaction, western blotting, immunohistochemistry and in situ hybridization and compared with the histological picture. The expression of TNC was upregulated at a very early stage of myocarditis. Immunostaining was detectable before cell infiltration and myocytolysis became histologically apparent, remained during the active stage while cell infiltration and necrosis continued, and disappeared in scar tissue with healing. TNC immunostaining was always observed at the periphery of necrotic or degenerating cardiomyocytes in foci of inflammation, the expression level correlating with histological evidence of inflammatory activity. Interstitial fibroblasts were the major source of TNC, expressing the large isoform containing alternative splicing sites. These data demonstrate that TNC is a useful marker for evaluation of disease activity in myocarditis. Copyright © 2002 John Wiley & Sons, Ltd.
Multiple complementary transcripts of pCMa1, a novel gene located at chromosome 11p15.1–2, and melanocytic cell transformation
Authors: Meije Clifton B. , Das Pranab K. , Jans Miranda M. E. , Hau Chi , van der Wal Allard C. , Alders Marielle , Hakvoort Theodorus B. M. , Weidle Ulrich H. , Lamers Wouter H. , Swart Guido W. M.
Published: October 2002

The cDNA clone pCMa1 (0.45 kb) is one of the 12 novel cDNAs, previously identified when comparing RNA expression profiles of melanocytes, naevus cells, and non‐metastatic melanoma cells. This clone did not reveal a unique long open reading frame. The pCMa1 gene localized to the distal, telomere proximal region on the short arm of chromosome 11.p15.1–2. Northern blot analyses with single‐stranded cRNA probes revealed the presence of various complementary pCMa1 transcripts of different lengths, which are not enriched in the poly(A)+ RNA fraction. The arbitrarily defined plus strand (used as a probe) mainly hybridized to 0.45 kb and 4.0 kb minus transcripts in total RNA samples, and the minus strand (used as a probe) hybridized to a major plus transcript of 4.0 kb. By RNA in situ hybridization, the highest levels of the plus transcripts were observed in melanocytic naevi (12/12), particularly in congenital naevi, whereas normal skin melanocytes (12/12) were negative. pCMa1 plus transcripts were detected in naevus cell nests (100%) near the dermo‐epidermal junction. Expression, however, diminished to some extent in the deeper parts of the melanocytic naevi. Although most of the cutaneous primary melanoma lesions (11/15) showed detectable, but variable levels of plus transcripts of pCMa1 in the papillary to reticular dermis, not more than 10% of the melanoma cells were positive. The majority of melanoma metastases (6/7) were negative, while the positive lesion originated from a patient with a positive primary melanoma. Furthermore, plus transcripts were present in the nuclei of non‐metastatic melanoma cells in culture, whereas metastatic cells showed elevated expression both in the nucleus and in the cytoplasm. Briefly, the data show transient up‐regulation of pCMa1 in neoplastic progression of melanocytic cells, with peak levels occurring during naevus stages, and suggest that pCMa1 is a molecular marker in melanocytes for the early changes from the proliferating phenotype to malignant transformation. Copyright © 2002 John Wiley & Sons, Ltd.
Epidermal stem cells
Authors: Janes Sam M. , Lowell Sally , Hutter Caroline
Published: October 2002

The clinical implications of understanding epidermal stem cell biology abound. Thousands of burns victims across the world have benefited from early research into the proliferation of epidermal keratinocytes in vitro. Advances now indicate there are a number of stem cell repositories within the epidermis, two of which, the interfollicular epidermis and the bulge region of the hair follicle, may supply each other when damaged. This review details the progress made in the identification and characterisation of stem cells within the epidermis and discusses the molecules involved in the epidermal stem cell's choice of fate. Finally, the skin, like bone marrow, could be a readily accessible source of stem cells for therapeutic intervention and evidence of skin stem cell plasticity is highlighted.
Analysis of the progression of fibroepithelial tumours of the breast by PCR‐based clonality assay
Authors: Kuijper Arno , Buerger Horst , Simon Ronald , Schaefer Karl‐Ludwig , Croonen Anita , Boecker Werner , van der Wall Elsken , van Diest Paul J.
Published: October 2002

Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A relationship between the two tumours has been suggested in the literature. This study investigated the clonality of both the stroma and the epithelium of these fibroepithelial tumours and attempted to construct a model in which fibroadenoma can progress in both an epithelial and a stromal direction. Fibroadenomas (n=25) and phyllodes tumours (n=12) were selected for analysis. Tissue was microdissected and analysed for clonality using a polymerase chain reaction (PCR)‐based assay targeted at an X‐linked polymorphic marker, the human androgen receptor gene (HUMARA). Nineteen fibroadenomas and nine phyllodes tumours could be analysed. Normal‐appearing epithelium, hyperplastic epithelium, and stroma removed from fibroadenomas were polyclonal. As expected, carcinoma in situ (CIS) removed from four fibroadenomas was monoclonal. Three areas of apparent stromal expansion within fibroadenoma were monoclonal, suggesting stromal progression. Mostly, the stroma of phyllodes tumours was monoclonal and the epithelium polyclonal. In two cases, however, the epithelium seemed to be monoclonal, whereas in three other cases the stromal component was polyclonal. These findings indicate that fibroadenoma can progress in an epithelial direction to CIS and in a stromal direction to phyllodes tumour. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic progression in sporadic endometrial and gastrointestinal cancers with high microsatellite instability
Authors: Furlan Daniela , Casati Barbara , Cerutti Roberta , Facco Carla , Terracciano Luigi , Capella Carlo , Maria Chiaravalli Anna
Published: October 2002

This study selected a series of 136 MSI‐H (microsatellite instability at high frequency) gastric, colorectal, and endometrial carcinomas combining immunohistochemical analysis for hMLH1 or hMSH2 gene products and microsatellite study. The clinico‐pathological profile of all tumours was correlated with the overall instability rates at coding and non‐coding repeats, in order to clarify the role and the mutation timing of seven target genes (TGFβRII, IGFIIR, BAX, hMSH3, hMSH6, CHK1, and BRCA2) in the progression of an MSI‐H neoplasm. Regardless of the primary site, the results confirm a model of oncogenesis in which inactivation of hMLH1, or less frequently hMSH2, may initiate a pathway culminating in a progressive accumulation of frameshifts in coding region (CDR) microsatellites. Comparing gastrointestinal and endometrial tumours, significantly lower levels of microsatellite instability at both coding and non‐coding repeats were observed. Among gastric and colorectal tumours, the detection of small shortening within Bat‐26 and Bat‐25 markers defines a subgroup of MSI‐H gastrointestinal tumours invariably characterized by early stage at diagnosis. In these tumours, mutations of TGFβRII or BAX genes precede frameshifts in the other tested genes. The analysis of correlations between the mutational and clinico‐pathological profiles of advanced gastrointestinal tumours revealed that the higher levels of microsatellite instability at both coding and non‐coding repeats were not associated with a more advanced clinico‐pathological stage or a less favourable outcome. A significant association was observed between a low number of CDR frameshifts and the presence of lymph‐node metastasis in advanced gastrointestinal tumours. The existence of advanced MSI‐H tumours with more aggressive behaviour and a ‘mild mutator phenotype’ could be explained by hypothesizing an overlapping of different mechanisms of tumourigenesis, including both the mutator and the suppressor pathways; this should be tested by further studies. Copyright © 2002 John Wiley & Sons, Ltd.
Potential impact of a new blood glucose monitoring device: the GlucoWatch® Biographer
Authors: Chan NN , Hurel SJ
Published: October 2002

Home blood glucose monitoring may be laborious, time‐consuming, inconvenient and painful. Failure to test may preclude optimisation of glycaemic control. We aimed to evaluate the potential usefulness of a new noninvasive automatic glucose monitor, the GlucoWatch® Biographer. Eight patients with type 1 diabetes and two with type 2 diabetes (4M:6F) aged between 23 and 65 years participated in this study. All participants were given 1 hour of instruction prior to provision of the GlucoWatch®. They were given contact numbers and reviewed weekly. Several disadvantages were encountered by the participants, which included the daily 3 hour calibration period (n = 10), skin irritations (n = 6) and skipped measurements (n = 2) due to unsatisfactory probe contact due to skin temperature or sweats. Several patients, however, found it invaluable to have their daily profile monitored to allow insulin dosage adjustment and detection of hypoglycaemia.

The GlucoWatch® Biographer is an invaluable tool that allows noninvasive detection of glucose trends, which contributes to glycaemic control. However, it is not suitable for every patient. Self‐motivation and ability to learn how to use the device are the key factors. Copyright © 2002 John Wiley & Sons, Ltd.