bluuebunny/crossref_metadata_2025 huggingface dataset:
A consistent splitting scheme for unsteady incompressible viscous flows I. Dirichlet boundary condition and applications
Authors: Wong J. C.‐F. , Chan M. K.‐H.
Published: December 2005

A well‐recognized approach for handling the incompressibility constraint by operating directly on the discretized Navier–Stokes equations is used to obtain the decoupling of the pressure from the velocity field. By following the current developments by Guermond and Shen, the possibilities of obtaining accurate pressure and reducing boundary‐layer effect for the pressure are analysed. The present study mainly reports the numerical solutions of an unsteady Navier–Stokes problem based on the so‐called consistent splitting scheme (J. Comput. Phys. 2003; 192:262–276). At the same time the Dirichlet boundary value conditions are considered. The accuracy of the method is carefully examined against the exact solution for an unsteady flow physics problem in a simply connected domain. The effectiveness is illustrated viz. several computations of 2D double lid‐driven cavity problems. Copyright © 2005 John Wiley & Sons, Ltd.
Numerical simulation of pollutant transport acted by wave for a shallow water sea bay
Authors: Tao Sun , JianHua Tao
Published: December 2005

A numerical model of pollutant transport acted by water waves on a shallow‐water mild‐slope beach is established in this study. The numerical model is combined with a wave propagation model, a multiple wave‐breaking model, a wave‐induced current model and a pollutant convection–dispersion model. The wave propagation model is based on the higher‐order approximation of parabolic mild‐slope equation which can be used to simulate the wave refraction, diffraction and breaking in a large area of near‐shore zone combined with the wave‐breaking model. The wave‐induced current model is established using the concept of the radiation stress and considering the effect of bottom resistance caused by waves. The numerical model is verified by laboratory experiment results of regular and irregular waves over two mild beaches with different slopes. The numerical results agree well with experimental results.

The numerical model has been applied in the near‐shore zone of Bohai bay in China. It is concluded that pollutant transport parallel to the shoreline due to the action of waves, which will induce serious pollution on the beach. Copyright © 2005 John Wiley & Sons, Ltd.
Flow effects of blood constitutive equations in 3D models of vascular anomalies
Authors: Neofytou Panagiotis , Tsangaris Sokrates
Published: December 2005

The effects of different blood rheological models are investigated numerically utilizing two three‐ dimensional (3D) models of vascular anomalies, namely a stenosis and an abdominal aortic aneurysm model. The employed CFD code incorporates the SIMPLE scheme in conjunction with the finite‐volume method with collocated arrangement of variables. The approximation of the convection terms is carried out using the QUICK differencing scheme, whereas the code enables also multi‐block computations, which are useful in order to cope with the two‐block grid structure of the current computational domain. Three non‐Newtonian models are employed, namely the Casson, Power‐Law and Quemada models, which have been introduced in the past for modelling the rheological behaviour of blood and cover both the viscous as well as the two‐phase character of blood. In view of the haemodynamical mechanisms related to abnormalities in the vascular network and the role of the wall shear stress in initiating and further developing of arterial diseases, the present study focuses on the 3D flow field and in particular on the distribution as well as on both low and high values of the wall shear stress in the vicinity of the anomaly. Finally, a comparison is made between the effects of each rheological model on the aforementioned parameters. Results show marked differences between simulating blood as Newtonian and non‐Newtonian fluid and furthermore the Power‐Law model exhibits different behaviour in all cases compared to the other models whereas Quemada and Casson models exhibit similar behaviour in the case of the stenosis but different behaviour in the case of the aneurysm. Copyright © 2005 John Wiley & Sons, Ltd.
Direct numerical simulation of settling of a large solid particle during bioconvection
Authors: Geng P. , Kuznetsov A. V.
Published: December 2005

Settling of a large solid particle in bioconvection flow caused by gyrotactic microorganisms is investigated. The particle is released from the top of the bioconvection chamber; its settling pattern depends on whether it is released in the centre of the bioconvection plume or at its periphery. The Chimera method is utilized; a subgrid is generated around a moving particle. The method suggested by Liu and Wang (Comput. Fluid 2004; 33:223–255) is further developed to account for the presence of a moving boundary in the streamfunction‐vorticity formulation using the finite‐difference method. A number of cases for different release positions of the particle are computed. It is demonstrated that bioconvection can either accelerate or decelerate settling of the particle depending on the initial position of the particle relative to the plume centre. It is also shown that the particle impacts bioconvection plume by changing its shape and location in the chamber. Copyright © 2005 John Wiley & Sons, Ltd.
Applications of the artificial compressibility method for turbulent open channel flows
Authors: Lee J. W. , Teubner M. D. , Nixon J. B. , Gill P. M.
Published: December 2005

A three‐dimensional (3‐D) numerical method for solving the Navier–Stokes equations with a standard k–ε turbulence model is presented. In order to couple pressure with velocity directly, the pressure is divided into hydrostatic and hydrodynamic parts and the artificial compressibility method (ACM) is employed for the hydrodynamic pressure. By introducing a pseudo‐time derivative of the hydrodynamic pressure into the continuity equation, the incompressible Navier–Stokes equations are changed from elliptic‐parabolic to hyperbolic‐parabolic equations. In this paper, a third‐order monotone upstream‐centred scheme for conservation laws (MUSCL) method is used for the hyperbolic equations. A system of discrete equations is solved implicitly using the lower–upper symmetric Gauss–Seidel (LU‐SGS) method. This newly developed numerical method is validated against experimental data with good agreement. Copyright © 2005 John Wiley & Sons, Ltd.
A generic, mass conservative local grid refinement technique for lattice‐Boltzmann schemes
Authors: Rohde M. , Kandhai D. , Derksen J. J. , van den Akker H. E. A.
Published: December 2005

A generic, mass conservative local grid refinement technique for the lattice‐Boltzmann method (LBM) is proposed. As a volumetric description of the lattice‐Boltzmann equation is applied, mass conservation can be imposed by allowing the lattice‐Boltzmann particles to move from coarse grid cells to fine grid cells and vice versa in the propagation step. In contrast to most existing techniques, no spatial and temporal interpolation of particle densities is applied. Moreover, since the communication between the coarse and the fine grids is independent on the collision step, the method can be used for any LBM scheme.

It was found that the method is second‐order accurate in space for 2‐D Poiseuille flow and different grid setups. The method was also applied to the case of 2‐D lid driven cavity flow at Re=1000, where half of the cavity was locally refined. It was found that the locations of the two lower vortices could be captured accurately. Finally, a direct numerical simulation (DNS) of turbulent channel flow at Reτ=360 was performed where the grid was locally refined near the walls of the channel. Good first‐ and second‐order turbulence statistics were obtained, showing the applicability of the local grid refinement technique for complex flows. Copyright © 2005 John Wiley & Sons, Ltd.
Three‐dimensional lattice Boltzmann BGK model and its application to flows with heat transfer in a rectangular microchannel
Authors: Chew Y. T. , Niu X. D. , Shu C.
Published: December 2005

In this paper, we present a 3D lattice Boltzmann BGK model for simulation of micro flows with heat transfer. This model is an extension of the two‐dimensional model that is based on the kinetic theory and the thermal lattice Boltzmann method. The kinetic relations of the relaxation times in this model were linked with the Knudsen number, and a diffuse scattering boundary condition for the velocity and thermal fields was presented for the 3D lattice Boltzmann method. The present 3D lattice Boltzmann model was successfully applied to simulate the flow and heat transfer in rectangular channels using the 3D TLLBM developed by the authors. Numerical results obtained by the present method show that the LBM can give a good prediction of the micro fluidic behaviours with thermal effects. Copyright © 2005 John Wiley & Sons, Ltd.
Mandevilles Reise in die weite Welt
Authors: Röhl Susanne
Published: December 2005

Einstmals war er so bekannt wie Marco Polo: Jean de Mandeville und sein Bericht über eine spektakuläre Weltreise. Die Verbreitung der französischen Handschriften dieses Bestsellers konnte jetzt rekonstruiert werden
Der Blutdruck und das Alltagsleben
Authors: Duschek Stefan , Schandry Rainer
Published: December 2005

Beeinträchtigt chronisch niedriger Blutdruck die Leistungsfähigkeit des Gehirns? Leistungstests und moderne Messverfahren geben in neuer Weise Auskunft
Dienst und Leistung
Authors: Schneider Christoph
Published: December 2005

Die Deutsche Forschungsgemeinschaft unterstützt die Wissenschaft „in allen ihren Zweigen”︁. Das verpflichtet ihre Geschäftsstelle zu fairem Wettbewerb für alle Disziplinen und zu einer Auswahl der unterstützten Projekte nach Qualität
Vom „Fingerabdruck”︁ der Wildbiene
Authors: Steinhage Volker , Schröder Stefan , Roth Volker , Cremers Armin B. , Drescher Wilhelm , Wittmann Dieter
Published: December 2005

Mithilfe des Systems ABIS können Wildbienen schnell und sicher erkannt werden. Das Verfahren setzt auf die automatisierte Bildanalyse von Bienenflügeln, die neue Wege für die computergestützte Artenbestimmung ermöglicht
Der gestrickte Hochleistungsrotor
Authors: Hufenbach Werner
Published: December 2005

Nicht nur Industrie und Maschinenbau verlangen nach immer leistungsfähigeren Rotoren, die höchsten Beanspruchungen standhalten. Starke Textilien können helfen und den Bau von federleichten Hochleistungsrotoren unterstützen
Die turbulente Geburt der Sterne
Authors: Jappsen Anne‐Katharina , Schmeja Stefan , Klessen Ralf Stephan
Published: December 2005

Das Entstehen von Sternen ist ein dramatischer Vorgang, der Physiker vor viele ungelöste Fragen stellt. Mit Computersimulationen sind Forscher den Mechanismen auf der Spur, die aus dem Gas der Milchstraße einen Stern wie unsere Sonne entstehen lassen
Der grüne Schatz der pharaonischen Ärzte
Authors: Seifert Karlheinz
Published: December 2005

Im Alten Ägypten spielten Heilpflanzen bei der Behandlung von Krankheiten eine große Rolle. Wenn heute die pharmakologischen Wirkungen dieser Pflanzen im Labor untersucht werden, ist dies nicht nur für Chemiker aufschlussreich
Das Klima aus dem Untergrund
Authors: Kögel‐Knabner Ingrid , v. Lützow Margit
Published: December 2005

Neue Nachrichten über alte Stoffe: In Böden sind vier Fünftel der weltweiten Kohlenstoffvorräte gebunden. Humus spielt dabei eine besondere Rolle
Human amyloid β‐induced neuroinflammation is an early event in neurodegeneration
Authors: Craft Jeffrey M. , Watterson D. Martin , Van Eldik Linda J.
Published: December 2005

Using a human amyloid β (Aβ) intracerebroventricular infusion mouse model of Alzheimer's disease‐related injury, we previously demonstrated that systemic administration of a glial activation inhibitor could suppress neuroinflammation, prevent synaptic damage, and attenuate hippocampal‐dependent behavioral deficits. We report that Aβ‐induced neuroinflammation is an early event associated with onset and progression of pathophysiology, can be suppressed by the glial inhibitor over a range of intervention start times, and is amenable to suppression without inhibiting peripheral tissue inflammatory responses. Specifically, hippocampal neuroinflammation and neurodegeneration occur in close time proximity at 4–6 weeks after the start of infusion. Intraperitoneal administration of inhibitor for 2‐week intervals starting at various times after initiation of Aβ infusion suppresses progression of pathophysiology. The glial inhibitor is a selective suppressor of neuroinflammation, in that it does not block peripheral tissue production of proinflammatory cytokines or markers of B‐ and T‐cell activation after a systemic lipopolysaccharide challenge. These results support a causal link between neuroinflammation and neurodegeneration, have important implications for future therapeutic development, and provide insight into the relative time window for targeting neuroinflammation with positive neurological outcomes. © 2005 Wiley‐Liss, Inc.
NG2 upregulation in the denervated rat fascia dentata following unilateral entorhinal cortex lesion
Authors: Dehn Doris , Burbach Guido J. , Schäfer Ruth , Deller Thomas
Published: December 2005

The chondroitin sulfate proteoglycan NG2 is a component of the glial scar following brain injury. Because of its growth inhibiting properties, it has been suggested to impede axonal regeneration. To study whether NG2 could also regulate axonal growth in denervated brain areas, changes in NG2 were studied in the rat fascia dentata following entorhinal deafferentation and were correlated with the post‐lesional sprouting response. Laser microdissection was employed to selectively harvest the denervated molecular layer and combined with quantitative RT‐PCR to measure changes in NG2 mRNA (6 h, 12 h, 2 days, 4 days, 7 days post‐lesion). This revealed increases of NG2 mRNA at day 2 (2.5‐fold) and day 4 (2‐fold) post‐lesion. Immunocytochemistry was used to detect changes in NG2 protein (1 days, 4 days, 7 days, 10 days, 14 days, 30 days, 6 months post‐lesion). NG2 staining was increased in the denervated outer molecular layer at day 1 post‐lesion, reached a maximum 10 days post‐lesion, and returned to control levels thereafter. Electron microscopy revealed NG2 immunoprecipitate on glial surfaces and in the extracellular matrix around neuronal profiles, indicating that NG2 is secreted following denervation. Double labeling of NG2‐immunopositive cells with markers for astrocytes, microglia/macrophages, and mature oligodendrocytes suggested that NG2 cells are a distinct glial subpopulation before and after entorhinal deafferentation. BrdU labeling revealed that some of the NG2‐positive cells are generated post‐lesion. Taken together, our data revealed a layer‐specific upregulation of NG2 in the denervated fascia dentata that coincides with the sprouting response. This suggests that NG2 could regulate lesion‐induced axonal growth in denervated areas of the brain. © 2005 Wiley‐Liss, Inc.
Discounting and cost‐effectiveness in NICE – stepping back to sort out a confusion
Authors: Claxton Karl , Sculpher Mark , Culyer Anthony , McCabe Chris , Briggs Andrew , Akehurst Ron , Buxton Martin , Brazier John
Published: December 2005

Brouwer and colleagues [1] argue that the reasons for specifying an equal discount rate for health outcomes and costs in the recent guidance on methods of technology appraisal issued by the National Institute for Clinical Excellence (NICE) [2] is both opaque and wrong. They argue that a lower rate should apply to health outcomes like QALYs. It is also claimed that the guidance on discounting represents a step backwards, that is both inconsistent with current theoretical insights and will prejudice the outcome of cost‐effectiveness studies of preventive interventions.

The reasoning behind the use of equal discount rates for costs and health outcomes is indeed not well developed in the published guidance. Nor does it reflect the debate that underpinned the guidance. We therefore welcome the opportunity to explain more completely the rationale in the minds of the principal authors of the current guidance. Copyright © 2006 John Wiley & Sons, Ltd.
Cyclin G‐associated kinase: A novel androgen receptor‐interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer
Authors: Ray Mira R. , Wafa Latif A. , Cheng Helen , Snoek Robert , Fazli Ladan , Gleave Martin , Rennie Paul S.
Published: December 2005

The androgen receptor (AR), a steroid receptor family member, is a ligand‐dependent transcription factor that has an integral role in normal prostate development. Alterations in AR‐mediated activity can result in abnormal gene expression, dysregulated cell growth and prostate cancer. Coregulator proteins that interact with AR to influence activity and specificity of the AR‐response may also have an important role in prostate cancer progression. Since the NH2‐terminal domain (NTD) of AR encodes the ligand‐independent activation function (AF)‐1, this domain is incompatible with conventional yeast two‐hybrid systems. Therefore, we have used the Tup1 repressed transactivator (RTA) system, which exploits the intrinsic transactivation properties of AR.NTD, for identification of novel AR‐interacting proteins. Using this system, cyclin G‐associated kinase (GAK) was identified as an AR interacting protein, and GST pull‐down assays were used to confirm the interaction. GAK was shown to enhance the AF‐1 function of AR activity in a ligand‐dependent manner. Additionally, GAK enhanced the AR transcriptional response even at low concentrations of androgens, which is relevant to AR activity in androgen‐independent prostate cancer. Finally, neo‐adjuvant hormone therapy (NHT) tissue microarray analysis demonstrated that GAK expression increased significantly with prostate cancer progression to androgen independence, which suggests a prognostic role for GAK in advanced disease. © 2005 Wiley‐Liss, Inc.
Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue
Authors: Meinl Walter , Pabel Ulrike , Osterloh‐Quiroz Mandy , Hengstler Jan G. , Glatt Hansruedi
Published: December 2005

Use of herbal preparations containing Aristolochia species has led to progressive nephropathy and urothelial cancer in humans. Analysis of DNA adducts formed in human target tissues and studies in animal models have pointed out a major role of the secondary plant metabolites, aristolochic acids, in these effects. Only a minority of the users of Aristolochia‐containing products developed nephropathy and cancer, suggesting differences in individual susceptibility. Differences in metabolic activation and inactivation frequently affect the susceptibility towards chemicals. Others have shown that the activation of aristolochic acids to DNA‐reactive and mutagenic metabolites requires reduction of their aryl nitro group. The biological activity of numerous nitro‐ and aminoarenes, after appropriate phase I metabolism, is strongly enhanced in the presence of acetyltransferases or sulphotransferases (SULTs). In the present study, we demonstrate that expression of human SULTs in bacterial and mammalian target cells reinforces the mutagenic activity of aristolochic acids. Using Salmonella typhimurium TA1538 as the recipient organism, we identified the expression of all 12 human SULT forms. SULT1A1 led to the strongest increase in the mutagenicity of aristolochic acids. Some activation was also observed with SULT1B1, but not with the remaining forms. The role of SULT1A1 in the activation of aristolochic acids was corroborated using S. typhimurium TA100‐ and Chinese hamster V79‐derived target cells engineered for expression of human SULT1A1 when compared with control cells. Furthermore, pentachlorophenol, an inhibitor of SULT1A1, strongly reduced the mutagenic effect of aristolochic acids in V79‐hCYP2E1‐hSULT1A1 cells. Moreover, we demonstrate that SULT1A1 and SULT1B1 are expressed in human kidney using immunoblot analysis, but their levels are substantially lower than in liver. Finally, we discuss the possibility that reactive sulphuric acid conjugates produced in other tissues are transferred to kidney and ureter. © 2005 Wiley‐Liss, Inc.
Clinical significance of altered expression of retinoid receptors in oral precancerous and cancerous lesions: Relationship with cell cycle regulators
Authors: Ralhan Ranju , Chakravarti Nitin , Kaur Jatinder , Sharma Chavvi , Kumar Anupam , Mathur Meera , Bahadur Sudhir , Shukla Nootan Kumar , Deo Suryanaryana VS
Published: December 2005

Alterations in expression of retinoid receptors are implicated in human cancers. We hypothesized that altered expression of retinoic acid receptors (RARα,β,γ) and retinoid X receptor RXRα and their relationship with cell cycle regulators (p53, p16, p21) is associated with development, progression and prognosis of oral cancer. Immunohistochemical analysis of RAR α, β, γ and RXRα proteins was carried out on serial sections from 244 oral squamous cell carcinomas (OSCCs), 102 potentially malignant lesions (65 hyperplasias, 37 dysplasias), 83 matched histologically normal oral tissues and 29 normal mucosa from non‐exposed individuals without oral lesions and correlated with expression of cell cycle regulators p53, p16 and p21 as well as with clinicopathological parameters. Expression of retinoid receptors RARβ, RARγ, RXRα and cell cycle regulators p16 and p21 was decreased in majority of oral SCCs as well as in potentially malignant lesions. Multivariate stepwise logistic regression analysis carried out for comparison of non‐exposed normal oral mucosa with histologically normal oral tissues from patients with oral lesions showed significant loss of RARβ or p53 accumulation (RARβ−/p53+ Odd's ratio, OR = 266.6, p = 0.000); non‐exposed normal mucosa from individuals without oral lesions with potentially malignant lesion was RARβ−/p21−/p53+ (OR = 215.7, p = 0.000); matched normal to potentially malignant stage was RARα+/p21− (OR = 4.414, p = 0.005); hyperplasia to dysplasia was RARα+/p53+ (OR = 4.72, p = 0.005) and potentially malignant to malignant phenotype was RARα+ (OR = 2.061, p = 0.004). The prognostic relevance of these factors was assessed in 115 of these SCC patients who were followed‐up for a maximum period of 94 months (median 21 months). Multivariate analysis using Cox's proportional Hazard's model showed that RARα+/p21− phenotype was associated with shorter disease‐free survival (Hazard's ratio, HR = 1.863, p = 0.0471). To our knowledge, this is the first large study showing alterations in expression of retinoid receptors at the protein level at different stages in development and progression of oral SCC. It also underscored the prognostic significance of retinoid receptors and their interactions with cell cycle regulators in multistep oral tumorigenesis. © 2005 Wiley‐Liss, Inc.
Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis
Authors: Scott Michael , McCluggage W. Glenn , Hillan Kenneth J. , Hall Peter A. , Russell S.E. Hilary
Published: December 2005

Ovarian carcinoma represents the most lethal gynaecological malignancy. A variety of morphological subtypes are recognised (e.g. serous, mucinous, endometrioid), which may be benign, borderline or malignant. While their relationship is controversial, knowledge of the molecular mechanisms of ovarian tumorigenesis may help resolve this issue and perhaps identify early markers of disease. Perturbed patterns of expression of the SEPT9 gene on chromosome 17q25.3 have been implicated in a variety of tumour types including both breast and ovarian neoplasia. In preliminary studies, we showed that SEPT9 mRNA was upregulated in a bank of ovarian tumours, which included benign, borderline and malignant tumours, and reported increased levels of one splice variant, SEPT9_v4*. We now describe a comprehensive analysis of SEPT9 expression specifically in serous and mucinous ovarian tumours (benign, borderline and malignant), using cDNA microarray, semi‐ and quantitative RTPCR of microdissected archival tumour material. Our data show consistent and specific overexpression of both SEPT9_v1 and SEPT9_v4* transcripts in the epithelial component of ovarian tumours. These transcripts show highest levels of expression in serous and mucinous borderline tumours. SEPT9_v1 is also upregulated in both serous and mucinous carcinomas. Interestingly, highest levels of expression are observed in serous borderline and low‐grade tumours rather than high‐grade in keeping with a model of progression of benign, borderline and low‐grade serous tumours. © 2005 Wiley‐Liss, Inc.
Immunocytochemistry in liquid‐based cervical cytology: Analysis of clinical use following a cross‐sectional study
Authors: Sahebali Shaira , Depuydt Christophe E. , Boulet Gaëlle A.V. , Arbyn Marc , Moeneclaey Liliane M. , Vereecken Annie J. , Van Marck Eric A. , Bogers Johannes J.
Published: December 2005

Cytological screening for cervical cancer is hampered by imperfect sensitivity and low inter‐observer reproducibility. Human papillomavirus (HPV) testing lacks specificity as a primary screening method. Studies indicate that immunocytochemical detection of alterations caused by HPV in the host cells can optimise screening. Here, the potential of p16INK4a (cyclin‐dependent kinase inhibitor p16) and MIB‐1 (Ki‐67 proliferation marker) as adjunct molecular markers for cervical lesions was investigated in a prospective, cross‐sectional study of 500 samples in the framework of opportunistic screening in Flanders, Belgium. A consecutive series of 200 samples and 100 samples from the cytological categories ASC, LSIL and HSIL were investigated. Surepath samples were interpreted according to the Bethesda 2001 reporting system. HPV testing was done with MY09/MY11 consensus PCR. Immunocytochemistry for p16INK4a and MIB‐1 was performed with an automated staining protocol. The number of immunoreactive cells/1,000 cervical cells was assessed. There was a higher mean number of p16INK4A and MIB‐1 immunoreactive cells/1,000 cells in HSIL (4.06 ± 1.93 and 11.13 ± 2.83, respectively) compared to other cytological categories. Both markers showed a large spread in counts, for all categories. In cases of HSIL without immunoreactive cells for either marker, low cellularity and long‐term storage in water were often the cause of false negativity. This study confirms that positive staining for p16INK4a and MIB‐1 is highly correlated with presence of high‐grade lesions. These markers could be used as adjuncts to increase the sensitivity of cytological screening as well as the specificity of the HPV test. However, clear methodological standards are needed for optimal performance of immunocytochemistry in a clinical setting. © 2005 Wiley‐Liss, Inc.
Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor
Authors: Panagopoulos Ioannis , Nilsson Therese , Domanski Henryk A. , Isaksson Margareth , Lindblom Pia , Mertens Fredrik , Mandahl Nils
Published: December 2005

Inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic spindle cells and infiltrating inflammatory cells. Cytogenetic analyses have revealed that a subgroup of IMT, in particular among children and young adults, harbors clonal chromosomal rearrangements involving chromosome band 2p23. Further, molecular genetic studies have shown that these rearrangements target the ALK gene, serving as the 3′‐partner in fusion genes with various translocation partners. In the present study, we describe the finding of a novel SEC31L1/ALK fusion gene in an intraabdominal IMT of a young man. G‐band analysis revealed a translocation t(2;4)(p23;q21) and subsequent fluorescence in situ hybridization with locus‐specific probes strongly indicated disruption of the ALK locus on chromosome 2. Immunostaining with monoclonal mouse anti‐human CD246 ALK Protein showed diffuse cytoplasmic positivity. Using reverse primers for the ALK‐gene, we could, by 5′‐RACE methodology, amplify a single 1.2 kb fragment. Sequence analysis showed that the fragment was a hybrid cDNA product in which nt 3012 of SEC31L1 (NM_016211), located in band 4q21, was fused in‐frame to nt 4080 of ALK (NM_004304). RT‐PCR with two sets of primer pairs specific for SEC31L1 and ALK amplified two transcripts, which at sequencing corresponded to two types of chimeric SEC31L1/ALK transcripts. In the long, type I, transcript nt 3012 of SEC31L1 (NM_016211) was fused in‐frame to nt 4080 of ALK. In the short, type II, transcript nt 2670 of SEC31L1 was fused in‐frame to nt 4080 of ALK. Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of SEC31L1 and intron 20 of ALK. © 2005 Wiley‐Liss, Inc.
Her‐2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab‐based therapy in patients with metastatic breast cancer
Authors: Hudelist Gernot , Köstler Wolfgang J. , Czerwenka Klaus , Kubista Ernst , Attems Johannes , Müller Ruth , Gschwantler‐Kaulich Daphne , Manavi Mahmood , Huber Isabell , Hoschützky Heinz , Zielinski Christoph C. , Singer Christian F.
Published: December 2005

Her‐2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti‐Her‐2/neu antibody trastuzumab (Herceptin®) has become a valuable therapeutic option for patients with Her‐2/neu‐overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her‐2/neu and EGFR in 46 Her‐2/neu‐overexpressing tumor samples from trastuzumab‐treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr‐1248 Her‐2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr‐845 and (p)tyr‐1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr‐1248 Her‐2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr‐845, ptyr‐1173 EGFR and EGFR did not. The presence of ptyr‐1248 Her‐2/neu and ptyr‐845 or ptyr‐1173 EGFR, however, was a strong predictor of both response to trastuzumab‐based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr‐845 EGFR and ptyr‐1248 Her‐2/neu were both independent predictors of progression‐free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr‐845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr‐1248 Her‐2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her‐2/neu and EGFR are key determinants for trastuzumab efficacy. © 2005 Wiley‐Liss, Inc.
RANK ligand expression in heat shock factor‐2 deficient mouse bone marrow stromal/preosteoblast cells
Authors: Kajiya Hiroshi , Ito Masahiro , Ohshima Hayato , Kenmotsu Shin‐ichi , Ries William L. , Benjamin Ivor J. , Reddy Sakamuri V.
Published: December 2005

Heat Shock Proteins (HSP) are molecular chaperones activated upon cellular stress/stimuli. HSP gene expression is regulated by Heat Shock Factors (HSF). We have recently demonstrated a functional role for heat shock factor‐2 (HSF‐2) in fibroblast growth factor‐2 (FGF‐2)‐induced RANK ligand (RANKL), a critical osteoclastogenic factor expression on stromal/preosteoblast cells. In the present study, we show that FGF‐2 treatment did not induce RANKL expression in HSF‐2 −/− stromal/preosteoblast cells. Interestingly, HSF‐2 deficiency resulted in rapid induction of alkaline phosphatase (ALP) activity and osteocalcin mRNA expression in these cells. Furthermore, FGF‐2 did not induce osteoclast formation in co‐culture of normal mouse spleen cells and HSF‐2 −/− stromal/preosteoblast cells. Electron microscopy analysis demonstrated that osteoclasts from HSF‐2 −/− mice have poorly developed ruffled borders. These data further confirm that HSF‐2 plays an important role in FGF‐2‐induced RANKL expression in stromal/preosteoblast cells. HSF‐2 deficiency has pleotropic effects on gene expression during osteoblast differentiation and osteoclastogenesis in the bone microenvironment. Novel therapeutic agents that modulate HSF‐2 activation may have therapeutic utility against increased levels of FGF‐2 and bone destruction associated with pathologic conditions. J. Cell. Biochem. 97: 1362–1369, 2006. © 2005 Wiley‐Liss, Inc.
Quality standards of CTC black teas as influenced by sources of potassium fertiliser
Authors: Venkatesan Selvaraj , Senthurpandian Velu Kalaipandian , Murugesan Subramanian , Maibuam Wolfgang , Ganapathy Muthukumar NK
Published: December 2005

The quality aspects of CTC (crush, tear and curl) black teas were examined against different sources of potassium fertiliser. Potassium supplied as muriate of potash (MOP) improved the liquor components such as theaflavin (TF), thearubigin (TR) and TF/TR ratio at higher levels. The same effect was noticed at lower level itself when the source of K was changed to sulfate of potash (SOP). Termination of K application reduced the TF/TR ratio drastically. The entity responsible for strength, body and colour of tea brew, namely highly polymerised substances, attained its optimum proportion at an NK ratio of 1:0.21 using SOP. Generally, there was a good response from SOP‐treated blocks to caffeine. The flavour index was a maximum at a 1:0.42 NK ratio, using SOP. A slight peak and trough were observed in the case of crude fibre content and water extract over control and MOP‐treated blocks. The leaf K content was negatively correlated with CFC content of made tea. An antagonism was observed between leaf K and Mg. Copyright © 2005 Society of Chemical Industry
Cover Picture: Macromol. Chem. Phys. 1/2006
Authors: Lorenzo Arnaldo T. , Arnal Maria L. , Müller Alejandro J. , Boschetti de Fierro Adriana , Abetz Volker
Published: December 2005

Cover: The figure shows how high speed SSA measurements improve thermal fractionation times without sacrificing signal quality. A distribution of lamellar thickness was obtained by TEM after SSA fractionation and compared to distributions calculated by the Thomson‐Gibbs equation. Further details can be found in the Full Paper by A. T. Lorenzo, M. L. Arnal, A. J. Müller,* A. Boschetti de Fierro, and V. Abetz on page 39.
Cover Picture: Macromol. Rapid Commun. 1/2006
Authors: Zheng Xuejing , Pimplapure Makarand S. , Weickert Günter , Loos Joachim
Published: December 2005

Cover: The cover shows a scanning electron microscopy image of a cross‐section through a polymer particle with catalyst fragments in the early stage of polymerization. Further details can be found in the Communication by X. Zheng, M. S. Pimplapure, G. Weickert and J. Loos* on page 15.
Electrospray mass spectrometry (ESI‐MS) in the study of metal–ligand solution equilibria
Authors: Di Marco Valerio B. , Bombi G. Giorgio
Published: December 2005

In the 20 years, since the introduction of electrospray mass spectrometry (ESI‐MS), the use of this technique in various fields of inorganic, organometallic, and analytical chemistry has been steadily increasing. In this study, the application of ESI‐MS to the study of metal–ligand solution equilibria is reviewed (till 2004 included). In a first section, advantages and drawbacks of ESI‐MS in this type of application are described. Subsequently, a list of ca. 300 studies is reported, in which ESI‐MS was used to give number and stoichiometry of the species at equilibrium, or also to estimate their stability constants. All studies are classified according to the metal ions under examination. Other related applications, such as host–guest interactions and metal ion‐protein binding studies, are briefly reviewed as well. © 2005 Wiley Periodicals, Inc., Mass Spec Rev 25:347–379, 2006
Time‐dependent resveratrol‐mediated mRNA and protein expression associated with cell cycle in WR‐21 cells containing mutated human c‐Ha‐Ras
Authors: Young Leeanne F. , Martin Keith R.
Published: December 2005

Cancer results from an undesirable imbalance between cellular proliferation and apoptosis. Both processes may be modulated at the level of gene expression, viz., p53 and c‐Ha‐ras, by dietary bioactive components such as resveratrol. We tested the time‐dependent effect of resveratrol on gene and protein expression in WR‐21 cells containing a mutated human c‐Ha‐ras oncogene. We demonstrate cyclic resveratrol‐mediated expression of p53, mdm2, p21cip/waf, Rb, and cyclin G at both the RNA and the protein level at < 8 h. However, ras was not differentially expressed at either the RNA or the protein level. p53 was upregulated followed by p21cip/waf, then mdm2, and cyclin G, all downstream p53‐activated targets. RNA transcription increased at > 8 h for all genes except p53, but protein levels did not suggest uncoupling of transcription and translation. At 24 h, both p53 and Rb expression returned to baseline, suggesting collapse of DNA structure and spindle assembly checkpoints characteristic of mitotic catastrophe. In summary, resveratrol at < 8 h induced p53‐mediated effects, including apoptosis and cell‐cycle arrest (G2/M). However, later, it induced cell‐cycle checkpoint dysfunction, indicative of mitotic catastrophe. Thus, future studies should better elucidate the temporal mechanism of the dietary bioactive agent resveratrol on cancer cells.
Advances in locally constrained k‐space‐based parallel MRI
Authors: Samsonov Alexey A. , Block Walter F. , Arunachalam Arjun , Field Aaron S.
Published: December 2005

In this article, several theoretical and methodological developments regarding k‐space‐based, locally constrained parallel MRI (pMRI) reconstruction are presented. A connection between Parallel MRI with Adaptive Radius in k‐Space (PARS) and GRAPPA methods is demonstrated. The analysis provides a basis for unified treatment of both methods. Additionally, a weighted PARS reconstruction is proposed, which may absorb different weighting strategies for improved image reconstruction. Next, a fast and efficient method for pMRI reconstruction of data sampled on non‐Cartesian trajectories is described. In the new technique, the computational burden associated with the numerous matrix inversions in the original PARS method is drastically reduced by limiting direct calculation of reconstruction coefficients to only a few reference points. The rest of the coefficients are found by interpolating between the reference sets, which is possible due to the similar configuration of points participating in reconstruction for highly symmetric trajectories, such as radial and spirals. As a result, the time requirements are drastically reduced, which makes it practical to use pMRI with non‐Cartesian trajectories in many applications. The new technique was demonstrated with simulated and actual data sampled on radial trajectories. Magn Reson Med, 2006. © 2005 Wiley‐Liss, Inc.
Three‐dimensional finite element analyses of passive pile behaviour
Authors: Miao L. F. , Goh A. T. C. , Wong K. S. , Teh C. I.
Published: December 2005

Piles may be subjected to lateral soil pressures as a result of lateral soil movements from nearby construction‐related activities such as embankment construction or excavation operations. Three‐dimensional finite element analyses have been carried out to investigate the response of a single pile when subjected to lateral soil movements. The pile and the soil were modelled using 20‐node quadrilateral brick elements with reduced integration. For compatibility between the soil–pile interface elements, 27‐node quadrilateral brick elements with reduced integration were used to model the soil around the pile adjacent to the soil–pile interface. A Mohr–Coulomb elastic–plastic constitutive model with large‐strain mode was assumed for the soil. The analyses indicate that the behaviour of the pile was significantly influenced by the pile flexibility, the magnitude of soil movement, the pile head boundary conditions, the shape of the soil movement profile and the thickness of the moving soil mass. Reasonable agreement is found between some existing published solutions and those developed herein. Copyright © 2005 John Wiley & Sons, Ltd.
Stability properties of superoptimal preconditioner from numerical range
Authors: Cheng Che‐Man , Jin Xiao‐Qing , Wei Yi‐Min
Published: December 2005

A matrix is said to be stable if the real parts of all the eigenvalues are negative. In this paper, for any matrix An, we give some sufficient and necessary conditions for the stability of superoptimal preconditioner EU(An) proposed by Tyrtyshnikov (SIAM J. Matrix Anal. Appl. 1992; 13:459–473). Copyright © 2005 John Wiley & Sons, Ltd.
A Simple Model for the Simulation of Delamination in Fiber‐ReinforcedComposite Laminates under Mixed‐Mode Loading Conditions
Authors: Balzani Claudio , Wagner Werner
Published: December 2005

For a reliable prediction of the mechanical behavior of unidirectional fiber‐reinforced composite laminates (FRCL), it is inevitable to take into account various damage and fracture mechanisms. In this work, delamination under arbitrary mixedmode loading conditions is examined in the framework of the finite element method. Delamination is assumed to be caused by failure of the resin‐rich area in the interface between two layers of FRCL's. In this work, a cohesive interface elementin terms of natural stress‐strain relationships which allows to describe the interlaminar mechanical behavior of FRCL's is introduced. The proposed model prevents the restoration of cohesion in the interface. The interpenetration of the crack faces is avoided by incorporating a simple contact algorithm. A representative numerical example shows the applicability of the proposed concept. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Variational approach for strain‐driven, incremental homogenization of inelastic solids
Authors: Dimitrov S. , Schnack E.
Published: December 2005

This study is devoted to finite element modeling of phenomenological rate independent elastoplasticity coupled to damage. The new aspect concerns the treatment of both types of inelasticities. Consistent with physical observations these are interpreted as two pseudophases characterized by specific incremental quasihyperelastic potentials. On this basis, the governing macroscopic energetics is derived as a quasiconvex potential for macro‐stresses and corresponding variational formulation is discretized and solved for two limit cases: pure plastic response and pure scalar damage response. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Finite Element Approach for the Simulation of Quasi‐Brittle Fracture
Authors: Hilgert Oliver , Schröder Jörg , Löblein Joachim
Published: December 2005

In the context of a strong discontinuity approach, we propose a finite element formulation with an embedded displacement discontinuity. The basic assumption of the proposed approach is the additive split of the total displacement field in a continuous and a discontinuous part. An arbitrary crack splits the linear triangular finite element into two parts, namely a triangular and a quadrilateral part. The discontinuous part of the displacement field in the quadrilateral portion is approximated using linear shape functions. For these purposes, the quadrilateral portion is divided into two triangular parts which is in this way similar to the approach proposed in [5]. In contrast, the discretisation is different compared to formulations proposed in [1] and [3], where the discontinuous part of the displacement field is approximated using bilinear shape functions. The basic theory of the underlying finite element formulation and a cohesive interface model to simulate brittle fracture are presented. By means of representative numerical examples differences and similarities of the present formulation and the formulations proposed in [1] and [3] are highlighted. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microcrack nucleation in brittle solids
Authors: Le K. C. , Berdichevsky V. L.
Published: December 2005

A theory of microcracks nucleation in brittle solids is proposed. Theoretical predictions are compared with the experimental data for silica glass. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Locally Embedded Strong Discontinuities at finite strains – Numerical Implementation
Authors: Mosler J. , Stanković L.
Published: December 2005

In this paper, a geometrically nonlinear finite element approximation for highly localized deformation in structures undergoing material failure in the form of strain softening, is developed. The basis for its numerical implementation in this class of problems is defined through the elaboration of Strong Discontinuity Approach‐fundamentals. Proposed numerical model uses an Enhanced Assumed Strain Concept for the additive decomposition of the displacement gradient into a conforming and an enhanced part. The discontinuous component of the displacement field which is associated with the failure in the modeled structure is isolated in the enhanced part of the deformation gradient. In contrast to previous works, this part of the deformation mapping is condensed out at the material level, without the application of static condensation technique. The resulting set of constitutive equations is formally identical to that of standard plasticity and therefore, can be solved using the return‐mapping algorithm. No assumptions regarding the interface law connecting the displacement discontinuity with the conjugate traction vector are made. As a result, the proposed numerical solution can be applied to a broad range of different mechanical problems including mode‐I fracture in brittle materials or the analysis of shear bands. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Micromechanics of fracture in Partially Stabilized Zirconia (PSZ) studiedby in‐situ Raman spectroscopy
Authors: Müller W. H. , Pezzotti G.
Published: December 2005

This paper presents some results on residual stress measurements in PSZ ceramics that were obtained by using confocal Raman spectroscopy. Moreover an attempt is made to understand and to model these stress fields by using anisotropic linear elasticity in context with Discrete Fourier Transforms (DFT). (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation von inelastischem Materialverhalten mit Hilfe eines kraftfeldbasierten FE‐Verfahrens
Authors: Nasdala Lutz , Ernst Gerald , Rothert Heinrich
Published: December 2005

Inelastisches Materialverhalten ist die Folge einer st?ndigen Umordnung von chemischen und physikalischen Bindungen. Am Beispiel eines f?r Elastomerwerkstoffe entwickelten mikromechanischen Ersatzmodells wird gezeigt, dass sich auf Grundlage der rein elastischen Potentialfunktionen des Kraftfeldansatzes, also ohne Verwendung von D?mpfer‐ oder Reibelementen,Ph?nomene wie der Mullins‐Effekt oder Hysteresen simulieren lassen. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical aspects of the eXtended Finite Element Method
Authors: Peters Markus , Hackl Klaus
Published: December 2005

The eXtended Finite Element Method (XFEM) is a very efficient way to reduce mesh dependencies when analysing crack growth. Displacements and stresses around the crack tip are calculated using additional shape functions which span the analytical displacement field around a crack tip.

In this paper the following numerical aspects of the XFEM are discussed:

• The integration of the stiffness matrix has to be done accurately. Therefore singular functions have to be integrated and an error estimator must be available. We will compare the estimated error and the necessary number of integration points when using different routines.

• In case a crack truncates a very small part of a finite element the global stiffness matrix may become singular. One possibility to overcome this problem is to delete some of the enhanced degrees of freedom in the finite element analysis. Another way is to remove zero eigenvalues in the global stiffness matrix algebraically by a stabilization term. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)