bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward direct mapping of neuronal activity: MRI detection of ultraweak, transient magnetic field changes
Authors: Bodurka Jerzy , Bandettini Peter A.
Published: October 2002

A novel method based on selective detection of rapidly changing ΔB0 magnetic fields and suppression of slowly changing ΔB0 fields is presented. The ultimate goal of this work is to present a method that may allow detection of transient and subtle changes in B0 in cortical tissue associated with electrical currents produced by neuronal activity. The method involves the detection of NMR phase changes that occur during a single‐shot spin‐echo (SE) echo‐planar sequence (EPI) echo time. SE EPI effectively rephases all changes in B0 that occur on a time scale longer than the echo time (TE) and amplifies all ΔB0 changes that occur during TE/2. The method was tested on a phantom that contains wires in which current can be modulated. The sensitivity and flexibility of the technique was demonstrated by modulation of the temporal position and duration of the stimuli‐evoked transient magnetic field relative to the 180 RF pulse in the imaging sequence—requiring precise stimulus timing. Currently, with this method magnetic field changes as small as 2 × 10−10 T (200 pT) and lasting for 40 msec can be detected. Implications for direct mapping of brain neuronal activity with MRI are discussed. Magn Reson Med 47:1052–1058, 2002. Published 2002 Wiley‐Liss, Inc.
Detection and modeling of non‐Gaussian apparent diffusion coefficient profiles in human brain data
Authors: Alexander D.C. , Barker G.J. , Arridge S.R.
Published: October 2002

This work details the observation of non‐Gaussian apparent diffusion coefficient (ADC) profiles in multi‐direction, diffusion‐weighted MR data acquired with easily achievable imaging parameters (b≈ 1000 s/mm2). A technique is described for modeling the profile of the ADC over the sphere, which can capture non‐Gaussian effects that can occur at, for example, intersections of different tissue types or white matter fiber tracts. When these effects are significant, the common diffusion tensor model is inappropriate, since it is based on the assumption of a simple underlying diffusion process, which can be described by a Gaussian probability density function. A sequence of models of increasing complexity is obtained by truncating the spherical harmonic (SH) expansion of the ADC measurements at several orders. Further, a method is described for selection of the most appropriate of these models, in order to describe the data adequately but without overfitting. The combined procedure is used to classify the profile at each voxel as isotropic, anisotropic Gaussian, or non‐Gaussian, each with reference to the underlying probability density function of displacement of water molecules. We use it to show that non‐Gaussian profiles arise consistently in various regions of the human brain where complex tissue structure is known to exist, and can be observed in data typical of clinical scanners. The performance of the procedure developed is characterized using synthetic data in order to demonstrate that the observed effects are genuine. This characterization validates the use of our method as an indicator of pathology that affects tissue structure, which will tend to reduce the complexity of the selected model. Magn Reson Med 48:331–340, 2002. © 2002 Wiley‐Liss, Inc.
Lateral spread response elicited by double stimulation in patients with hemifacial spasm
Authors: Yamashita Shinya , Kawaguchi Tadashi , Fukuda Masafumi , Suzuki Kenji , Watanabe Masatoshi , Tanaka Ryuichi , Kameyama Shigeki
Published: October 2002

In patients with hemifacial spasm (HFS), a lateral spread response (or abnormal muscle response) is recorded from facial muscles after facial nerve stimulation. The origin of this response is not completely understood. We studied the lateral spread responses elicited by double stimulation in 12 patients with HFS during microvascular decompression. The response was recorded from the mentalis muscle by electrical stimulation of the temporal branch of the facial nerve or from the orbicularis oculi muscles by stimulation of the marginal mandibular branch. The interstimulus intervals (ISIs) of double stimulation ranged from 0.5 to 7.0 ms. R1 was defined as the response elicited by the first stimulus, and R2 as the response elicited by the second stimulus. R1 had a constant latency and amplitude regardless of the ISI, whereas R2 appeared after a fixed refractory period without facilitation or depression in a recovery curve of latency and amplitude. From these findings, we consider that the lateral spread response is due to cross‐transmission of facial nerve fibers at the site of vascular compression rather than arising from facial nerve motor neurons. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Hypothyroid myopathy with a strikingly elevated serum creatine kinase level
Authors: Scott Kevin R. , Simmons Zachary , Boyer Philip J.
Published: October 2002

Although serum creatine kinase (CK) levels are frequently modestly elevated in patients with hypothyroid myopathy, elevations in serum CK to the levels usually seen in inflammatory myopathies or dystrophies are rare. We report a patient with progressive proximal weakness and a serum CK level of over 29,000 IU/L, in whom subsequent laboratory evaluation identified profound hypothyroidism. Thyroid hormone replacement therapy resulted in resolution of clinical symptoms and a marked reduction in the serum CK level. Such a high serum CK level in a patient with hypothyroidism underscores the importance of assessing thyroid function in patients with weakness, regardless of serum CK levels, even when systemic symptoms and signs of hypothyroidism are minimal or absent. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 141–144, 2002
Lack of apoptosis in patients with progressive external ophthalmoplegia and mutated adenine nucleotide translocator‐1 gene
Authors: Fagiolari Gigliola , Sciacco Monica , Chiveri Luca , Lamperti Costanza , Comi Giacomo Pietro , Scarlato Guglielmo , Moggio Maurizio , Prelle Alessandro
Published: October 2002

Adenine nucleotide translocator‐1 (ANT‐1), encoded by chromosome 4 (4q34‐35 locus), is a component of the mitochondrial permeability transition pores that are involved in apoptotic mechanisms. We studied muscle biopsies from seven individuals with autosomal dominant progressive external ophthalmoplegia caused by ANT‐1 mutations. We found no instance of terminal deoxynucleotidyltransferase‐mediated dUTP nick end labeling (TUNEL) positivity nor significant expression of apoptosis‐related proteins. Furthermore, there was no morphological evidence of apoptosis at the ultrastructural level. Thus, degeneration of muscle in this disorder is nonapoptotic. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 265–269, 2002
Meshless approach to shape optimization of linear thermoelastic solids
Authors: Bobaru Florin , Mukherjee Subrata
Published: October 2002

This paper presents a formulation for shape optimization in thermoelasticity using a meshless method, namely the element‐free Galerkin method. Two examples are treated in detail and comparisons with previously published finite element analysis results demonstrate the excellent opportunities the EFG offers for solving these types of problems. Smoother stresses, no remeshing, and better accuracy than finite element solutions, permit answers to shape optimization problems in thermoelasticity that are practically unattainable with the classical FEM without remeshing. For the thermal fin example, the EFG finds finger shapes that are missed by the FEM analysis, and the objective value is greatly improved compared to the FEM solution. A study of the influence of the number of design parameters is performed and it is observed that the EFG can give better results with a smaller number of design parameters than is possible with traditional methods. Copyright © 2001 John Wiley & Sons, Ltd.
A flux‐limited numerical method for solving the MHD equations to simulate propulsive plasma flows
Authors: Sankaran K. , Martinelli L. , Jardin S. C. , Choueiri E. Y.
Published: October 2002

For numerical simulations to be effective tools in plasma propulsion research, a high‐order accurate solver that captures MHD shocks monotonically and works reliably for strong magnetic fields is needed. For this purpose, a characteristics‐based scheme for the MHD equations, with flux limiters to improve spatial accuracy, has been developed. In this method, the symmetric form of the MHD equations, accounting for waves propagating in all directions, are solved. The required eigensystem of axisymmetric MHD equations, with appropriate normalization, is presented. This scheme was validated with unsteady (Riemann problem) and force‐free equilibrium (Taylor state) test cases, as well as with measured current density patterns in a magnetoplasmadynamic thruster. Copyright © 2001 John Wiley & Sons, Ltd.
Non‐singular boundary integral formulations for plane interior potential problems
Authors: Hwang W. S. , Hung L. P. , Ko C. H.
Published: October 2002

In this article, a non‐singular formulation of the boundary integral equation is developed to solve smooth and non‐smooth interior potential problems in two dimensions. The subtracting and adding‐back technique is used to regularize the singularity of Green's function and to simplify the calculation of the normal derivative of Green's function. After that, a global numerical integration is directly applied at the boundary, and those integration points are also taken as collocation points to simplify the algorithm of computation. The result indicates that this simple method gives the convergence speed of order N −3 in the smooth boundary cases for both Dirichlet and mix‐type problems. For the non‐smooth cases, the convergence speed drops at O(N −1/2) for the Dirichlet problems. Copyright © 2001 John Wiley & Sons, Ltd.
Design space optimization using a numerical design continuation method
Authors: Kim Il Yong , Kwak Byung Man
Published: October 2002

A generalized optimization problem in which design space is also a design to be found is defined and a numerical implementation method is proposed. In conventional optimization, only a portion of structural parameters is designated as design variables while the remaining set of other parameters related to the design space are often taken for granted. A design space is specified by the number of design variables, and the layout or configuration. To solve this type of design space problems, a simple initial design space is selected and gradually improved while the usual design variables are being optimized. To make the design space evolve into a better one, one may increase the number of design variables, but, in this transition, there are discontinuities in the objective and constraint functions. Accordingly, the sensitivity analysis methods based on continuity will not apply to this discontinuous stage. To overcome the difficulties, a numerical continuation scheme is proposed based on a new concept of a pivot phase design space. Two new categories of structural optimization problems are formulated and concrete examples shown. Copyright © 2001 John Wiley & Sons, Ltd.
Singularities in anisotropic steady‐state heat conduction using a boundary element method
Authors: Mera N. S. , Elliott L. , Ingham D. B. , Lesnic D.
Published: October 2002

In many heat conduction problems, boundaries with sharp corners or abrupt changes in the boundary conditions give rise to singularities of various types which tend to slow down the rate of convergence with decreasing mesh size of any standard numerical method used for obtaining the solution. In this paper, it is shown how this difficulty may be overcome in the case of an anisotropic medium by a modified boundary element method. The standard boundary element method is modified to take account of the form of the singularity, without appreciably increasing the amount of computation involved. Two test examples, the first with a singularity caused by an abrupt change in a boundary condition and the second with a singularity caused by a sharp re‐entrant corner, are investigated and numerical results are presented. Copyright © 2002 John Wiley & Sons, Ltd.
h‐Adaptive FE methods applied to single‐ and multiphase problems
Authors: Ehlers W. , Ammann M. , Diebels S.
Published: October 2002

A major problem in using the finite element method for solving numerous engineering problems in the framework of single‐ and multiphase materials is the assessment of discretization errors and the design of suitable meshes. To overcome this problem, adaptive finite element methods have been developed. Based on the error indicator by Zienkiewicz and Zhu, it is the goal of the present paper to present a new error indicator which is especially designed for multiphase problems. Furthermore, efficient h‐adaptive strategies concerning both the generation of new meshes in the framework of independent and hierarchical remeshing strategies and the data transfer between old and new meshes are pointed out. Finally, numerical examples are given to exhibit the efficiency and the quality of the presented h‐adaptive methods and to compare the different strategies to each other. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐local dispersive model for wave propagation in heterogeneous media: one‐dimensional case
Authors: Fish Jacob , Chen Wen , Nagai Gakuji
Published: October 2002

Non‐local dispersive model for wave propagation in heterogeneous media is derived from the higher‐order mathematical homogenization theory with multiple spatial and temporal scales. In addition to the usual space–time co‐ordinates, a fast spatial scale and a slow temporal scale are introduced to account for rapid spatial fluctuations of material properties as well as to capture the long‐term behaviour of the homogenized solution. By combining various order homogenized equations of motion the slow time dependence is eliminated giving rise to the fourth‐order differential equation, also known as a ‘bad’ Boussinesq problem. Regularization procedures are then introduced to construct the so‐called ‘good’ Boussinesq problem, where the need for C1 continuity is eliminated. Numerical examples are presented to validate the present formulation. Copyright © 2002 John Wiley & Sons, Ltd.
Stress recovery and error estimation for the scaled boundary finite‐element method
Authors: Deeks Andrew J. , Wolf John P.
Published: October 2002

The scaled boundary finite‐element method is a novel semi‐analytical technique, combining the advantages of the finite element and the boundary element methods with unique properties of its own. This paper develops a stress recovery procedure based on a modal interpretation of the scaled boundary finite‐element method solution process, using the superconvergent patch recovery technique. The recovered stresses are superconvergent, and are used to calculate a recovery‐type error estimator. A key feature of the procedure is the compatibility of the error estimator with the standard recovery‐type finite element estimator, allowing the scaled boundary finite‐element method to be compared directly with the finite element method for the first time. A plane strain problem for which an exact solution is available is presented, both to establish the accuracy of the proposed procedures, and to demonstrate the effectiveness of the scaled boundary finite‐element method. The scaled boundary finite‐element estimator is shown to predict the true error more closely than the equivalent finite element error estimator. Unlike their finite element counterparts, the stress recovery and error estimation techniques work well with unbounded domains and stress singularities. Copyright © 2002 John Wiley & Sons, Ltd.
Anisotropic damage coupled to plasticity: Modelling based on the effective configuration concept
Authors: Menzel A. , Ekh M. , Steinmann P. , Runesson K.
Published: October 2002

A model framework for anisotropic damage, that is kinetically coupled to inelastic deformations, is outlined. Key ingredients are the concept of the effective undamaged configuration and the assumption of energy equivalence. The pertinent rate equations for the chosen internal variables are integrated using the standard fully implicit scheme, and the Jacobian matrix of the resulting non‐linear incremental constitutive problem is used to compute the algorithmic tangent stiffness in straightforward fashion. Numerical results showing the effect of deformation‐induced anisotropy conclude the paper. Copyright © 2002 John Wiley & Sons, Ltd.
The least‐squares finite element method in elasticity. Part II: Bending of thin plates
Authors: Jiang Bo‐nan
Published: October 2002

A least‐squares finite element method (LSFEM) for bending problems of thin plates is developed. This LSFEM is based on the first‐order deflection‐slope‐moment‐shear force formulation. Four compatibility conditions are added into the first‐order system; thus, the method can accommodate all kinds of equal‐order interpolations. Numerical experiments on various examples show that the method achieves an optimal rate of convergence for all eight variables. Copyright © 2002 John Wiley & Sons, Ltd.
A finite difference solution of non‐linear systems of radiative–conductive heat transfer equations
Authors: Asllanaj F. , Milandri A. , Jeandel G. , Roche J. R.
Published: October 2002

A finite difference solution for a system of non‐linear integro–differential equations modelling the steady‐state combined radiative–conductive heat transfer is proposed. A new backward–forward finite difference scheme is formulated for the Radiative Transfer Equation. The non‐linear heat conduction equation is solved using the Kirchhoff transformation associated with a centred finite difference scheme. The coupled system of equations is solved using a fixed‐point method, which relates to the temperature field. An application on a real insulator composed of silica fibres is illustrated. The results show that the method is very efficient. Copyright © 2002 John Wiley & Sons, Ltd.
The economic lot size of the integrated vendor‐buyer inventory system derived without derivatives
Authors: Yang P.C. , Wee H.M.
Published: October 2002

In previous modellings of the integrated vendor–buyer system, the buyer's economic order quantity and the vendor's optimal number of deliveries are derived by setting the first derivatives to zero and solving the simultaneous equations. The Hessian matrix of second derivatives is used to prove the convexity of the objective function. This procedure can be difficult for students who lack the background of differential calculus. This study develops algebraically the optimal policy of the integrated vendor–buyer inventory system without using differential calculus. A significant cost reduction is also achieved when Goyal's model is modified. Copyright © 2002 John Wiley & Sons, Ltd.
Methylation‐specific PCR for detection of neoplastic DNA in biopsy washings
Authors: Goessl Carsten , Müller Markus , Heicappell Rüdiger , Krause Hans , Schostak Martin , Straub Bernd , Miller Kurt
Published: October 2002

Epigenetic DNA alterations such as promoter hypermethylation of glutathione S‐transferase P1 (GSTP1) in prostatic adenocarcinoma frequently constitute tumour biomarkers. Neoplastic transformation was identified in washings of prostate biopsies by GSTP1 promoter hypermethylation, using methylation‐specific PCR (MSP). Twenty‐six patients undergoing sextant transrectal prostate biopsies for clinically suspected prostate cancer were enrolled. All ten patients diagnosed with adenocarcinoma (100%) and four of six patients with prostatic intraepithelial neoplasia (67%), but none of ten patients with benign hyperplasia (0%), exhibited GSTP1 promoter hypermethylation in at least one out of six biopsy washings. Since this approach is transferable to various cancer entities, a sensitive and specific DNA‐based analysis of biopsy material seems generally feasible without impeding routine histopathological examination. Copyright © 2002 John Wiley & Sons, Ltd.
Markers of senescence?
Authors: Coates Philip J.
Published: October 2002

The specific identification of cellular senescence in clinical material has important implications for determining the role of senescence in age‐related pathologies and in neoplasia in certain tumours. One suggested marker of senescence is the histochemical identification of a specific β‐galactosidase enzyme operative at pH 6.0. However, recent data indicate that this enzyme may not be specific for senescence in all tissues and probably represents the expression of endogenous lysosomal acid β‐galactosidase, which is expressed by a variety of differentiated cell types. Copyright © 2002 John Wiley & Sons, Ltd.
Secretion of interleukin‐6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so‐called ‘vascular neoplasia’)
Authors: Kakiuchi Chihiro , Ishida Tsuyoshi , Sato Hitoshi , Katano Harutaka , Ishiko Tositaka , Mukai Hiroyuki , Kogi Mieko , Kasuga Naoki , Takeuchi Kengo , Yamane Kenichi , Fukayama Masashi , Mori Shigeo
Published: October 2002

So‐called ‘vascular neoplasia’ (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin‐6 (IL‐6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60‐year‐old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node‐like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit‐like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL‐6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL‐6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon. Copyright © 2002 John Wiley & Sons, Ltd.
Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil‐dependent and ‐independent events
Authors: Foster Paul A. , Wicks Sharon , Foster Martyn , Brain Susan D.
Published: October 2002

Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil‐dependent hyperalgesia in the rat. The purpose of the present study was to examine the pathological consequence of NGF injected intradermally into mature rat skin and to examine further the role of neutrophils. Standard histopathology techniques (H & E) were employed to determine inflammatory cell counts. Circulating neutrophils were depleted using an anti‐rat neutrophil antiserum and results were compared to treatment with vehicle controls. Saline‐pretreated rats exhibited normal circulating neutrophil numbers and the dorsal skin showed a significant increase of neutrophil and macrophages at 3 and 5 h and lymphocytes at 5 h after NGF treatment. By comparison, skin sites from neutrophil‐depleted rats did not demonstrate a significant increase in neutrophil and macrophage accumulation after NGF administration. All NGF‐treated sites, independent of pretreatment, demonstrated abnormal muscle fibre morphology and proliferation of the muscle sarcolemmal nuclei after NGF injection, indicative of tissue injury. In addition, oedema and some fibroplasia were also noted. Furthermore, fibrin production was increased at 3 and 5 h after NGF administration. It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF‐induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil‐depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration. Copyright © 2002 John Wiley & Sons, Ltd.
Immunohistochemical detection of CD79a expression in precursor T cell lymphoblastic lymphoma/leukaemias
Authors: Hashimoto Mitsuyoshi , Yamashita Yoriko , Mori Naoyoshi
Published: October 2002

Twenty‐three cases of precursor T cell lymphoid malignancies were examined with respect to CD79a expression. Immunohistochemical staining was performed on frozen tissue sections using a broad panel of antibodies and Southern blot analysis was undertaken using DNA probes encoding immunoglobulin heavy chain (IgH) gene and T‐cell receptor (TCR) β, γ and δ genes. Twelve (52%) of the 23 cases examined demonstrated CD79a expression. IgH and TCRβ, γ and δ gene rearrangements were found in 5, 9, 12 and 20 cases, respectively. CD79a‐positive neoplastic cells exhibited a phenotype and genotype characteristic of an early stage of T cell differentiation. Immunohistochemical staining was also performed on human thymus and thymoma to investigate the normality of CD79a expression, to discover that low‐level expression of CD79a is common in thymocytes and thymoma‐associated lymphocytes. These results suggest that CD79a is expressed weakly and transiently in immature T‐lineage cells. Copyright © 2002 John Wiley & Sons, Ltd.
Haematopoietic stem cells1
Authors: Bonnet Dominique
Published: October 2002

Considerable efforts have been made in recent years in determining the composition of the cell types that constitute the human haematopoietic stem cell (HSC) compartment. These studies have emphasized the heterogeneity of the human HSC in terms of proliferative and self‐renewal capacities. Recent studies have indicated that CD34 is not the universal marker of all human HSCs. New markers for purifying HSCs have been described. A number of genes that regulate the formation, self‐renewal, or differentiation of HSCs has been identified. The elucidation of the molecular phenotype of the HSC has just begun. Finally, an unexpected degree of developmental or differentiation plasticity of HSC has emerged. This review summarizes all the recent advances made in the human HSC field and examines the impacts that these discoveries may have both clinically and in understanding the organization of the human haematopoietic system. Copyright © 2002 John Wiley & Sons, Ltd.
Muscle stem cells
Authors: Goldring Kirstin , Partridge Terence , Watt Diana
Published: October 2002

Since its discovery four decades ago, the satellite cell of skeletal muscle has been implicated as the major source of myogenic cells involved in growth and repair of muscle fibres. This review not only looks at the role of the satellite cell in these processes but discusses how cells derived from other sources and tissues have recently been implicated in muscle formation and regeneration. Muscle itself also yields cells that contribute to other cell lineages although it is currently debated as to whether these cells originate within muscle or have migrated there from other tissues. The reality of using cells from muscle or other tissues to repair diseased muscle fibres is also addressed.
Apoptosis, necrosis, or whatever: how to find out what really happens?
Authors: Aigner T
Published: October 2002

There is no doubt that thorough knowledge of apoptotic cell death is of paramount importance for many areas of current research. Despite many available ways of detecting apoptotic cell death, the analysis of apoptosis reveals considerable conceptual and technological problems. In this issue of The Journal of Pathology, Grogan and colleagues offer an interesting study, in which they present a promising model system for investigating the spatio‐temporal events of initiation and progression of apoptosis (and other forms of cell death). The confusing complexity of results based on parallel experiments in this paper might be partly due to technical variability or insufficiency; more likely, however, this provides evidence that most if not all approaches thought to be ‘specific’ for apoptotic cell death address different aspects of cell death, have different sensitivities and specificities, and are rather complementary than redundant. Grogan and colleagues provide an excellent demonstration of the uncertainties and ambiguities which result from basically all currently available technologies, yielding, even in one system, results which are partly confusing, because they are partly contradictory. This situation is typical for cell death analysis at present—not only in the cartilage field. Copyright © 2002 John Wiley & Sons, Ltd.
An introduction to stem cells
Authors: Alison Malcolm R. , Poulsom Richard , Forbes Stuart , Wright Nicholas A.
Published: October 2002

1998 saw the publication of two papers describing the growth in vitro of human embryonic stem (ES) cells derived either from the inner cell mass (ICM) of the early blastocyst or the primitive gonadal regions of early aborted fetuses. Work on murine ES cells over many years had already established the amazing flexibility of ES cells, essentially able to differentiate into almost all cells that arise from the three germ layers. The realization of such pluripotentiality (see below) has, of course, resulted in the field of stem cell research going into overdrive, the establishment of many new biotechnology companies (http://www.stemcellresearchnew.com/catalog1677.html), and a genuine belief that stem cell research will deliver a revolution in terms of how we treat cardiovascular disease, neurodegenerative disease, cancer, diabetes, and the like. However, many people believe that early human embryos should be accorded the same status as any sentient being and thus their ‘harvesting’ for stem cells is morally unjustifiable. With this in mind, other sources of malleable stem cells have been sought. In the adult, organ formation and regeneration was thought to occur through the action of organ‐ or tissue‐restricted stem cells (i.e. haematopoietic stem cells giving rise to all the cells of the blood, neural stem cells making neurons, astrocytes, and oligodendrocytes). However, it is now believed that stem cells from one organ system, for example the haematopoietic compartment can develop into the differentiated cells within another organ system, such as the liver, brain or kidney. Thus, certain adult stem cells may turn out be as malleable as ES cells and so also be useful in regenerative medicine. This brief overview summarizes the important attributes of tissue‐based stem cells and clarifies the terms used. Copyright © 2002 John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis for single gene disorders: experience with five single gene disorders
Authors: Harper Joyce C. , Wells Dagan , Piyamongkol Wirawit , Abou‐Sleiman Patrick , Apessos Angela , Ioulianos Antonis , Davis Mary , Doshi Alpesh , Serhal Paul , Ranieri Massimo , Rodeck Charles , Delhanty Joy D. A.
Published: October 2002

We report our experience of 14 preimplantation genetic diagnosis (PGD) cycles in eight couples carrying five different single gene disorders, during the last 18 months. Diagnoses were performed for myotonic dystrophy (DM), cystic fibrosis (CF) [ΔF508 and exon 4 (621+1 G>T)], fragile X and CF simultaneously, and two disorders for which PGD had not been previously attempted, namely neurofibromatosis type 2 (NF2) and Crouzon syndrome. Diagnoses for single gene disorders were carried out on ideally two blastomeres biopsied from Day 3 embryos. A highly polymorphic marker was included in each diagnosis to control against contamination. For the dominant disorders, where possible, linked polymorphisms provided an additional means of determining the genotype of the embryo hence reducing the risk of misdiagnosis due to allele dropout (ADO). Multiplex fluorescent polymerase chain reaction (F‐PCR) was used in all cases, followed by fragment analysis and/or single‐stranded conformation polymorphism (SSCP) for genotyping. Embryo transfer was performed in 13 cycles resulting in one biochemical pregnancy for CF, three normal deliveries (a twin and a singleton) and one early miscarriage for DM and a singleton for Crouzon syndrome. In each case the untransferred embryos were used to confirm the diagnoses performed on the biopsied cells. The results were concordant in all cases. The inclusion of a polymorphic marker allowed the detection of extraneous DNA contamination in two cells from one case. Knowing the genotype of the contaminating DNA allowed its origin to be traced. All five pregnancies were obtained from embryos in which two blastomeres were biopsied for the diagnosis. Our data demonstrate the successful strategy of using multiplex PCR to simultaneously amplify the mutation site and a polymorphic locus, fluorescent PCR technology to achieve greater sensitivity, and two‐cell biopsy to increase the efficiency and success of diagnoses. Copyright © 2002 John Wiley & Sons, Ltd.
Paracetamol pack size restriction: the impact on paracetamol poisoning and the over‐the‐counter supply of paracetamol, aspirin and ibuprofen
Authors: Sheen Christopher L. , Dillon John F. , Bateman D. Nicholas , Simpson Kenneth J. , MacDonald Thomas M.
Published: October 2002

Purpose

Self‐poisoning occurs with over‐the‐counter (OTC) drugs, particularly paracetamol (acetaminophen). In 1998, OTC pack sizes of paracetamol were reduced. We have studied the effect of this pack size restriction on OTC supply of paracetamol, aspirin and ibuprofen.

Methods

IMS Health UK provided data on the UK sales of paracetamol, aspirin and ibuprofen. The total mass and number of packs of each drug supplied were compared for the years 1998, 1999 and 2000.

Results

The mass of aspirin and paracetamol sold fell, that of ibuprofen increased. The number of paracetamol packs sold was unchanged, the analgesic dose of aspirin fell and ibuprofen supply increased.

Conclusions

It seems that the paracetamol pack size reduction has not achieved as large an overdose rate reduction as might have been expected. Instead, a shift to the use of ibuprofen may lead to an increase in gastrointestinal adverse events and continue the burden on healthcare resources. Copyright © 2002 John Wiley & Sons, Ltd.
Spectroelectrochemistry of pyrrole oligomers in the presence of acrylamide
Authors: Saraç A Sezai , Sönmez Gürsel
Published: October 2002

Soluble pyrrole oligomers were characterized during electropolymerization of pyrrole in the presence of acrylamide (in acetonitrile) which stabilizes radical cations of pyrrole allowing the reaction to be followed by spectroscopic and spectroelectrochemical means. The role of the applied electrical conditions and the effect of the presence of acrylamide on the formation of pyrrole oligomers in solution, and on the resulting polymer on an electrode surface (both Pt and indium tin oxide), were investigated. The soluble and insoluble products were characterized using UV‐visible and FTIR spectroscopy, cyclic voltammetry and a four‐point probe technique. Polypyrrole and poly(pyrrole–acrylamide) free‐standing films had conductivity values of about 90 and 1 S cm−1, respectively. Spectroscopic, cyclovoltammetric and conductivity results support the incorporation of acrylamide into intermediate species that may have useful application in industry.

© 2002 Society of Chemical Industry
Electrochemical behaviour and electrochemical polymerization of fluoro‐substituted anilines
Authors: Cihaner Atilla , Önal Ahmet M
Published: October 2002

The electrochemical behaviour of three fluoro‐substituted aniline monomers, 2‐fluoroaniline (2FAN), 3‐fluoroaniline (3FAN) and 4‐fluoroaniline (4FAN), was investigated in aqueous acidic and organic media by means of cyclic voltammetry (CV) studies. Constant potential electrolysis (CPE) of the monomers in acetonitrile–water mixture (1:1 by volume) using NaClO4 as supporting electrolyte yielded soluble polymers. The mechanism of electrochemical polymerization was investigated using in situ electron spin resonance (ESR) and in situ UV–VIS spectroscopic techniques for one of the monomers (4FAN). Both CV and in situ UV–VIS measurements indicated that the polymers obtained are in the emeraldine base form. In situ ESR studies indicated that electrochemical polymerization involves a radical‐cation as an intermediate. Characterization of polymer products have been carried out using FTIR and NMR spectroscopic techniques, and thermal behaviour was studied using differential scanning calorimetry (DSC). It was found that conductivity can be imparted to as‐synthesized polyfluoroanilines via iodine doping.

© 2002 Society of Chemical Industry
Reliability and comparability of a Spanish‐language form of the preschool and kindergarten behavior scales
Authors: Carney Amy G. , Merrell Kenneth W.
Published: October 2002

Comparability of a Spanish language translation of the Preschool and Kindergarten Behavior Scales was examined in relation to the English language version. Children ages 3–6 enrolled in preschool, kindergarten, or Head Start programs were rated concurrently by respondents on English and Spanish versions of the PKBS. Results showed virtually identical internal consistency of scores on both forms on Social Skills (.93) and Problem Behavior (.96) Scales. Correlations between forms for Social Skills and Problem Behavior scores were .93 and .94, respectively. Implications of these findings, directions for future research and the importance of continued work toward development/translation of other Spanish language assessment instruments for the early childhood population are discussed. © 2002 Wiley Periodicals, Inc.
High‐pressure mechanistic delineation based on activation volumes
Authors: Jenner Gérard
Published: October 2002

High‐pressure kinetics is a useful tool for the determination and the assessment of mechanisms in organic chemistry. The volume of activation ΔV* deduced from these kinetic measurements is an indicator of the position of the transition state. In addition, if accurately determined, ΔV* permits the detection of fine mechanistic effects such as alteration of mechanism according to substrates within the same reaction type, operation of secondary orbital interactions in Diels–Alder cycloadditions, angular hydrogen transfer in ene reactions, etc. Copyright © 2001 John Wiley & Sons, Ltd.
Spectrophotometric determination of the transition system for interactions involving model hydrogen bonds in acetonitrile
Authors: Magoński Józef
Published: October 2002

The bonds formed by interactions of picric acid (HA) with each of 12 (un)substituted pyridines (B) in acetonitrile (AN) were studied by UV–vis spectrophotometry to determine the $\Delta \hbox{p}K_{\rm a}^{\rm AN}=$ $\hbox{p}K_{{\rm BH}^{+}}^{\rm AN} - \hbox{p}K_{\rm HA}^{\rm AN}$ corresponding to the transition system. The choice of both model system and experimental technique enabled the effect of heteroconjugation to be observed and the effects of formation of two theoretically possible homoconjugates (AHA− and BHB+) to be eliminated. The relationship between the wavelength at the absorbance maximum (λmax) for 10−4 M solutions of complexes of picric acid with (un)substituted pyridines in acetonitrile and $\Delta \hbox{p}K_{\rm a}^{\rm AN}$ was found to have a sigmoidal shape with an inflection point at $\Delta \hbox{p}K_{\rm a}^{\rm AN}$ of ca −0.3. On the basis of this relationship and UV–vis spectra, the picric acid–3‐acetylpyridine system was recognized as that being the nearest to the transition system. The fact that the transition $\Delta \hbox{p}K_{\rm a}^{\rm AN}$ was lower than zero has been explained by the remarkable effect of species having the average structures A−···+HB on the established λmax values. The general results of this work and our previous results based on IR and 1H NMR studies, and also the lack of any experimental counterexamples, indicate that the zero value of $\Delta \hbox{p}K_{\rm a}^{\rm AN}$ constitutes a fundamental basis for predicting which one, among the given family of protonic hetero systems, is the most likely to show transitional properties in acetonitrile. Finally, it is postulated that the protonic hetero systems which are the most likely to show transitional properties in a given solvent S are those for which $\Delta \hbox{p}K_{\rm a}^{\rm S}$ is close to zero, the eventual shift arising from peculiarity of the technique applied. Copyright © 2002 John Wiley & Sons, Ltd.
Space‐demanding intramolecular isomerizations in the solid state
Authors: Kaupp G. , Schmeyers J. , Kato M. , Tanaka K. , Toda F.
Published: October 2002

The thermal isomerizations of meso‐ and rac‐3,4‐dibromo‐1,6‐diphenyl‐1,6‐bis(p‐tolyl)‐1,2,4,5‐hexatetraene (1) to give stereospecifically the 3,4‐bis(phenyl‐p‐tolylmethylene)‐1,2‐dibromocyclobutenes 3 and 5 + 6 were studied in the solid state using atomic force microscopy (AFM) and interpreted on the basis of known crystal structural data. These isomerizations run to completion in the bulk and include highly space‐demanding internal rotations around the central bond. Far‐reaching anisotropic molecular movements are detected on the major faces that align the surface features along cleavage planes in the initial phase rebuilding stage. Only one of three identified cleavage planes of meso‐1 is successful, owing to closer interactions of the bromine substituents in the non‐used cleavage planes. Thus, very fine details can be correlated and predicted for the occurrence of internal rotations and molecular movements in the crystal lattice. The second stage in these intramolecular isomerizations, the phase transformation, produces very high features up to 100 nm and still parallel to the preferred cleavage plane of meso‐1 but in the µm range without relation to the initial crystal structure in the case of rac‐1. Copyright © 2002 John Wiley & Sons, Ltd.
An NMR, IR and theoretical investigation of the methyl effect on conformational isomerism in 3‐fluoro‐3‐methyl‐2‐butanone and 1‐fluoro‐3,3‐dimethyl‐2‐butanone
Authors: Tormena Cláudio F. , Rittner Roberto , Abraham Raymond J.
Published: October 2002

The solvent dependence of the 1H and 13C NMR spectra of 3‐fluoro‐3‐methyl‐2‐butanone (FMB) and 1‐fluoro‐3,3‐dimethyl‐2‐butanone (FDMB) was examined and the 4JHF, 1JCF and 2JCF couplings are reported. Density functional theory (DFT) at the B3LYP/6–311 ++ G(2df,2p) level with ZPE (zero point energy) corrections was used to obtain the conformer geometries. In both FMB and FDMB, the DFT method gave only two minima for cis (FCCO, 0°) and trans (FCCO, 180°) rotamers. Assuming the cis and trans forms, the observed couplings in FMB when analysed by solvation theory gave the energy difference E
cis − E
trans of 3.80 kcal mol−1 (1 kcal = 4.184 kJ) in the vapour phase (cf. the DFT value of 3.21 kcal mol−1), decreasing to 2.6 kcal mol−1 in CCl4 and to 0.27 kcal mol−1 in DMSO. In FDMB the observed couplings when analysed similarly by solvation theory gave E
cis − E
trans = 1.80 kcal mol−1 in the vapour phase, decreasing to 0.47 kcal mol−1 in CCl4 and to −1.25 kcal mol−1 in DMSO. The introduction of a methyl group geminal to the fluorine atom shifts the conformational equilibrium towards the trans rotamer, in contrast to no significant effect when the methyl group is introduced at the α‐carbon further from the fluorine atom. Copyright © 2002 John Wiley & Sons, Ltd.
Structure–reactivity correlation for the ligand‐decelerated catalytic osmium tetraoxide dihydroxylation of alkenes
Authors: Erdik Ender , Kâhya Didem
Published: October 2002

Kinetic studies on the ligand‐decelerated catalytic OsO4 dihydroxylation of seven substituted styrenes with trimethylamine‐N‐oxide in the absence and in the presence of pyridine ligand have been carried out. The rates correlate with the Hammett relationship and V‐shaped plots with a maximum are in agreement with the oxidation of osmate(VI) ester in the rate‐determining step. Copyright © 2002 John Wiley & Sons, Ltd.
The nitro anomaly and Brønsted βnuc values in SN2 reactions on chlorine
Authors: Eliad Linoam , Hoz Shmaryahu
Published: October 2002

The kinetics of chlorine transfer reactions between N‐chlorosuccinimide (NCS) and four carbon nucleophiles (the conjugated bases of phenyldinitromethane, Meldrum's acid, phenylmalononitrile and phenylnitro‐methane) in water were determined. A plot of log k for the SN2 reactions vs the pKa of the first three conjugated acids of the nucleophiles gave a straight line with a slope (βnuc) of 1.8. The data point for the mononitro derivative, phenylnitromethane, deviates negatively from the line by 6.7 log units. This deviation is typical of proton transfer reactions and was recently shown to occur also in SN2 reactions on bromine. Copyright © 2002 John Wiley & Sons, Ltd.
Vinyl‐ and ethynylsilanes, ‐germanes and ‐stannanes. A new case of dissociative proton attachment
Authors: Mó Otilia , Yáñez Manuel , Gal Jean‐François , Maria Pierre Charles , Guillemin Jean‐Claude
Published: October 2002

The gas‐phase protonation of H2CC(H)XH3and HC≡CXH3(X = Si, Ge, Sn) compounds was investigated through the use of high‐level density functional theory methods. The structures of neutral and protonated species were optimized at the B3LYP/6–31G* level of theory, while the final energies were obtained by single‐point B3LYP/6–311 + G(3df,2p) calculations. In the gas phase, vinyl‐ and ethynylsilanes, ‐germanes and ‐stannanes behave as carbon bases of moderate strength, with the only exception of vinylstannane, which is predicted to be about 20 kJ mol−1more basic than ammonia. In all cases Cαprotonation is the most favorable process. This protonation is followed by a C—X bond cleavage, so that the protonated form corresponds to a tightly bound complex between ethylene (or acetylene) and the corresponding XH3+cation. This implies that dissociative proton attachments can be observed when the basic center is an atom of low electronegativity, provided that the other atoms bonded to it are much less electronegative than the basic center itself, and that the fragments formed as products of the dissociation are intrinsically stable. Copyright © 2002 John Wiley & Sons, Ltd.