bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate analysis of maturity stages, including quality and aroma, in ‘Royal Glory’ peaches and ‘Big Top’ nectarines
Authors: Lavilla T , Recasens I , Lopez M L , Puy J
Published: November 2002

Ethylene production, quality attributes and aroma compounds were analysed to determine the maturity evolution of ‘Big Top’ nectarines and ‘Royal Glory’ peaches at harvest dates ranging from 89 to 116 days after full bloom (DAFB) for nectarines and from 85 to 112 DAFB for peaches. These cultivars are highly coloured even in the early stages of maturity. However, the two cultivars had different patterns of ethylene production, this being slower in nectarines than in peaches. Principal component analysis (PCA) was used to provide partial visualisation of the complete data set in a reduced dimension plot. Separation of the two cultivars can be shown by means of a two‐dimensional plot of the samples. Although only some aroma compounds are slightly correlated with quality parameters, when aroma volatiles were included in the PCA, the aroma compound set allowed both cultivars to be classified into three stages of maturity: immature, intermediate and fully mature. Compounds such as propanol, hexyl acetate, 2‐methylpropyl acetate, limonene, butanol, (Z)‐3‐hexenyl acetate, buthyl acetate, linalool, ethanol, propyl acetate and ethyl acetate are the most important volatiles for ‘Big Top’ nectarines. It is suggested that the presence of these compounds can be used to indicate when the fruit should be harvested. The presence of γ‐decalactone, δ‐octalactone, γ‐octalactone, ethyl butyrate, hexanal and (E)‐2‐hexenol can be used to indicate the harvesting maturity stage for ‘Royal Glory’ peaches. The optimum maturity date for harvest would be 105–107 DAFB for ‘Big Top’ nectarines and 93–95 DAFB for ‘Royal Glory’ peaches.

© 2002 Society of Chemical Industry
Influence of spray drying conditions on functionality of dried whole egg
Authors: Franke Knut , Kießling Martina
Published: November 2002

Instead of traditional liquid eggs, more and more dried whole egg products are being used in the manufacture of fine bakery goods, since dried semi‐finished products have some advantages regarding storage, handling and microbiological safety. However, the spray drying process leads to changes in sensitive egg components, eg proteins, and affects the functional properties of whole egg after reconstitution. Knowledge of the influence of drying conditions on the resulting functionality is necessary to enable the production of dried egg with tailor‐made properties for applications in different food products. Some of these relationships were determined using a pilot spray dryer for drying experiments and an appropriate statistical evaluation of the results. It could be demonstrated that higher temperatures during spray drying lead to a considerable decrease in the foaming properties of whole egg powder but increase the capability of emulsion stabilisation. Additionally, a simplified example demonstrates the use of these relationships for the selection of optimal drying conditions of whole egg with respect to its application in a cake with higher fat content.

© 2002 Society of Chemical Industry
In vitro determination of digestible and unavailable protein in edible seaweeds
Authors: Goñi Isabel , Gudiel‐Urbano Montserrat , Saura‐Calixto Fulgencio
Published: November 2002

Edible seaweeds are considered a complementary source of food protein for human and animal nutrition. The physiological effects of seaweed protein depend on the degree of enzymatic digestion of protein in the small intestine and bacterial fermentation in the large intestine. The objective of this work was to estimate total, digestible, fermentable and unavailable protein in some red and brown seaweeds. Brown seaweeds Fucus vesiculosus, Laminaria digitata and Undaria pinnatifida and red seaweeds Chondrus crispus and Porphyra tenera were treated with pepsin and pancreatin to separate digestible protein. Residues containing indigestible protein were inoculated for 24 h with rat caecal droppings, and protein contents were evaluated in the non‐fermented residue. Protein content in the seaweeds ranged from 8.9 to 25% of dry matter. Digestible protein was the major protein fraction (69%) only in P tenera; in the other seaweeds, this fraction ranged from 15 to 45%. Significant amounts of unavailable protein were found in all samples (2–24%). The distribution of total protein among the three fractions, ie digestible, fermentable and unavailable protein, could yield information about the physiological and metabolic consequences of the intake of seaweed proteins.

© 2002 Society of Chemical Industry
Nicotinic receptors in aging and dementia
Authors: Picciotto Marina R. , Zoli Michele
Published: November 2002

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects. Smoking has also been shown in some epidemiological studies to be protective against the development of neurodegenerative diseases. This is supported by animal studies that have shown nicotine to be neuroprotective both in vivo and in vitro. Treatment with nicotinic agonists may therefore be useful in both slowing the progression of neurodegenerative illnesses, and improving function in patients with the disease. While increased nicotinic function has been shown to be beneficial, loss of cholinergic markers is often seen in patients with dementia, suggesting that decreased cholinergic function could contribute to both the cognitive deficits, and perhaps the neuronal degeneration, associated with dementia. In this article we will review the literature on each of these areas. We will also present hypotheses that might address the mechanisms underlying the ability of nAChR function to protect against neurodegeneration or improve cognition, two potentially distinct actions of nicotine. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 641–655, 2002
Autoimmune diseases involving nicotinic receptors
Authors: Lindstrom Jon
Published: November 2002

The antibody‐mediated autoimmune response to α1 muscle nicotinic acetylcholine receptors that causes myasthenia gravis is one of the best characterized autoimmune diseases. Antibody‐mediated autoimmune responses to neuronal nicotinic receptors are just beginning to be discovered and characterized. One of these causes dysautonomia through antibodies to α3 nicotinic receptors of autonomic ganglia. Another causes pemphigus through antibodies to α9 nicotinic receptors in skin. Other autoimmune responses to nicotinic receptors may be discovered as the many functional roles of nicotinic receptors are revealed. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 656–665, 2002
Desensitization of neuronal nicotinic receptors
Authors: Quick Michael W. , Lester Robin A.J.
Published: November 2002

The loss of functional response upon continuous or repeated exposure to agonist, desensitization, is an intriguing phenomenon if not as yet a well‐defined physiological mechanism. However, detailed evaluation of the properties of desensitization, especially for the superfamily of ligand‐gated ion channels, reveals how the nervous system could make important use of this process that goes far beyond simply curtailing excessive receptor stimulation and the prevention of excitotoxicity. Here we will review the mechanistic basis of desensitization and discuss how the subunit‐dependent properties and regulation of nicotinic acetylcholine receptor (nAChR) desensitization contribute to the functional diversity of these channels. These studies provide the essential framework for understanding how the physiological regulation of desensitization could be a major determinant of synaptic efficacy by controlling, in both the short and long term, the number of functional receptors. This type of mechanism can be extended to explain how the continuous occupation of desensitized receptors during chronic nicotine exposure contributes to drug addiction, and highlights the potential significance of prolonged nAChR desensitization that would also occur as a result of extended acetylcholine lifetime during treatment of Alzheimer's disease with cholinesterase inhibitors. Thus, a clearer picture of the importance of nAChR desensitization in both normal information processing and in various diseased states is beginning to emerge. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 457–478, 2002
Regulatory mechanisms that govern nicotinic synapse formation in neurons
Authors: Rosenberg Madelaine M. , Blitzblau Rachel C. , Olsen Douglas P. , Jacob Michele H.
Published: November 2002

Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression—innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 542–555, 2002
Nicotinic receptor signaling in nonexcitable cells
Authors: Sharma Geeta , Vijayaraghavan Sukumar
Published: November 2002

The finding that neuronal nicotinic acetylcholine receptors (nAChRs) are present in non‐neuronal cells both within and outside the nervous system raises some interesting issues. The mechanisms underlying receptor signaling and its downstream consequences in these cells remain to be elucidated. Factors controlling the release of acetylcholine and the extent of its diffusion are likely to be different for these cells than for traditional neuronal synapses. Recent advances on the physiologic functions of some of these cell types have provided a better insight into possible functional roles for nAChRs in nonexcitable cells. The presence of nAChRs on these cells also implies a broader scope for the actions of nicotine that needs to be considered from a clinical viewpoint. Revealing the potential physiologic roles for nAChRs on nonexcitable cells is likely to provide a more complete understanding of cholinergic signaling. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 524–534, 2002
Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons
Authors: Berg Darwin K. , Conroy William G.
Published: November 2002

Nicotinic receptors are cation‐ion selective ligand‐gated ion channels that are expressed throughout the nervous system. Most have significant calcium permeabilities, enabling them to regulate calcium‐dependent events. One of the most abundant is a species composed of the α7 gene product and having a relative calcium permeability equivalent to that of NMDA receptors. The α7‐containing receptors can be found presynaptically where they modulate transmitter release, and postsynaptically where they generate excitatory responses. They can also be found in perisynaptic locations where they modulate other inputs to the neuron and can activate a variety of downstream signaling pathways. The effects the receptors produce depend critically on the sites at which they are clustered. Instructive preparations for examining α7‐containing receptors are the rat hippocampus, where they are thought to play a modulatory role, and the chick ciliary ganglion, where they participate in throughput transmission as well as regulatory signaling. Relatively high levels of α7‐containing receptors are found in the two preparations, and the receptors display a variety of synaptic options and functions in the two cases. Progress is starting to be made in understanding the mechanisms responsible for localizing the receptors at specific sites and in identifying components tethered in the vicinity of the receptors that may facilitate signal transduction and downstream signaling. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 512–523, 2002
The nicotinic receptor ligand binding domain
Authors: Sine Steven M.
Published: November 2002

The ligand binding domain (LBD) of the nicotinic acetylcholine receptor has served as a prototype for understanding molecular recognition in the family of neurotransmitter‐gated ion channels. During the past fifty years, studies progressed from fundamental electrophysiological analyses of ACh‐evoked ion flow, to biochemical purification of the receptor protein, pharmacological measurements of ligand binding, molecular cloning of receptor subunits, site‐directed mutagenesis combined with functional analysis and recently, atomic structural determination. The emerging picture of the nicotinic receptor LBD is a specialized pocket of aromatic and hydrophobic residues formed at interfaces between protein subunits that changes conformation to convert agonist binding into gating of an intrinsic ion channel. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 431–446, 2002
The role of nAChR‐mediated spontaneous retinal activity in visual system development
Authors: Feller Marla B.
Published: November 2002

In the developing vertebrate retina, nAChR synapses are among the first to appear. This early cholinergic circuitry plays a key role in generating “retinal waves,” spontaneously generated waves of action potentials that sweep across the ganglion cell layer. These retinal waves exist for a short period of time during development when several circuits within the visual system are being established. Here I review the cholinergic circuitry of the developing retina and the role these early circuits play in the development of the retina itself and of retinal projections to the lateral geniculate nucleus of the thalamus. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 556–567, 2002
Nicotinic mechanisms in the autonomic control of organ systems
Authors: De Biasi Mariella
Published: November 2002

Most visceral organs are under the control of the autonomic nervous system (ANS). Information on the state and function of these organs is constantly relayed to the central nervous system (CNS) by sensory afferent fibers. The CNS integrates the sensory inputs and sends neural commands back to the organ through the ANS. The autonomic ganglia are the final site for the integration of the message traveling from the CNS. Nicotinic acetylcholine receptors (nAChRs) are the main mediators of fast synaptic transmission in ganglia, and therefore, are key molecules for the processing of neural information in the ANS. This review focuses on the role of nAChRs in the control of organ systems such as heart, gut, and bladder. The autonomic control of these organ systems is discussed in the light of the results obtained from the analysis of mice carrying mutations targeted to nAChR subunits expressed in the ANS. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 568–579, 2002
Unconventional ligands and modulators of nicotinic receptors
Authors: Pereira Edna F.R. , Hilmas Corey , Santos Mariton D. , Alkondon Manickavasagom , Maelicke Alfred , Albuquerque Edson X.
Published: November 2002

Evidence gathered from epidemiologic and behavioral studies have indicated that neuronal nicotinic receptors (nAChRs) are intimately involved in the pathogenesis of a number of neurologic disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In the mammalian brain, neuronal nAChRs, in addition to mediating fast synaptic transmission, modulate fast synaptic transmission mediated by the major excitatory and inhibitory neurotransmitters glutamate and GABA, respectively. Of major interest, however, is the fact that the activity of the different subtypes of neuronal nAChR is also subject to modulation by substances of endogenous origin such as choline, the tryptophan metabolite kynurenic acid, neurosteroids, and β‐amyloid peptides and by exogenous substances, including the so‐called nicotinic allosteric potentiating ligands, of which galantamine is the prototype, and psychotomimetic drugs such as phencyclidine and ketamine. The present article reviews and discusses the effects of unconventional ligands on nAChR activity and briefly describes the potential benefits of using some of these compounds in the treatment of neuropathologic conditions in which nAChR function/expression is known to be altered. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 479–500, 2002
Nicotinic receptor‐mediated effects on appetite and food intake
Authors: Jo Young‐Hwan , Talmage David A. , Role Lorna W.
Published: November 2002

It is well known, although not well understood, that smoking and eating just do not go together. Smoking is associated with decreased food intake and lower body weight. Nicotine, administered either by smoking or by smokeless routes, is considered the major appetite‐suppressing component of tobacco. Perhaps the most renowned example of nicotine's influence on appetite and feeding behavior is the significant weight gain associated with smoking cessation. This article presents an overview of the literature at, or near, the interface of nicotinic receptors and appetite regulation. We first consider some of the possible sites of nicotine's action along the complex network of neural and non‐neural regulators of feeding. We then present the hypothesis that the lateral hypothalamus is a particularly important locus of the anorectic effects of nicotine. Finally, we discuss the potential role of endogenous cholinergic systems in motivational feeding, focusing on cholinergic pathways in the lateral hypothalamus. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 618–632, 2002
Cellular and synaptic mechanisms of nicotine addiction
Authors: Mansvelder Huibert D. , McGehee Daniel S.
Published: November 2002

The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laboratories have provided new insights into the biologic processes that contribute to nicotine self‐administration. Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 606–617, 2002
Cholinergic interneuron characteristics and nicotinic properties in the striatum
Authors: Zhou Fu‐Ming , Wilson Charles J. , Dani John A.
Published: November 2002

The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 590–605, 2002
Nicotinic receptor subtypes and cognitive function
Authors: Levin Edward D.
Published: November 2002

Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine‐induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial‐arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both α4β2 and α7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either α4β2 or α7 antagonists. Ventral hippocampal α4β2 blockade‐induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal α7 blockade‐induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, α4β2 and α7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, α7 antagonist cotreatment actually reversed the working memory impairment caused by α4β2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 633–640, 2002
Nicotinic receptors in circuit excitability and epilepsy
Authors: Raggenbass Mario , Bertrand Daniel
Published: November 2002

Neuronal nicotinic acetylcholine receptors belong to the family of excitatory ligand‐gated channels and result from the assembly of five subunits. Functional heteromeric nictonic receptors are present in the hippocampus and neocortex, thalamus, mesolimbic dopamine system and brainstem motor nuclei, where they may play a role, respectively, in memory, sensory processing, addiction and motor control. Some forms of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) have been found to be associated with mutations in the genes coding for the α4 or β2 subunits of the nicotinic receptor. Mutant receptors display an increased acetylcholine sensitivity with respect to normal receptors. Since the thalamus and the cortex are strongly innervated by cholinergic neurons projecting from the brainstem and basal forebrain, an umbalance between excitation and inhibition, brought about by the presence of mutant receptors, could generate seizures by facilitating and synchronizing spontaneous oscillations in thalamo‐cortical circuits. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 580–589, 2002
The diversity of subunit composition in nAChRs: Evolutionary origins, physiologic and pharmacologic consequences
Authors: Le Novère Nicolas , Corringer Pierre‐Jean , Changeux Jean‐Pierre
Published: November 2002

Nicotinic acetylcholine receptors are made up of homologous subunits, which are encoded by a large multigene family. The wide number of receptor oligomers generated display variable pharmacological properties. One of the main questions underlying research in molecular pharmacology resides in the actual role of this diversity. It is generally assumed that the observed differences between the pharmacology of homologous receptors, for instance, the EC50 for the endogenous agonist, or the kinetics of desensitization, bear some kind of physiologic relevance in vivo. Here we develop the quite challenging point of view that, at least within a given subfamily of nicotinic receptor subunits, the pharmacologic variability observed in vitro would not be directly relevant to the function of receptor proteins in vivo. In vivo responses are not expected to be sensitive to mild differences in affinities, and several examples of functional replacement of one subunit by another have been unravelled by knockout animals. The diversity of subunits might have been conserved through evolution primarily to account for the topologic diversity of subunit distribution patterns, at the cellular and subcellular levels. A quantitative variation of pharmacological properties would be tolerated within a physiologic envelope, as a consequence of a near‐neutral genetic drift. Such a “gratuitous” pharmacologic diversity is nevertheless of practical interest for the design of drugs, which would specifically tackle particular receptor oligomers with a defined subunit composition among the multiple nicotinic receptors present in the organism. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 447–456, 2002
Genetic analysis of nicotinic signaling in worms and flies
Authors: Schafer William R.
Published: November 2002

The nicotinic acetylcholine receptor is among the most thoroughly characterized molecules in the nervous system, and its role in mediating fast cholinergic neurotransmission has been broadly conserved in both vertebrates and invertebrates. However, the accessory molecules that facilitate or regulate nicotinic signaling remain mostly unknown. One approach to identify such molecules is to use molecular genetics in a simple, experimentally accessible organism to identify genes required for nicotinic signaling and to determine the molecular identity of the mutant genes through molecular cloning. Because cellular signaling pathways are often highly conserved between different animal phyla, the information gained from studies of simple organisms has historically provided many critical insights into more complex organisms, including humans. Genetic screens essentially make no prior assumptions about the types of molecules involved in the process being studied; thus, they are well suited for identifying previously unknown components of cell signaling pathways. The sophisticated genetic tools available in organisms such as the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster have also proven extremely powerful in elucidating complex biologic pathways in the absence of prior biochemical information and for assessing a molecule's in vivo function of in the context of an intact nervous system. This review describes how genetic analysis has been used to investigate nicotinic signaling mechanisms in worms and flies, and the prospects for using these studies to gain insight into nicotinic receptor function and regulation in humans. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 535–541, 2002
Development of geometrically exact new shell elements based on general curvilinear co‐ordinates
Authors: Cho Maenghyo , Roh Hee Yuel
Published: November 2002

In the present study first‐order shear deformable shell finite elements based on general curvilinear co‐ordinates are proposed. For the development of the present shell elements, a partial mixed variational functional with independently assumed strains is provided in order to avoid the severe locking troubles known as transverse shear and membrane lockings. Bubble functions are included in the shape function of displacement to improve the performance of the developed element. The proposed assumed strain four‐ and nine‐node elements based on the general tensor shell theory provide an efficient linkage framework for shell surface modelling and finite element analysis. In the several benchmark problems, the present shell elements with exact geometric representations demonstrate their performance compared to previously reported results. Copyright © 2002 John Wiley & Sons, Ltd.
3D dynamics of discrete element systems comprising irregular discrete elements—integration solution for finite rotations in 3D
Authors: Munjiza A. , Latham J. P. , John N. W. M.
Published: November 2002

An algorithm for transient dynamics of discrete element systems comprising a large number of irregular discrete elements in 3D is presented. The algorithm is a natural extension of contact detection, contact interaction and transient dynamics algorithms developed in recent years in the context of discrete element methods and also the combined finite‐discrete element method. It complements the existing algorithmic procedures enabling transient motion including finite rotations of irregular discrete elements in 3D space to be accurately integrated. Copyright © 2002 John Wiley & Sons, Ltd.
Moving kriging interpolation and element‐free Galerkin method
Authors: Gu Lei
Published: November 2002

A new formulation of the element‐free Galerkin (EFG) method is presented in this paper. EFG has been extensively popularized in the literature in recent years due to its flexibility and high convergence rate in solving boundary value problems. However, accurate imposition of essential boundary conditions in the EFG method often presents difficulties because the Kronecker delta property, which is satisfied by finite element shape functions, does not necessarily hold for the EFG shape function. The proposed new formulation of EFG eliminates this shortcoming through the moving kriging (MK) interpolation. Two major properties of the MK interpolation: the Kronecker delta property (ϕI(sJ)=δIJ) and the consistency property (∑InϕI(x)=1 and ∑InϕI(x)xIi=xi) are proved. Some preliminary numerical results are given. Copyright © 2002 John Wiley & Sons, Ltd.
Adaptive damping for dynamic relaxation problems with non‐monotonic spectral response
Authors: Metzger Don R.
Published: November 2002

Non‐inertial transients may be effectively solved using explicit time integration with arbitrary inertial and damping properties. The usual approach relies on a diagonal lumped mass on which strictly mass proportional damping is based. While the damping coefficient can be adaptively determined on the basis of the estimated frequency of the predominant response, local changes in stiffness, often associated with changing contact conditions, can cause abrupt changes in the damping coefficient. This can substantially impede the progress of the solution, particularly when deformations involve large translations or rotations of parts of the system. A modification to the mass proportional damping is developed and implemented to avoid the deleterious effects of sudden changes in the damping coefficient. A new procedure is thus implemented so that the usual dynamic relaxation method will automatically adapt to changing conditions of response in such a way as to avoid overdamping low modes due to subsequent higher frequency events. Copyright © 2002 John Wiley & Sons, Ltd.
Fully coupled non‐linear analysis of piezoelectric solids involving domain switching
Authors: Zeng Wenjun , Manzari Majid T. , Lee James D. , Shen Yin‐Lin
Published: November 2002

Domain switching is the cause of significant non‐linearity in the response of piezoelectric materials to mechanical and electrical effects. In this paper, the response of piezoelectric solids is formulated by coupling thermal, electrical, and mechanical effects. The constitutive equations are non‐linear. Moreover, due to the domain switching phenomenon, the resulting governing equations become highly non‐linear. The corresponding non‐linear finite element equations are derived and solved by using an incremental technique. The developed formulation is first verified against a number of benchmark problems for which a closed‐form solution exists. Next, a cantilever beam made of PZT‐4 is studied to evaluate the effect of domain switching on the overall force–displacement response of the beam. A number of interesting observations are made with respect to the extent of non‐linearity and its progressive spread as the load on the beam increases. Copyright © 2002 John Wiley & Sons, Ltd.
New approaches for error estimation and adaptivity for 2D potential boundary element methods
Authors: Jorge Ariosto B. , Ribeiro Gabriel O. , Fisher Timothy S.
Published: November 2002

This work presents two new error estimation approaches for the BEM applied to 2D potential problems. The first approach involves a local error estimator based on a gradient recovery procedure in which the error function is generated from differences between smoothed and non‐smoothed rates of change of boundary variables in the local tangential direction. The second approach involves the external problem formulation and gives both local and global measures of error, depending on a choice of the external evaluation point. These approaches are post‐processing procedures. Both estimators show consistency with mesh refinement and give similar qualitative results. The error estimator using the gradient recovery approach is more general, as this formulation does not rely on an ‘optimal’ choice of an external parameter. This work presents also the use of a local error estimator in an adaptive mesh refinement procedure. This r‐refinement approach is based on the minimization of the standard deviation of the local error estimate. A non‐linear programming procedure using a feasible‐point method is employed using Lagrange multipliers and a set of active constraints. The optimization procedure produces finer meshes close to a singularity and results that are consistent with the problem physics. Copyright © 2002 John Wiley & Sons, Ltd.
An evaluation of the Lyapunov characteristic exponent of chaotic continuous systems
Authors: Rugonyi Sandra , Bathe Klaus‐Jürgen
Published: November 2002

A procedure to calculate the Lyapunov characteristic exponent of the response of structural continuous systems, discretized using finite element methods, is proposed. The Lyapunov characteristic exponent can be used to characterize the asymptotic stability of the system dynamic response, and it is frequently employed to identify a chaotic behaviour. The proposed procedure can also be used in the stability characterization of fluid–structure interaction systems in which the focus of the analysis is on the behaviour of the structural part. Copyright © 2002 John Wiley & Sons, Ltd.
Human atherosclerotic plaques express DC‐SIGN, a novel protein found on dendritic cells and macrophages
Authors: Soilleux EJ , Morris LS , Trowsdale J , Coleman N , Boyle JJ
Published: November 2002

The association of autoimmune phenomena with atherosclerosis suggests that plaques may contain specialized antigen‐presenting cells, dendritic cells (DCs). DC‐SIGN is a C‐type lectin expressed by DCs. This study assessed whether human atherosclerotic plaques expressed DC‐SIGN and several other macrophage/DC markers. Plaques from human coronary and carotid arteries and aorta contained DC‐SIGN‐immunoreactive cells. Double‐labelling showed co‐expression of DC‐SIGN and macrophage/DC lineage markers CD14, CD68, HLA‐DR, and S100. There was no immunoreactivity for the DC activation markers CD83 or CMRF‐44. Since DC‐SIGN mediates adhesion to T‐lymphocytes and endocytosis, its expression in atherosclerotic plaques may have functional implications. Activated DCs migrate quickly from areas of inflammation to regional lymph nodes, possibly explaining the paucity of activated DCs in atherosclerotic plaques. In conclusion, this study has shown that DC‐SIGN is expressed in atherosclerosis. Copyright © 2002 John Wiley & Sons, Ltd.
Interstitial cell cyclooxygenase‐2 expression is associated with increased angiogenesis in human sporadic colorectal adenomas
Authors: Chapple Keith S , Scott Nigel , Guillou Pierre J , Coletta P Louise , Hull Mark A
Published: November 2002

Cyclooxygenase (COX)‐2 plays an important role in intestinal tumorigenesis and angiogenesis in animal models. In superficial areas of human sporadic colorectal adenomas, COX‐2 is expressed predominantly by interstitial macrophages, in close proximity to microvessels. The aim of this study was to investigate the association between microvessel density (MVD) and COX‐2 expression in human sporadic colorectal adenomas. Immunohistochemistry and immunofluorescence for CD31 and COX‐2 were performed on a well‐characterized series of human sporadic colorectal adenomas (n = 37). The mean MVD and COX‐2 expression level (scored 0–3) in superficial and deep interstitial cells of adenomas were assessed by two independent observers. Superficial MVD was increased in COX‐2‐positive adenomas, compared with COX‐2‐negative adenomas (p = 0.037). There was a significant correlation between superficial MVD and increasing superficial interstitial cell COX‐2 expression score (p = 0.048). COX‐2‐expressing interstitial cells aggregated in areas of high MVD. No relationship was evident between MVD and COX‐2 expression in either deep interstitial cells or epithelial cells. Multivariate analysis demonstrated that only adenoma size (p = 0.005) was a significant independent predictor of MVD. COX‐2 protein expression by superficial interstitial cells in human sporadic colorectal adenomas is associated with increased angiogenesis. Promotion of angiogenesis may play a role in the pro‐tumourigenic activity of COX‐2 during growth of human colorectal adenomas. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas; regulation by the von Hippel‐Lindau gene and hypoxia
Authors: Currie Margaret J , Gunningham Sarah P , Turner Kevin , Han Cheng , Scott Prudence AE , Robinson Bridget A , Chong Wen , Harris Adrian L , Fox Stephen B
Published: November 2002

Angiogenesis is essential for tumour growth and metastasis, and is co‐ordinated by several classes of angiogenic factors. To determine the significance and regulation of the angiopoietin (Ang) pathway in highly vascular human renal cell carcinomas (RCCs), this study has investigated the expression of the Ang‐1, Ang‐2, Ang‐4, and Tie2 genes in a series of normal (n = 26) and neoplastic (n = 45; clear cell n = 35, papillary n = 10) human kidney tissues, examined the pattern of Ang‐2 and Tie2 protein expression, and correlated expression with clinicopathological variables. The effect of the von Hippel‐Lindau (VHL) gene and hypoxia in the renal cell lines RCC786‐0 and RCC4 has also been investigated. Ang‐1, Ang‐2 and Tie2, but not Ang‐4 mRNA, were detected in normal and tumour samples. A significant increase in Ang‐2 (p < 0.001) and a decrease in Tie2 receptor mRNA (p = 0.001) were observed, but no significant difference was observed in Ang‐1 mRNA abundance between normal kidney and RCC (p = 0.37). Immunohistochemistry for Ang‐2 showed strong expression in vascular endothelium and weak expression in tumour cells, whereas Tie2 was expressed exclusively on endothelium. Tie2 gene expression was positively correlated with Ang‐2 expression in cancers (p = 0.001) and showed a borderline significant association with Ang‐1 (p = 0.06), but there was no significant relationship between Ang‐1 and Ang‐2 (p = 0.69). No significant relationships were observed in clear cell carcinomas between Ang‐1, Ang‐2 and Tie2 mRNA abundance and patient sex, patient age, or tumour size (p > 0.05). However, there was significantly greater Ang‐1 (p = 0.02), Ang‐2 (p = 0.03), and Tie2 (p = 0.04) mRNA abundance in clear cell than in chromophil RCCs. Ang‐2 gene expression was down‐regulated by hypoxia in VHL wild‐type RCC786‐0 and RCC4 transfectants (p = 0.0002 and p = 0.04, respectively), mirroring the low expression in human tumour cells. These data suggest that it is endothelial induction of Ang‐2 in tumours that regulates vessel stability and supports targeting Tie2 as an effective novel anti‐angiogenic therapy in clear cell RCCs. Copyright © 2002 John Wiley & Sons, Ltd.
Activation and apoptosis of macrophages in cat scratch disease
Authors: Schweyer S , Fayyazi A
Published: November 2002

Cat scratch disease is an infectious disease usually caused by Bartonella henselae. Within 1–3 weeks after inoculation, patients typically develop regional self‐limited lymphadenopathy. Lymph nodes reveal granulomas consisting of central necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and non‐palisading macrophages. In animals, cat‐scratch disease leads to an interferon‐γ (IFNγ)‐mediated T‐helper 1 immune response, resulting in macrophage recruitment, stimulation, and thereby granuloma formation. The present study has sought to find in situ evidence for macrophage migration, activation, and cell death in human cat scratch disease. By non‐radioactive in situ hybridization and immunohistochemistry on serial sections, it was demonstrated that IFNγ+ T lymphocytes and S100A8+, S100A9+ macrophages embrace granulomas, which consisted of S100A8–, S100A9–, HLA‐DR+, CD40+, TNFα+ macrophages. Combination of in situ end‐labelling and immunofluorescence revealed large numbers of DNA‐fragmented CD68+ cells with intact plasma membranes corresponding to apoptotic macrophages. On the basis of these data, it was hypothesized that in human cat scratch disease, S100A8+, S100A9+ macrophages continuously migrate to the granulomas. During this process, they may be activated by IFNγ T‐helper 1 lymphocytes and be differentiated to S100A8–, S100A9–sessile, HLA‐DR+, CD40+ antigen‐presenting, TNFα+ pro‐inflammatory macrophages forming granulomas. In parallel, macrophages undergo apoptosis in the centre of granulomata, a phenomenon that may restrict the destructive potential of macrophages and contribute to self‐limitation of cat scratch disease. Copyright © 2002 John Wiley & Sons, Ltd.
Oestrogen receptors alpha and beta differ in normal human breast and breast carcinomas
Authors: Shaw Jacqueline A , Udokang Kufre , Mosquera Juan‐Miguel , Chauhan Hina , Jones J Louise , Walker Rosemary A
Published: November 2002

The identification of a second oestrogen receptor, oestrogen receptor (ER) β, has led to a need to assess the relative importance of the classical ERα and ERβ in human breast and breast carcinomas. ERα and ERβ mRNA was assessed in 61 carcinomas, 8 benign breast lesions, and 30 samples of normal breast using reverse transcriptase (RT)‐nested polymerase chain reaction (PCR). Immunohistochemical analysis of ERα and ERβ was performed in 62 carcinomas, the 38 non‐malignant breast tissues, and 32 normal breast samples with menstrual cycle data. ERα mRNA was detected in 92% of breast cancers, with ERβ mRNA (wild‐type and/or variant form) in 85%; 72% had ERα protein, 62% progesterone receptor (PgR), and 32% ERβ. ERα protein had a strong correlation with grade; ERβ did not, although it was present in three of four grade I carcinomas and in special types. There was no correlation between the presence of ERα and ERβ protein. In non‐malignant breast, similar expression of ERα and β was observed, apart from expression of ERβ in stromal cells and myoepithelium, the latter being confirmed by RT‐PCR and western blotting. There were differences in ERα in relation to the menstrual cycle but not PgR or ERβ. The findings indicate a need to understand the role and regulation of ERβ in normal breast and the reason for its down‐regulation in mammary carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Differential expression of p63 isoforms in normal tissues and neoplastic cells
Authors: Nylander Karin , Vojtesek Borek , Nenutil Rudolf , Lindgren Britta , Roos Göran , Zhanxiang Wang , Sjöström Björn , Dahlqvist Åke , Coates Philip J
Published: November 2002

The p63 gene encodes at least six different proteins with homology to the tumour suppressor protein p53 and the related p53 family member p73. So far, there have been limited data concerning the expression patterns of individual p63 proteins, due to a lack of reagents that distinguish between the different isoforms. Three antibodies have been produced specifically directed against the two N‐terminal isoforms (TAp63 and ΔNp63) and the C‐terminal region of the p63α proteins. TAp63 proteins are located suprabasally in stratified epithelia compared with the N‐terminal truncated forms, which are more abundantly expressed in the basal cell layer, indicating a switch in expression of p63 isoforms during normal cellular differentiation. Analysis of squamous cell carcinomas shows ΔNp63α to be the most widely expressed isoform, compatible with a role for this protein in promoting neoplastic cell growth in these tissues. ΔNp63 protein expression is also restricted to basal cells in breast and prostate, whilst TAp63 isoforms are more widely expressed in these tissues as well as in tumours at these sites. TAp63, but not ΔNp63 or p63α, is detected in normal colon and in colon carcinoma. TAp63 proteins are also expressed in the nuclei of a sub‐population of lymphoid cells and in most malignant lymphomas, whereas ΔNp63 proteins are not expressed. Taken together, a hitherto unrecognized regulation of p63 isoform expression in vivo has been uncovered, with different p63 proteins expressed during differentiation and in different cell types. The data indicate roles for specific p63 isoforms not only in maintaining epithelial stem cell populations, but also in cellular differentiation and neoplasia. Copyright © 2002 John Wiley & Sons, Ltd.