bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and synaptic mechanisms of nicotine addiction
Authors: Mansvelder Huibert D. , McGehee Daniel S. 
Published: November 2002

AbstractThe 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

AbstractThe 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

AbstractNicotinic 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

AbstractNeuronal 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

AbstractNicotinic 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

AbstractThe 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

AbstractIn 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

AbstractAn 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

AbstractA 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

AbstractNon‐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

AbstractDomain 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

AbstractThis 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

AbstractA 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

AbstractThe 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

AbstractCyclooxygenase (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

AbstractAngiogenesis 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.