bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclin A2 is phosphorylated during the G2/M transition in mouse two‐cell embryos
Authors: Ohashi Akihiro , Imai Hiroshi , Minami Naojiro
Published: October 2003

In the present study, we investigated the expression of cyclin A2 in mouse two‐cell embryos to elucidate the role of cyclin A2 at the G2/M transition. Two forms of cyclin A2 on SDS–PAGE (an upper and a lower band) were detected in two‐cell embryos synchronized at the M phase by nocodazole. To investigate the nature of this shift, embryos synchronized at the M phase were treated with alkaline phosphatase (AP). The upper band of cyclin A2 was fainter in AP‐treated embryos than in nontreated embryos. This result indicates that cyclin A2 in mouse two‐cell embryos is phosphorylated and the band on SDS–PAGE shifts up during the G2/M transition. In addition, we examined the sequential expression of cyclin A2 in two‐cell blocked embryos after OA treatment. The upper band of cyclin A2 was first detected at 2 hr after the treatment, corresponding to the timing of Cdc2 kinase activation. In two‐cell embryos after removal from nocodazole treatment, the phosphorylated form of cyclin A2 protein decreased abruptly just before cytokinesis. These results suggest that the mechanism of cyclin A2 degradation in mouse two‐cell embryos may be different from that in somatic cells. Mol. Reprod. Dev. 66: 343–348, 2003. © 2003 Wiley‐Liss, Inc.
Ground response curves for rock masses exhibiting strain‐softening behaviour
Authors: Alonso E. , Alejano L. R. , Varas F. , Fdez‐Manin G. , Carranza‐Torres C.
Published: October 2003

A literature review has shown that there exist adequate techniques to obtain ground reaction curves for tunnels excavated in elastic‐brittle and perfectly plastic materials. However, for strain‐softening materials it seems that the problem has not been sufficiently analysed. In this paper, a one‐dimensional numerical solution to obtain the ground reaction curve (GRC) for circular tunnels excavated in strain‐softening materials is presented.

The problem is formulated in a very general form and leads to a system of ordinary differential equations. By adequately defining a fictitious ‘time’ variable and re‐scaling some variables the problem is converted into an initial value one, which can be solved numerically by a Runge–Kutta–Fehlberg method, which is implemented in MATLAB environment.

The method has been developed for various common particular behaviour models including Tresca, Mohr–Coulomb and Hoek–Brown failure criteria, in all cases with non‐associative flow rules and two‐segment piecewise linear functions related to a principal strain‐dependent plastic parameter to model the transition between peak and residual failure criteria.

Some particular examples for the different failure criteria have been run, which agree well with closed‐form solutions—if existing—or with FDM‐based code results. Parametric studies and specific charts are created to highlight the influence of different parameters.

The proposed methodology intends to be a wider and general numerical basis where standard and newly featured behaviour modes focusing on obtaining GRC for tunnels excavated in strain‐softening materials can be implemented. This way of solving such problems has proved to be more efficient and less time consuming than using FEM‐ or FDM‐based numerical 2D codes. Copyright © 2003 John Wiley & Sons, Ltd.
Fabric evolution of granular assembly under K0 loading/unloading
Authors: Liou Jyh‐Chau , Pan Yii‐Wen
Published: October 2003

This study attempted to investigate the fabric evolution in K0 loading/unloading. The work made use of a field simulator to control K0 loading/unloading in large specimens prepared by air‐pluviation. In each loading stage, wave velocities along various propagation directions were measured. On the basis of the theories of micro‐mechanics and wave propagation, the microscopic parameters of the granular assembly were back calculated to investigate the fabric evolution of granular soil during K0 loading/unloading.

In this study, the Geometric fabric was modelled by fabric tensors of ranks 2 and 4. The comparison of calibrated results using ranks 2 and 4 revealed the advantage of the usage of rank‐4 fabric tensor in modelling fabric evolution in spite of its complexity.

By comparing relative magnitudes of vertical and horizontal components of geometric fabric, it was demonstrated that relative constraint in lateral directions increased during K0‐unloading in order to maintain a K0 condition. It revealed that fabric evolution was responsible for a higher K0 in unloading than K0 in loading. Copyright © 2003 John Wiley & Sons, Ltd.
A model for step‐stress accelerated life testing
Authors: Dharmadhikari A.D. , Rahman Md. Monsur
Published: October 2003

Modern technology is producing high reliability products. Life testing for such products under normal use condition takes a lot of time to obtain a reasonable number of failures. In this situation a step‐stress procedure is preferred for accelerated life testing. In this paper we assume a Weibull and Lognormal model whose scale parameter depends upon the present level as well as the age at the entry in the present stress level. On the basis of that we propose a parametric model to the life distribution for step‐stress testing and suggest a suitable design to estimate the parameters involved in the model. A simulation study has been done by the proposed model based on maximum likelihood estimation. © 2003 Wiley Periodicals, Inc. Naval Research Logistics, 2003
The stochastic single resource service‐provision problem
Authors: Dye Shane , Stougie Leen , Tomasgard Asgeir
Published: October 2003

The service‐provision problem described in this paper comes from an application of distributed processing in telecommunications networks. The objective is to maximize a service provider's profit from offering computational‐based services to customers. The service provider has limited capacity and must choose which of a set of software applications he would like to offer. This can be done dynamically, taking into consideration that demand for the different services is uncertain. The problem is examined in the framework of stochastic integer programming. Approximations and complexity are examined for the case when demand is described by a discrete probability distribution. For the deterministic counterpart, a fully polynomial approximation scheme is known S. Dye, L. Stougie, and A. Tomasgard, Approximation algorithms and relaxations for a service provision problem on a telecommunication network, Working Paper #2‐98, Department of Industrial Economics and Technology Management, Norwegian University of Science and Technology, Trondheim, Norway, 1998, Discrete Appl Math, to appear. We show that introduction of stochasticity makes the problem strongly NP‐hard, implying that the existence of such a scheme for the stochastic problem is highly unlikely. For the general case a heuristic with a worst‐case performance ratio that increases in the number of scenarios is presented. Restricting the class of problem instances in a way that many reasonable practical problem instances satisfy allows for the derivation of a heuristic with a constant worst‐case performance ratio. Worst‐case performance analysis of approximation algorithms is classical in the field of combinatorial optimization, but in stochastic programming the authors are not aware of any previous results in this direction. © 2003 Wiley Periodicals, Inc. Naval Research Logistics, 2003
The value of information sharing in a two‐stage supply chain with production capacity constraints
Authors: Simchi‐Levi David , Zhao Yao
Published: October 2003

We consider a simple two‐stage supply chain with a single retailer facing i.i.d. demand and a single manufacturer with finite production capacity. We analyze the value of information sharing between the retailer and the manufacturer over a finite time horizon. In our model, the manufacturer receives demand information from the retailer even during time periods in which the retailer does not order. To analyze the impact of information sharing, we consider the following three strategies: (1) the retailer does not share demand information with the manufacturer; (2) the retailer does share demand information with the manufacturer and the manufacturer uses the optimal policy to schedule production; (3) the retailer shares demand information with the manufacturer and the manufacturer uses a greedy policy to schedule production. These strategies allow us to study the impact of information sharing on the manufacturer as a function of the production capacity, and the frequency and timing in which demand information is shared. © 2003 Wiley Periodicals, Inc. Naval Research Logistics, 2003
When to commit in a serial supply chain with forecast updating
Authors: Ferguson Mark E.
Published: October 2003

Negotiations between an end product manufacturer and a parts supplier often revolve around two main issues: the supplier's price and the length of time the manufacturer is contractually held to its order quantity, commonly termed the “commitment time frame.” Because actual demand is unknown, the specification of the commitment time frame determines how the demand risk is shared among the members of the supply chain. Casual observation indicates that most manufacturers prefer to delay commitments as long as possible while suppliers prefer early commitments. In this paper, we investigate whether these goals are always in the firm's best interest. In particular, we find that the manufacturer may sometimes be better off with a contract that requires an early commitment to its order quantity, before the supplier commits resources and the supplier may sometimes be better off with a delayed commitment. We also find that the preferred commitment time frame depends upon which member of the supply chain has the power to set their exchange price. © 2003 Wiley Periodicals, Inc. Naval Research Logistics, 2003
A Bayesian analysis on the effect of multiple supply options in a quick response environment
Authors: Kim Hag‐Soo
Published: October 2003

In the apparel industry, vendors often suffer from high mismatches in supply and demand. To cope with this problem, they procure the same style product from different suppliers with different manufacturing costs. Especially in the quick response environment, which allows vendors to monitor trends in customer demand and search for available suppliers through the electronic market, they have additional opportunities to improve their decision‐making. In this paper, we propose an analytical profit maximization model and develop efficient decision tools to help both the middle and lower level managers pursuing this strategy. Furthermore, we have shown how significantly the vendors' potential competitive edge can be improved by exploiting multiple supply options, even at the expense of high premium procurement costs for late orders. The effect is critical, especially in a highly competitive market, and it has important implications for the top managers. © 2003 Wiley Periodicals, Inc. Naval Research Logistics, 2003
The modeling and numerical analysis of wrinkled membranes
Authors: Ding Hongli , Yang Bingen
Published: October 2003

In this paper three fundamental issues regarding modeling and analysis of wrinkled membranes are addressed. First, a new membrane model with viable Young's modulus and Poisson's ratio is proposed, which physically characterizes stress relaxation phenomena in membrane wrinkling, and expresses taut, wrinkled and slack states of a membrane in a systematic manner. Second, a parametric variational principle is developed for the new membrane model. Third, by the variational principle, the original membrane problem is converted to a non‐linear complementarity problem in mathematical programming. A parametric finite element discretization and a smoothing Newton method are then used for numerical solution. The proposed membrane model and numerical method are capable of delivering convergent results for membranes with a mixture of wrinkled and slack regions, without iteration of membrane stresses. Three numerical examples are provided. Copyright © 2003 John Wiley & Sons, Ltd.
Dynamic crack propagation based on loss of hyperbolicity and a new discontinuous enrichment
Authors: Belytschko Ted , Chen Hao , Xu Jingxiao , Zi Goangseup
Published: October 2003

A methodology is developed for switching from a continuum to a discrete discontinuity where the governing partial differential equation loses hyperbolicity. The approach is limited to rate‐independent materials, so that the transition occurs on a set of measure zero. The discrete discontinuity is treated by the extended finite element method (XFEM) whereby arbitrary discontinuities can be incorporated in the model without remeshing. Loss of hyperbolicity is tracked by a hyperbolicity indicator that enables both the crack speed and crack direction to be determined for a given material model. A new method was developed for the case when the discontinuity ends within an element; it facilitates the modelling of crack tips that occur within an element in a dynamic setting. The method is applied to several dynamic crack growth problems including the branching of cracks. Copyright © 2003 John Wiley & Sons, Ltd.
Factors of positive appraisal of care among Japanese family caregivers of older adults
Authors: Yamamoto‐Mitani Noriko , Ishigaki Kazuko , Kawahara‐Maekawa Noriko , Kuniyoshi Midori , Hayashi Kunihiko , Hasegawa Kiyomi , Sugishita Chieko
Published: October 2003

The purpose of this study was to examine factors of positive appraisal of care among Japanese family caregivers of older adults. The Positive Appraisal of Care (PAC) scale used in this study is a multidimensional Japanese measure and has four domains: relationship satisfaction, consequential gain, role confidence, and normative fulfillment. Three hundred and thirty‐seven caregivers participated in this survey. Multiple regression analyses revealed that social support and caregiver belief in caregiving had a consistent impact on all domains of the PAC, whereas the impact of caregiver and care recipient characteristics varied among the domains. For example, caregiver age had a significant impact on role confidence and normative fulfillment but not on relationship satisfaction and consequential gain. The differential impact of caregiver and care recipient characteristics on the domains of the PAC underlines the usefulness of a multidimensional measurement. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:337–350, 2003
Fluorescent dyes as probes to study lipid‐binding proteins
Authors: Pastukhov Alexander V. , Ropson Ira J.
Published: October 2003

We studied the equilibrium binding of two hydrophobic fluorescent dyes, ANS and bisANS, to four members of a family of intracellular lipid‐binding proteins: IFABP, CRABP I, CRABP II, and ILBP. The spectral and binding parameters for the probes bound to the proteins were determined. Typically, there was a single binding site on each protein for the ligands. However, IFABP cooperatively bound a second bisANS molecule in the binding pocket. Comparative analysis of affinities and spectral characteristics for the two probes allowed us to examine the contributions of electrostatic and hydrophobic interactions to the binding process, and to address some aspects of the internal structure of the studied proteins. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
The importance of explicit chain representation in protein folding models: An examination of ising‐like models
Authors: Karanicolas John , Brooks Charles L.
Published: October 2003

A class of models that represents a protein chain as a sequence of “folded” and “unfolded” residues has recently been used to correlate rates and mechanisms of protein folding with the protein native structure. In order to better understand the conditions under which these “Ising‐like” models apply, we compare results from this model to those obtained from an off‐lattice model which uses the same potential function. We find that Ising‐like models by construction impose folding via a highly sequential nucleation‐condensation mechanism, which in turn leads to more rugged energy landscapes, fewer “pathways” to the native state, and in the specific case examined here, the cold shock protein A from Escherichia coli, a qualitative difference in the most likely order of events in folding. Proteins 2003;53:740–747. © 2003 Wiley‐Liss, Inc.
Three‐dimensional structural location and molecular functional effects of missense SNPs in the T cell receptor Vβ domain
Authors: Wang Zhen , Moult John
Published: October 2003

The mechanisms by which human single nucleotide polymorphisms (SNPs) influence susceptibility to disease are not yet well understood. In a previous study, we developed a structure‐based model that may be used to identify which missense SNPs are neutral and which are deleterious to protein function and so potentially involved in disease (Wang and Moult, Hum Mutat 2001;263–270). The model has now been applied to a set of 54 missense cSNPs in the 46 functional T‐cell receptor Vβ‐genes. Most of these missense cSNPs are found to be neutral, but 10 are identified as likely deleterious to protein function. Only one was previously associated with disease. We suggest that the others may be disease related but that redundancy in the T‐cell response prevents any simple, monogenic effect. Therefore, these SNPs are the most likely contributors to complex, polygenic disease traits. It has been noted that there is a surprisingly high (74%) fraction of nonsynonymous SNPs in these genes. Contrary to expectation, the analysis shows that these are not associated with an unusually high fraction of deleterious SNPs, nor do they significantly contribute to a larger range of antigen recognition or a reduced superantigen‐binding repertoire. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Turning virulence on and off in Staphylococci
Authors: Muir Tom W.
Published: October 2003

The progress made in a multidisciplinary research programme designed to elucidate the molecular basis of the interaction of Staphylococcus aureus secreted autoinducing peptides (AIPs) with their respective cell surface receptors is reviewed. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
General dispersion equation of exchange spin waves in an antiferromagnetic superlattice
Authors: Tanriverdiyev V. A. , Tagiyev V. S. , Seyid‐Rzaeva S. M.
Published: October 2003

A general dispersion equation for exchange spin waves propagating in a general direction in an antiferromagnetic superlattice is derived by the recurrence relations technique. The elementary unit cell of the superlattice under consideration consists of N different antiferromagnetic layers. The results are illustrated numerically for a particular choice of parameters. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Unusual structural and electronic properties of SnxGe1−x alloys
Authors: Chibane Y. , Bouhafs B. , Ferhat M.
Published: October 2003

First‐principles pseudopotential plane‐wave calculations are used to investigate the structural and electronic properties of cubic SnxGe1−x alloys. The studies focus on the determination of the variation of the lattice parameter and the optical band gap bowing of these alloys. An unusual behavior is found for the variation of the lattice parameter; in particular, a positive deviation from Vegard's law is found. This unusual feature is consistent with recent X‐ray data. The calculated optical band gap bowing parameter is found to be strongly composition dependent. At x = 0.125, the calculated bowing parameter is in good agreement with experiment. It is shown that both structural and chemical effects are important for this material. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ab‐initio statistical mechanics for ordered compounds: single‐defect theory vs. cluster‐expansion techniques
Authors: Drautz R. , Schultz I. , Lechermann F. , Fähnle M.
Published: October 2003

An explicit link is established between the two types of ab‐initio statistical mechanics for ordered compounds, the single‐defect theory which is used for low defect concentrations and the cluster‐expansion technique which is commonly used for large defect concentrations. Furthermore, it is shown how the single defect theory can be extended by including the elastic interaction effects between various defects. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin polarization of phase delay time in a magnetic–electric barrier structure
Authors: Xu H. Z. , Liu Pijun , Zhang Yafei
Published: October 2003

The spin‐dependent phase delay time of two‐dimensional electrons through a magnetic–electric barrier structure with/without an external electric field has been systematically investigated. The dependence of electron spin polarization on the applied bias, the incident wave vector, the incident electron energy and the height of the electric barrier has been addressed. It is found that the magnetic–electric barrier structure exhibits significant spin polarization under an external electric field, especially for electrons with small energies, where the spin polarization also displays a considerable wave vector‐dependent feature. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effect of crystal‐field anisotropy on the magnetization of a spin pair within various decoupling schemes
Authors: Ilkovič V.
Published: October 2003

The Green's function theory for a Heisenberg Hamiltonian with exchange parameter plus a single‐ion anisotropy term is applied to a system of two spinsS= 1. In order to assess the accuracy of the various decoupling schemes of the Green's functions, which involve products of operators at the same site, the magnetization of a spin pair is calculated within various decoupling procedures, and the results compared with exact solutions. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Homogeneous linewidth of quantum well excitonsfrom resonance fluorescence spectra
Authors: Schwedt D. , Nacke Ch. , Stolz H. , Eshlaghi S. , Reuter D. , Wieck A.
Published: October 2003

Editor's Choice of this issue is the article by D. Schwedt et al. [1] on high resolution measurements of resonance fluorescence spectra from GaAs quantum wells. In the cover picture, the authors point out the connection between the experimental data and the model of disordered excitons. The lower left part shows a series of polarized photoluminescence spectra, fitted with very good agreement by a model of statistically distributed three‐level‐systems. The upper right part images the excitation mechanism. Only those excitons of an inhomogeneous distribution (indicated by the blue line) contribute to the resonance fluorescence (red line) which overlap spectrally with the monochromatic laser. It could be verified experimentally that the resonance fluorescence exhibits two parts: delta‐like Rayleigh scattering and Lorentzian luminescence.

Daniel Schwedt is working in the DFG research group 'Quantum Optics in Semiconductor Nanostructures' and concentrates on quantum optical experiments on III–V semiconductor quantum well structures.
Solid Phase Combinatorial Library of 1,3‐Azole Containing Peptides for the Discovery of Matrix Metallo Proteinase Inhibitors
Authors: Christensen Caspar , Bruun Schiødt Christine , Tækker Foged Niels , Meldal Morten
Published: October 2003

A solid phase combinatorial library of approximately 240,000 putative inhibitors were prepared and screened for activity against MMP‐14. The compounds of the library had the common structure H‐XX‐azole‐XX‐NH2 in which X is an arbitrary amino acid and azole is one of four oxazole or thiazole dipeptidomimetics (8a–d). The library was generated by the split and mix strategy resulting in a one‐bead‐two‐compounds library format in such a way that each bead contained a common quenched fluorogenic substrate and a different putative inhibitor. Application of ladder synthesis [22] during library construction enabled full sequence determination by MALDI‐TOF mass spectrometry. The library was screened against MMP‐14 activity, by performing multiple, sequential incubations in which beads containing active inhibitors were selected by a novel automated “bead‐sorting” apparatus, in order to isolate only the best inhibitors. Statistical analysis of the sequences obtained from overall 184 beads gave rise to a series of 20 sequences; 4 truncated and 16 full sequences were resynthesized. The inhibitors were investigated in an enzyme kinetic assay with MMP‐14 revealing compounds with Ki values in the low micromolar area, whereas the truncated sequences derived from the library showed poor inhibitor activity.
Mockup‐driven fast‐prototyping methodology for Web application development
Authors: Zhang Jia , Chung Jen‐Yao
Published: October 2003

Web application development can be very complicated without an appropriate framework, architecture and application model. A good implementation model can help application developers communicate with clients, consolidate the design before starting the development, speed up the development, and make the code highly reusable. This paper proposes a mockup‐driven fast prototyping methodology (MODFM) for the development of Web applications. It is built on the most recent Web technologies: EJB, JSP, Servlet, XML, Struts, and Web application server. A two‐tier Model‐View‐Controller (MVC) architecture is proposed as the underlying backbone and a supporting environment is tailored specifically in order to enable development. Two basic supporting tools are provided: the dynamic menu generator and the generic code generator, which produce code for front‐end, back‐end and database schemas. MODFM helps to generate fully functional mockup systems for the client to review at an early analysis stage, and continues to provide guidance throughout follow‐on development phases. Real‐life experiences on the use of this methodology in industry are presented as examples. Copyright © 2003 John Wiley & Sons, Ltd.
Differential projections of the infralimbic and prelimbic cortex in the rat
Authors: Vertes Robert P.
Published: October 2003

The medial prefrontal cortex has been associated with diverse functions including attentional processes, visceromotor activity, decision‐making, goal‐directed behavior, and working memory. The present report compares and contrasts projections from the infralimbic (IL) and prelimbic (PL) cortices in the rat by using the anterograde anatomical tracer,Phaseolus vulgaris‐leucoagglutinin. With the exception of common projections to parts of the orbitomedial prefrontal cortex, olfactory forebrain, and midline thalamus, PL and IL distribute very differently throughout the brain. Main projection sites of IL are: 1) the lateral septum, bed nucleus of stria terminalis, medial and lateral preoptic nuclei, substantia innominata, and endopiriform nuclei of the basal forebrain; 2) the medial, basomedial, central, and cortical nuclei of amygdala; 3) the dorsomedial, lateral, perifornical, posterior, and supramammillary nuclei of hypothalamus; and 4) the parabrachial and solitary nuclei of the brainstem. By contrast, PL projects at best sparingly to each of these structures. Main projection sites of PL are: the agranular insular cortex, claustrum, nucleus accumbens, olfactory tubercle, the paraventricular, mediodorsal, and reuniens nuclei of thalamus, the capsular part of the central nucleus and the basolateral nucleus of amygdala, and the dorsal and median raphe nuclei of the brainstem. As discussed herein, the pattern of IL projections is consistent with a role for IL in the control of visceral/autonomic activity homologous to the orbitomedial prefrontal cortex of primates, whereas those of PL are consistent with a role for PL in limbic‐cognitive functions homologous to the dorsolateral prefrontal cortex of primates. Synapse 51:32–58, 2004. © 2003 Wiley‐Liss, Inc.
Comparative phenotypic resolution of spontaneous, D2‐like and D1‐like agonist‐induced orofacial movement topographies in congenic mutants with dopamine D2 vs. D3 receptor “knockout”
Authors: Tomiyama Katsunori , Mcnamara Fergal N. , Clifford Jeremiah J. , Kinsella Anthony , Drago John , Fuchs Sara , Grandy David K. , Low Malcolm J. , Rubinstein Marcelo , Tighe Orna , Croke David T. , Koshikawa Noriaki , Waddington John L.
Published: October 2003

Using a novel system, the role of D2‐like dopamine receptors in distinct topographies of orofacial movement was assessed in mutant mice with congenic D2 vs. D3 receptor knockout, and compared with findings in D1A mutants. Under spontaneous conditions, D2 mutants evidenced increased vertical jaw movements and unaltered horizontal jaw movements, with reductions in tongue protrusions and incisor chattering; in D3 mutants, only incisor chattering was reduced. Given previous evidence that D1A mutants show reduced horizontal but not vertical jaw movements, this indicates that apparent oppositional D1‐like:D2‐like interactions in the regulation of composited jaw movements may in fact reflect the independent actions of D2 receptors to inhibit vertical jaw movements and of D1A receptors to facilitate horizontal jaw movements. Effects of the D2‐like agonist RU 24213 to exert greater reduction in horizontal than in vertical jaw movements were not altered prominently in either D2 or D3 mutants. The D1‐like agonists A 68930 and SK&F 83959 induced vertical jaw movements, tongue protrusions, and incisor chattering; induction of tongue protrusions by A 68930 was reduced in D2 mutants. D2 receptors exert topographically specific regulation of orofacial movements in a manner distinct from their D1A counterparts, while D3 receptors exert only minor regulation of such movements. Synapse 51:71–81, 2004. © 2003 Wiley‐Liss, Inc.
Dependable information infrastructures as complex adaptive systems
Authors: Ye Nong , Lai Ying‐Cheng , Farley Toni
Published: October 2003

Information infrastructures, such as the Internet and Computational Grids, have enabled a networked computing and communication environment. Although many organizations depend on network‐centric information operations to support critical missions, existing information infrastructures provide little guarantee of the dependability of network‐centric computing and communication. This paper discusses some problems with the dependability of existing information infrastructures, such as stateless or centralized resource management. A Complex Adaptive Systems approach to dependability of futuristic information infrastructures is then presented with emphasis on the detection of emergent states at the regional and global levels of these infrastructures, and the self‐synchronized control of such infrastructures in response to emergent states. The key concept underlying our control strategy at the regional or global level is that the two attributes of the Complex Adaptive System in a dynamic environment, accessibility to many states and sensitivity to small perturbation, present us with an opportunity to manipulate the system's dynamics. © 2003 Wiley Periodicals, Inc. Syst Eng 6: 225–237, 2003
A new approach to generic attributes
Authors: Wells Curt , Ibrahim Linda , LaBruyere Larry
Published: October 2003

Generic Attributes (GAs) are measures of process performance introduced by the systems engineering capability model, EIA/IS 731. The systems model defines two GAs—Effectiveness and Value. While the concept of GAs is generally accepted as valid, they have been used very little, due to difficulties in interpretation and appraisal. Revised definitions and a new approach for appraising and using GAs have been developed for the Federal Aviation Administration Integrated Capability Maturity Model® v2.0 (FAA‐iCMM®). The improved approach to Generic Attributes provides the needed clarity and measurement objectivity. Definitions of the iCMM® GAs and their relationship to process model concepts are described in this paper, along with a practical approach to appraising GAs. © 2003 Wiley Periodicals, Inc. Syst Eng 6: 301–308, 2003
Evolutionary analysis of rhodopsin and cone pigments: connecting the three‐dimensional structure with spectral tuning and signal transfer
Authors: Teller David C. , Stenkamp Ronald E. , Palczewski Krzysztof
Published: October 2003

Extensive sequence data and structural sampling of expressed proteins from different species lead to the idea that entire molecules or specific domain folds belong to large superfamilies of proteins. A subset of G protein‐coupled receptors, one of the largest families involved in cellular signaling, rod and cone opsins are involved in phototransduction in photoreceptor cells. Here, the evolutionary analysis of opsin sequences and structures predicts key residues involved in the transmission of the signal from the binding site of the chromophore to the cytoplasmic surface and residues that are involved in the spectral tuning of opsins to short wavelengths of light.
Direct interaction between α‐actinin and hepatitis C virus NS5B
Authors: Lan Shuiyun , Wang Hua , Jiang Hong , Mao Hongxia , Liu Xiaoying , Zhang Xiaonan , Hu Yunwen , Xiang Li , Yuan Zhenghong
Published: October 2003

It has been suggested that cellular proteins are involved in hepatitis C virus (HCV) RNA replication. By using the yeast two‐hybrid system, we isolated seven cDNA clones encoding proteins interacting with HCV RNA polymerase (NS5B) from a human liver cDNA library. For one of these, α‐actinin, we confirmed the interaction by coimmunoprecipitation, immunofluorescent staining and confocal microscopic analysis. Experiments with deletion mutants showed that domains NS5B84–95, NS5B466–478, and α‐actinin621–733 are responsible for the interaction. Studies of the HCV subgenomic replicon system with small interference RNA indicate that α‐actinin is essential for HCV RNA replication. Our results suggest α‐actinin may be a component of the HCV replication complex.
Lamotrigine for intractable sciatica: correlation between dose, plasma concentration and analgesia
Authors: Eisenberg Elon , Damunni Gassan , Hoffer Erica , Baum Yelena , Krivoy Norberto
Published: October 2003

An open trial was conducted to study the potential efficacy of the antiepileptic agent lamotrigine in relieving the sciatic pain and the relationship between lamotrigine dosage, plasma concentration and the clinical response. Subsequent to a 1 week washout period from previous analgesics, lamotrigine dose was titrated on a weekly basis from 25 to 400 mg/day and was maintained at that dose for additional 4 weeks. Spontaneous pain, the Short Form McGill Pain Questionnaire (SFMPQ), the Straight Leg Raise (SLR) test, and range of motion of the lumbar spine (leaning foreword, to the affected side) were used to assess lamotrigine efficacy. Lamotrigine plasma concentration was tested at the end of each week during the titration period and at the end of the study. Fourteen patients were enrolled in the study. All outcome measurers improved compared to baseline during the titration period, but reached a statistically significant level of improvement only at the 400 mg dose. A linear correlation was found between mean lamotrigine dose, mean plasma concentration and mean weekly spontaneous pain, mean SLR and mean bending the affected side, but not with the SFMPQ score. Study results suggest lamotrigine is a potentially effective and safe compound for the treatment of painful lumbar radiculopathy, and that it is likely to act in a dose‐ and plasma concentration‐dependent fashion.
Nerve terminals extend into the temporomandibular joint of adjuvant arthritic rats
Authors: Shinoda Masamichi , Honda Takashi , Ozaki Noriyuki , Hattori Hisashi , Mizutani Hideki , Ueda Minoru , Sugiura Yasuo
Published: October 2003

The innervation of the temporomandibular joint (TMJ) has attracted particular interest because of the close association with complex mandibular movement. Although the pathological changes of disk innervation may have a crucial role in the development of TMJ pain, the innervation of the TMJ disk by experimentally induced arthritis has rarely been examined in detail. Arthritic rats were induced by injection with 0.1 ml solution of Complete Freund's adjuvant (CFA). We investigated three‐dimensional distribution of nerve fibers in the TMJ disk using immunohistochemistry for protein gene product‐9.5 (PGP‐9.5) and calcitonin gene‐related peptide (CGRP) in naive and arthritic rats. To clarify the possible role of nerve growth factor (NGF) and its receptor on changes in peripheral innervation of the TMJ, the expressions of trkA and p75 receptor in trigeminal ganglia were examined. Although PGP‐9.5 and CGRP immunoreactive (ir) fibers were seen in the peripheral part of the TMJ disk, they were not seen in its central part. The total length and the length density of PGP‐9.5 ir and CGRP ir nerve fibers increased in arthritic rats. The innervation area of fibers proliferating in the rostro‐medial part merged with that of fibers in the rostro‐lateral part in the arthritic rats. In addition, the ratio of trkA‐ and p75‐positive small‐ and medium‐sized cells increased in trigeminal ganglia. It is assumed that increasing innervation of the TMJ disk may be important for the pathophysiology of TMJ pain. NGF and its receptors are likely involved in pathological changes of the TMJ disk.
Efficacy of spinal cord stimulation for neuropathic pain: assessment by abstinence
Authors: Monhemius Russell , Simpson Brian A
Published: October 2003

Assessment of the efficacy of spinal cord stimulation (SCS) against neuropathic pain remains problematic. Some patients may underestimate this, as revealed by their reaction to stimulator malfunction. This study investigated whether abstinence from SCS would provide an indication of its effectiveness. Patients were invited to complete two brief questionnaires each day for 50 days including two periods of 14 days without stimulation. Pain level, sleep quality, activity level and drug intake were recorded. Of 75 patients thought to be using their stimulators, 12 did not respond to the invitation, eight had unresolved technical problems and one no longer needed SCS. Of the 54 remaining, 10 did not wish to be without SCS and 15 declined without giving a reason. Thus 29 agreed to take part but three then dropped out through illness and questionnaires were not received from 10. Ten returned completed questionnaires but failed to follow the protocol; five of these were unable to leave their stimulators off. Only six took part correctly. Twenty of the 29 had received a preliminary explanatory home visit and for nine this was done by telephone. The former produced a considerably higher yield. All six who completed the study correctly had statistically significantly lower pain scores during stimulation. Four had improved sleep but only one reduced his medication and none of the six increased their activity levels. Correlation with previous clinical assessments is discussed. It is concluded that the abstinence principle might provide a useful tool but its power is very methodology‐dependent.
Multi‐modal induction and assessment of allodynia and hyperalgesia in the human oesophagus
Authors: Drewes Asbjørn Mohr , Schipper Klaus‐Peter , Dimcevski Georg , Petersen Poul , Andersen Ole Kæseler , Gregersen Hans , Arendt‐Nielsen Lars
Published: October 2003

Background and aims. Experimental pain models based on single stimuli have to some degree limited visceral pain studies in humans. Hence, the aim of this study was to investigate the effect of multi‐modal visceral pain stimuli of the oesophagus in healthy subjects before and after induction of visceral hyperalgesia. We used a multi‐modal psychophysical assessment regime and a neurophysiological method (nociceptive reflex) for the characterisation of the experimentally induced hyperalgesia.

Methods. A probe for multi‐modal (cold, warm, electrical, and mechanical) visceral stimulation was positioned in the lower part of the oesophagus in eleven healthy subjects. Mechanical stimuli were applied as distensions with a bag, which also had electrodes mounted for electrical stimulation. Thermal stimulation with temperatures from 0 to 60 °C was applied with re‐circulating water in the bag. To assess the interaction between visceral and somatic pathways, the nociceptive withdrawal reflex to electrical stimuli at the ankle was measured with and without simultaneous mechanical oesophageal distension to painful levels. Finally, the oesophageal sensitisation was induced by perfusion with hydrochloric acid. Multimodal responses (pain threshold, stimulus response function, size of nociceptive reflex, and referred pain areas) were assessed before and after the induced hyperalgesia.

Results. The multi‐modal psychophysical responses and reflex sizes were assessed twice before sensitisation, and the parameters were reproducible. Sensitisation of the oesophagus resulted in hyperalgesia to electrical and mechanical stimuli (29 and 35% decrease in pain threshold) and allodynia to cold and warmth stimuli (11% increase in sensory rating). After sensitisation, the referred pain area to mechanical stimuli increased more than 300% with a change in the localisation of the referred pain to all stimuli, and the amplitude of nociceptive reflex increased 100%, all indicating the presence of central hyperexcitability.

Conclusions. Visceral hyperalgesia/allodynia can be induced experimentally and assessed quantitatively by the newly introduced multi‐modal psychophysical assessment approach. The significant changes of the experimentally evoked referred pain patterns and of the nociceptive reflex evoked from a distant somatic structure indicate that even short‐lasting visceral hyperalgesia can generate generalised sensitisation.
The natural course of chronic benign pain in childhood and adolescence: a two‐year population‐based follow‐up study
Authors: Perquin Christel W , Hunfeld Joke A.M , Hazebroek‐Kampschreur Alice A.J.M , van Suijlekom‐Smit Lisette W.A , Passchier Jan , Koes Bart W , van der Wouden Johannes C
Published: October 2003

Study objective. To assess the course of chronic benign pain in childhood and adolescence longitudinally.

Setting. Cohort of children with chronic pain recruited from the open population.

Patients. A cohort of 987 children and adolescents aged 0–18 years with chronic pain (continuous or recurrent pain > 3 months), who were identified in a previous population‐based prevalence study, were approached for a two‐year follow‐up study. Subjects were asked to keep a 3‐week diary on their pain and to fill out questionnaires about background factors, pain and pain‐related consequences. This assessment was repeated annually for two years.

Results. At baseline, 254 subjects reported chronic benign pain; of these, 124 (48%) and 77 (30%) subjects still experienced chronic benign pain at one‐year and two‐year follow‐up, respectively. Except for the estimated pain intensity, which decreased marginally, pain remained stable over the follow‐up period. Minor changes occurred in the consequences of pain; the main changes were a decrease of the impact of pain on the child's behavior, social functioning and use of health care. Subjects with persistent pain (9.4%) differed from those with non‐persistent pain in frequency, history and location of the pain, emotional problems and their mother's health.

Conclusions. Chronic benign pain in childhood and adolescence is common, and seems to persist in a considerable proportion (30–45%), although pain generally does not deteriorate over time.
Looking at the sky: the visual context of Victorian meteorology
Authors: ANDERSON KATHARINE
Published: October 2003

This article investigates visual methods in Victorian meteorology in the second half of the nineteenth century. While studies of visual representations in scientific work during this period have proliferated, there has been less attention paid to the relationships between scientific images and the broader visual culture in which they developed. Meteorology offers ideal ground for exploring visual culture and science, both because of the familiarity of the sky as an aesthetic subject, and because of the visual epistemology associated with popular forms of weather knowledge, called weather wisdom. Using examples from the study of clouds, especially the work of Charles Piazzi Smyth, the paper analyses the ways in which the challenges of meteorology raised questions about the nature of observation and precision. It concludes by suggesting that the broader context of Victorian visual culture must include the relationship of language and images, and traces those concerns in the history of cloud classification.
M. du Bois-Reymond goes to Paris
Authors: FINKELSTEIN GABRIEL
Published: October 2003

This article examines the science of electrophysiology developed by Emil du Bois-Reymond in Berlin in the 1840s. In it I recount his major findings, the most significant being his proof of the electrical nature of nerve signals. Du Bois-Reymond also went on to detect this same ‘negative variation’, or action current, in live human subjects. In 1850 he travelled to Paris to defend this startling claim. The essay concludes with a discussion of why his demonstration failed to convince his hosts at the French Academy of Sciences.

La science ne consiste pas en faits, mais dans les conséquences que l'on en tire.Claude Bernard, Introduction à l'étude de la médicine expérimentale

Good talkers are only found in Paris.François Villon, Des Femmes de Paris
Research schools of chemistry from Lavoisier to Wurtz
Authors: CROSLAND MAURICE
Published: October 2003

The group which worked with Lavoisier in his laboratory also collaborated with him in publication and jointly edited the journal Annales de chimie. It has a good claim to be considered as a research school. Most historians of chemistry, who have studied the ‘chemical revolution’ in France, have focused uniquely on Lavoisier, giving scant attention to his co-workers and ignoring his assistants, thus overlooking their collective research, which created something of a precedent for nineteenth-century science. It has also been too easily assumed that the Lavoisier story ends with his death in 1794. After his demise, continuity with his ideas and method of working was provided by his former associates, particularly Berthollet in the Society of Arcueil. Further continuity was provided by the successive careers of Gay-Lussac, Dumas and Wurtz. In an increasing spirit of nationalism in the nineteenth century there developed a strong French tradition which looked back to Lavoisier as the founder of modern chemistry and a source of inspiration for collaboration in chemical research.