bluuebunny/crossref_metadata_2025 huggingface dataset:
Business process re‐engineering to total quality management
Authors: González‐Benito J. , Martinez‐Lorente A.R. , Dale B.G.
Published: July 2002

This paper examines two research questions. First, is a re‐engineered company a suitable platform for the subsequent application of TQM principles? Second, is BPR an appropriate means to transform an organisation operating along traditional lines into one which is managed using TQM principles? It is posited that these questions have been given scant attention by the academic fraternity. Considers, for example, characteristics of BPR which facilitate or hamper TQM and also TQM considerations when reengineering. It is argued that a company can apply TQM and BPR simultaneously, thus yielding more improvements than if only one of them was used on its own. The analysis presented in the paper indicates that the application of BPR can provide the base for the subsequent development of TQM.
Customer‐aligned inventory strategies: agility maxims
Authors: Tersine Richard J. , Wacker John G.
Published: July 2002

Traditionally, aggregate inventory realignment has tended to be a reactive response to crisis signals revealed by financial performance measurements. Symptoms and problems are usually confounded, while corrective actions are localized with less than adequate customer connectivity. This article links inventory requirements to customer requirements for response, quality, and their benefit‐to‐cost ratio by focusing on reduction of valueless time, valueless activity, and valueless variance in business processes. Interestingly, what satisfies customers can also efficiently align inventory. Several maxims are introduced throughout the paper to align the purpose and significance of inventory to a customer context.
Web‐based information access for agile management
Authors: Bajgoric Nijaz
Published: July 2002

Information agility, or informational efficiency, represents the major prerequisite for agile management and means eliminating inefficiencies in accessing, exchanging and disseminating all kinds of information. Presents a framework for implementation of Web technology in enhancing information access for agile management. Web‐to‐host access tools as a specific subset of Web technology are used to improve and ease access to several types of information such as legacy data, messaging system, electronic documents, and business intelligence.
The thesis of leagility revisited
Authors: van Hoek Remko I.
Published: July 2002

Both postponement and information decoupling have been considered as relevant initiatives in making the agile supply chain a reality. It is commonly argued that the two can be combined into “leagility”, which is the combination of agility with lean capabilities within one supply chain. Based upon a one‐year study of agility in the supply chain, this paper indicates that leagility might work well in operational terms as lean capabilities can contribute to agile performance and might often be a prerequisite. If the leagility approach is to work, though, it is required to fit within a purely agile supply chain strategy, rather than a purely lean approach. Thus it is concluded that the leagility thesis does not fundamentally challenge the agility concept. Specific suggestions on how to move forward in creating the agile supply chain are then developed.
The strategic implications of flexibility in manufacturing systems
Authors: Narain Rakesh , Yadav R.C. , Sarkis Joseph , Cordeiro James J.
Published: July 2002

Flexibility in manufacturing has aroused considerable interest among researchers and professionals. However, the vast body of literature on flexibility does not adequately address the kind of flexibility a company needs to meet its strategic objectives, nor how this flexibility can be achieved. An overview is provided of different types of flexibility, a classification scheme based on the strategic positioning and goals of the firm is provided, and suggestions are made on how these goals may be achieved. The importance of such a classification in the design and investment justification of flexible manufacturing is also discussed.
Application of lean production and agile manufacturing concepts in a telecommunications environment
Authors: Robertson Michael , Jones Carole
Published: July 2002

Agile manufacturing, a strategy developed from lean production methods, is aimed at providing companies with the capabilities to succeed in the twenty‐first century, serving ever more sophisticated customer demand. In this paper, the application of this strategy, originally developed for manufacturing industry, is described in a telecommunications context. Examples of ways in which it is being used in BT are presented.
Difficulties arising from dysfunctional information systems in manufacturing SMEs – case studies
Authors: Thoburn J.G. , Arunachalam S. , Gunasekaran A.
Published: July 2002

The necessity of maintaining optimal operations and becoming an agile and responsive enterprise is becoming increasingly important to survive in the global market. Consequently, all resources in the companies need to be effectively marshalled. Traditionally SMEs have concentrated on the 4Ms ± money, materials, machine and manpower but have often neglected the effective management of information, which many authors suggest is at the heart of any agile organisation. The effect is inadequate or fragmented information systems (IS) that do not address the demands of operational or the wider strategic needs of the company. The study reported here examines the diversities of problems that occur in three different companies and, compares their systems to the ideals of agile manufacturing.
Fitting the pieces together: selling to regional networks, consortia and libraries
Authors: Hurtt James
Published: July 2002

Increasingly, publishers are looking to sell through library consortia. The advantages of consortia to publishers include the ability to simplify the sales process, to help publishers increase their market penetration and communication with more libraries, and increase the speed of sales. However, all consortia are not organized in the same way, which requires that publishers work with different consortia in different ways. Publishers will need to continue to maintain their own marketing and sales staff to augment the services that may be available through the consortium, and to overcome problems such as inconsistent communications to libraries. Publishers will also need to have strategies to work with multiple consortia with overlapping memberships.
Hand picked for quality – a reflection on biz/ed
Authors: Sladen Catherine , Spence Mary
Published: July 2002

Subject gateways have been encouraged and financially supported by the Joint Information System Committee of the UK Higher Education and Research Funding Councils as a potential solution to the ever increasing cost of library provision and Internet based information resources. The gateway for Business Education, biz/ed, was developed using both existing procedures for quality assuring such resources, and new approaches. The four key elements – DESIRE, ROADS, TIPs and the Focus Group – are described and their effectiveness in achieving a quality output assessed. The overall conclusion is that there are still conceptual barriers to the use of gateways by academics, and that, while they may serve a useful purpose, the process of quality assurance and maintenance is continuous and resource intensive.
Use levels and new models for consortial purchasing of electronic journals
Authors: Sanville Tom
Published: July 2002

The current practices of journal acquisition are grounded in the legacy of a print‐bound world in which each library is an island of access for its own patrons. But with electronic desktop delivery of information, the increased ease of access allows far greater information use than previously possible. The extent of this additional use is still an open question, but based on the OhioLINK experience thus far, it appears that improved ease of access has demonstrated the high elasticity in information usage. Libraries and consortia must seek to enable this desirable outcome by adopting purchase models that provide for expanded journal access. The first 18 months of operation of the OhioLINK Electronic Journal Center (EJC) is an exemplary illustration of the dramatic benefits of expanded access. Patrons have executed over 535,000 article downloads. On average each Ohio university uses three times more titles than they previously held in print, and over 50 per cent of downloaded articles were not available in print on each campus. Small and two‐year colleges are also beneficiaries through first‐time access to scholarly journals. As the evolution to broad scale electronic access continues, libraries and consortia must take advantage of the opportunities illustrated by the EJC that fashion a sustainable economic model of information purchase that maximizes information use.
Benchmarking in rehabilitation: comparing physiotherapy services
Authors: Enderby Pam , John Alexandra , Hughes Anthony , Petheram Brian
Published: July 2002

This report presents outcome data from 3,176 consecutive prospective patients referred to physiotherapy for the treatment of soft tissue injuries. The results detailed here are part of a larger study collecting data from different NHS trusts in a benchmarking study. The Therapy Outcome Measure was used to collect data on each patient in four domains: Impairment, Disability/activity, Handicap/participation, and Distress/wellbeing on the entry and the exit from physiotherapy. The study concludes that patients do not have equal opportunity of accessing therapy for their specific condition according to their abilities and needs. Therapy provided in the Trusts did not produce similar changes in the patients’ abilities and some dimensions appeared to improve more significantly in some locations. Furthermore this study would suggest that there are no common criteria for discharge of patients with similar conditions from physiotherapy across the Trusts as measured by the Therapy Outcome Measure.
Thromboembolic prophylaxis: practice in oral and maxillofacial surgery
Authors: Clark S. , Greenwood M.
Published: July 2002

Describes how the implementation of thromboembolic prophylaxis in patients undergoing oral and maxillofacial surgical procedures was audited. In 1997, four oral and maxillofacial units were asked about their practice of prophylaxis for thromboembolic disease (TED). Proformas were sent to each unit to assess 45 patients retrospectively. These patients were chosen at random from within defined groups of surgery. The audit was repeated in 1998, after presentation and discussion of initial findings. Of 117 patients at low risk of TED, 72 (62 per cent) and 50 (81 per cent) of 62 patients at moderate risk received prophylaxis. In the second run of the audit, there was a 7 per cent increase in the number of patients at moderate risk receiving prophylaxis. Patients admitted for trauma surgery were the most likely to have TED prophylaxis omitted. Concludes that there was an improvement between the first and second run of the audit, but some patients were still not being treated appropriately.
Being kind to babies: an audit of paediatric radiology for first urinary infections
Authors: Dearlove John
Published: July 2002

A retrospective audit from 1 June 1993 to 31 May 1994 of all new paediatric referrals (921 children) was performed to evaluate a popular radiological protocol for the investigation of first urinary tract infections (UTIs). Of the 71 children with their first UTI, 12 were investigated inadequately. These were younger (average age 16 months) and their investigations were modified not by their parents but by their paediatricians who reinterpreted the protocol such that invasive investigations were avoided. However, GP follow‐up three years later showed that none of the 12 had recurrence of their symptoms.
Quality of health and medical information on the Internet
Authors: Cooke Alison
Published: July 2002

This article examines some of the problems associated with health and medical information available via the Internet. An overview is provided of gateway services that seek to provide access to high quality materials. Quality principles for health and medical Internet‐based materials are highlighted and suggestions are offered for evaluating sources of information retrieved via the Internet. The article concludes that, although there is undeniably a vast quantity of useful material available via the Internet, the principles of basing health care on the best available evidence still apply and potential users need to critically appraise any information they wish to use.
“Sustainability? Never heard of it!”
Authors: Jucker Rolf
Published: July 2002

Presents the results of an Internet survey of all the humanities faculties in Germany, Switzerland, The Netherlands and the UK and of a review of the international debate both on sustainability in general and education for sustainability in particular. Argues for a complex, transdisciplinary and broad approach to education for sustainability (EfS). Such an approach has to acknowledge the relative relevance of education within contemporary society, along with other “educators” such as the media, the economy and the shadow curriculum of institutional practice. It has to be fully aware of the reasons and the extent of the unsustainability of our current situation, but it also has to sketch out what a sustainable society might mean. Only on this basis can we then develop effective and sensible proposals for EfS. Ends with ten practical strategies to further EfS in higher education institutions.
Demi: a case study in design for sustainability
Authors: Fletcher Kate , Dewberry Emma
Published: July 2002

The Design for the Environment Multimedia Implementation Project – demi – links design and sustainability information in a Web‐based resource and was set up in response to a number of UK Government reports which highlighted the dearth of knowledge and activity about sustainability in higher education design courses across the country. This paper details the design and development of demi, discussing its content, structure and educational potential. Also included is an investigation of design and sustainability pedagogy, which discusses the importance to the demi Web‐resource of a sustainability (rather than design) context and an exploration of the possible transferability of the demi structure to other disciplines, promoting practical and widespread action in education for sustainability.
Information gateways: collaboration on content
Authors: Heery Rachel
Published: July 2002

Information gateways provide targeted discovery services for their users, giving access to Web resources selected according to quality and subject coverage criteria. Information gateways recognise that they must collaborate on a wide range of issues relating to content to ensure continued success. This report is informed by discussion of content activities at the 1999 Imesh Workshop. The author considers the implications for subject based gateways of co‐operation regarding coverage policy, creation of metadata, and provision of searching and browsing across services. Other possibilities for co‐operation include working more closely with information providers, and disclosure of information in joint metadata registries.
The evolution of Web searching
Authors: Green David
Published: July 2002

The interrelation between Web publishing and information retrieval technologies is explored. The different elements of the Web have implications for indexing and searching Web pages. There are two main platforms used for searching the Web – directories and search engines – which later became combined to create one‐stop search sites, resulting in the Web business model known as portals. Portalisation gave rise to a second‐generation of firms delivering innovative search technology. Various new approaches to Web indexing and information retrieval are listed. PC‐based search tools incorporate intelligent agents to allow greater manipulation of search strategies and results. Current trends are discussed, in particular the rise of XML, and their implications for the future. It is concluded that the Web is emerging from a nascent stage and is evolving into a more complex, diverse and structured environment.
The Internet in Syria
Authors: Askhita Hasna
Published: July 2002

The Internet has become a cornerstone of modern libraries. This paper presents a comprehensive overview of the Internet in Syria from the lobbying efforts that took place beforehand, to the implementation phase and its problems. The paper describes the most important Internet projects. Future projects are discussed as well as the plans of selected organisations. Some Syrian Web sites are listed.
Project LIS: a Web‐based resource of IOLS information
Authors: Kochtanek Thomas R. , Hein Karen K.
Published: July 2002

Project URL originated while identifying electronic resources that promote access to information about integrated online library systems (IOLS). Over 40 students, enrolled in a Web‐based asynchronous distance learning graduate level course “Library information systems”, searched the Web for resources that contribute to IOLS. Several hundred sites were initially identified, together with the difficulties associated with such a large set of unorganised pointers to Web‐based resources. A project team was assembled to organise unique URLs as identified by fellow students, adding value and commentary to those sites that met certain criteria of excellence. The product is a metasite of URLs that points to information about IOLS vendors, electronic journal titles and specific e‐journal articles addressing IOLS topics of interest, and general information sources that might be accessed by library professionals involved in decision‐making processes for integrated library systems. Recent efforts have been made to add to this base of IOLS resources. Future revisions are also discussed.
An evaluation of help mechanisms in natural language information retrieval systems
Authors: Kreymer Oleg
Published: July 2002

The field of natural language processing (NLP) demonstrates rapid changes in the design of information retrieval systems and human‐computer interaction. While natural language is being looked on as the most effective tool for information retrieval in a contemporary information environment, the systems using it are only beginning to emerge. This study attempts to evaluate the current state of NLP IR systems from the user’s point of view: what techniques are used by these systems to guide their users through the search process? The analysis focused on the structure and components of the systems’ help mechanisms. Results of the study demonstrated that systems which claimed to be using natural language searching in fact used a wide range of information retrieval techniques from real natural language processing to Boolean searching. As a result, the user assistance mechanisms of these systems also varied. While pseudo‐NLP systems would suit a more traditional method of instruction, real NLP systems primarily utilised the methods of explanation and user‐system “dialogue”.
Intellectual capital: a Habermasian introduction
Authors: O’Donnell David , O’Regan Philip , Coates Brian
Published: July 2002

Intellectual capital creation is theorised in this conceptual paper as a dynamic process of collective knowing that is capable of being leveraged into market value. The tacit, intangible and socially unconscious nature of substantive parts of this dynamic process presents some daunting theoretical challenges. Adopting a broadly social constructionist epistemology and a pluralist ontology, the point of departure introduced here is the set of symmetric and reciprocal relations presupposed in Jürgen Habermas’ theory of communicative action. In this worldview, interaction, as distinct from individual action, becomes the germ‐cell or basic unit of theoretical analysis. The relations and validity claims built into the medium of communicative action, viewed here as the nexus of intellectual capital creation, are substantive and real phenomena; they are thus open to empirical investigation.
Social innovation capital
Authors: McElroy Mark W.
Published: July 2002

Current conceptions of how to measure and manage intellectual capital (IC) suffer from a failure to take “social capital” rigorously into account. This is a shortcoming of current thinking in the IC arena. Of particular concern is the absence of “social innovation capital” (SIC) from the scope of leading IC schemes. SIC, the collective capacity of a firm to innovate, is arguably the most valuable form of IC because it underlies a firm’s fundamental capacity to learn, innovate, and adapt. Using one leading IC scheme as a basis for analysis (Skandia’s), the absence of social capital, and SIC in particular, is highlighted, along with a description of what Skandia’s taxonomy would look like if it were to take social capital fully into account. Finally, recommendations are offered on how managers can build and manage SIC, thereby enhancing their organizations’ capacities to learn, innovate, and adapt in the marketplace.
Measuring the value of Lincoln Re’s R&D
Authors: DeTore Arthur , Clare Mark , Weide James
Published: July 2002

This case study of the valuation of intangible assets compares an internally generated estimate of discounted cash flow (DCF) with an estimate of knowledge capital (KC). It describes Lincoln Re’s mortality research and development (R&D) capability, the knowledge management (KM) strategies used to leverage it and the management decisions that were made to create economic value. This paper reviews a theory of KM and a valuation approach with DCF measures. The decisions to invest in R&D and the Lincoln Mortality System, an expert system for product development, produced a 23.9 percent growth in DCF and created substantial value for Lincoln Re. Using Baruch Lev’s approach to KC, it is suggested that 0.45 percent is a good working figure for the return on asset for life insurance firms versus the previously published 10.5 percent due to the overwhelming percentage of financial assets on the balance sheet of financial companies and the fact that the return on financial assets is imbedded in product pricing. The correlation between DCF and KC measures is approximated by a DCF/comprehensive value ratio and the results show 70‐80 percent correlation at the enterprise, division and asset levels.
Fair value of intellectual property
Authors: Kossovsky Nir
Published: July 2002

Intellectual property (IP), a significant source of intangible value, has been felt by some to be resistant to fair valuation and more amenable to estimations of intrinsic value. With the recently issued Financial Accounting Standards Board guidelines for IP that promote fair valuation, practitioners and clients alike may seek additional methods to determine the fair value of IP quickly and cost effectively. In this study, nearly 8,000 IP assets were valued using TRRU1 Metrics. The data show a log normal distribution of IP value. Furthermore, the assets valued in this study showed a mean of $20.76 million, a median of $5.19 million, and a mode of less than $8 million. When viewed as a real option the features of a patent that behave like a financial instrument are exposed. When these features are used to drive options‐pricing algorithms, a method for calculating an indication of value of IP with greater objectivity and transparency becomes operationally practical. Suggests that professionally calculated indications of IP value based on TRRU1 Metrics may yield valuation results that, similar to indications of value calculated with the Black‐Scholes options pricing formula, satisfy the tests of reasoned judgment, objectivity, and market‐price verisimilitude.
Corporate governance reform in East Asia
Authors: Walker Gordon , Fox Mark
Published: July 2002

Asks the question: how can we enhance corporate governance practices in East Asia? To address this question, reviews recent research findings that have greatly enhanced our understanding of corporate governance practices in East Asian jurisdictions. Concludes by examining three areas of reform. First, investor protection may require radical changes to law and the enforcement of such laws. Second, market‐based changes, which do not require legal reform per se. Finally, observes that corporate governance may be enhanced through the use of mid‐1990s techniques of strategic management in national planning for capital market development.
Evaluating corporate board cultures and decision making
Authors: Cutting Bruce , Kouzmin Alexander
Published: July 2002

This paper relies on a “trinity of menetypes” of group knowing which captures the essential decision‐making dynamics of board membership. Formal, corporate decision‐making processes require higher commitments of time and cognitive energy of directors – certainly, the requirement is of non‐executive directors to make more formal contributions to the “political” process that determines corporate commitment to appropriate courses of action. There is a fundamental shift from “managerialism” to “politicism” in the corporate dynamics of organization – a shift in “menetype” driving governance dynamics. This wholesale shift in orientation has accentuated personal and group values as key determinants of corporate efficacy. The paper proposes structural reforms to corporate/agency governance conventions, including a greater focus on performance and strategy, greater independence of more effective and extensive audit processes and a greater transparency in the nomination and remuneration of top‐executive appointments.
The fibril_one on‐line database: Mutations, experimental conditions, and trends associated with amyloid fibril formation
Authors: Siepen Jennifer A. , Westhead David R.
Published: July 2002

The association of amyloid fibril formation with a number of important diseases, and the extensive study of this process in vitro, has resulted in a large literature containing a vast amount of information about the fibril formation process. This includes mutations and experimental conditions that promote or protect against fibril formation. A database (fibril_one) was designed to hold information relating to the formation of fibrils. It was populated by extensive searches of the literature and other databases. A powerful World Wide Web query interface to the database was developed, enabling a simple and effective method to view amyloidogenic mutations associated with specific proteins. The Web interface was used to identify trends in the data. This revealed that mutations promoting fibril formation through altered folding tend to be associated with destabilization of the native fold. In particular, tendancies of mutations to disrupt the native secondary structure and packing in the hydrophobic core were discovered to be significant. Query access to the database is available freely on the World Wide Web at http://www.bioinformatics.leeds.ac.uk/group/online/fibril_one.
Correlation of protein functional properties in the crystal and in solution: The case study of T‐state hemoglobin
Authors: Noble Robert W. , Kwiatkowski Laura D. , Hui Hilda L. , Bruno Stefano , Bettati Stefano , Mozzarelli Andrea
Published: July 2002

The relevance of three‐dimensional structures of proteins, determined by X‐ray crystallography, is an important issue that is becoming even more critical in light of the Structural Genomics Initiative. As a case study, a detailed comparison of functional properties of the T quaternary states of genetically or chemically modified human hemoglobins (Hbs) in solution and in the crystal was performed. Oxygen affinities of Hbs in crystals correlate with the rate constants of their initial combination with carbon monoxide (CO) in solution, indicating that changes in ligand affinity caused by the modifications are similarly observed in both physical states.
Sulfate anion stabilization of native ribonuclease A both by anion binding and by the Hofmeister effect
Authors: Ramos Carlos H.I. , Baldwin Robert L.
Published: July 2002

Data are reported for Tm, the temperature midpoint of the thermal unfolding curve, of ribonuclease A, versus pH (range 2–9) and salt concentration (range 0–1 M) for two salts, Na2SO4 and NaCl. The results show stabilization by sulfate via anion‐specific binding in the concentration range 0–0.1 M and via the Hofmeister effect in the concentration range 0.1–1.0 M. The increase in Tm caused by anion binding at 0.1 M sulfate is 20° at pH 2 but only 1° at pH 9, where the net proton charge on the protein is near 0. The 10° increase in Tm between 0.1 and 1.0 M Na2SO4, caused by the Hofmeister effect, is independent of pH. A striking property of the NaCl results is the absence of any significant stabilization by 0.1 M NaCl, which indicates that any Debye screening is small. pH‐dependent stabilization is produced by 1 M NaCl: the increase in Tm between 0 and 1.0 M is 14° at pH 2 but only 1° at pH 9. The 14° increase at pH 2 may result from anion binding or from both binding and Debye screening. Taken together, the results for Na2SO4 and NaCl show that native ribonuclease A is stabilized at low pH in the same manner as molten globule forms of cytochrome c and apomyoglobin, which are stabilized at low pH by low concentrations of sulfate but only by high concentrations of chloride.
Interactions between PEG and type I soluble tumor necrosis factor receptor: Modulation by pH and by PEGylation at the N terminus
Authors: Kerwin Bruce A. , Chang Byeong S. , Gegg Colin V. , Gonnelli Margherita , Li Tiansheng , Strambini Giovanni B.
Published: July 2002

The effects of polyethylene glycol (PEG) on protein structure and the molecular details that regulate its association to polypeptides are largely unknown. These issues were addressed using type I soluble tumor necrosis factor receptor (sTNF‐RI) as a model system. Changes in solution viscosity established that a truncated form of sTNF‐RI bound free PEG in a pH‐dependent manner. Above pH 5.3, the viscosity escalated as the pH increased, while no effect occurred below pH 5.0. Conjugation of 2 kD, 5 kD, or 20 kD PEG to the N terminus attenuated the viscosity at the higher pH values. Tryptophan phosphorescence spectroscopy correlated changes in the protein structure about Trp‐107, at the C terminus, with the pH‐dependent and PEGylation‐dependent attenuation of the viscosity. The results indicate that specific interactions between PEG and the truncated form of sTNF‐RI are elicited by an increased flexibility of the truncated protein combined perhaps with removal of steric or charge barriers. Covalently bound PEG at the N terminus reduced the protein affinity for the free polymer and induced a more rigid and polar configuration around Trp‐107. Deprotonation of His‐105, which is perpendicular to Trp‐107, was integral to the binding mechanism producing a pH‐dependent switching mechanism. These findings stress the importance of surface charge and structural plasticity in determining macromolecular binding affinities and demonstrate the ability of conjugated PEG to modify the localized surface structure in proteins away from the site of conjugation.
Key interactions in the immunoglobulin‐like structure of apo‐neocarzinostatin: Evidence from nuclear magnetic resonance relaxation data and molecular dynamics simulations
Authors: Izadi‐Pruneyre Nadia , Quiniou Éric , Blouquit Yves , Perez Javier , Minard Philippe , Desmadril Michel , Mispelter Joël , Adjadj Élisabeth
Published: July 2002

The three‐dimensional structure of apo‐neocarzinostatin (apo‐NCS, MW: ca.11000, antitumoral chromophore carrier protein) is based on a seven‐stranded antiparallel β‐sandwich, very similar to the immunoglobulin folding domain. We investigated the backbone dynamics of apo‐NCS by 13C‐NMR relaxation measurements and molecular dynamics simulation. Model‐free parameters determined from the experimental data are compared with a 1.5‐nsec molecular simulation of apo‐NCS in aqueous solution. This comparison provides an accurate description of both local and collective movements within the protein. This analysis enabled us to correlate dynamic processes with key interactions of this β‐protein. Local motions that could be relevant for the intermolecular association with the ligand are also described.
Prediction of the membrane‐spanning β‐strands of the major outer membrane protein of Chlamydia
Authors: Rodríguez‐Marañón María José , Bush Robin M. , Peterson Ellena M. , Schirmer Tilman , de la Maza Luis M.
Published: July 2002

There is preliminary experimental evidence indicating that the major outer‐membrane protein (MOMP) of Chlamydia is a porin. We tested this hypothesis for the MOMP of the mouse pneumonitis serovar of Chlamydia trachomatis using two secondary structure prediction methods. First, an algorithm that calculates the mean hydrophobicity of one side of putative β‐strands predicted the positions of 16 transmembrane segments, a structure common to known porins. Second, outer loops typical of porins were assigned using an artificial neural network trained to predict the topology of bacterial outer‐membrane proteins with a predominance of β‐strands. A topology model based on these results locates the four variable domains (VDs) of the MOMP on the outer loops and the five constant domains on β‐strands and the periplasmic turns. This model is consistent with genetic analysis and immunological and biochemical data that indicate the VDs are surface exposed. Furthermore, it shows significant homology with the consensus porin model of the program FORESST, which contrasts a proposed secondary structure against a data set of 349 proteins of known structure. Analysis of the MOMP of other chlamydial species corroborated our predicted model.
Ca2+ and membrane binding to annexin 3 modulate the structure and dynamics of its N terminus and domain III
Authors: Sopkova Jana , Raguenes‐Nicol Céline , Vincent Michel , Chevalier Anne , Lewit‐Bentley Anita , Russo‐Marie Françoise , Gallay Jacques
Published: July 2002

Annexin 3 (ANX A3) represents ∼1% of the total protein of human neutrophils and promotes tight contact between membranes of isolated specific granules in vitro leading to their aggregation. Like for other annexins, the primary molecular events of the action of this protein is likely its binding to negatively charged phospholipid membranes in a Ca2+‐dependent manner, via Ca2+‐binding sites located on the convex side of the highly conserved core of the molecule. The conformation and dynamics of domain III can be affected by this process, as it was shown for other members of the family. The 20 amino‐acid, N‐terminal segment of the protein also could be affected and also might play a role in the modulation of its binding to the membranes. The structure and dynamics of these two regions were investigated by fluorescence of the two tryptophan residues of the protein (respectively, W190 in domain III and W5 in the N‐terminal segment) in the wild type and in single‐tryptophan mutants. By contrast to ANX A5, which shows a closed conformation and a buried W187 residue in the absence of Ca2+, domain III of ANX A3 exhibits an open conformation and a widely solvent‐accessible W190 residue in the same conditions. This is in agreement with the three‐dimensional structure of the ANX A3‐E231A mutant lacking the bidentate Ca2+ ligand in domain III. Ca2+ in the millimolar concentration range provokes nevertheless a large mobility increase of the W190 residue, while interaction with the membranes reduces it slightly. In the N‐terminal region, the W5 residue, inserted in the central pore of the protein, is weakly accessible to the solvent and less mobile than W190. Its amplitude of rotation increases upon binding of Ca2+ and returns to its original value when interacting with membranes. Ca2+ concentration for half binding of the W5A mutant to negatively charged membranes is ∼0.5 mM while it increases to ∼1 mM for the ANX A3 wild type and to ∼3 mM for the W190 ANX A3 mutant. In addition to the expected perturbation of the W190 environment at the contact surface between the protein and the membrane bilayer, binding of the protein to Ca2+ and to membranes modulates the flexibility of the ANX A3 hinge region at the opposite of this interface and might affect its membrane permeabilizing properties.
Exact Slopes of Test Statistics for the Multivariate Exponential Family
Authors: Kim Gie‐Whan
Published: July 2002

The objective of this paper is to investigate exact slopes of test statistics {Tn} when the random vectors X1, ..., Xn are distributed according to an unknown member of an exponential family {Pθ; θ∈Ω. Here Ω is a parameter set. We will be concerned with the hypothesis testing problem of H0θ∈Ω0 vs H1: θ∉Ω0 where Ω0 is a subset of Ω. It will be shown that for an important class of problems and test statistics the exact slope of {Tn} at η in Ω−Ω0 is determined by the shortest Kullback–Leibler distance from {θ: Tn(λ(θ)) = Tn(λ(π))} to Ω0, λθ = Eθ)(X).
Induced Surfaces and Their Integrable Dynamics Ii. Generalized Weierstrass Representations in 4‐d Spaces and Deformations via Ds Hierarchy
Authors: Konopelchenko B. G. , Landolfi G.
Published: July 2002

Extensions of the generalized Weierstrass representation to generic surfaces in 4‐D Euclidean and pseudo‐Euclidean spaces are given. Geometric characteristics of surfaces are calculated. It is shown that integrable deformations of such induced surfaces are generated by the Davey–Stewartson hierarchy. Geometrically, these deformations are characterized by the invariance of an infinite set of functionals over surface. The Willmore functional (the total squared mean curvature) is the simplest of them. Various particular classes of surfaces and their integrable deformations are considered.
BASTIAT VERSUS BLAIR
Authors: Harris Lord
Published: July 2002

Bastiat describes the ideal of a free society with government limited to protecting life, liberty and property. Thatcherism approached Bastiat's ideal more closely than any other twentieth‐century government. Despite the rhetoric of the ‘Third Way,’ in some respects New Labour has gone beyond Thatcherism, for example in its education and health policies and in giving independence to the Bank of England. However, New Labour has increased taxes, extended regulation and shows authoritarian tendencies.
Serotonin suppresses the slow afterhyperpolarization in rat intralaminar and midline thalamic neurones by activating 5‐HT7 receptors
Authors: Goaillard Jean‐Marc , Vincent Pierre
Published: July 2002

While the highest expression level of 5‐HT7 receptors in the brain is observed in intralaminar and midline thalamic neurones, the physiological role of these receptors in this structure is unknown. In vivo recordings have shown that stimulation of the serotonergic raphe nuclei can alter the response of these neurones to a nociceptive stimulus, suggesting that serotonin modulates their firing properties. Using the patch‐clamp technique in rat thalamic brain slices, we demonstrate that activation of 5‐HT7 receptors can strongly modulate the excitability of intralaminar and midline thalamic neurones by inhibiting the calcium‐activated potassium conductance that is responsible for the slow afterhyperpolarization (sAHP) following a spike discharge. This sAHP was inhibited after activation of the cAMP pathway, either by bath application of forskolin or intracellular perfusion with 8‐bromo‐cAMP. The inhibitory effect of 5‐HT7 receptors on sAHPs was blocked by the protein kinase A antagonist RP‐cAMPS. Calcium‐imaging experiments showed no change in intracellular calcium levels during the 5‐HT7 response, indicating that in these neurones, a global calcium signal was not necessary to activate the cAMP cascade. Finally, bath application of serotonin produced a strong increase in cytosolic cAMP concentration, as measured using the fluorescent probe FlCRhR, and an inhibition of the sAHP. Taken together, these results suggest that 5‐HT7 receptors are implicated in the effect of 5‐HT on sAHP in intralaminar and midline thalamic neurones, an effect that is mediated by the cAMP second‐messenger cascade.
Whole body and leg acetate kinetics at rest, during exercise and recovery in humans
Authors: van Hall G. , Sacchetti M. , Rådegran G.
Published: July 2002

We have used a constant [1,2‐13C]acetate infusion (0.12 μmol min−1 kg1) for 2 h at rest, followed by 2 h of one‐legged knee‐extensor exercise at 65 % of leg maximal workload, and 3 h of recovery in six post‐absorptive volunteers to quantify whole‐body and leg acetate kinetics and determine whether the whole‐body acetate correction factor can be used to correct leg substrate oxidation. The acetate whole‐body rate of appearance (Ra) was not significantly different at rest, during exercise or during recovery (365‐415 μmol min−1). The leg net acetate uptake was similar at rest and during recovery (≈10 μmol min−1), but increased ∼5‐fold with exercise. At rest the leg acetate uptake (≈15 μmol min−1) and release (≈5 μmol min−1) accounted for 4 and 1.5 % of whole‐body acetate disposal (Rd) and Ra, respectively. When the leg acetate kinetics were extrapolated to the total body skeletal muscle mass, then skeletal muscle accounted for ∼16 and ∼6 % of acetate Rd and Ra. With exercise, leg acetate uptake increased ∼6‐fold, whereas leg acetate release increased 9‐fold compared with rest. Whole‐body acetate carbon recovery increased with time of infusion at rest and during recovery from 21 % after 1.5 h of infusion to 45 % in recovery after 7 h of infusion. Leg and whole‐body acetate carbon recovery were similar under resting conditions, both before and after exercise. During exercise whole‐body acetate carbon recovery was ∼75 %, however, acetate carbon recovery of the active leg was substantially higher (≈100 %). It is concluded that inactive skeletal muscle plays a minor role in acetate turnover. However, active skeletal muscle enhances several‐fold acetate uptake and subsequent oxidation, as well as release and its contribution to whole‐body acetate turnover. Furthermore, under resting conditions the whole‐body acetate correction factor can be used to correct for leg, skeletal muscle, substrate oxidation, but not during exercise.
Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?
Authors: Tschakovsky Michael E. , Sujirattanawimol Kittiphong , Ruble Stephen B. , Valic Zoran , Joyner Michael J.
Published: July 2002

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n= 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n= 7) and two doses of sodium nitroprusside (SNP) infusion (n= 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non‐invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose‐dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42‐46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest −43.4 ± 3.7 %, moderate exercise −27.5 ± 2.3 %, heavy exercise −16.7 ± 3.6 %;P< 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosinevs.rest (P< 0.05). Finally, percentage change in FVC was greater during low dose SNP infusionvs.rest (P< 0.05), but not different from rest at the high dose of SNP infusion (P= 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity‐dependent.
Chronotropic effects of nitric oxide in the denervated human heart
Authors: Chowdhary S. , Harrington D. , Bonser R. S. , Coote J. H. , Townend J. N.
Published: July 2002

Nitric oxide synthase is expressed in the sino‐atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitorNG‐monomethyl‐l‐arginine (l‐NMMA) (3 mg kg−1) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection ofl‐NMMA increased mean arterial pressure by 17 ± 2 mmHg (mean ±s.e.m.;P< 0.001) and also had a significant negative chronotropic effect, lengthening the R‐R interval by 54 ± 8 ms (P< 0.001). This bradycardia was not reflex in origin since injection of the non‐NO‐dependent vasoconstrictor, phenylephrine (100 μg) achieved a similar rise in mean arterial pressure (18 ± 3 mmHg;P< 0.001) but failed to change R‐R interval duration (ΔR‐R =−3 ± 4 ms). Furthermore, no change in levels of circulating adrenaline was observed withl‐NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose‐dependent shortening of R‐R interval duration, peak ΔR‐R =−25 ± 8 ms with 130 μg (P< 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino‐atrial node.
Carrier‐mediated uptake and release of taurine from Bergmann glia in rat cerebellar slices
Authors: Barakat L. , Wang D. , Bordey A.
Published: July 2002

Taurine uptake is essential for the maintenance of millimolar intracellular concentrations of taurine, which is released during ischaemia and is thought to be neuroprotective. To determine whether Bergmann glia express functional transporters that can mediate both taurine uptake and efflux, whole‐cell patch‐clamp recordings were obtained from these cells in rat cerebellar slices. Taurine‐induced inward currents can be pharmacologically separated into GABAA receptor and taurine transporter currents. In the presence of GABA receptor blockers, residual taurine currents averaged −28 pA at −70 mV and were strictly inwardly rectifying between −70 and +50 mV. These residual currents were also abolished by external Na+ removal and diminished by reduction of external Cl−, consistent with transport currents. Taurine transport currents were reduced by a taurine transporter inhibitor, guanidinoethyl sulphonate (GES). Other classical inhibitors reduced taurine transport currents with an order of potency (hypotaurine > β‐alanine > GES > GABA) similar to that reported for cloned rat taurine transporters. Following intracellular taurine perfusion during the recording, a progressively developing outward current could be observed at −50 mV but not at −70 mV. Intracellular perfusion of taurine also decreased taurine‐induced inward currents at both holding potentials. Outward currents induced by intracellular taurine increased in amplitude with depolarization, activated near −50 mV, and were affected by GES. For the first time, these results demonstrate that taurine activates both GABAA receptors and Na+/Cl−‐dependent taurine transporters in Bergmann glia in slices. In addition, our data show that taurine transporters can work in reverse and can probably mediate taurine efflux under ischaemic conditions.