bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing clinical governance in paediatric cochlear implantation
Authors: O’Neill C. , Archbold S. , O’Donoghue G. , Gibbin K.P. , McCormick B.
Published: July 2002

The protracted and multidisciplinary nature of paediatric cochlear implantation presents particular challenges in addressing issues of clinical governance. The implantation process is one that involves many disciplines in acute and community settings over several years. Reviews the difficulties presented by a protracted, multidisciplinary intervention for addressing issues of clinical governance within the context of paediatric cochlear implantation. Discusses the activities of the Nottingham Paediatric Cochlear Implant Programme in tackling these problems and gives some details of its progress and success in these areas.
The contribution of the wound care nurse in developing a diabetic foot clinic
Authors: Bale Sue
Published: July 2002

Reports on a study that focuses on the specific roles of the nurse within the interdisciplinary team as an example of how nursing contributes to developing clinical effectiveness in wound healing. The multidisciplinary team approach used here builds on recommendations by Edmonds as the most effective method of delivering care to patients with diabetic foot ulceration. In particular, monitors the evolution of the service provided and patient outcomes by measuring the number of ulcers treated, the level of service provided, record keeping and patient outcome. The contribution of the wound care nurse includes the assessment of the status and progress of ulcers presented at the clinic. Argues that, as research in wound care has evolved, so the contribution of the nurse has grown (in line with NHS recommendations) with a broader range of wound features assessed and documented. In evaluating improvements in recording information, three indicators were used. Ulcer size and type were recorded in 1993 on 2.2 per cent and 17.8 per cent of occasions respectively. By 1999 these had progressed to being recorded on 100 per cent of occasions. Assessments of ulcer edge also showed an improvement, being recorded on 11.1 per cent of occasions in 1993 and 50.6 per cent of occasions in 1999. The detail of record keeping allowed the data collection.
Adopting guideline review criteria as part of a regional project to improve heart failure management in general practice
Authors: Jeacocke David , Sprogis Arn , Lowe Julia , Heller Richard
Published: July 2002

Describes a process of adopting a set of review criteria for use in a regional project to improve heart failure management in general practice. Published guideline review criteria were assessed using a protocol examining indicator relevance, practicality and the clinical evidence on which indicators were based. An expert panel with experience in general practice, cardiology and general internal medicine, ethics, and research methodology was used to evaluate the indicators. Good overall agreement was observed with the review criteria. Areas of disagreement related to poor wording of the criteria, the need to incorporate more up‐to‐date evidence and criteria based on weak evidence. A need exists for greater training of health practitioners about how regional indicators can be used as screening tools for quality improvement. Nationally endorsed sets of regularly updated review criteria for common and important conditions would be helpful in guiding similar quality improvement projects.
Incomplete excision of basal cell carcinomas: an audit
Authors: Schreuder Fred , Powell B.W.E.
Published: July 2002

The Plastic Surgery Department undertook an audit of the rate of excision of basal cell carcinomas (BCCs) at St George’s Hospital. The aim of the audit was to determine the rate of incomplete excision of BCCs excised by the department over a six‐month period and compare with national audit figures. The rate of incomplete excision was 13.73 per cent or seven out of 51 BCCs, which compared favourably with the rates quoted in the literature. No change in the management of basal cell carcinomas was made.
Effective practice in the NHS and the contribution from public health: a qualitative study
Authors: Melvin Kate , Wright John , Harrison Stephen R. , Robinson Mike , Connelly Jim , Rhys Williams D.R.
Published: July 2002

Reports on a study which explored the views of key stakeholders regarding the meaning and implementation of effective health care and clinical governance in NHS Trusts, and the role for public health professionals. The authors used a national questionnaire survey to derive a sample for qualitative telephone interviews and two area case studies. The authors found that the meaning of effective health care and the means employed for implementation varied. Mergers were seen as hindrances to gaining organisational engagement whilst others, such as the White Paper on quality and the notion of clinical governance, were seen as facilitating. A widespread aspiration was a more integrated and corporate quality culture where quality was central, not marginal. The authors conclude that there is widespread concern among Trusts to change their culture and assert effective health care as a central value. Public health skills, rather than the discipline itself, are seen as important for such culture change.
Lifting the fog: maps and spatial information emerging as grey literature
Authors: McGlamery Patrick
Published: July 2002

Maps as a genre are not typically dealt with in the study of grey literature. The transformation of information from maps to spatial data could likely be omitted from discussions as well. The author argues for an approach that focuses not on product, but on content. Three types of grey map presentations are profiled: a series, the US Geological Survey’s (USGS) Open‐file Report series; a collection, the Long Island Sound Resource Center; and an annual publication, the Environmental Sciences Research Institute’s (ESRI) Map Book. Significant research issues are indicated.
Interview with Dominic Farace, founder of GreyNet
Authors: Gelfand Julia
Published: July 2002

Covers how Dominic Farace, the GreyNet director, first became involved in the grey literature scene, and explains how and why the Grey Literature Network Service has developed. Discusses the future prospects of GreyNet and grey literature. Highlights many of the issues concerning the GreyNet movement and looks at Farace’s inspiration for his career therein.
Information Technology Road Maps: a bibliographic database pilot project
Authors: McKiernan Gerry
Published: July 2002

In an effort to facilitate the identification and use of highly‐relevant publications and resources relating to the social and economic implications of information, computation, and communication technologies, the National Science Foundation (NSF) recently funded a pilot project to create a Web‐based bibliographic database of significant materials. Within the framework of this database, users are able to browse citations to relevant topics or search for specific aspects. The nature of the selected resources, their description, and associated methods for searching, viewing, saving, and exporting are outlined. The features and functionalities of the host Web‐based database management software are also described.
Using an online stock market simulation as a cross‐disciplinary learning enhancer: simulation as an example of grey literature
Authors: Altmyer Donald J.
Published: July 2002

This article demonstrates how some nontraditional learning styles and use of software create a more successful learning environment. An online stock market simulation emphasizes the integration of the computer into academic curricula and can be used with different audiences to begin teaching about how the stock market functions with students as young as elementary school, effectively with secondary school students and definitely with undergraduate business students. The stock market simulation involves teams of students investing US$100,000 in “play” money into a portfolio of stocks that the students research and track and from which they make discretionary buy and sell decisions. Teachers have experienced many learning benefits by utilizing a stock market simulation. By working in small groups, team‐building skills are introduced. Through the research and tracking stage of stock selection, critical thinking and deductive reasoning skills are developed and a new curriculum is born that mirrors the reality of the stock market.
Architecture and software solutions
Authors: Gardner Tracy , Iannella Renato
Published: July 2002

The current subject gateways have evolved over time when the discipline of Internet resource discovery was in its infancy. This is reflected by the lack of well‐established, light‐weight, deployable, easy‐to‐use, standards for metadata and information retrieval. We provide an introduction to the architecture, standards and software solutions in use by subject gateways, and to the issues that must be addressed to support future subject gateways.
HTTP cookies – a promising technology
Authors: Peng Weihong , Cisna Jennifer
Published: July 2002

This paper discusses the introduction of cookies into Web technology and their role as a user‐tracking device. While cookies contribute to the user‐friendliness of Web sites, their placement on client‐side computers is a cause for concern. The authors look at both sides of the technology, pointing out benefits and drawbacks.
A case study in designing Chinese metadata
Authors: Chen Ya‐ning , Chen Shu‐jiun , Chiang Hui‐ying , Liu Chia‐hui
Published: July 2002

Metadata are fundamental in establishing a digital library and museum while domain communities describe, interpret and manage different digital objects. Although many metadata formats and sets have been developed, it is difficult to choose an appropriate format and conversion is problematical, especially for the Chinese materials. This paper is a progress report from the Metadata Taskforce Group designing Chinese metadata for the digital library and museum project (DLMP) at Academia Sinica in Taiwan. The group’s top priority is to construct goals, principles and procedures while designing the metadata format for Chinese contents. Not only does the Metadata Taskforce Group present the analysis of content attributes of Formosan Plain indigenous people, but also several marked achievements and findings are suggested, such as the metadata record structure and criteria of selecting and evaluating the current metadata formats.
Creating and nurturing distributed asynchronous learning environments
Authors: Kochtanek Thomas R. , Hein Karen K.
Published: July 2002

The introduction of Web‐based course instruction into an existing degree programme offers the opportunity to re‐examine models supporting learning and the transfer of knowledge among students enrolled in such courses. By removing the barriers of time and place, instructors can create and sustain student learning communities supported by interactive communication tools grounded in asynchronous learning models. The instructor’s role moves to that of a facilitator who seeks to stimulate interactions between students and between students and the instructor, in the pursuit of improved learning and knowledge base construction.
An information method for achieving value‐added processing of bibliographic databases in science and technology
Authors: Kardos Dragotin , Boh Bojana
Published: July 2002

The article presents and discusses a methodological procedure based on the functional density of information, which can be used for value‐added processing of bibliographic databases with scientific and technological information to predict and recognise trends in research and development fields. The concept of functional information density can be applied in processing bibliographic databases by specific search fields, such as: number of documents by the publication year, number of articles and patents by year, patent assignee, patent applications and granted patents by country, international patents classification codes, and journal titles. The proposed information procedure was tested on the research topics microencapsulation technology, microencapsulated pesticides, microencapsulated repellents and superabsorbents, and was used as an information support for design of research hypotheses, planning of research, development and marketing of products.
A study of graduate student end‐users’ use and perception of electronic journals
Authors: Li Liew Chern , Foo Schubert , Chennupati K.R.
Published: July 2002

The growth and diversity of electronic journals (e‐journals) in the past five years has led many to predict the extinction of print journals and that a new paradigm is sweeping scholarship. Some others, however, believe that future electronic scholarly journals will be different from their print antecedents and fill a different niche, and will be necessary for the growth of knowledge. This paper considers the future of e‐journals in the light of the use and perception of graduate student end‐users, and their expectations of future e‐journals. Some results from a recent user study presenting significant implications for the design of future e‐journals are reported. The results show a significantly high acceptance of e‐journals by this category of users. Generally, e‐journals are expected to be different from print journals, with novel forms of functionality not possible in their print counterparts.
Internet‐based experiential learning in international marketing: the case of Globalview.org
Authors: Alon Ilan , Cannon Nancy
Published: July 2002

The paper discusses a unique Internet‐based learning forum, Globalview.org (www.globalview. org), which involves the construction of international business plans for real companies seeking internationalisation. The purpose of global cases is to link student teams in international collaborative learning projects by empowering students to participate in setting learning goals and learning processes, and enabling instructors to be closer to the students in the learning process. This article reports on the experience of one college using Globalview.org, and discusses likely outcomes that may emerge from using Internet‐based experiential projects in the classroom.
Developing knowledge management metrics for measuring intellectual capital
Authors: Liebowitz Jay , Suen Ching Y.
Published: July 2002

Measuring intellectual capital is a growing area of interest in the knowledge management field. Metrics are being developed and applied by some organizations, but there needs to be more research throughout the international community to better define these measures. One limitation of the current measures is that they do not necessarily address the “knowledge level” and the types of value‐added knowledge that individuals obtain. This paper takes a look at the current measures, discusses some possible limitations, and suggests some additional measures that could be used in the intellectual capital area to complement existing measures.
Using intellectual capital to evaluate educational technology projects
Authors: Joia Luiz Antonio
Published: July 2002

Intellectual capital has been used to measure the intangible assets of corporations. Intellectual capital can also be used to assess and evaluate the outcomes of social projects, i.e. ones that do not have either a book or a market value. This article aims to present a framework to evaluate the intangible outcomes generated by the deployment of Informatics in Education, measuring the human and innovation capital associated with this enterprise. The PROINFO, a Brazilian nationwide program to deploy 100,000 computers in the public K‐12 schools, is analyzed as a case study in order to apply the developed methodology. Some conclusions are presented to policy makers, educational researchers and practitioners in order to enable them to better understand the dynamics and the overall mechanism of a nationwide intervention aiming to deploy information and communication technologies in education.
Why does subjectivity make us nervous?
Authors: Jankowicz Devi
Published: July 2002

Many occupations require people to draw on their experience to make decisions based on intuition and subjective judgement; this includes craft‐ and skill‐based tasks, and the more cognitive tasks associated with strategic decision‐making by senior managers. Discussion of the processes involved tends to regard them as somehow inappropriate or illegitimate, excessively subjective because not open to scrutiny. The repertory grid is a powerful and precise way of making tacit knowledge explicit; moreover, it rests on a detailed and epistemologically convincing theory of knowledge, personal construct psychology. Both have been used in a great variety of occupations, and this paper will sample some of them, concentrating on the identification of the intuitive factors involved in bank commercial lending, and venture capital investment, decision processes. The willingness of financial institutions to support, and their reluctance to adopt, this particular approach to the identification of tacit knowledge will also be examined.
The linkage between management practices, intangibles performance and stock returns
Authors: Hurwitz Jason , Lines Stephen , Montgomery Bill , Schmidt Jeffrey
Published: July 2002

Intangible assets have grown in size and importance to individual firms and to the economy as a whole. Many have examined and written about ways to value the intangible assets of firms and the overall economy. Professor Baruch Lev of New York University has developed an approach to measure intangibles performance for any company, or division of a company, that uses GAAP financial reporting and that has publicly traded equity. Professor Lev has also established how intangibles performance is linked to stock returns. The collaborative research of the co‐authors has extended this linkage by identifying certain management practices as drivers of intangibles performance. The culmination of this work is a breakthrough – for the first time, specific management practices can be linked to stock returns.
Towards a financial reporting framework for intangibles
Authors: Wyatt Anne
Published: July 2002

In the context of possible future directions in the accounting regulatory arena, this paper considers what policy makers can learn from the experiences of Australian managers and investors in relation to capitalization of intangible assets. Focuses on features of the Australian institutional setting, the motivations behind Australian managers’ decisions to capitalize intangible assets, and capital market efficiency implications. Australian GAAP leaves corporate managers wide discretion to capitalize intangible assets irrespective of whether the assets are acquired or generated internally. One central element of this accounting discretion is the historically liberal attitude of Australian accounting regulators to deviations from the historic cost basis of measurement. Concerns about the availability, and abuses, of reliable measures in relation to intangible assets and revalued assets prompted the USA to proscribe these practices generally. Evidence from the Australian setting suggests these concerns could be overstated. Evidence to date suggests Australian equity markets are no less efficient than the USA markets. Existing evidence suggests uncertainty about intangible investment outcomes is a central property of intangible investment which could quasi‐regulate accounting capitalization practice in a discretionary accounting setting. Supports future regulatory deliberations and research focus on the economics of intangible investments, and information search behaviours of investors, as one way to move forward in the regulatory sphere.
Enron, board governance and moral failings
Authors: Zandstra Gerald
Published: July 2002

The failure of the Enron Corporation has brought attention to the roles played by the chief executive officer and other executives of the modern corporation. Its failure has also produced discussion of further regulations that will, it is hoped, prevent another collapse similar to that of Enron. This article argues that the central reason for Enron’s crash was not a lack of regulations or the deceptions of executives but rather a failure of the board of directors of Enron to function in a morally and ethically responsible manner.
Nucleotide affinity for a stable phosphorylated intermediate of nucleoside diphosphate kinase
Authors: Schneider Benoit , Norda Ameli , Karlsson Anna , Veron Michel , Deville‐Bonne Dominique
Published: July 2002

Nucleoside diphosphate (NDP) kinase is transiently phosphorylated on a histidine of the active site during the catalytic cycle. In the presence of a nucleotide acceptor, the phosphohistidine bond is unstable and the phosphate is transferred to the acceptor in less than 1 msec. We describe the synthesis of an analog of the phosphoenzyme intermediate with an inactive mutant of NDP kinase in which the catalytic histidine is replaced by a cysteine. In two sequential disulfide exchange reactions, a thiophosphate group reacts with the thiol function of the cysteine that had previously reacted with dithionitrobenzoate (DTNB). The thiophosphoenzyme presents a 400,000‐fold increased stability in the presence of NDPs compared with the phosphoenzyme. The binding of NDP is studied at the steady state and presteady state. Data were analyzed according to a bimolecular association model. For the first time, the true equilibrium dissociation constants of NDP for the analog of the phosphoenzyme are determined in the absence of phosphotransfer, allowing a better understanding of the catalytic mechanism of the enzyme.
Insights into the alkaline transformation of ferricytochrome c from 1H NMR studies in 30% acetonitrile–water
Authors: Sivakolundu Sivashankar G. , Mabrouk Patricia Ann
Published: July 2002

Recently, we found that ferricytochrome c (ferricyt c) undergoes significant structural changes in mixed aqueous–nonaqueous media, resulting in the formation of a mixture of alkaline‐like species. The equilibrium composition of this mixture of species is dependent on the dielectric constant of the mixed solvent medium. One‐dimensional (1D) and two‐dimensional (2D) 1H nuclear magnetic resonance (NMR) methods have now been used to study these alkaline‐like forms in 30% acetonitrile–water solution. A native‐like (M80‐ligated) III* form, two lysine‐ligated forms (IVa* and IVb*), and a hydroxide‐ligated form (V*) were observed. Heme proton resonance assignments for these forms were accomplished using 1D 1H NMR and 2D nuclear Overhauser effect spectroscopy methods at 20°C and 35°C. The chemical exchange between the alkaline forms in 30% acetonitrile solution facilitated heme proton resonance assignments. Based on examination of the heme proton chemical shifts and several highly conserved amino acid residues, the electronic structure, secondary structure, and hydrogen bond network in the vicinity of the heme in the III* form were found to be intact. Similarly, the heme electronic structure of the IVa* form was found to be comparable to that of the IVa form. Differences in the order of the heme methyl resonances in the IVb* form, however, suggest that the heme active site in this form is somewhat different from that observed in aqueous alkaline solution. In addition, resonance assignments for the 8‐ and 3‐methyl heme protons were made for the hydroxide‐ligated V* form for the first time. The observation of chemical exchange peaks between all species except IVb* and IVa* or V* was used to propose an exchange pathway between the different forms of ferricyt c in 30% acetonitrile solution. This pathway may be biologically significant because ferricyt c, which resides in the intermembrane space of mitochondria, is exposed to medium of relatively low dielectric constant when it interacts with the mitochondrial membrane.
Peptide‐plane flipping in proteins
Authors: Hayward Steven
Published: July 2002

A peptide‐plane flip is a large‐scale rotation of the peptide plane that takes the ϕ,ψ angles at residues i and i + 1 to different structural regions in the Ramachandran plot with a comparatively small effect on the relative orientation of their side chains. This phenomenon, which is expected to play an important role during the early stages of protein folding, has been investigated using 76 proteins for which two high‐resolution X‐ray conformations are available. Peptide‐plane flips are identified by looking for those cases where changes in |ψi| + |ϕi + 1| are large (>200°), but changes in |ψi + ϕi + 1| are comparatively small (<50°). Of a total of 23 cases, the most common peptide‐plane flip was identified to be the type I to type II β‐turn interconversion. Although individually rarer, there are many other types of flips that are collectively more common. Given the four main accessible regions αR, αL, β and ε, identified from the ϕ,ψ distribution corresponding to non‐hydrogen‐bonded peptide planes, 32 main types of peptide‐plane flip are identified. Only 8 of these are “passive,” in that they require only relatively minor adjustments in the orientation of adjacent peptide planes. Of these, only the type I to type II β‐turn interconversion, denoted, β(i) + αL(i + 1) ― αR(i) + αR(i + 1), and the rarer αR(i) + αL(i + 1) ― β(i) + αR(i + 1), do not involve the ε region. “Active” peptide‐plane flips affect the orientation of adjacent peptide planes. The flip, αL(i) + αL(i + 1) ― β(i) + β(i + 1), of which one example was found, shows how concerted peptide‐plane flips can convert the αL structure to the β structure without affecting the relative orientations of the side chains.
Chaperone‐like activity of peptidyl‐prolyl cis‐trans isomerase during creatine kinase refolding
Authors: Ou Wen‐Bin , Luo Wei , Park Yong‐Doo , Zhou Hai‐Meng
Published: July 2002

Porcine kidney 18 kD peptidyl‐prolyl cis‐trans isomerase (PPIase) belongs to the cyclophilin family that is inhibited by the immunosuppressive drug cyclosporin A. The chaperone activity of PPIase was studied using inactive, active, and alkylated PPIase during rabbit muscle creatine kinase (CK) refolding. The results showed that low concentration inactive or active PPIase was able to improve the refolding yields, while high concentration PPIase decreased the CK reactivation yields. Aggregation was inhibited by inactive or active PPIase, and completely suppressed at 32 or 80 times the CK concentration (2.7 μM). However, alkylated PPIase was not able to prevent CK aggregation. In addition, the ability of inactive PPIase to affect CK reactivation and prevent CK aggregation was weaker than that of active PPIase. These results indicate that PPIase interacted with the early folding intermediates of CK, thus preventing their aggregation in a concentration‐dependent manner. PPIase exhibited chaperone‐like activity during CK refolding. The results also suggest that the isomerase activity of PPIase was independent of the chaperone activity, and that the proper molar ratio was important for the chaperone activity of PPIase. The cysteine residues of PPIase may be a peptide binding site, and may be an essential group for the chaperone function.
Modeling of denatured state for calculation of the electrostatic contribution to protein stability
Authors: Kundrotas Petras J. , Karshikoff Andrey
Published: July 2002

Existing models of the denatured state of proteins consider only one possible spatial distribution of protein charges and therefore are applicable to a limited number of cases. In this article, a more general framework for the modeling of the denatured state is proposed. It is based on the assumption that the titratable groups of an unfolded protein can adopt a quasi‐random distribution restricted by the protein sequence. The model was applied for the calculations of electrostatic interactions in two proteins, barnase and N‐terminal domain of the ribosomal protein L9. The calculated free energy of denaturation, ΔG(pH), reproduces the experimental data better than the commonly used null approximation (NA). It was shown that the seemingly good agreement with experimental data obtained by NA originates from the compensatory effect between the pairwise electrostatic interactions and the desolvation energy of the individual sites. It was also found that the ionization properties of denatured proteins are influenced by the protein sequence.
Cryptosporidium Dose Response Studies: Variation Between Isolates
Authors: Teunis Peter F. M. , Chappell Cynthia L. , Okhuysen Pablo C.
Published: July 2002

The infectivity of three different isolates of the waterborne protozoan parasite Cryptosporidium parvum has been tested in human feeding studies. These three isolates (Iowa, TAMU, and UCP) have different ID50s, indicating substantial variation in their infectivity for humans. This finding is of great importance for quantitative risk assessment as it provides strong evidence for heterogeneity in infectivity among isolates of the same species.
Estimation of Diffusion Processes by Simulated Moment Methods
Authors: Clement Emmanuelle
Published: July 2002

We consider the parameter estimation of a diffusion process and we suppose that the trend and the diffusion coefficient depend on the parameter θ. The process is observed at time (ti)i=0,...,n with Δ = ti+1−ti fixed and we propose here to estimate θ from simulated moment methods.
Contextual Variability in Young Children’s Gender Ingroup Stereotype
Authors: Sani Fabio , Bennett Mark
Published: July 2002

Self‐categorization theorists (Oakes, Haslam & Turner, 1994) have shown that stereotypes are not rigid and fixed, and that they vary to reflect variations in the comparative context within which they are formed. In this paper we investigate stereotype variability in a sample of 6/7‐year‐old children. Participants describe a specific outgroup, and then describe the ingroup (that is ‘boys’ or ‘girls’, depending on the sex of the participant). There are two conditions: in condition one the outgroup is represented by adult ‘men’, if participants are boys, or by adult ‘women’, if participants are girls. In condition two the outgroup is represented by ‘girls’, if participants are boys, or by ‘boys’, if participants are girls. Results show that stereotypical traits attributed to the ingroup change significantly with changes in the frame of reference.
Slow Passage Through the Nonhyperbolic Homoclinic Orbit of the Saddle‐Center Hamiltonian Bifurcation
Authors: Diminnie David C. , Haberman Richard
Published: July 2002

Slowly varying Hamiltonian systems, for which action is a well‐known adiabatic invariant, are considered in the case where the system undergoes a saddle center bifurcation. We analyze the situation in which the solution slowly passes through the nonhyperbolic homoclinic orbit created at the saddle‐center bifurcation. The solution near this homoclinic orbit consists of a large sequence of homoclinic orbits surrounded by near approaches to the autonomous nonlinear nonhyperbolic saddle point. By matching this solution to the strongly nonlinear oscillations obtained by averaging before and after crossing the homoclinic orbit, we determine the change in the action. If one orbit comes sufficiently close to the nonlinear saddle point, then that one saddle approach instead satisfies the nonautonomous first Painlevé equation, whose stable manifold of the unstable saddle (created in the saddle‐center bifurcation) separates solutions approaching the stable center from those involving sequences of nearly homoclinic orbits.
Eigenfunctions of Linearized Integrable Equations Expanded Around an Arbitrary Solution
Authors: Yang Jianke
Published: July 2002

Eigenfunctions of linearized integrable equations expanded around an arbitrary solution are obtained for the Ablowitz–Kaup–Newell–Segur (AKNS) hierarchy and the Korteweg–de Vries (KdV) hierarchy. It is shown that the linearization operators and the integrodifferential operator that generates the hierarchy are commutable. Consequently, eigenfunctions of the linearization operators are precisely squared eigenfunctions of the associated eigenvalue problem. Similar results are obtained for the adjoint linearization operators as well. These results make a simple connection between the direct soliton/multisoliton perturbation theory and the inverse‐scattering based perturbation theory for these hierarchy equations.
Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals
Authors: Druzin Michael , Haage David , Malinina Evgenya , Johansson Staffan
Published: July 2002

Calcium influx into the presynaptic nerve terminal is well established as a trigger signal for transmitter release by exocytosis. By studying dissociated preoptic neurons with functional adhering nerve terminals, we here show that presynaptic Ca2+ influx plays dual and opposing roles in the control of spontaneous transmitter release. Thus, application of various Ca2+ channel blockers paradoxically increased the frequency of spontaneous (miniature) inhibitory GABA‐mediated postsynaptic currents (mIPSCs). Similar effects on mIPSC frequency were recorded upon washout of Cd2+ or EGTA from the external solution. The results are explained by a model with parallel Ca2+ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca2+‐activated K+ channels at a distance from the release site.
In vivo analysis of Kvβ2 function in Xenopus embryonic myocytes
Authors: Lazaroff Meredith A. , Taylor Alison D. , Ribera Angeles B.
Published: July 2002

Kv1 potassium channels consist of pore‐forming α subunits as well as auxiliary β subunits. In heterologous systems, Kv1α subunits suffice for induction of voltage‐dependent potassium current (IKv). Although Kv1 channels can be expressed without auxiliary subunits in heterologous systems, coexpression with Kvβ subunits has dramatic effects on surface expression and kinetic properties. Much less is known about the functional roles of Kvβ subunits in vivo, despite their presence in the majority of native Kv1 channel complexes. We used an antisense approach to probe the contribution of Kvβ2 subunits to native Kv1 channel function in embryonic myocytes. We compared the effects of antisense Kvβ2 treatment on the whole cell IKv to those produced by overexpression of a dominant‐negative Kv1α subunit. The reductions in the maximal potassium conductance produced by antisense Kvβ2 treatment and elimination of Kv1α subunit function were not significantly different from each other. In addition, simultaneous elimination of Kv1α and Kvβ2 subunit function resulted in no further reduction of the maximal conductance. The Kv channel complexes targeted by Kvβ2 and/or Kv1α subunit elimination contributed to action potential repolarization because elimination of either or both subunits led to increases in the duration of the action potential. As for potassium conductance, the effects of elimination of both α and β subunits on the duration of the action potential were not additive. Taken together, the results suggest that Kv1 potassium channel complexes in vivo have a strong requirement for both α and β subunits.
Differential regulation of SK and BK channels by Ca2+ signals from Ca2+ channels and ryanodine receptors in guinea‐pig urinary bladder myocytes
Authors: Herrera Gerald M. , Nelson Mark T.
Published: July 2002

Small‐conductance (SK) and large‐conductance (BK) Ca2+‐activated K+ channels are key regulators of excitability in urinary bladder smooth muscle (UBSM) of guinea‐pig. The overall goal of this study was to define how SK and BK channels respond to Ca2+ signals from voltage‐dependent Ca2+ channels (VDCCs) in the surface membrane and from ryanodine‐sensitive Ca2+ release channels or ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) membrane. To characterize the role of SK channels in UBSM, the effects of the SK channel blocker apamin on phasic contractions were examined. Apamin caused a dose‐dependent increase in the amplitude of phasic contractions over a broad concentration range (10−10 to 10−6m). To determine the effects of Ca2+ signals from VDCCs and RyRs to SK and BK channels, whole cell membrane current was measured in isolated myocytes bathed in physiological solutions. Depolarization (‐70 to +10 mV for 100 ms) of isolated myocytes caused an inward Ca2+ current (ICa), followed by an outward current. The outward current was reduced in a dose‐dependent manner by apamin (10−10 to 10−6m), and designated ISK. ISK had a mean amplitude of 53.8 ± 6.1 pA or ∼1.4 pA pF−1 at +10 mV. The amplitude of ISK correlated with the peak ICa. Blocking ICa abolished ISK. In contrast, ISK was insensitive to the RyR blocker ryanodine (10 μM). These data indicate that Ca2+ signals from VDCCs, but not from RyRs, activate SK channels. BK channel currents (IBK) were isolated from other currents by using the BK channel blockers tetraethylammonium ions (TEA+; 1 mm) or iberiotoxin (200 nm). Voltage steps evoked transient and steady‐state IBK components. Transient BK currents have previously been shown to result from BK channel activation by local Ca2+ release through RyRs (‘Ca2+ sparks’). Transient BK currents were inhibited by ryanodine (10 μM), as expected, and had a mean amplitude of 152.6 pA at +10 mV. The mean number of transient BK currents during a voltage step (range 0 to 3) correlated with ICa. There was a long delay (52.4 ± 2.7 ms) between activation of ICa and the first transient BK current. In contrast, ryanodine did not affect the steady‐state BK current (mean amplitude 135.4 pA) during the voltage step. The steady‐state BK current was reduced 95 % by inhibition of VDCCs, suggesting that this process depends largely on Ca2+ entry through VDCCs and not Ca2+ release through RyRs. These results indicate that Ca2+ entry through VDCCs activates both BK and SK channels, but Ca2+ release (Ca2+ sparks) through RyRs activates only BK channels.
Responses of human sensory and motor axons to the release of ischaemia and to hyperpolarizing currents
Authors: Lin Cindy S.‐Y. , Kuwabara Satoshi , Cappelen‐Smith Cecilia , Burke David
Published: July 2002

This study compared directly the post‐ischaemic behaviour of sensory and motor axons in the human median nerve, focusing on the excitability changes produced by ischaemia and its release and by continuous polarizing DC. The decrease in threshold during ischaemia for 13 min was greater, the post‐ischaemic increase in threshold was more rapid, and the return to the pre‐ischaemic excitability took longer in sensory axons. However, a transient depolarizing threshold shift developed in sensory axons a few minutes after release of ischaemia. This pattern could not be reproduced by polarizing currents designed to mimic the probable pump‐induced changes in membrane potential, even though the applied currents produced greater changes in threshold. Hyperpolarizing currents of equivalent intensity produced a greater increase in threshold for motor axons than sensory axons and, in studies of threshold electrotonus using graded hyperpolarizing DC, accommodation was greater in sensory than motor axons. The post‐ischaemic changes in threshold were not uniform for axons of different threshold, whether sensory or motor, the threshold increase was usually less prominent for low‐threshold axons. A transient post‐ischaemic depolarization could be produced in motor axons with ischaemia of 20 min duration. Greater ischaemic and post‐ischaemic changes in threshold for sensory axons could reflect greater dependence on the electrogenic Na+‐K+ pump to maintain resting membrane potential and/or greater extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due to extracellular K+ accumulation would then be more likely to trigger a depolarizing shift in membrane potential, the degree of K+ accumulation and pump activity being dependent on the duration of ischaemia. In sensory axons the greater tendency to accommodate to hyperpolarizing stimuli presumably contributes to shaping their post‐ischaemic behaviour but is probably insufficient to explain why their behaviour differs from that of motor axons.
Quantitative evolutionary design
Authors: Diamond Jared
Published: July 2002

The field of quantitative evolutionary design uses evolutionary reasoning (in terms of natural selection and ultimate causation) to understand the magnitudes of biological reserve capacities, i.e. excesses of capacities over natural loads. Ratios of capacities to loads, defined as safety factors, fall in the range 1.2‐10 for most engineered and biological components, even though engineered safety factors are specified intentionally by humans while biological safety factors arise through natural selection. Familiar examples of engineered safety factors include those of buildings, bridges and elevators (lifts), while biological examples include factors of bones and other structural elements, of enzymes and transporters, and of organ metabolic performances. Safety factors serve to minimize the overlap zone (resulting in performance failure) between the low tail of capacity distributions and the high tail of load distributions. Safety factors increase with coefficients of variation of load and capacity, with capacity deterioration with time, and with cost of failure, and decrease with costs of initial construction, maintenance, operation, and opportunity. Adaptive regulation of many biological systems involves capacity increases with increasing load; several quantitative examples suggest sublinear increases, such that safety factors decrease towards 1.0. Unsolved questions include safety factors of series systems, parallel or branched pathways, elements with multiple functions, enzyme reaction chains, and equilibrium enzymes. The modest sizes of safety factors imply the existence of costs that penalize excess capacities. Those costs are likely to involve wasted energy or space for large or expensive components, but opportunity costs of wasted space at the molecular level for minor components.
Phosphorylation‐dependent differences in the activation properties of distal and proximal dendritic Na+ channels in rat CA1 hippocampal neurons
Authors: Gasparini Sonia , Magee Jeffrey C.
Published: July 2002

At distal dendritic locations, the threshold for action potential generation is higher and the amplitude of back‐propagating spikes is decreased. To study whether these characteristics depend upon Na+ channels, their voltage‐dependent properties at proximal and distal dendritic locations were compared in CA1 hippocampal neurons. Distal Na+ channels activated at more hyperpolarized voltages than proximal (half‐activation voltages were −20.4 ± 2.4 mV vs.−12.0 ± 1.7 mV for distal and proximal patches, respectively, n= 16, P < 0.01), while inactivation curves were not significantly different. The resting membrane potential of distal regions also appeared to be slightly but consistently more hyperpolarized than their proximal counterpart. Staurosporine, a non‐selective protein kinase inhibitor, shifted the activation curves for both proximal and distal Na+ channels to the left so that they overlapped and also caused the resting potentials to be comparable. Staurosporine affected neither the inactivation kinetics of Na+ currents nor the reversal potential for Na+. These results suggest that the difference in the voltage dependence of activation of distal and proximal Na+ channels can be attributed to a different phosphorylation state at the two locations.
Transport of volatile solutes through AQP1
Authors: Cooper Gordon J. , Zhou Yuehan , Bouyer Patrice , Grichtchenko Irina I. , Boron Walter F.
Published: July 2002

For almost a century it was generally assumed that the lipid phases of all biological membranes are freely permeable to gases. However, recent observations challenge this dogma. The apical membranes of epithelial cells exposed to hostile environments, such as gastric glands, have no demonstrable permeability to the gases CO2 and NH3. Additionally, the water channel protein aquaporin 1 (AQP1), expressed at high levels in erythrocytes, can increase membrane CO2 permeability when expressed in Xenopus oocytes. Similarly, nodulin‐26, which is closely related to AQP1, can act as a conduit for NH3. A key question is whether aquaporins, which are abundant in virtually every tissue that transports O2 and CO2 at high levels, ever play a physiologically significant role in the transport of small volatile molecules. Preliminary data are consistent with the hypothesis that AQP1 enhances the reabsorption of HCO3− by the renal proximal tubule by increasing the CO2 permeability of the apical membrane. Other preliminary data on Xenopus oocytes heterologously expressing the electrogenic Na+‐HCO3− cotransporter (NBC), AQP1 and carbonic anhydrases are consistent with the hypothesis that the macroscopic cotransport of Na+ plus two HCO3− occurs as NBC transports Na+ plus CO32‐ and AQP1 transports CO2 and H2O. Although data ‐ obtained on AQP1 reconstituted into liposomes or on materials from AQP1 knockout mice ‐ appear inconsistent with the model that AQP1 mediates substantial CO2 transport in certain preparations, the existence of unstirred layers or perfusion‐limited conditions may have masked the contribution of AQP1 to CO2 permeability.
Loads, capacities and safety factors of maltase and the glucose transporter SGLT1 in mouse intestinal brush border
Authors: Lam Mandy M. , O'Connor Timothy P. , Diamond Jared
Published: July 2002

Safety factors are defined as ratios of biological capacities to prevailing natural loads. We measured the safety factor of the mouse intestinal brush‐border hydrolase maltase in series with the glucose transporter SGLT1, for comparison with previous studies of sucrase and lactase. Dietary maltose loads increased 4‐fold from virgin to lactating mice. As in previous studies of intestinal adaptive regulation, that increase in load without change in dietary composition resulted in an increase in maltase and SGLT1 capacities mediated non‐specifically by an increase in intestinal mass, without change in maltase or SGLT1 activities per milligram of tissue. Maltase and SGLT1 capacities increased only sublinearly with load during lactation, such that safety factors decreased with load: from 6.5 to 2.4 for maltase, and from 1.1 to 0.5 for SGLT1. The apparently high safety factor for maltase may be related to the multiple natural substrates hydrolysed by the multiple sites of maltase activity. The apparently low safety factor for SGLT1 is made possible by the contribution of hindgut fermentation to carbohydrate digestion. SGLT1 activity is paradoxically higher for mice consuming sucrose than for mice consuming maltose, despite maltose hydrolysis yielding double the glucose load yielded by sucrose hydrolysis, and despite glucose constituting the load upon SGLT1.
Optimization of Design Tolerances Through Response Surface Approximations
Authors: Jordaan J. P. , Ungerer C. P.
Published: July 2002

A methodology whereby the optimal set of design tolerances is assigned to the dimensions of a general mechanical assembly, is developed and tested. The manufacturing cost is minimized, while the design is constrained to a specified probability of meeting functional requirements, called the yield of the design. An analytical relationship for the assembly yield surface is generally unknown, and use is made of response surface approximations in the optimization algorithm. Yield values are determined at design space points through Monte Carlo simulations, seen as the response surface experiments. The methodology is benchmarked on example problems from the literature, and the optimum compares superior to published results.