bluuebunny/crossref_metadata_2025 huggingface dataset:
Employees, teamwork and social interdependence – a formula for successful business?
Authors: Tarricone Pina , Luca Joe
Published: October 2002

Business expects far more from employees than technical and generic skills. There is a growing emphasis on employees to not just do their job but to contribute to business success. As the emphasis is placed on individuals contributing to the effective, positive perpetuation of the business through the development of professional and work related skills; the team culture of business today places additional emphasis on the ability to work effectively within a team environment. Specifically, this paper will discuss the importance of social interdependence and teamwork and the implications for business success and team success
Palliative care teams and organisational capability
Authors: Davison Graydon , Hyland Paul
Published: October 2002

This paper is the first in a series that will examine the management of innovation by cross‐functional, multi‐disciplinary patient care teams in a palliative care environment. This highly innovative environment is singularly focused on relieving the suffering of patients and their socially related carers during an end of life experience. The singular focus enables and encourages palliative care practitioners to break through and diminish or accommodate professionally‐based paradigm conflicts and organisational politics. This facilitates collaborative team‐based efforts, including the patient and the patient’s social support group, to address the multi‐causal uncertainties that characterise end of life in palliative care. The continuous innovation model used in the European Union funded CIMA project is used as a starting point for this research. While many businesses have struggled to implement self‐regulating teams and have invested considerable resources in attempting to gain some advantage from teamwork it appears palliative care professionals have adopted self‐regulating work teams in a highly uncertain environment as the most suitable human resource structure and practice.
Is bigger better?
Authors: Grünhagen Marko , Mittelstaedt Robert A.
Published: October 2002

This paper explores from a US perspective two size‐related issues that may motivate aspiring franchisees to consider multi‐unit franchising as a superior alternative to the traditional single‐unit approach. First, one of the reasons for multi‐unit franchising might be the enhanced influence opportunity upon the franchisor’s decision making that arises from owning multiple outlets. Second, a potential franchisee may be interested in engaging in multi‐unit franchising in the anticipation of scale efficiencies, i.e. efficiencies that arise because of the size of the operation. The managerial relevance of the discovered issues and their potential for future research is outlined.
Improving organizational performance through the use of effective elements of organizational structure
Authors: Hunter Judy
Published: October 2002

This paper looks at organizations at work to determine various effects on productivity. Six research‐based organizations were studied against a backdrop of dynamic impacts. After the application of several tests, the conclusion indicates that the optimal approach uses a variety of structures and elements to ensure a fluid and flexible organization able to deal with shifts in direction or impacts.
An inquiry into the motivations of knowledge workers in the Japanese financial industry
Authors: Kubo Izumi , Saka Ayse
Published: October 2002

The knowledge base of companies is increasingly seen as underlying a firm’s performance, and the role of knowledge workers within this framework is seen as strongly associated with a firm’s competitive performance. This perspective views the effective management of knowledge workers as crucial in sustaining an organisation’s competitive advantage. The paper views the financial industry as a knowledge intensive sector which nurtures the idea that financial firms rely on specialists’ knowledge or expertise relating to a specific technical and functional domain. It is an exploratory study that aims to investigate the motivational needs of, and organisational environments best suited to, company analysts within the Japanese financial system. It identifies three key motivators as having an impact on the company analysts: monetary incentives; human resource development; and job autonomy. The paper concludes that the traditional Japanese management system is incompatible with the expectations of company analysts in the Japanese financial industry.
The distribution model in the diffusion of innovations: a comparison of different European countries
Authors: Ruíz Conde Enar , José Más Ruíz Francisco
Published: October 2002

The objective of this study was two fold: first, we wanted to test the goodness of fit of different diffusion models that include the variable “distribution”, and then analyze the existence of the effects of “country” and “time” in the parameters of diffusion currently employed in different European countries. The literature on the matter suggests, on the one hand, that the diffusion models applied so far that employ multi‐equation systems are not obviously better than other single‐equation models that ignore marketing variables; and, on the other hand, that the socio‐economic environment and the time‐lag are both factors of the differences that the diffusion process offers among different geographical areas. As a novelty, our methodology proposes single‐equation models that include the distribution, to which several indicators of the goodness of fit are applied, along with statistical tests on the differences in parameters among countries. The empirical application carried out in Spain, France and Italy demonstrates the superiority of the model proposed here, based on the Generalized Bass model. It also indicates a “country” effect, between Spain and France as well as between Italy and France
The long‐run diversification attributes of commercial property
Authors: Fraser W.D. , Leishman C. , Tarbert H.
Published: October 2002

Correlation coefficients measuring the historical relationships of returns on commercial property and both equities and conventional gilts appear to be low. Conversely, the correlation between gilts and equities appears to be relatively high. This implies that property provides diversification benefits to a mixed asset portfolio dominated by equities and gilts. However, there is some debate as to the reliability of these correlations and property’s diversification benefits. In this paper we use Granger causality tests and cointegration techniques to demonstrate that there is no long‐run relationship between property returns and those of either gilts or equities. This confirms the diversification benefits of including property in a mixed asset portfolio.
Mean reversion of Singapore property stock prices towards their fundamental values
Authors: Foo Sing Tien , Hiang Liow Kim , Chan Wei‐Jin
Published: October 2002

Market critics often cited an apparent lack of relationship between corporate performance and stock prices as the main reason for a poor prediction of stock prices. This study attempts to examine whether prices of 15 sample listed property stocks in Singapore reflect their corporate fundamental values over a ten‐year period from June 1989 to June 1999. Proxies for corporate fundamental values used in our study are earnings per share (EPS), dividends per share (DPS) and net asset values (NAV) of the individual property stocks listed in Singapore. From the Johansen’s cointegration test results, there were long‐run convergence relationships of stock prices with their fundamental values for nine of the 15 sample stocks, which implied some forms of mean reversion process of stock prices towards their fundamental values. For the nine sampled cointegrating stocks, NAV and EPS, particularly in the second‐lag orders, were the most significant fundamental values in explaining the short‐run dynamics of the stock price changes. The error correction mechanism (ECM) was also found to be statistically significant in the long‐run convergence relationships with four sample stock prices. DPSs and lagged changes in stock prices, in comparison, were statistically significant, but in only two of the sample vector ECM relationships. The results imply that institutional investors should pay more attention to the underlying performance of stocks, in particularly the EPS and NAV, in their stock selection process.
Policy implications of structural options in the development of real estate investment trusts in Europe
Authors: Campbell Robert D. , Sirmans C.F.
Published: October 2002

This is a policy paper that examines the most important issues that must be addressed in designing the institutional structure for tax‐advantaged public real estate companies in Europe. The real estate investment trust form of corporate structure was first created in the USA in 1960. In Europe, the real estate invstment trust (REIT) regime has been authorized only in The Netherlands, and very recently in Belgium. However, the establishment of REIT‐like public investment vehicles is under discussion in the UK, and in several Continental European nations. Advocates of European REITs believe that these investment vehicles would reduce costs of capital, improve liquidity in local real estate markets, and promote more efficient allocation of capital. European countries that are moving toward the establishment of REITs face a series of important decisions regarding the features of the institutional environment in which these firms will operate. This paper summarizes the most important decisions that must be made, and considers the policy implications of each. We conclude that the US model should not be adopted uncritically in Europe; instead, structural options should be considered carefully. Problems of international taxation are identified, and the possible development of a pan‐European REIT structure is discussed.
Appraising property with rough set theory
Authors: d’Amato Maurizio
Published: October 2002

This research is focused on a methodology created to analyse imprecise information, that is full of attributes defined as “rough set”. The methodology will be then applied to the real estate appraisal question, representing a further possible method of evaluation. Up to now the main approaches to the real estate appraisal have been income, market and cost. My intention is to analyse this theory showing a practical application on a group of real estate transactions made by a real estate agent. This application will show how it is possible to get values to classify a real estate. A comparison between this method and the most common statistics instruments will be highlighted.
Three layers of the electronic commerce network: challenges for the developed and developing worlds
Authors: Singh J.P. , Gilchrist Sarah M.
Published: October 2002

As electronic commerce expands, credible property rights in key sectors are necessary. This article identifies three layers of an electronic commerce network – infrastructure, commercial services, and trust – and then outlines five conditions of property rights that are being fulfilled in varying degrees in the developed and developing worlds. The main challenge for the developing world is to concentrate on adequate infrastructural provision. The challenge for the developed world is in determining appropriate property rights for the supportive commercial services needed for electronic commerce as well as issues of consumer and business trust. Given the global nature of electronic commercial transactions, both developed and developing countries are involved in framing rules at the global level that resonate and are credible with domestic conditions and institutions.
Internet portals for chemists
Authors: Glander‐Höbel Cornelia
Published: October 2002

This paper is to give an overview of freely available subject services providing information for chemists on the Internet. An attempt is made to differentiate between portals and other kinds of resources encountered on the Web. A definition of portals is given. Subject collections of general chemistry, analytical chemistry, environmental research, toxicology and patents are described. Internet chemistry portals can be regarded as a valuable addition to the traditional print and online information sources used by chemists.
Chemical e‐journals, chemical e‐preprints
Authors: Town William G. , Vickery Bryan A. , Kuras Jan , Weeks James R.
Published: October 2002

Chemists communicate in structures. The nature of information available to chemists therefore has to take this into account. With the migration from print to electronic publication nearly complete, the Internet offers the chemical information user many advantages. Journal articles are accessible quickly and easily from the desktop, long before their appearance in paper form. Additionally, research papers can now be uploaded to preprint servers before they even enter the publishing process. This paper discusses the many advantages this brings with it for chemists, but also discusses the disadvantages some may see as a possible result.
Developing reflexive corporate leadership
Authors: Barratt Ruth , Korac‐Kakabadse Nada
Published: October 2002

In recent decades, there have been far too many examples of the world’s business being not sufficiently attentive to governance, with little foresight as to emerging consequences, such as major oil spills, chemical leaks and Enron. Many leaders do not seem to address issues beyond short‐term profitability. The emerging worldwide view is that corporations need to adopt governance models that are more holistic in their approach, pluralistic in representing varying interests, egalitarian in the treatment of stakeholders and essentially more collaborative in their mode of operation. Corporate leaders must emerge more cognitively, emotively and behaviourally reflexive. Such reflexivity comes through the application of practical wisdom to facilitate corporate change. Fully realising value from the board of directors as the guide of the organisation, and specifically from non executive directors (NEDs) is crucial to enduring sustainable change. NEDs’ abilities to span the boundary between the needs and wants of a variety of legitimate stakeholders and the survival requirements of the firm poses a unique management development challenge. NEDs who effectively provide holistic and reflexive insight into the challenges of corporate systems are likely to enhance organisational, societal and environmental wellbeing. Through reflexivity, well skilled and capable NEDs can stimulate the desire to change in the leadership of the organisation and may, as such, prevent future crisis. Towards this end, this presentation will examine how NEDs can leverage their role to promote corporate social performance.
Creating innovation and synergy through a parallel action learning structure
Authors: Passfield Ron
Published: October 2002

This paper explains the underlying dynamics of the University of Queensland action learning program (1991‐1999) through discussion of the parallel action learning structure (PALS) model. The author developed the PALS model as an outcome of his action research PhD study of the program, which was a development program for senior academic and administrative staff based on the principles of action learning and action research. This program achieved outstanding success and became a best practice model for other universities throughout Australia and elsewhere in the world. The PALS model described in this paper links the program design elements with personal and organisational outcomes and shows how these contribute to synergy and ongoing organisational energy and innovation. It also serves as a model for designing action learning interventions in other environments.
Energetic and entropic contributions to the interactions between like‐charged groups in cationic peptides: A molecular dynamics simulation study
Authors: Villarreal Marcos , Montich Guillermo
Published: October 2002

The interaction between like‐charged amino acid residues has been proposed to stabilize the folded state of peptides and proteins, and to modulate the substrate binding and the action mechanism of enzymes. We have used an alanine‐ and lysine‐based peptide as a model system to study the interaction between like charges, and we have performed a 16‐nsec molecular dynamics simulation in solution. The calculated potential of mean force for the approach of the lysine's Nζ atoms showed a minimum at a distance of 0.7 nm, in agreement with the separation probabilities obtained from analysis of protein crystal structures. The analysis of the individual energy components showed that the solvent polarization pays for the approach of the like charges and that the van der Waals energies do not contribute significantly. The entropic contributions have been divided in conformational and desolvation terms. Both terms favor the formation of the charge pair. A 10‐fold increase in counterion concentration was observed—with respect to its bulk concentration—next to the peptide charges, which helps to stabilize the peptide charges at a close distance.
Fast‐folding protein kinetics, hidden intermediates, and the sequential stabilization model
Authors: Ozkan S. Banu , Dill Ken A. , Bahar Ivet
Published: October 2002

Do two‐state proteins fold by pathways or funnels? Native‐state hydrogen exchange experiments show discrete nonnative structures in equilibrium with the native state. These could be called hidden intermediates (HI) because their populations are small at equilibrium, and they are not detected in kinetic experiments. HIs have been invoked as disproof of funnel models, because funnel pictures appear to indicate (1) no specific sequences of events in folding; (2) a continuum, rather than a discrete ladder, of structures; and (3) smooth landscapes. In the present study, we solve the exact dynamics of a simple model. We find, instead, that the present microscopic model is indeed consistent with HIs and transition states, but such states occur in parallel, rather than along the single pathway predicted by the sequential stabilization model. At the microscopic level, we observe a huge multiplicity of trajectories. But at the macroscopic level, we observe two pathways of specific sequences of events that are relatively traditional except that they are in parallel, so there is not a single reaction coordinate. Using singular value decomposition, we show an accurate representation of the shapes of the model energy landscapes. They are highly complex funnels.
Sequence conservation in the chagasin family suggests a common trend in cysteine proteinase binding by unrelated protein inhibitors
Authors: Rigden Daniel J. , Mosolov Vladimir V. , Galperin Michael Y.
Published: October 2002

The recently described inhibitor of cysteine proteinases fromTrypanosoma cruzi, chagasin, was found to have close homologs in several eukaryotes, bacteria and archaea, the first protein inhibitors of cysteine proteases in prokaryotes. These previously uncharacterized 110–130 residue‐long proteins share a well‐conserved sequence motif that corresponds to two adjacent β‐strands and the short loop connecting them. Chagasin‐like proteins also have other conserved, mostly aromatic, residues, and share the same predicted secondary structure. These proteins adopt an all‐β fold with eight predicted β‐strands of the immunoglobulin type. The phylogenetic distribution of the chagasins generally correlates with the presence of papain‐like cysteine proteases. Previous studies have uncovered similar trends in cysteine proteinase binding by two unrelated inhibitors, stefin and p41, that belong to the cystatin and thyroglobulin families, respectively. A hypothetical model of chagasin–cruzipain interaction suggests that chagasin may dock to the cruzipain active site in a similar manner with the conserved NPTTG motif of chagasin forming a loop that is similar to the wedge structures formed at the active sites of papain and cathepsin L by stefin and p41.
Modern analytical ultracentrifugation in protein science: A tutorial review
Authors: Lebowitz Jacob , Lewis Marc S. , Schuck Peter
Published: October 2002

Analytical ultracentrifugation (AU) is reemerging as a versatile tool for the study of proteins. Monitoring the sedimentation of macromolecules in the centrifugal field allows their hydrodynamic and thermodynamic characterization in solution, without interaction with any matrix or surface. The combination of new instrumentation and powerful computational software for data analysis has led to major advances in the characterization of proteins and protein complexes. The pace of new advancements makes it difficult for protein scientists to gain sufficient expertise to apply modern AU to their research problems. To address this problem, this review builds from the basic concepts to advanced approaches for the characterization of protein systems, and key computational and internet resources are provided. We will first explore the characterization of proteins by sedimentation velocity (SV). Determination of sedimentation coefficients allows for the modeling of the hydrodynamic shape of proteins and protein complexes. The computational treatment of SV data to resolve sedimenting components has been achieved. Hence, SV can be very useful in the identification of the oligomeric state and the stoichiometry of heterogeneous interactions. The second major part of the review covers sedimentation equilibrium (SE) of proteins, including membrane proteins and glycoproteins. This is the method of choice for molar mass determinations and the study of self‐association and heterogeneous interactions, such as protein–protein, protein–nucleic acid, and protein–small molecule binding.
Unfolding of the loggerhead sea turtle (Caretta caretta) myoglobin: A 1H‐NMR and electronic absorbance study
Authors: Castelli Daniela Delli , Lovera Elena , Ascenzi Paolo , Fasano Mauro
Published: October 2002

The effect of urea concentration on the backbone solution structure of the cyanide derivative of ferric Caretta caretta myoglobin (at pH 5.4) is reported. By addition of urea, sequential and long‐range nuclear Overhauser effects (NOEs) are gradually lost. By using the residual NOE constraints to build the molecular model, a picture of the unfolding pathway was obtained. When the urea concentration is raised to 2.2 M, helices A and B appear largely disordered; helices C, D, and F loose structural constraints at 3.0 M urea. At urea concentration >6 M, the protein appears to be fully unfolded, including the GH hairpin and helix E stabilizing the prosthetic group. Reversible and cooperative denaturation isotherms obtained by following NOE peaks are considerably different from those obtained by monitoring electronic absorption changes. The reversible and cooperative urea‐dependent folding‐unfolding process of C. caretta myoglobin follows the minimum three‐state mechanism N⟷X⟷D, where X represents a disordered globin structure (occurring at ∼4 M urea) that still binds the heme.
Osmolyte effects on helix formation in peptides and the stability of coiled‐coils
Authors: Celinski Scott A. , Scholtz J. Martin
Published: October 2002

The ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine‐based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine‐N‐oxide (TMAO) is the best structure‐inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE). We also provide a semiquantitative study of the ability of TMAO to induce helix formation and urea, which acts as a helix (and protein) denaturant. We find that on a molar basis, these agents are exactly counteractive as structure inducing and unfolding agents. Finally, we extend the investigations to the effects of urea and TMAO on the stability of a dimeric coiled‐coil peptide and find identical results. Together these results support the tenets of the osmophobic hypothesis and highlight the importance of the polypeptide backbone in protein folding and stability.
Interatomic potentials and solvation parameters from protein engineering data for buried residues
Authors: Lomize Andrei L. , Reibarkh Mikhail Y. , Pogozheva Irina D.
Published: October 2002

Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (H‐bonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of free‐energy differences. The set of mutants included substitutions of uncharged, inflexible, water‐inaccessible residues in α‐helices and β‐sheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and H‐bonds were smaller than in molecular mechanics and followed the “like dissolves like” rule, as expected in condensed media but not in vacuum. The depths of modified Lennard‐Jones potentials were −0.34, −0.12, and −0.06 kcal/mole for similar atom types (polar–polar, aromatic–aromatic, and aliphatic–aliphatic interactions, respectively) and −0.10, −0.08, −0.06, −0.02, and nearly 0 kcal/mole for different types (sulfur–polar, sulfur–aromatic, sulfur–aliphatic, aliphatic–aromatic, and carbon–polar, respectively), whereas the depths of H‐bond potentials were −1.5 to −1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, −1, −21, and −66 cal/moleÅ2 for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the water–protein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.
Crucial stages of protein folding through a solvable model: Predicting target sites for enzyme‐inhibiting drugs
Authors: Micheletti Cristian , Cecconi Fabio , Flammini Alessandro , Maritan Amos
Published: October 2002

An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key sites for the folding of human immunodeficiency virus type 1 (HIV‐1) protease. The predicted sites are found to correlate well with clinical data on resistance to Food and Drug Administration‐approved drugs. It has been observed that the effects of drug therapy are to induce multiple mutations on the protease. The sites where such mutations occur correlate well with those involved in folding bottlenecks identified through the deterministic procedure proposed in this study. The high statistical significance of the observed correlations suggests that the approach may be promisingly used in conjunction with traditional techniques to identify candidate locations for drug attacks.
Strongly Continuous Semigroups and Stochastic Representation
Authors: Liu Genqian
Published: October 2002

Second‐order elliptic operators realized under Dirichlet boundary conditions in bounded domains are shown to generate strongly continuous semigroups in the topology of uniform convergence. The stochastic representation and integral representation with kernel for the strongly continuous semigroups are given. Furthermore, several useful formulae for the principal eigenvalue of second‐order elliptic operators are obtained.
Spectral Synthesis and Masa‐Bimodules
Authors: Todorov I. G.
Published: October 2002

The interaction between harmonic analysis and operator theory has been fruitful. In [1] Arveson related results in the theory of operator algebras to spectral synthesis. He defined synthesis for subspace lattices and proved that certain classes of lattices are synthetic. The main result in this paper is a generalization of a result of Arveson for the case of subspace maps. In order to describe in more detail the content of the present work, we need to introduce some definitions and facts from [2] and [9].

Let H1 and H2 be separable complex Hilbert spaces, and Pi be the lattice of all (orthogonal) projections on Hi, i = 1, 2. Following Erdos [1], we let M(P1, P2) denote the set of all maps φ : P1 → P2 which are 0‐preserving and v‐continuous (that is, they preserve arbitrary suprema). We will call such maps subspace maps. It was shown in [2] that each φ ∈ M(P1, P2) uniquely defines semi‐lattices S1φ ⊆ P1 and S2φ = φ(P1) ⊆ P2 such that φ is a bijection between S1φ and S2φ and is uniquely determined by its restriction to S1φ. Moreover, S1φ is meet‐complete and contains the identity projection while S2φ is join‐complete and contains the zero projection. If S1φ and S2φ are commutative, we say that φ is a commutative subspace map.
Sharp Weighted Estimates for Multilinear Commutators
Authors: Pérez C. , Trujillo-González R.
Published: October 2002

Multilinear commutators with vector symbol =(b1,…,bm) defined by are considered, where K is a Calderón–Zygmund kernel. The following a priori estimates are proved for w ∈ A∞. For 0 < p < ∞, there exists a constant C such that and where

and ML(log L)α is an Orlicz type maximal operator. This extends, with a different approach, classical results by Coifman.

As a corollary, it is deduced that the operators are bounded on Lp(w) when w ∈ Ap, and that they satisfy corresponding weighted L(log L)1/r‐type estimates with w ∈ A1.
Schemes of Line Modules I
Authors: Shelton Brad , Vancliff Michaela
Published: October 2002

It is proved that there exists a scheme that represents the functor of line modules over a graded algebra, and it is called the line scheme of the algebra. Its properties and its relationship to the point scheme are studied. If the line scheme of a quadratic, Auslander‐regular algebra of global dimension 4 has dimension 1, then it determines the defining relations of the algebra.

Moreover, the following counter‐intuitive result is proved. If the zero locus of the defining relations of a quadratic (not necessarily regular) algebra on four generators with six defining relations is finite, then it determines the defining relations of the algebra. Although this result is non‐commutative in nature, its proof uses only commutative theory.

The structure of the line scheme and the point scheme of a 4‐dimensional regular algebra is also used to determine basic incidence relations between line modules and point modules.
Time course and magnitude of the calcium release induced by bright light in salamander rods
Authors: Matthews Hugh R. , Fain Gordon L.
Published: October 2002

Changes in fluorescence were measured with an argon ion laser from the outer segments of isolated salamander rods containing the Ca2+‐sensitive fluorescent dye fluo‐5F. When the outer segments were exposed to a 0Ca2+/0Na+ solution designed to minimise surface membrane Ca2+ fluxes, exposure to intense light from the laser evoked a slow increase in fluorescence, reflecting a light‐induced rise in outer segment [Ca2+]i. The time course of this slow fluorescence rise could be fitted with the sum of two asymptotic exponential functions of approximately equal amplitude, having time constants of approximately 200 ms and 5.7 s. When rods were exposed to saturating background light to reduce outer segment [Ca2+]i before laser illumination, the relative amplitude of the two exponentials was altered so as to reduce the contribution from the one with the shorter time constant. Examination of the initial time course of fluorescence when recording at high temporal resolution revealed a further rapid rise with a time constant of 1–2 ms, which could be observed even from rods in Ringer solution. This initial rapid rise could be abolished by pre‐exposing the rod to bleaching illumination, whether the bleach was given in Ringer solution or in 0Ca2+/0Na+ solution. It would therefore appear that the rapid rise in fluorescence is generated in some way by the bleaching of the photopigment. Unlike the slower components of fluorescence increase, the rapid initial rise was virtually unaffected in waveform or amplitude when rods were pre‐exposed in Ringer solution to light which was bright enough to suppress completely the circulating current but which bleached a negligible fraction of the photopigment. Furthermore, pre‐incubation with the AM ester of the Ca2+ chelator BAPTA, although completely abolishing the slower components of fluorescence increase, had virtually no effect on the rapid rise. These results indicate that the rapid component, though triggered by rhodopsin bleaching, does not reflect an increase in outer segment [Ca2+]i. Neither the rapid nor the slower components of fluorescence increase were affected by exposure of the outer segment to 10 μm of the membrane‐permeant compound N,N,N′,N′‐tetrakis(2‐pyridyl‐methyl)ethylenediamine (TPEN), which chelates heavy metals such as Zn2+, or 100 μm 2‐aminoethoxydiphenylborate (2‐APB), a membrane‐permeant blocker of IP3 receptors. These results appear to exclude a role for changes in heavy metal concentration or Ca2+ release via IP3 receptors in the light‐induced increases in dye fluorescence. Estimates of absolute Ca2+ concentration and of rod buffering capacity suggest that the slower components of fluorescence increase represent the release of around 10–50 μmoles Ca2+ per litre cytoplasmic volume from bound or sequestered stores after bleaching.
Cellular mechanisms for apical ATP effects on intracellular pH in human bronchial epithelium
Authors: Urbach V. , Hélix N. , Renaudon B. , J. Harvey B.
Published: October 2002

The effect of external ATP on intracellular pH (pHi) was investigated using a pH imaging system in a human bronchial epithelial cell line (16HBE14o‐) loaded with BCECF‐AM. The steady‐state pHi of 16HBE14o‐ epithelial monolayers was 7.137 ± 0.027 (n= 46). Apical addition of ATP (10−4m) to epithelial monolayers induced a rapid and sustained pHi decrease of 0.164 ± 0.024 pH units (n= 17; P < 0.001). The intracellular acidification was rapidly reversed upon removal of external ATP. In contrast, the non‐hydrolysable ATP analogue AMP‐PNP did not produce any significant change in pHi. Inhibition of purinoreceptors by suramin did not affect the acidification induced by apical ATP. Inhibition of Na+‐H+ exchange by apical Na+ removal or addition of amiloride (0.5 mm) reduced the apical ATP‐induced pHi decrease, suggesting the involvement of a Na+‐H+ exchanger or surface pH effects on the ATP‐induced pHi response. Inhibitors of proton channels such as ZnCl2 (10−4m) also partially inhibited the ATP response. The pHi response to ATP was dependent on the external pH (pHo), with increasing acidification produced at lower pHo values. Neither the basal pHi nor the ATP‐induced intracellular acidification was affected by thapsigargin (a Ca2+‐ATPase inhibitor), chelerythrine chloride (a protein kinase C (PKC) inhibitor), RpcAMP (a protein kinase A (PKA) inhibitor) or PMA (a PKC activator). Therefore, the intracellular acidification of human bronchial epithelial cells induced by apical ATP does not involve signalling via Ca2+, PKC or PKA nor binding to a purinoreceptor. We interpret the effect of ATP to produce an intracellular acidification as a three step process: activation of H+ channels, inhibition of Na+‐H+ exchange and influx of protonated ATP.
Crosstalk between ryanodine receptors and IP3 receptors as a factor shaping spontaneous Ca2+‐release events in rabbit portal vein myocytes
Authors: Gordienko D. V. , Bolton T. B.
Published: October 2002

In smooth muscle cells freshly isolated from rabbit portal vein, there was only one site discharging the majority of spontaneous Ca2+‐release events; the activity of this single site was studied using laser scanning confocal imaging after loading the cells with the fluorescent Ca2+ indicator fluo‐4 acetoxymethyl ester. Localised spontaneous Ca2+‐release events visualised by line‐scan imaging revealed two predominant spatiotemporal patterns: (i) small‐amplitude, fast events similar to Ca2+ sparks in cardiomyocytes and (ii) larger and slower events. The sum of two Gaussian profiles was well fitted to the amplitude histogram (peak frequencies at 1.8 and 3.2 F/F0) and spatial spread (full width at half‐maximal amplitude) histogram (peak frequencies at 2 and 3.8 μm) for the 230 localised Ca2+‐release events analysed. The existence of two populations of Ca2+‐release events was also supported by the histograms of the rise times and half‐decay times, which revealed modes at 38 and 65 ms, respectively. Shifting the scan line along the z‐axis during imaging from a single discharge site suggested that the appearance of two populations of Ca2+‐release events is not due to out‐of‐focus imaging. Both small and large events persisted upon 3–5 min exposure to 1–5 μm nicardipine, but were abolished after 10–15 min exposure to 50–100 μm ryanodine, 0.1 μm thapsigargin or 10 μm cyclopiazonic acid. Only small‐amplitude, fast events persisted in the presence of inhibitors of inositol 1,4,5‐trisphosphate (IP3)‐induced Ca2+ release, 10 μm xestospongin C or 30 μm 2‐aminoethoxy‐diphenylborate (2‐APB), or in the presence of 2.5 μm U‐73122 (a phospholipase C (PLC) inhibitor). Coupling between neighbouring Ca2+‐release domains giving rise to spontaneous [Ca2+]i waves was abolished in the presence of 2‐APB. Examination of the saltatory propagation of the waves suggested that the critical factor that determines propagation between domains is a time‐dependent change in the sensitivity of ryanodine receptors and/or IP3 receptors to Ca2+, which can give rise to ‘loose coupling’ between release sites. These results suggest that activation of IP3 receptors (due to the tonic activity of PLC and ongoing production of IP3) recruits neighbouring domains of ryanodine receptors, leading to larger Ca2+ releases and saltatory propagation of [Ca2+]i waves in portal vein myocytes.
Dendrotoxin‐sensitive K+ currents contribute to accommodation in murine spiral ganglion neurons
Authors: Mo Zun‐Li , Adamson Crista L. , Davis Robin L.
Published: October 2002

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation (Mo & Davis, 1997a). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α‐dendrotoxin (α‐DTX) to eliminate the contribution of a class of voltage‐gated K+ channels and assessed its effects on a variety of electrophysiological properties by using the whole‐cell configuration of the patch‐clamp technique. Exposure to α‐DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non‐monotonic relationship between number of action potentials fired and membrane potential in the presence of α‐DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α‐DTX‐sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half‐maximal activation voltages of –63 and 12 mV for the two components. Because α‐DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1‐selective blocker dendrotoxin K (DTX‐K). We found that this antagonist reproduced the effects of α‐DTX on neuronal firing, and that the DTX‐K‐sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage‐activated component of DTX‐sensitive current with a potential contribution from the high voltage‐activated component at more depolarized potentials. In addition, the effects of DTX‐K indicate that Kv1.1 subunits are important constituents of the underlying voltage‐gated potassium channels.
Functional glycine receptor maturation in the absence of glycinergic input in dopaminergic neurones of the rat substantia nigra
Authors: Mangin J. M. , Guyon A. , Eugène D. , Paupardin‐Tritsch D. , Legendre P.
Published: October 2002

The postnatal maturation pattern of glycine receptor channels (GlyRs) expressed by dopaminergic (DA) neurones of the rat substantia nigra pars compacta (SNc) was investigated using single‐channel and whole‐cell patch‐clamp recordings in brain slices from rats aged 7–21 postnatal days (P). In neonatal rats (P7‐P10), GlyRs exhibited a main conductance state of 100–110 pS with a mean open time of 16 ms. In juvenile rats (P19‐P22), both the GlyR main conductance state (46‐55 pS) and the mean open time (6.8 ms) were decreased. In neonatal rats, application of 30 μm picrotoxin, which is known to block homomeric GlyRs, strongly reduced glycine‐evoked responses, while it was much less effective in juvenile rats. These results suggest that these GlyRs correspond functionally to α2 homomeric GlyRs in neonatal rats and α1/β heteromeric GlyRs in juvenile rats. A drastic but transient decrease in the glycine responsiveness of DA neurones occurred around P17 concomitant to the functional switch from the homomeric state to the heteromeric state. This age corresponds to a maturation phase for DA neurones. The application of 1 μm gabazine blocked spontaneous or evoked inhibitory synaptic current, while the addition of 1 μm strychnine had no effect, suggesting a lack of functional glycinergic synapses on DA neurones. Although it has been proposed that taurine is co‐released with GABA at GABAergic synapses on DA neurones, in the present study the stimulation of GABAergic fibres failed to activate GlyRs. Blockade of taurine transporters and applications of high K+ and hyposmotic solutions were also unable to induce any strychnine‐sensitive current. We conclude that functional maturation of GlyRs can occur in the absence of any detectable GlyR activation in DA neurones of the SNc.
Substantial elevation of interleukin‐6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans
Authors: Langberg Henning , Olesen Jens L. , Gemmer Carsten , Kjær Michael
Published: October 2002

Plasma interleukin‐6 (IL‐6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL‐6 in skeletal muscle and connective tissue. The present study represents the first attempt to simultaneously measure IL‐6 in plasma, skeletal muscle and peritendinous connective tissue in response to prolonged exercise. Six healthy well‐trained volunteers completed a 36 km run (flat, 12 km h−1). IL‐6 was measured before, 2 h post‐exercise and 24 h, 48 h, 72 h and 96 h post‐exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post‐exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut‐off value (3000 kDa). The plasma concentration of IL‐6 was measured simultaneously, and in addition every hour during the exercise, by enzyme‐linked immunosorbent assay (ELISA). The plasma concentration of IL‐6 was found to increase throughout the exercise, reaching peak values immediately after completion of the run (50‐fold increase). Using the microdialysis technique, the interstitial concentration of IL‐6 was found to increase dramatically from 0 ± 0 pg ml−1 to 3618 ± 1239 pg ml−1 in the peritendinous tissue in the hours following the exercise. The pattern of changes was similar in plasma and peritendinous tissue, although approximately 100‐fold higher in the latter. For comparison the interstitial muscle concentration was found to be 465 ± 176 pg ml−1 when measured 2 h post‐exercise and 223 ± 113 pg ml−1 and 198 ± 96 pg ml−1 48 h and 96 h post‐exercise, respectively. The present study demonstrates that the connective tissue around the human Achilles tendon produces significant amounts of IL‐6 in response to prolonged physical activity, which might contribute to the exercise‐induced increase in IL‐6 found in plasma.
Interleukin‐6 production in human subcutaneous abdominal adipose tissue: the effect of exercise
Authors: Lyngsø Dorthe , Simonsen Lene , Bülow Jens
Published: October 2002

The interleukin‐6 (IL‐6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two‐legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose tissue IL‐6 output was measured by direct Fick technique. An artery and a subcutaneous vein on the anterior abdominal wall were catheterized. Adipose tissue blood flow was measured using the 133Xe‐washout method. In both studies there was a significant IL‐6 output in the basal state and no significant change was observed during exercise. Post‐exercise the IL‐6 output began to increase after 30 min. Three hours post‐exercise it was 58.6 ± 22.2 pg (100 g)−1 min−1. In the control experiments the IL‐6 output also increased, but it only reached a level of 3.5 ± 0.8 pg (100 g)−1 min−1. The temporal profile of the post‐exercise change in the IL‐6 output closely resembles the changes in the outputs of glycerol and fatty acids, which we have described previously in the same adipose tissue depot. The difference is that it begins to increase ≈30 min before the glycerol and fatty acid outputs begin to increase. Thus, we suggest that the enhanced IL‐6 production post‐exercise in abdominal, subcutaneous adipose tissue may act locally via autocrine/paracrine mechanisms influencing lipolysis and fatty acid mobilization rate from this lipid depot.
An asymmetry in the phosphate dependence of tension transients induced by length perturbation in mammalian (rabbit psoas) muscle fibres
Authors: Ranatunga K. W. , Coupland Moira E. , Mutungi G.
Published: October 2002

The effects of inorganic phosphate (Pi, a product released during ATP hydrolysis in active muscle) on tension transients induced by length perturbation (∼0.3 ms) were examined in chemically skinned (0.5 % Brij), maximally Ca2+‐activated rabbit psoas muscle fibres at 10 °C (ionic strength 200 mm, pH 7.1). In one type of experiment, the tension transients induced by length release and stretch of a standard amplitude (0.4‐0.5 % of Lo, muscle fibre length) were examined at a range of added [Pi] (range 3–25 mm). The steady active tension was depressed ∼45 % with 25 mm added Pi. The initial tension recovery (from T1, extreme tension reached after length step, to T2, tension after quick recovery) was analysed by half‐time measurement and also by exponential curve fitting ‐ extracting a fast (phase 2a) and a slow (phase 2b) component. The tension decay after a stretch became faster with increased [Pi], whereas the quick tension rise induced by a length release was insensitive to added Pi. Consequently, the asymmetry in the speed of tension recovery from stretch and release was reduced at high [Pi]. A plot of the phase 2b rate (or 1/half‐time) of tension decay after stretch versus[Pi] was approximately hyperbolic and showed saturation at higher [Pi] levels. In a second type of experiment, the tension transients induced by length steps of different amplitudes were examined in control (no added Pi) and in the presence of 25 mm added Pi. Over a range of length step amplitudes (up to 1 % L0), the tension decay after stretch was consistently faster in the presence of Pi than in the control; this was particularly pronounced in phase 2b. The rate of tension rise after length release remained high but similar in the presence and absence of added Pi. These observations indicate that a stretch and release perturb different molecular steps in the crossbridge cycle. The Pi sensitivity of tension decay (phase 2b) after stretch is similar to that seen using other perturbations (e.g. [Pi] jumps, hydrostatic pressure jumps and temperature jumps and sinusoidal length oscillations). The results indicate that the Pi‐sensitive force generation identified in previous studies is strain sensitive (as expected), but it is seen only with respect to positive strain (stretches).