bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated protein identification using atmospheric‐pressure matrix‐assisted laser desorption/ionization
Authors: Mehl John T. , Cummings John J. , Rohde Ellen , Yates Nathan N.
Published: July 2003

Atmospheric‐pressure matrix‐assisted laser desorption/ionization (AP‐MALDI) ion trap mass spectrometry (ITMS) has been evaluated for automated protein identification. By using signal averaging and long ion‐injection times, protein identification limits in the 50‐fmol range are achieved for standard protein digests. Data acquisition requires 7.5 min or less per sample and the MS/MS spectra files are automatically processed using the SEQUEST database searching algorithm. AP‐MALDI‐ITMS was compared with the widely used methods of μLC/MS/MS (ion trap) and automated MALDI‐TOF peptide mass mapping. Sample throughput is 10‐fold greater using AP‐MALDI compared with microcapillary liquid chromatography/tandem mass spectrometry (μLC/MS/MS). The protein sequence coverage obtained from AP‐MALDI‐MS/MS spectra matched by SEQUEST is lower compared with μLC/MS/MS and MALDI‐TOF mass mapping. However, by using the AP‐MALDI full‐scan peptide mass fingerprint spectrum, sequence coverage is increased. AP‐MALDI‐ITMS was applied for the analysis of Coomassie blue stained gels and was found to be a useful platform for rapid protein identification. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of temperature on isotopic enrichment inDaphnia magna: implications for aquatic food‐web studies
Authors: Power M. , Guiguer K. R. R. A. , Barton D. R.
Published: July 2003

Laboratory experiments were conducted withDaphnia magnaandHyalellasp. grown on a single food source of known isotopic composition at a range of temperatures spanning the physiological optima for each species.Daphniaraised at 26.5°C were enriched inδ13C andδ15N by 3.1 and 2.8‰, respectively, relative to diet.Daphniaraised at 12.8°C were enriched 1.7 and 5.0‰ inδ13C andδ15N, respectively. Results imply a significant negative relationship between theδ13C andδ15N of primary consumers when a temperature gradient exists. Similar responses were observed forHyalella.Results indicate a general increase inδ13C enrichment and decrease inδ15N enrichment as temperature rises. Deviations from the commonly applied isotopic enrichment values used in aquatic ecology were attributed to changes in temperature‐mediated physiological rates. Field data from a variety of sources also showed a general trend towardδ13C enrichment with increasing temperature in marine and lacustrine zooplankton. Multivariate regression models demonstrated that, in oligotrophic and mesotrophic lakes, zooplanktonδ13C was related to lake‐specific POMδ13C, lake surface temperature and latitude. Temperature‐dependent isotopic separation (enrichment) between predator and prey should be taken into consideration when interpreting the significance of isotopic differences within and among aquatic organisms and ecosystems, and when assigning organisms to food‐web positions on the basis of observed isotope values. Copyright © 2003 John Wiley & Sons, Ltd.
About one application of the general method of Lyapunov functionals construction
Authors: Kolmanovskii V. , Shaikhet L.
Published: June 2003

Some peculiarities of the general method of Lyapunov functionals construction proposed and developed by the authors during last decade for stability investigation of stochastic hereditary systems are considered. It is shown, in particular, that using this method one can construct a sequence of extended stability regions for stochastic difference Volterra equations. Copyright © 2003 John Wiley & Sons, Ltd.
On decoupling of linear time delay systems by generalized output feedback
Authors: Rabah Rabah , Malabre Michel
Published: June 2003

We consider the row‐by‐row decoupling problem for linear delay systems by output feedback. The characterization of the solvability of this problem is given in terms of some easily checkable structural conditions. The main contribution is, in particular, to use generalized output feedback laws which may incorporate derivatives of the delayed new reference. Copyright © 2003 John Wiley & Sons, Ltd.
Integral science: rethinking civilization using the learning universe lens
Authors: Goerner S. J.
Published: June 2003

The agoras dialogues are part of a larger transformation, the rise of integral society, which reflects the birth of a unified ‘web’ worldview emerging throughout the global community. The natural child of Systems Theory, a similar renaissance is sweeping through every field in science. Integral science, the fusing of ‘web’ insights into a single lens, provides the logically coherent framework we need to unify the social movement by showing how all parts fit within an evolving ecological whole. Ironically, however, the story that will unite us, is not simply one of a web world, but of a Learning Universe in which humanity is a collaborative learning species that still follow natural laws. This article summarizes how the integral renaissance concretizes our understanding of humanity as a learning society and how nature's laws of learning help illuminate the causes, goals and direction of the current social transformation. Copyright © 2002 John Wiley & Sons, Ltd.
No Magic Answers
Authors: Maid Barry M.
Published: June 2003

This chapter discusses what technology will not do for higher education and also what it has the potential to provide.
Design and performance analysis of leader election and initialization protocols on ad hoc networks
Authors: Hsu Chih‐Shun , Sheu Jang‐Ping
Published: June 2003

Leader election and initialization are two fundamental problems in mobile ad hoc networks (MANETs). The leader can serve as a coordinator in the MANETs and the initialization protocol can assign each host a sequential, unique, and short ID. As we know, no research on initialization for IEEE 802.11‐based MANETs has been done. Here, we propose two contention‐based leader election and initialization protocols for IEEE 802.11‐based single‐hop MANETs. We also provide an efficient approach to evaluate the performance of the proposed protocols, such that the performance can be evaluated in polynomial time. The evaluation results provide a guideline to set the size of the contention window and thus improve the performance of the proposed leader election and initialization protocols. The results can also be used as a guideline to set the size of the contention window for any contention‐based protocol. Simulation results justify that the evaluation results provide a good guideline to set the size of the contention window. Copyright © 2003 John Wiley & Sons, Ltd.
Changes in older people's living arrangements in Flanders, 1993–98
Authors: AUDENAERT VEERLE
Published: July 2003

The living arrangements of older people are changing. An analysis of official registration data (1993–1998) in Flanders, Belgium, shows that while the number of single person households has been increasing, the proportion of people aged 75 or more years living alone has been falling and the proportion living with a spouse or partner increasing. No less than one third of the older people who lived alone in 1993 sustain a one-person household into very old age. It was also found that those who are widowed at a very advanced age change house or move very quickly, women to a greater extent and at younger ages than men. The principal destinations are residential care homes and, to a lesser extent, child's households. Living alone appears to be a decreasingly acceptable option. Since very old people with a disability appear to have an increasing preference for residential care and a lessening preference for co-residence with relatives, these developments have consequences for both informal family care and public social services. Particular attention needs to be paid to men who live alone as a risk-group, and residential care provision requires expansion.
Is ‘world music’ the ‘classic music’ of our time?
Authors: Ling Jan
Published: July 2003

On the way to my library there is a little shop named ‘World Music. The Oasis of Music from Asia, Africa’. One morning I stopped my bike and went in just curious to see what world music could be in my little town. In the racks even the smallest country from Asia or Africa was represented with one or two CDs, most of them produced in Paris or London. The other customers were half my age (around thirty to thirty-five, nobody over fifty or under twenty). The owner, an immigrant who has lived in Sweden for more than ten years, had this to say:

The youngsters do not come here, all my customers are between twenty-five and forty. There is a growing interest in world music: people with money are visiting foreign countries as tourists and when they come home they come to me, asking for artists or groups they have heard. Most of them have an academic background and speak English fluently.
Composing instrument control dynamics
Authors: Menzies Dylan
Published: July 2003

The expression gestural mapping is well imbedded in the language of instrument designers, describing the function from interface control parameters to synthesis control parameters. This function is in most cases implicitly assumed to be instantaneous, so that at any time its output depends only on its input at that time. Here more general functions are considered, in which the output depends on the history of input, especially functions that behave like physical dynamic systems, such as a damped resonator. Acoustic instruments are rich in dynamical behaviour. Introducing dynamics at the control stage of an electronic instrument can help compensate for lack of dynamics in later non-physical synthesis stages. A broadening of the function space offers new aesthetic possibilities for composing instruments. Examples are presented to illustrate the new design/composition mode as well as practical techniques. In this context, it is suggested that the word mapping be updated with the more descriptive expression dynamic control processing.
Experiments with a new customisable interactive evolution framework
Authors: Collins Nick
Published: July 2003

This article collates results from a number of applications of interactive evolution as a sound designer's tool for exploring the parameter spaces of synthesis algorithms. Experiments consider reverberation algorithms, wavetable synthesis, synthesis of percussive sounds and an analytical solution of the stiff string. These projects share the property of being difficult to probe by trial and error sampling of the parameter space. Interactive evolution formed the guidance principle for what quickly proved a more effective search through the multitude of parameter settings.

The research was supported by building an interactive genetic algorithm library in the audio programming language SuperCollider. This library provided reusable code for the user interfaces and the underlying genetic algorithm itself, whilst preserving enough generality to support the framework of each individual investigation.

Whilst there is nothing new in the use of genetic algorithms in sound synthesis tasks, the experiments conducted here investigate new applications such as reverb design and an analytical stiff string model not previously encountered in the literature. Further, the focus of this work is now shifting more into algorithmic composition research, where the generative algorithms are less clear-cut than those of these experiments. Lessons learned from the deployment of interactive evolution in sound design problems are very useful as a reference for the extension of the problem set.
Interactivity, where to from here?
Authors: Paine Garth
Published: July 2003

This article is intended to raise some points of interest and mark out some pointers for alternative approaches to the design and execution of interactive music systems and artworks which pursue interaction that:

[bull ] does not include any pre-defined pathways,

[bull ] takes dynamic morphology as its foundation, and

[bull ] implements dynamic software infrastructures, built on the object-oriented model, providing dynamic instrument
instantiation, orchestration and timbral control.

It is intended that such design would be a precursor to a new approach to interactivity that responds more directly and uniquely to those who engage in the work, and in so doing rewards them more richly for their time, energy and enthusiasm.
Modalys-ER for OpenMusic (MfOM): virtual instruments and virtual musicians
Authors: Polfreman Richard
Published: July 2003

Modalys-ER is a graphical environment for creating physical model instruments and generating musical sounds with them. While Modalys-ER provides users with a relatively simple-to-use interface, it has only limited methods for mapping control data onto model parameters for performance. While these are sufficient for many interesting applications, they do not bridge the gap from high-level specifications such as MIDI files or Standard Western Notation (SWN) down to low-level parameters within the physical model. With this issue in mind, a part of Modalys-ER has now been ported to OpenMusic, providing a platform for developing more sophisticated automation and control systems that can be specified through OpenMusic's visual programming interface. An overview of the MfOM library is presented and illustrated with several musical examples using some early mapping designs. Also, some of the issues relating to building and controlling virtual instruments are discussed and future directions for research in this area are suggested. The first release is now available via the IRCAM Software Forum.
Seasonal and diurnal variations in Martian surface ultraviolet irradiation: biological and chemical implications for the Martian regolith
Authors: Patel M. R. , Bérces A. , Kolb C. , Lammer H. , Rettberg P. , Zarnecki J. C. , Selsis F.
Published: July 2003

The issue of the variation of the surface ultraviolet (UV) environment on Mars was investigated with particular emphasis being placed on the interpretation of data in a biological context. A UV model has been developed to yield the surface UV irradiance at any time and place over the Martian year. Seasonal and diurnal variations were calculated and dose rates evaluated. Biological interpretation of UV doses is performed through the calculation of DNA damage effects upon phage T7 and Uracil, used as examples for biological dosimeters. A solar UV ‘hotspot’ was revealed towards perihelion in the southern hemisphere, with a significant damaging effect upon these species. Diurnal profiles of UV irradiance are also seen to vary markedly between aphelion and perihelion. The effect of UV dose is also discussed in terms of the chemical environment of the Martian regolith, since UV irradiance can reach high enough levels so as to have a significant effect upon the soil chemistry. We show, by assuming that H2O is the main source of hydrogen in the Martian atmosphere, that the stoichiometrically desirable ratio of 2:1 for atmospheric H and O loss rates to space are not maintained and at present the ratio is about 20:1. A large planetary oxygen surface sink is therefore necessary, in contrast with escape to space. This surface oxygen sink has important implications for the oxidation potential and the toxicology of the Martian soil. UV-induced adsorption of {\rm O}_{2}^{-} super-radicals plays an important role in the oxidative environment of the Martian surface, and the biologically damaging areas found in this study are also shown to be regions of high subsurface oxidation. Furthermore, we briefly cover the astrobiological implications for landing sites that are planned for future Mars missions.
Useful Source Materials on the European Family Policy Process
Authors: Leaman Jeremy
Published: July 2003

The items selected below to exemplify recent literature on the European family policy process from national and international perspectives highlight the specificity of family policy research, as reported in the themed articles in this issue of the journal. The publications cited indicate both the need for country-specific solutions and for cross-national comparative research, where potentially transportable examples of best practice can be identified. In multinational studies that straddle the developed countries of western Europe and the emerging countries of Central and Eastern Europe, the contrastive dimension is a key and driving factor of the analysis. Notwithstanding the similarities – in demographic trends, changes in family formation, education and labour market participation – the contrasts remain overwhelming and reflect the specific conditions obtaining in any given country. In turn, these conditions are reflected in the central themes and preoccupations of the analyses of national policy agencies, non-governmental organisations and academics. The position of family-related issues in the respective policy hierarchy is most obviously reflected in the institutional location of these issues. In all European countries, the dominant imperative of economic growth and stability leads to family policy being subsumed predominantly under ministries of social affairs. The experience of former communist states with rapidly growing income disparities, unemployment and meagre state funding has produced a patchwork of institutional and policy initiatives, dominated by the imperative of economic growth and modernisation. The disappearance of the comprehensive infrastructure of childcare in former state socialist countries compounds the problems of adjustment and helps to define the focus of post-communist research. A common feature in many European countries is that, notwithstanding self-funded research on the part of university research groups and NGOs, the influence of ministerial funding priorities on family policy research also determines the focus and weighting of national research output.
Policy Perspectives on Changing Intergenerational Relations
Authors: Jönsson Ingrid
Published: July 2003

The combination of population ageing, changing family structures and patterns of employment is having an increasing impact on intergenerational relations in Western societies. The ‘generational contract’ is being affected by women's growing labour market participation, especially among mothers with young children, the extension of the period spent in education and training and the curtailment of welfare expansion. Since women carry the main burden of care work, the organisation of social care is a key issue in understanding changing intergenerational relations. This article explores the perceptions that European families in different socio-political contexts have of changing intergenerational relations and their expectations of policy actors.
Mapping Relations between Family Policy Actors
Authors: Appleton Louise , Byrne Paul
Published: July 2003

In line with calls from the European Commission for greater involvement of non-governmental organisations in the policy process, this article draws on research across EU member and applicant states to investigate the potential for enhancing cooperation between political and civil society actors in family policy formulation. The authors argue that the role of civil society is highly differentiated between countries, due to three key factors: party ideology, political culture and political transitions, which determine the capacity for improving alliances. Structural barriers to development may prevent the Commission's advocacy of closer cooperation between policy actors from being successful in the shorter term.
Eltern-Kind-Beziehungen studierender und berufstätiger junger Erwachsener
Authors: Buhl Heike M. , Wittmann Simone , Noack Peter
Published: June 2003

Zusammenfassung. Die Eltern-Kind-Beziehung im Erwachsenenalter kann in Anlehnung an individuationstheoretische Konzeptionen anhand der übergeordneten Faktoren Verbundenheit und Abgrenzung beschrieben werden. Zugleich postuliert der individuationstheoretische Ansatz Beziehungsdyamik, insbesondere im Bereich der Abgrenzung. Empirische Evidenzen sprechen darüber hinaus für Veränderungen auch im Bereich der Verbundenheit, die oft in Zusammenhang mit biographischen Übergängen beobachtet worden sind. In Weiterführung vorliegender Arbeiten, mit denen vor allem private Übergänge untersucht wurden, ist die Transition in den Beruf Gegenstand dieses Artikels. Dazu wurden Studierende und Berufstätige im frühen Erwachsenenalter sowie nach Möglichkeit beide Eltern befragt. Es nahmen 130 junge Erwachsene (Alter 21 bis 34 Jahre), 114 Mütter (40 bis 73 Jahre) und 89 Väter (43 bis 75 Jahre) teil. Abgrenzung und Verbundenheit wurden jeweils anhand eines Fragebogens hinsichtlich emotionaler, kognitiver und behavioraler Merkmale erfasst. In den Angaben der Kinder, nicht aber in denen der Eltern, zeigen sich Unterschiede zwischen Studierenden und Berufstätigen, die sich als weniger verbunden und stärker abgegrenzt beschreiben. Es finden sich Generationen- und Geschlechtsunterschiede, letztere besonders zwischen Müttern und Vätern. Die Ergebnisse werden als Erweiterung individuationstheoretischer Arbeiten diskutiert.
Testing hypotheses about mechanisms for the unknown carbon sink: A time series analysis
Authors: Kaufmann Robert K. , Stock James H.
Published: June 2003

We test hypotheses about the unknown sink for carbon by analyzing time series for the unknown carbon sink, carbon emissions, atmospheric concentrations, and surface temperature between 1860 and 1990. During this period, the time series for the unknown carbon sink is determined by annual changes in carbon emissions and summer land surface temperature in the northern hemisphere. The first difference of carbon emissions indicates that an increase in carbon emissions may generate a short run increase in oceanic uptake that is not simulated correctly by models. The temperature effect may have its greatest impact on terrestrial vegetation in the midlatitudes and high latitudes of Eastern North America and Europe. We also test and reject hypotheses that increases in the atmospheric concentration of CO2, nitrogen deposition associated with fossil fuel combustion, or uncertainty about the rate at which forests are cut and/or regrow are responsible for changes in the unknown carbon sink over time.
Single level turbulence measurements to determine roughness parameters of complex terrain
Authors: Toda Motomu , Sugita Michiaki
Published: June 2003

An attempt was made to determine roughness length z0 and zero‐plane displacement height d0 from single level turbulence measurements over a complex area in tropical monsoon environment where standard procedures to derive those parameters were found difficult to apply. The value of d0 was derived from the nondimensional standard deviation of temperature ϕθ and of vertical wind speed ϕw by making use of the fact that ϕθ and ϕw versus atmospheric stability relationship is sensitive to the d0 value, by following and by extending the proposal of Rotach [1994]. This method was applied to the two turbulence data sets obtained at 30 and 60 m above a complex terrain in central part of Thailand, and they produced d0 = 15.7 m. However, investigations into the accuracy of the d0 value obtainable by this method have revealed that it is probably of the order of meters and thus a simultaneous application of the method to both vertical wind speed and temperature data are recommended to allow an intercomparison of the derived d0 values to enhance the reliability of the result. The z0 value was also determined from the single level turbulence data by a method in which the z0 value that produced the best agreement of the friction velocity values obtained from the eddy correlation method and those from a wind profile equation with the derived d0 value, the given value of z0 and single level wind speed data, was selected. This method is not very sensitive to the exact value of d0 and z0 = 0.31 m was obtained. Overall, single level turbulence data were found useful to evaluate roughness parameters of a complex area.
Increased survival and breeding performance of double breeders in little penguins Eudyptula minor, New Zealand: evidence for individual bird quality?
Authors: Johannesen Edda , Houston Dave , Russell Janis
Published: July 2003

The little penguin Eudyptula minor is unique among penguin species in being able to fledge chicks from two clutches in one breeding season. Pairs laying two clutches in a given season make a higher reproductive investment, and may be rewarded by a higher reproductive success as they may raise twice as many chicks as pairs laying one clutch. The higher effort made by pairs laying two clutches could correlate negatively with survival, future reproductive performance or offspring survival, indicating a cost of reproduction. Conversely, a positive relationship between the number of clutches produced in a given breeding season and survival, future reproductive performance or offspring survival would indicate that birds laying two clutches belonged to a category of birds with higher fitness, compared to birds laying only one clutch in the season. In this study we used a long‐term data set taken from an increasing population of little penguins in Otago, SE New Zealand. We modelled the relationship between the number of clutches laid in a breeding season and survival probability, reproductive performance in the next breeding season and first year survival of offspring using capture‐recapture modelling.  Birds laying two clutches produced 1.7 times more fledglings during a breeding season than pairs laying one clutch. We found that birds laying two clutches had a higher probability of breeding in the following breeding season, a higher probability of laying two clutches in the following breeding season and a higher survival probability. There was no overall difference in post‐fledging survival between the young of birds producing one clutch and the young of birds producing two clutches. However, the survival of young of single clutch breeders declined with laying date, whereas the young of double clutch breeders had the same survival rate irrespective of laying date. For a subset of data with birds of known age, we found evidence that the probability of laying two clutches increased with age. However, there were also indications for differences among birds in the tendency to lay two clutches that could not be attributed to age. We tentatively interpret our results as evidence of quality difference among little penguin breeders.
Folivory in the white‐tipped plantcutter Phytotoma rutila: seasonal variations in diet composition and quality
Authors: Bucher Enrique H. , Tamburini Daniela , Abril Adriana , Torres Patricia
Published: July 2003

Plantcutters (Phytotomidae) represent the only Passeriformes with a predominantly folivorous diet. Little is known however about their feeding habits and adaptations for leaf consumption. Here we analyze the relationship between diet composition and nutritional value in the white‐tipped plantcutter Phytotoma rutila in a Chaco woodland in Córdoba, Argentina. The white‐tipped plantcutter consumed mainly dicot leaves (91%), complemented with a small proportion of fruits (7%) and flowers (2%). Eleven plant species were utilized, of which five were strongly dominant: Lycium cestroides (38%), Prosopis alba and P. nigra (28%), Celtis tala (22%), and Schinus longifolius (8%). No animal food was consumed. The leaf material ingested by the white‐tipped plantcutter had high protein content and low proportion of fibers and phenols. In multivariate analysis, leaf chemical properties accounted for over 81% of the variation in diet composition throughout the year. However, only protein and phenols content related significantly with diet composition in single regressions. The quality index that relates protein with lignin and phenols showed the highest correlation with diet composition. Availability of highly nutritive leaves of Lycium cestroides during the dry season seems to be a key factor for the occurrence of the white‐tipped plantcutter in the study area. Our results confirm that plantcutters are truly folivorous passerine species, being able to obtain a highly nutritional diet throughout the year.
Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart
Authors: Sattari Saeed , Dryden William F , Eliot Lise A , Jamali Fakhreddin
Published: July 2003

Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism.

The effect of interferon‐induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg−1, p.o.) and nifedipine (0.1 mg kg−1, i.v.) was studied in Sprague–Dawley rats.

The effect of both acute and chronic inflammation on radioligand binding to cardiac L‐type calcium channels was also investigated.

Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected.

As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation.

Maximum binding of 3H‐nitrendipine to cardiac cell membrane was significantly reduced from 63.2±2.5 fmol mg−1 protein in controls to 46.4±2.0 in acute inflammation and from 66.8±2.2 fmol mg−1 protein in controls to 42.2±2.0 in chronic inflammation.

Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml−1 of rat tissue necrosis factor‐α did not influence the binding indices to the calcium channels.

Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels.

British Journal of Pharmacology (2003) 139, 945–954. doi:10.1038/sj.bjp.0705202
VIP and PACAP are autocrine factors that protect the androgen‐independent prostate cancer cell line PC‐3 from apoptosis induced by serum withdrawal
Authors: Gutiérrez‐Cañas Irene , Rodríguez‐Henche Nieves , Bolaños Oscar , Carmena María J , Prieto Juan C , Juarranz María G
Published: July 2003

In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP) as well as their receptors in PC‐3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by serum starvation.

By RT–PCR and immunocytochemistry assays, we have demonstrated the production of VIP and PACAP in PC‐3 cells.

We have demonstrated by RT–PCR and binding assays the expression of common PACAP/VIP (VPAC1 and VPAC2) receptors, but not PACAP‐specific (PAC1) receptors. The pharmacological profile of [125I]‐VIP binding assays was as follows: VPAC1 antagonist=VPAC1 agonist>VIP>VPAC2 agonist (IC50=1.2, 1.5, 2.3 and 30 nM, respectively). In addition, both receptor subtypes are functional since VIP, PACAP‐27 or VPAC1 and VPAC2 agonists all increased the intracellular levels of cAMP.

The expression of both peptides and their receptors is similar in serum‐cultured and serum‐deprived PC‐3 cells. The treatment of serum‐deprived PC‐3 cells with exogenous VIP or PACAP‐27 increases cell number and viability in a dose‐dependent manner, as demonstrated by cellular counting and MTT assays. The increased cell survival is exerted through the VPAC1 receptor, since a VPAC1, but not VPAC2, receptor agonist, mimics the effects and a VPAC1 receptor antagonist blocks it. Moreover, VIP and PACAP‐27 inhibit genomic DNA fragmentation in PC‐3 cells triggered by serum starvation, and increase the immunoreactivity of the antiapoptotic protein bcl‐2.

Our results suggest that VIP and PACAP are autocrine/paracrine factors that protect PC‐3 cells from apoptosis through VPAC1 receptors.

British Journal of Pharmacology (2003) 139, 1050–1058. doi:10.1038/sj.bjp.0705317
Various intracellular compartments cooperate in the release of nitric oxide from glycerol trinitrate in liver
Authors: Kozlov Andrey V , Dietrich Barbara , Nohl Hans
Published: July 2003

Glycerol trinitrate (GTN) has been used in therapy for more than 100 years. Biological effects of GTN are due to the release of the biomediator nitric oxide (NO). However, the mechanism by which GTN provides NO, in particular in liver, is still unknown. In this study, we provide experimental evidence showing that cytoplasm, endoplasmic reticulum, and mitochondria are required for the release of NO from GTN in the liver.

NO and nitrite (NO2−) were determined using low‐temperature electron paramagnetic resonance and the Griess reaction, respectively.

The first step of GTN biotransformation is the release of NO2−. This step is performed in cytoplasm and catalyzed by glutathione‐S‐transferase. The second step is the rate‐limiting step where NO2− is slowly reduced to NO. This is mainly catalyzed by cytochrome P‐450. The second phase can be significantly enhanced by decreasing the pH value, a situation which occurs during ischemia. At high NADPH concentrations exceeding physiological values, cytochrome P‐450 catalyzes GTN biotransformation without the involvement of cytoplasmic glutathione‐S‐transferase.

In conclusion, our data show that NO2− derived from the first step of biotransformation of GTN in the liver is the precursor of NO but not a product of NO degradation; consequently, NO2− levels are not likely to be a marker of NO release from GTN as earlier suggested.

British Journal of Pharmacology (2003) 139, 989–997. doi:10.1038/sj.bjp.0705323
Evidence that central 5‐HT2A and 5‐HT2B/C receptors regulate 5‐HT cell firing in the dorsal raphe nucleus of the anaesthetised rat
Authors: Boothman L J , Allers K A , Rasmussen K , Sharp T
Published: July 2003

Systemic administration of phenethylamine‐derived, 5‐hydroxytryptamine2 (5‐HT2) receptor agonists inhibits the firing of midbrain 5‐HT neurones, but the 5‐HT receptors involved are poorly defined, and the contribution of peripheral mechanisms is uncertain. This study addresses these issues using extracellular recordings of 5‐HT neurones in the dorsal raphe nucleus of anaesthetised rats.

The 5‐HT2 receptor agonists DOI ((±)‐2,5‐dimethoxy‐4‐iodoamphetamine hydrochloride) and DOB ((±)‐2,5‐dimethoxy‐4‐bromoamphetamine hydrobromide), caused a dose‐related (10–100 μg kg−1 i.v.) inhibition of 5‐HT neuronal activity, with the highest dose reducing firing rates by >80%.

Pretreatment with the 5‐HT2 receptor antagonist ritanserin (1 mg kg−1 i.v.) completely blocked the action of DOI. The 5‐HT2A receptor antagonist MDL 100,907 (0.2 mg kg−1 i.v.) blocked the action of both DOI and DOB. In comparison, the 5‐HT2B/C receptor antagonist SB 206553 (0.5 mg kg−1 i.v.) caused a small, but statistically significant, shift to the right in the dose response to DOI and DOB.

Pretreatment with the peripherally acting 5‐HT2 receptor antagonist BW 501C67 (0.1 mg kg−1 i.v.) had no effect on the DOI‐induced inhibition of 5‐HT cell firing, but completely blocked the DOI‐induced rise in mean arterial blood pressure.

These data indicate that the inhibition of 5‐HT cell firing induced by systemic administration of DOI and DOB is mediated predominantly by the 5‐HT2A receptor‐subtype, but that 5‐HT2B/C receptors also play a minor role. Moreover, central and not peripheral mechanisms are involved. Given evidence that 5‐HT2 receptors are not located on 5‐HT neurones, postsynaptic 5‐HT feedback mechanisms are implicated.

British Journal of Pharmacology (2003) 139, 998–1004. doi:10.1038/sj.bjp.0705328
Manipulation of the endocannabinoid system by a general anaesthetic
Authors: Di Marzo Vincenzo
Published: July 2003

An article appearing in this issue of the British Journal of Pharmacology shows for the first time that the general anaesthetic propofol inhibits one of the enzymes catalysing endocannabinoid hydrolysis and inactivation, the fatty acid amide hydrolase, thereby enhancing the brain levels of anandamide and 2‐arachidonoylglycerol in mouse brain. The authors provide evidence that this effect of propofol underlies part of the sedative effects of this compound. The importance of these findings in the light of the likely role of the endocannabinoid system in the control of sleep–wake cycles, and of the possibility of developing therapeutic drugs from substances that manipulate endocannabinoid levels, is discussed.

British Journal of Pharmacology (2003) 139, 885–886. doi:10.1038/sj.bjp.0705333
The general anesthetic propofol increases brain N‐arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase
Authors: Patel Sachin , Wohlfeil Eric R , Rademacher David J , Carrier Erica J , Perry LaToya J , Kundu Abhijit , Falck J R , Nithipatikom Kasem , Campbell William B , Hillard Cecilia J
Published: July 2003

Propofol (2,6‐diisopropylphenol) is widely used as a general anesthetic and for the maintenance of long‐term sedation. We have tested the hypothesis that propofol alters endocannabinoid brain content and that this effect contributes to its sedative properties.

A sedating dose of propofol in mice produced a significant increase in the whole‐brain content of the endocannabinoid, N‐arachidonylethanolamine (anandamide), when administered intraperitoneally in either Intralipid or emulphor‐ethanol vehicles.

In vitro, propofol is a competitive inhibitor (IC50 52 μM; 95% confidence interval 31, 87) of fatty acid amide hydrolase (FAAH), which catalyzes the degradation of anandamide. Within a series of propofol analogs, the critical structural determinants of FAAH inhibition and sedation were found to overlap. Other intravenous general anesthetics, including midazolam, ketamine, etomidate, and thiopental, do not affect FAAH activity at sedative‐relevant concentrations. Thiopental, however, is a noncompetitive inhibitor of FAAH at a concentration of 2 mM.

Pretreatment of mice with the CB1 receptor antagonist SR141716 (1 mg kg−1, i.p.) significantly reduced the number of mice that lost their righting reflex in response to propofol. Pretreatment of mice with the CB1 receptor agonist, Win 55212‐2 (1 mg kg−1, i.p.), significantly potentiated the loss of righting reflex produced by propofol. These data indicate that CB1 receptor activity contributes to the sedative properties of propofol.

These data suggest that propofol activation of the endocannabinoid system, possibly via inhibition of anandamide catabolism, contributes to the sedative properties of propofol and that FAAH could be a novel target for anesthetic development.

British Journal of Pharmacology (2003) 139, 1005–1013. doi:10.1038/sj.bjp.0705334
Automated three‐dimensional analysis of particle measurements using an optical profilometer and image analysis software
Authors: Bullman V.
Published: July 2003

The automated collection of topographic images from an optical profilometer coupled with existing image analysis software offers the unique ability to quantify three‐dimensional particle morphology. Optional software available with most optical profilers permits automated collection of adjacent topographic images of particles dispersed onto a suitable substrate. Particles are recognized in the image as a set of continuous pixels with grey‐level values above the grey level assigned to the substrate, whereas particle height or thickness is represented in the numerical differences between these grey levels. These images are loaded into remote image analysis software where macros automate image processing, and then distinguish particles for feature analysis, including standard two‐dimensional measurements (e.g. projected area, length, width, aspect ratios) and third‐dimensional measurements (e.g. maximum height, mean height). Feature measurements from each calibrated image are automatically added to cumulative databases and exported to a commercial spreadsheet or statistical program for further data processing and presentation. An example is given that demonstrates the superiority of quantitative three‐dimensional measurements by optical profilometry and image analysis in comparison with conventional two‐dimensional measurements for the characterization of pharmaceutical powders with plate‐like particles.
Disseminated aspergillosis due to Aspergillus flavus in an experimental model: efficacy of azole therapy
Authors: Kaliamurthy J. , Geraldine P. , Thomas P. A.
Published: July 2003

The aim of this investigation was to create a reproducible experimental model of disseminated Aspergillus flavus aspergillosis, and to compare the relative therapeutic efficacies of itraconazole and fluconazole in this model. Temporarily immunosuppressed male Wistar rats received intravenous challenge by A. flavus conidia. Treatment was initiated 24 h later with oral itraconazole (1 mg kg−1 BW day−1), oral fluconazole (1 mg kg−1 BW day−1) or excipient only (infected‐untreated rats); this was continued for 10 days. At this time, although 100% mortality had occurred among all infected‐untreated rats, no mortality was noted among the control‐uninfected, infected‐itraconazole‐treated or infected‐fluconazole‐treated rats. After killing, essential organs were processed for microbiological and histopathological studies. Aspergillus flavus was recovered in high colony counts from the organs of infected‐untreated rats (lungs > liver > brain > kidneys), but in significantly lower colony counts, or not at all, from the organs of itraconazole‐treated and fluconazole‐treated rats. Histopathological alterations were pronounced in tissues of infected‐untreated rats, but less so in treated rats. These data suggest that administration of itraconazole or fluconazole sufficiently early may prevent, or retard, progression of lesions in disseminated aspergillosis.
Antifungal susceptibility of clinical and environmental isolates of Cryptococcus neoformans to four antifungal drugs determined by two techniques
Authors: Moraes E. M. P. , Prímola N. S. , Hamdan Júnia Soares
Published: July 2003

A total of 64 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates var. neoformans and var. gattii, were tested for susceptibility to amphotericin B, 5‐flucytosine, fluconazole and itraconazole. The tests were performed according to the recommendations of National Committee of Clinical Laboratory Standards and the method of macrodilution in liquid medium of Shadomy et al. [Manual de Microbiologia Clínica, 4th edn. Buenos Aires: Editorial Medica Panamericana, 1987: 1229–38]. For most drugs there was a significant difference between the readings taken at 24 and 48 h with both methods. When the minimum inhibitory concentrations obtained by the two techniques were compared, significant differences were observed for amphotericin B and fluconazole. Overall, differences in drug susceptibility with respect to the origin of the isolates or the variety of the fungus were not observed. As an exception, the gattii variety exhibited a high resistance rate to amphotericin B when the technique of Shadomy et al. was applied, a fact possibly related to the greater difficulty for treatment of the disease caused by this fungal variety.
Prevalence of tinea capitis in primary schools in Turkey
Authors: Altindis M. , Bilgili E. , Kiraz N. , Ceri A.
Published: July 2003

The aim of our study was to determine the prevalence of tinea capitis in Middle Anatolia. Between February 2000 and April 2000, a school survey of 4760 primary school children was carried out and 34 cases of tinea capitis were clinically diagnosed. Sixteen (0.3%) of them were diagnosed both clinically and using culture. Eighteen cases (52.9%) were diagnosed microscopically whereas the remaining 16 cases (47.0%) had a clinical diagnose. We also isolated and identified the following species of fungi causing the infection: Trichophyton verrucosum (five cases), T. rubrum (three), T. mentagrophytes var. mentagrophytes (three), Microsporum canis (three) and T. tonsurans (two). We detected a higher rate of infection than that of the country's average.
Critical technological and architectural choices for access and preservation in a digital library environment
Authors: Arne Solbakk Svein
Published: July 2003

The article describes some basic architectural choices for the access to and preservation of digital objects at the National Library of Norway. A digital repository is a core element for the handling of both access to and preservation of the digital objects. Strategies for giving access to the complete holdings include the use of a powerful search engine and the OAI protocol to harvest metadata from conventional catalogue systems to make textual or structured indexes.
An investigation into the features of OPACs in Tamil Nadu (India)
Authors: Ramesh Babu B. , Tamizhchelvan M.
Published: July 2003

Describes the results of a research survey conducted at the Department of Library and Information Science, University of Madras, Chennai, India which examines features provided in online public access catalogues (OPACs) in Tamil Nadu. OPACs are recent developments in libraries in India in general and Tamil Nadu in particular. A review of the literature reveals that only a few studies on OPACs in India have been conducted and there is no comprehensive study about the OPACs in Tamil Nadu. A sample of 50 libraries in Tamil Nadu were selected at random, out of which 36 responded. The analysis of the data represents the state‐of‐the‐art of the libraries in the summer of 2002. The major findings of the survey reveal emerging trends in OPAC.
Project management concepts, methods and application
Authors: Bryde David James
Published: July 2003

This paper reports the findings of an empirical study of project management (PM) practice and of attitudes and opinions of people involved in projects in UK organisations, to determine the extent to which PM has evolved into being broader in its concepts, methods and application than “traditional” PM. Based on previous research and survey data, characteristics of an “emergent” PM approach are described. This leads to the establishment of a number of possible normative theories relating to the management of projects, but empirical evidence shows situations in which there are problems in applying the theories in practice. It is concluded that there is an opportunity for the PM community to provide leadership through the development of valid and useful theories, but in order to do this there is a need for further research.
How e‐CRM can enhance customer loyalty
Authors: Lee‐Kelley Liz , Gilbert David , Mannicom Robin
Published: July 2003

Internet‐based companies need to remain competitive. One way of improving competitive advantage is to attract more customers and increase customer retention; for example, by developing long‐term, secure relationships between the buyers and sellers. Little empirical research has been conducted on the link between customer relationship management and customer loyalty within an Internet, or e‐commerce, context. This study provides evidence of how to improve planning for customer management by presenting and testing a conceptual model of the process by which the implementation of electronic relationship marketing (e‐CRM), can enhance loyalty. While building the research framework, price sensitivity was found to be a primary confounding element on loyalty and was included in the study for control. An exploratory study of Internet retailers, e‐retailers, and their customers was conducted and the findings revealed that e‐retail companies (with CD, DVD, video and book products) should consider customers’ perceptions of relationship marketing efforts, as they are fundamental to enhancing customer loyalty and that an enhancement of customer loyalty reduces price sensitivity.