bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse 15N‐metabolic labeling/mass spectrometry for comparative proteomics and rapid identification of protein markers/targets
Authors: Wang Y. Karen , Ma Zhixiang , Quinn Douglas F. , Fu Emil W.
Published: October 2002

The inverse labeling/mass spectrometry strategy has been applied to protein metabolic 15N labeling for gel‐free proteomics to achieve the rapid identification of protein markers/targets. Inverse labeling involves culturing both the perturbed (by disease or by a drug treatment) and control samples each in two separate pools of normal and 15N‐enriched culture media such that four pools are produced as opposed to two in a conventional labeling approach. The inverse labeling is then achieved by combining the normal 14N‐control with the 15N‐perturbed sample, and the 15N‐control with the 14N‐perturbed sample. Both mixtures are then proteolyzed and analyzed by mass spectrometry (coupled with on‐line or off‐line separation). Inverse labeling overcomes difficulties associated with protein metabolic labeling with regard to isotopic peak correlation and data interpretation in the single‐experiment approach (due to the non‐predictable/variable mass difference). When two data sets from inverse labeling are compared, proteins of differential expression are readily recognized by a characteristic inverse labeling pattern or apparent qualitative mass shifts between the two inverse labeling analyses. MS/MS fragmentation data provide further confirmation and are subsequently used to search protein databases for protein identification. The methodology has been applied successfully to two model systems in this study. Utilizing the inverse labeling strategy, one can use any mass spectrometer of standard unit resolution, and acquire only the minimum, essential data to achieve the rapid and unambiguous identification of differentially expressed protein markers/targets. The strategy permits quick focus on the signals of differentially expressed proteins. It eliminates the detection ambiguities caused by the dynamic range of detection. Finally, inverse labeling enables the detection of covalent changes of proteins responding to a perturbation that one might fail to distinguish with a conventional labeling experiment. Copyright © 2002 John Wiley & Sons, Ltd.
Quantification of clenbuterol in equine plasma, urine and tissue by liquid chromatography coupled on‐line with quadrupole time‐of‐flight mass spectrometry
Authors: Guan Fuyu , Uboh Cornelius E. , Soma Lawrence R. , Luo Yi , Li Runbo , Birks Eric K. , Teleis Donna , Rudy Jeffrey A. , Tsang Deborah S.
Published: October 2002

Clenbuterol (CBL) is a potent β2‐adrenoceptor agonist used for the management of respiratory disorders in the horse. The detection and quantification of CBL can pose a problem due to its potency, the relatively low dose administered to the horse, its slow clearance and low plasma concentrations. Thus, a sensitive method for the quantification and confirmation of CBL in racehorses is required to study its distribution and elimination. A sensitive and fast method was developed for quantification and confirmation of the presence of CBL in equine plasma, urine and tissue samples. The method involved liquid‐liquid extraction (LLE), separation by liquid chromatography (LC) on a short cyano column, and pseudo multiple reaction monitoring (pseudo‐MRM) by electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (ESI‐QTOF‐MS/MS). At very low concentrations (picograms of CBL/mL), LLE produced better extraction efficiency and calibration curves than solid‐phase extraction (SPE). The operating parameters for electrospray QTOF and yield of the product ion in MRM were optimized to enhance sensitivity for the detection and quantification of CBL. The quantification range of the method was 0.013–10 ng of CBL/mL plasma, 0.05–20 ng/0.1 mL of urine, and 0.025–10 ng/g tissue. The detection limit of the method was 13 pg/mL of plasma, 50 pg/0.1 mL of urine, and 25 pg/g of tissue. The method was successfully applied to the analysis of CBL in plasma, urine and various tissue samples, and in pharmacokinetic (PK) studies of CBL in the horse. CBL was quantified for 96 h in plasma and 288 h in urine post‐administration of CLB (1.6 µg/kg, 2 × daily × 7 days). This method is useful for the detection and quantification of very low concentrations of CBL in urine, plasma and tissue samples. Copyright © 2002 John Wiley & Sons, Ltd.
Metal ion migration model for cationization of low‐molecular‐weight oligomers of poly(ethylene glycol) dodecyl ether in matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Togashi Hisashi , Kobayashi Yoshinori
Published: October 2002

The process by which cationized oligomers of poly(ethylene glycol) dodecyl ether [CH3(CH2)11(OCH2CH2)nOH, n = 1–8] are formed in matrix‐assisted laser desorption/ionization mass spectrometry was investigated. The observed relative intensities of molecules cationized by Li+,Na+, or K+ were analyzed using a one‐dimensional random walk model, assuming metal ion migration in the ethylene glycol chain of the oligomer and loss from the chain as the result of lack of sufficient coordination sites at the chain ends. Copyright © 2002 John Wiley & Sons, Ltd.
Speciation of Fe(III)–chelate complexes by electrospray ionization ion trap and laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry
Authors: Neubert Hendrik , Hider Robert C. , Cowan David A.
Published: October 2002

Electrospray ionization mass spectrometry (ESI‐MS) was employed as a relatively simple technique to investigate the speciation of complexes formed between Fe(III), the iron chelator 3‐hydroxy‐2‐methyl‐1‐propyl‐1H‐pyridin‐4‐one (L) and citrate. The major species in aqueous solution at pH 6.0 of a 1:2:10 molar mixture Fe(III)/L/citrate is the Fe(III)L2 complex. No evidence for a mixed citrate complex was observed. Furthermore, evidence for the existence of a number of dimeric iron species is presented. All observed species in ESI were singly charged as evidenced by the isotopic envelopes. Laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (LDI‐FTICRMS) provided data that complemented and confirmed the ESI findings. We also demonstrate the possibility of chelated Fe(III) being converted to Fe(II) under ESI and LDI conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Mass spectrometric studies of benzoxazine resorcarenes
Authors: Hakala Kati , Nuutinen Jari M. J. , Straub Thomas , Rissanen Kari , Vainiotalo Pirjo
Published: October 2002

Eleven differently substituted 3,4‐dihydro‐2H‐1,3‐benzoxazine resorcarenes were studied by electrospray ionisation (ESI) and matrix‐assisted laser desorption/ionisation (MALDI) mass spectrometry, using Fourier transform ion cyclotron resonance (FT‐ICR) and time‐of‐flight (TOF) mass spectrometers, respectively. Under ESI conditions it was possible to transfer the intact resorcarenes from solution to the gas phase, yielding [M + H]+ and [M + 2H]+ ions as the main ions observed. Energy increase of the ions induced ready decomposition through successive eliminations of four CH2NR groups. Ion‐molecule reactions showed that the ionising proton was situated somewhere inside the molecule and could not be reached with neutral reagent gases. In the host‐guest complexation experiments, the benzoxazine resorcarenes studied turned out to be poor hosts for alkali metal and ammonium ions. In MALDI experiments, 2,5‐dihydroxybenzoic acid proved to be the best matrix for these compounds. However, the intensity of the [M + H]+ ions was low for all compounds, and extensive fragmentation with consecutive elimination of CH2NR groups was observed. Copyright © 2002 John Wiley & Sons, Ltd.
Reproductive success of the interior least tern (Sterna antillarum) in relation to hydrology on the Lower Mississippi River
Authors: Dugger Katie M. , Ryan Mark R. , Galat David L. , Renken Rochelle B. , Smith John W.
Published: October 2002

The annual hydrograph of large rivers, including flood pulses and low‐flow periods, is believed to play a primary role in the productivity of biota associated with these ecosystems. We investigated the relationship between river hydrology and Interior least tern (Sterna antillarum) reproductive success on the Lower Mississippi River from April to July 1986–1993. The number of fledglings produced per adult pair was negatively correlated with July mean (r=−0.95, p=0.0004) and July maximum river elevation (r=−0.97, p=0.0001), but no other aspects of river hydrology were related to tern reproduction. Low‐water elevations in July may benefit least tern reproductive success by increasing sand island area or the area of shallow‐water habitat that surrounds islands. Loss of deep‐water habitats in conjunction with an increase in shallow habitat during stage decreases may concentrate fish prey in shallow‐water habitats and backwater areas, thereby increasing food availability during chick‐rearing. Copyright © 2002 John Wiley & Sons, Ltd.
Dynamic fade restoration in Ka‐band satellite systems
Authors: Paraboni A. , Capsoni C. , Masini G. , Poiares Baptista J. P. V. , Riva C.
Published: October 2002

Atmospheric precipitation can seriously affect the propagation of centimeter and millimeter electromagnetic waves. As a consequence, in some applications, it is necessary to make use of a fade countermeasure technique in order to satisfy the system availability and quality requirements. This study analyses the performance of a satellite‐based system in geo‐stationary orbit operating at 20 GHz, dynamically assigning the antenna directivity pattern to counteract tropospheric attenuation. The on‐board power is spatially distributed over the covered region to minimize, at any time, the number of users undergoing outage because of the tropospheric attenuation. Both the aspects of broadcasting and telecommunication services are addressed. The reflector antenna of the system is supposed to be illuminated by a cluster of feeds driven by a set of excitation coefficients, continuously modified and optimized according to the meteorological information derived by processing METEOSAT satellite data and ECMWF (European Centre for Medium‐Range Weather Forecasts) data. Copyright © 2002 John Wiley & Sons, Ltd.
A mechanism for inferring approximate solutions under incomplete knowledge based on rule similarity
Authors: Nguyen Viet Ha , Ishikawa Tsutomu , Abe Akinori
Published: October 2002

This paper proposes an inference method which can obtain an approximate solution even if the knowledge stored in the problem‐solving system is incomplete. When a rule needed for solving the problem does not exist, the problem can be solved by using rules similar to the existing rules. In an implementation using SLD procedure, a resolution is executed between a subgoal and a rule if an atom of the subgoal is similar to the consequence atom of the rule. Similarities between atoms are calculated using a knowledge base of words with account of the reasoning situation, and the reliability of the derived solution is calculated based on these similarities. If many solutions are obtained, they are grouped into classes of similar solutions and a representative solution is then selected for each class. The proposed method was verified experimentally by solving simple problems. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(9): 78–89, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.1154
A three‐dimensional model for the tooth‐loss patterns by multi‐plane regression analysis
Authors: Sasahara Hisako , Sasahara Hideo , Kawamura Makoto
Published: October 2002

The construction of dental condition models is one of the useful methods for analysis of epidemiological surveys. The purpose of this investigation was to make a simple model with clear turning points for the longitudinal tooth‐loss patterns of Japanese adults by means of multi‐plane regression analysis. Since 1957, the Japanese Ministry of Health and Welfare has carried out national surveys of dental conditions every six years.The data of present tooth numbers by age (24–79 years) and sex from these surveys were used for this study. When there are turning points between two variables, intersecting straight lines regression is a valid means. However, a new method was developed so that the data of this study had three variables. The new three‐dimensional model by multi‐plane regression analysis seemed to fit tooth‐loss patterns of Japanese adults within three phases. Younger subjects are represented in the first phase followed by the third phase of elders, where tooth loss was rather slow. However, in the second phase, middle‐aged subjects, people lost their teeth rapidly. Thus, prolongation of the first phase could be an important factor to improve overall dental health. Copyright © 2002 John Wiley & Sons, Ltd.
The predictive value of microbiologic diagnostic tests if asymptomatic carriers are present
Authors: Gunnarsson Ronny K. , Lanke Jan
Published: October 2002

If a proper gold standard is not available, then the predictive value of a test cannot be estimated. In this paper the concept of etiologic predictive value (EPV) is introduced. It is a quantity that will yield the predictive value of a test to predict presence of a specified disease in situations for which no proper gold standard is available. This is achieved by using information obtained from a healthy control population. This quantity requires that the marker in our test is present in all individuals having the specified disease, as in the case where the marker is the aetiologic factor for the specified disease. Furthermore this quantity requires that asymptomatic carriers are present. This means that not all individuals with the marker has the specified disease. EPV is developed with special reference to the evaluation of bacterial cultures, or rapid tests to detect a bacterium, but the quantity might be used in other circumstances as well. EPV is applied to an example in which conventional throat culture is evaluated. Further information concerning EPV can be found at http://www.infovice.se/fou/epv. Copyright © 2002 John Wiley & Sons, Ltd.
Receiver operating characteristic (ROC) analysis for diagnostic examinations with uninterpretable cases
Authors: Lu Ying , Heller Daniel N. , Zhao Shoujun
Published: October 2002

Receiver operating characteristic (ROC) analysis plots true positive rates over false positive rates to describe the discriminatory power of a test to differentiate between two specifiable populations (that is ‘normal’ from ‘abnormal’) using a continuous dichotomous threshold. This assumes that the test separates cases into observed ‘normal’ or ‘abnormal’. However, in practice many tests have some uninterpretable results as an inherent feature of the test itself, whether independent or dependent on the sample populations. This paper defines a method to describe the ability of tests to discriminate between specifiable populations when uninterpretable results occur non‐informatively about disease status. A mixed model modified ROC curve is developed. Formulae to estimate the area under the modified ROC curve are given. Comparisons of conventional with the mixed model ROC analysis are shown in mathematical formulae as well as simulated experiments. An example of diagnosis of spinal fracture in renal transplant patients is presented. Copyright © 2002 John Wiley & Sons, Ltd.
Robustness of choice of number of doses for maximum likelihood estimation of the ED50 in bioassay
Authors: Huang Yangxin
Published: October 2002

A number of studies have looked at the choice of number of doses for estimating the median effective dose (ED50) when the form of a dose–response curve is correctly assumed (see, for example, Müller and Schmitt, 1990). Here we address the question of the robustness of number of doses chosen using Müller and Schmitt's method when a logistic dose–response curve is incorrectly assumed. The underlying true dose–response curves considered include the probit, cubic‐logistic and Aranda‐Ordaz asymmetric models. The simulation results show that, for the above true dose–response curves and the uniform design density with doses spaced symmetrically or slightly asymmetrically around the assumed ED50, choosing as many doses as possible either minimizes the mean squared error (MSE) or produces a MSE chosen to the minimum. Copyright © 2002 John Wiley & Sons, Ltd.
A Bayesian approach to parameter estimation in HIV dynamical models
Authors: Putter H. , Heisterkamp S. H. , Lange J. M. A. , de Wolf F.
Published: October 2002

In the context of a mathematical model describing HIV infection, we discuss a Bayesian modelling approach to a non‐linear random effects estimation problem. The model and the data exhibit a number of features that make the use of an ordinary non‐linear mixed effects model intractable: (i) the data are from two compartments fitted simultaneously against the implicit numerical solution of a system of ordinary differential equations; (ii) data from one compartment are subject to censoring; (iii) random effects for one variable are assumed to be from a beta distribution. We show how the Bayesian framework can be exploited by incorporating prior knowledge on some of the parameters, and by combining the posterior distributions of the parameters to obtain estimates of quantities of interest that follow from the postulated model. Copyright © 2002 John Wiley & Sons, Ltd.
Plasma isatin is increased in maternal anxiety and obstetrical stress
Authors: Manjari  , Pandey S. , Chakrabarti A. , Pandey L. K. , Bhattacharya S. K.
Published: October 2002

Isatin (2,3‐dioxoindole) is a component of tribulin. Tribulin, an inhibitor of monoamine oxidase (MAO) and benzodiazepine (BDZ) receptor binding, has been identified as an endogenous marker of stress and anxiety. In animal experiments, isatin has been found to produce an anxiety‐like action and its level is increased during stress and anxiety. Maternal anxiety and obstetrical complications are two different stressors that can affect perinatal outcome. In this study we investigated plasma isatin levels in maternal anxiety and stress. The study was conducted in 279 pregnant and non‐pregnant women. The patients were stratified into five groups—A, B, C, D and E. Plasma cortisol was measured to assess the intensity of the stressor and plasma isatin was measured by a high‐performance liquid chromatography (HPLC) method. Perinatal outcome was measured by gestational weight and birth weight of the baby. Non‐pregnant women (group D) had a significantly lower plasma isatin level (P < 0.001) compared to women with normal pregnancies (group E), whose plasma isatin was monitored once in each trimester. Patients with anxiety and psychological stress (group B) and patients with obstetrical stress from obstetrical complications (group C) had significantly higher levels of plasma cortisol (P < 0.001) and plasma isatin (P < 0.001) compared to women with normal pregnancies (group A). Perinatal outcome data were significantly lower (P < 0.001) in both groups B and C. In conclusion, our data proved that maternal anxiety and obstetrical complications are two different stressors evidenced by higher plasma cortisol and isatin levels in patients of these two groups. The present study further validated the postulated role of isatin as a marker of anxiety and stress in a clinically relevant condition in humans. Copyright © 2002 John Wiley & Sons, Ltd.
Unix tools as visual programming components in a GUI‐builder environment
Authors: Spinellis Diomidis
Published: October 2002

Development environments based on ActiveX controls and JavaBeans are marketed as ‘visual programming’ platforms; in practice their visual dimension is limited to the design and implementation of an application's graphical user interface (GUI). The availability of sophisticated GUI development environments and visual component development frameworks is now providing viable platforms for implementing visual programming within general‐purpose platforms, i.e. for the specification of non‐GUI program functionality using visual representations. We describe how specially designed reflective components can be used in an industry‐standard visual programming environment to graphically specify sophisticated data transformation pipelines that interact with GUI elements. The components are based on Unix‐style filters repackaged as ActiveX controls. Their visual layout on the development environment canvas is used to specify the connection topology of the resultant pipeline. The process of converting filter‐style programs into visual controls is automated using a domain‐specific language. We demonstrate the approach through the design and the visual implementation of a GUI‐based spell‐checker. Copyright © 2001 John Wiley & Sons, Ltd.
Non‐intrusive object introspection in C++
Authors: Chuang Tyng‐Ruey , Kuo Y. S. , Wang Chien‐Min
Published: October 2002

We describe the design and implementation of system architecture to support object introspection in C++. In this system, information is collected by parsing class declarations, and is used to build a supporting environment for object introspection. Our approach is non‐intrusive because it requires no changes in the original class declarations and libraries; hence, binary compatibility between objects before and after the addition of introspective capability is ensured. This is critical if one wants to integrate third‐party class libraries, which are often supplied as black boxes and allow no modification, into highly dynamic applications. We present two applications: the first is automatic I/O support for C++ objects, and the other is interactive exercise of dynamically loaded C++ class libraries. Copyright © 2001 John Wiley & Sons, Ltd.
Vmgen—a generator of efficient virtual machine interpreters
Authors: Ertl M. Anton , Gregg David , Krall Andreas , Paysan Bernd
Published: October 2002

In a virtual machine interpreter, the code for each virtual machine instruction has similarities to code for other instructions. We present an interpreter generator that takes simple virtual machine instruction descriptions as input and generates C code for processing the instructions in several ways: execution, virtual machine code generation, disassembly, tracing, and profiling. The generator is designed to support efficient interpreters: it supports threaded code, aching the top‐of‐stack item in a register, combining simple instructions into superinstructions, and other optimizations. We have used the generator to create interpreters for Forth and Java. Theresulting interpreters are faster than other interpreters for the same languages and they are typically 2–10 times slower than code produced by native‐code compilers. We also present results for the effects of the individual optimizations supported by the generator. Copyright © 2002 John Wiley & Sons, Ltd
Engineering software reuse for on‐board embedded real‐time systems
Authors: Vardanega Tullio , Caspersen Gert
Published: October 2002

The dimensions of concern to ambitious reuse initiatives largely exceed the provision of desired functionalities. A domain‐specific blend of functional, technical and quality considerations determines the reuse potential of software reuse assets. In a recent project we realized considerable reuse dividends from coupling the definition of a reference software architecture and of an associated set of standard interfaces with the selection of a powerful computational model equipped with reuse‐geared enabling technology. In this paper we present our engineering approach to the project and show how it earned us a good balance between the preservation of predictability and scalability and the maximization of the reuse objective. Copyright © 2001 John Wiley & Sons, Ltd.
TPF: a dynamic system thrashing protection facility
Authors: Jiang Song , Zhang Xiaodong
Published: October 2002

Operating system designers attempt to keep high CPU utilization by maintaining an optimal multiprogramming level (MPL). Although running more processes makes it less likely to leave the CPU idle, too many processes adversely incur serious memory competition, and even introduce thrashing, which eventually lowers CPU utilization. A common practice to address the problem is to lower the MPL with the aid of process swapping out/in operations. This approach is expensive and is only used when the system begins serious thrashing. The objective of our study is to provide highly responsive and cost‐effective thrashing protection by adaptively conducting priority page replacement in a timely manner. We have designed a dynamic system Thrashing Protection Facility (TPF) in the system kernel. Once TPF detects system thrashing, one of the active processes will be identified for protection. The identified process will have a short period of privilege in which it does not contribute its least recently used (LRU) pages for removal so that the process can quickly establish its working set, improving the CPU utilization. With the support of TPF, thrashing can be eliminated in its early stage by adaptive page replacement, so that process swapping will be avoided or delayed until it is truly necessary. We have implemented TPF in a current and representative Linux kernel running on an Intel Pentium machine. Compared with the original Linux page replacement, we showthat TPF consistently and significantly reduces page faults and the execution time of each individual job in several groups of interacting SPEC CPU2000 programs. We also show that TPF introduces little additional overhead to program executions, and its implementation in Linux (or Unix) systems is straightforward. Copyright © 2002 John Wiley & Sons, Ltd.
A safe variant of the unsafe integer arithmetic of Java™
Authors: Winkler Jürgen F. H.
Published: October 2002

Computers are finite machines and, therefore, the arithmetic operations in a programming language are different from their mathematical counterparts. These restrictions seem not to have been, in general, fully appreciated in programming languages and in computer science textbooks. One example is the programming language Java, which makes it difficult to warn the user in cases in which arithmetic operations produce incorrect results. In this paper we look at integer arithmetic in Java and develop a safe variant of the arithmetic operations in Java. The design of the safe variant of $+$, $-_{\rm un}$, $-_{\rm bin}$, $*$, $/$ and $**$ for the types byte, short, int and long reveals a number of deficiencies of Java in integer arithmetic, floating point arithmetic and program structure. Some of these deficiencies are also present in other contemporary programming languages. The paper therefore ends with some proposals for the design of the arithmetic elements of programming languages. Copyright © 2002 John Wiley & Sons, Ltd.
Developing object‐oriented enterprise quality frameworks using proto‐frameworks
Authors: Campo Marcelo , Pace Andrés Díaz , Zito Mario
Published: October 2002

In this article, we present an approach to architecture‐driven design of object‐oriented frameworks based on the notion of object‐oriented materialization of architectural styles. This approach leads us to the development of the proto‐framework concept, which is a new denomination for an object‐oriented framework that provides the essential basis to build other frameworks that adopt an underlying architectural design derived from non‐object‐oriented styles. In this context, we describe the approach to framework design, the design of a particular proto‐framework called Bubble, and a real example of its application to the design of an enterprise framework. Copyright © 2002 John Wiley & Sons, Ltd.
Extending the object model to provide explicit support for crosscutting concerns
Authors: Constantinides Constantinos A. , Elrad Tzilla , Fayad Mohamed E.
Published: October 2002

Concurrent systems tend to have certain properties that are not localized in single modular units, but their implementations cut across functional components, increasing coupling and making modular units difficult to reuse and adapt. Example properties include concurrency, synchronization, and authentication. This problem is particularly apparent in systems with evolving requirements, as adapting code that is not localized in single modular units proves to be a tedious process. In this paper we discuss issues related to requirements of concurrent software systems to provide explicit support for these cross‐cutting concerns, and we present the Aspect Moderator, a framework extension to the object model that can ease the development of concurrent object‐oriented systems. Copyright © 2002 John Wiley & Sons, Ltd.
Command‐line interfaces can be efficiently brought to graphics: COLIMATE (the COmmand LIne MATE)
Authors: Sorzano C. O. S. , Carazo J. M. , Trelles O.
Published: October 2002

Scientific computing has traditionally been done on workstations, most of the time running on UNIX‐like operating systems. These systems are often very robust, powerful and especially suited to heavy computation tasks; however, the usual user interface is based on a command line with all the information needed for the appropriate functioning of the algorithm. These command lines are seldom user‐friendly but, on the other hand, they allow batch processes to be built. In this work, a model for command‐line‐driven packages is given, and at the same time the model includes objects that can be directly translated into a graphical user interface. A language (Colimate) implementing this model is shown to serve as a bridge between command‐line‐driven programs and more friendly user interfaces. Exploiting the specificness of the user interfaces addressed, powerful graphical interfaces can be built with a very simple syntax and small programming effort. Furthermore, the command‐line program needs not to be modified, so in this way the possibility of making batches is not lost. Copyright © 2002 John Wiley & Sons, Ltd.
Engineering plug‐in software components to support collaborative work
Authors: Grundy J. , Hosking J.
Published: October 2002

Many software applications require co‐operative work support, including collaborative editing, group awareness, versioning, messaging and automated notification and co‐ordination agents. Most approaches hard‐code such facilities into applications, with fixed functionality and limited ability to reuse groupware implementations. We describe our recent work in seamlessly adding such capabilities to component‐based applications via a set of collaborative work‐supporting plug‐in software components. We describe a variety of applications of this technique, along with descriptions of the novel architecture, user interface adaptation and implementation techniques for the collaborative work‐supporting components that we have developed. We report on our experiences to date with this method of supporting collaborative work enhancement of component‐based systems, and discuss the advantages of our approach over conventional techniques. Copyright © 2002 John Wiley & Sons, Ltd.
Estimating the number of components with defects post‐release that showed no defects in testing
Authors: Stringfellow C. , Andrews A. , Wohlin C. , Petersson H.
Published: October 2002

Components that have defects after release, but not during testing, are very undesirable as they point to ‘holes’ in the testing process. Either new components were not tested enough, or old ones were broken during enhancements and defects slipped through testing undetected. The latter is particularly pernicious, since customers are less forgiving when existing functionality is no longer working than when a new feature is not working quite properly. Rather than using capture–recapture models and curve‐fitting methods to estimate the number of remaining defects after inspection, these methods are adapted to estimate the number of components with post‐release defects that have no defects in testing. A simple experience‐based method is used as a basis for comparison. The estimates can then be used to make decisions on whether or not to stop testing and release software. While most investigations so far have been experimental or have used virtual inspections to do a statistical validation, the investigation presented in this paper is a case study. This case study evaluates how well the capture–recapture, curve‐fitting and experience‐based methods work in practice. The results show that the methods work quite well. A further benefit of these techniques is that they can be applied to new systems for which no historical data are available and to releases that are very different from each other. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacological evaluation of a Br‐76 analog of epibatidine: A potent ligand for studying brain nicotinic acetylcholine receptors
Authors: Kassiou Michael , Bottlaender Michel , Loc'h Christian , Dolle Frederic , Musachio John L. , Coulon Christine , Ottaviani Michele , Dannals Robert F. , Maziere Bernard
Published: October 2002

[76Br]‐Norchlorobromoepibatidine ([76Br]BrPH) is a specific and high affinity radioligand for the nicotinic acetylcholine receptors (nAChRs). In vitro, on rat thalamus membranes [76Br]BrPH bound to two sites with apparent affinities of 8 pM and 3 nM. The density of binding sites were 1.9 and 70 fmol/mg protein, respectively. In vivo, in biodistribution and autoradiographic studies in rats the regional distribution of [76Br]BrPH paralleled the neuroanatomical localization of nAChRs. Two hours postinjection, the highest concentration in the brain was found in thalamus and colliculi (4% ID/g). Competition experiments with specific nicotinic, muscarinic, dopaminergic, and serotoninergic drugs confirmed that the in vivo binding of [76Br]BrPH was consistent with neuronal nicotinic receptors. PET imaging of [76Br]BrPH in baboon demonstrated a rapid and high uptake in the brain. Peak uptake occurred at 30–40 min for the thalamus. Due to the constant washout in the cerebellum, the thalamus to cerebellum ratio was 5 at 2 h postinjection. Subcutaneous injection of cytisine (1 mg/kg), 3 h postinjection of [76Br]BrPH reduced the radioactivity concentration in thalamus and cortex by 58 and 50%, respectively, as observed 1 h later. Cytisine pretreatment (5 mg/kg s.c.) inhibited completely the radioligand accumulation in the thalamus. Chronic MPTP pretreatment resulted in reduction of [76Br]BrPH uptake in all brain regions except in cerebellum. These preliminary results suggest that [76Br]BrPH has the potential to be a useful radioligand for studying the pharmacology of nicotinic acetylcholine receptors in preclinical experiments. Synapse 45:95–104, 2002. © 2002 Wiley‐Liss, Inc.
LTP in the mouse nucleus accumbens is developmentally regulated
Authors: Schramm Nicole L. , Egli Regula E. , Winder Danny G.
Published: October 2002

Glutamatergic transmission in the nucleus accumbens (NAc) has been shown to be important for behavioral adaptations in response to drugs of abuse. NMDA‐receptor dependent long‐term potentiation (LTP) of glutamatergic synaptic transmission has been hypothesized to underlie many lasting alterations in behavior. Thus, we examined LTP in NAc core and find that it is developmentally regulated. Specifically, tetanus‐evoked, NMDA receptor‐dependent LTP is observed in the NAc of “adolescent” (3‐week‐old) mice more frequently than in adult (6–20‐week‐old) mice. In contrast, cAMP‐dependent enhancement of transmission is not developmentally regulated. Removal of extracellular Mg2+ restores LTP in adult NAc core, suggesting developmental regulation of induction processes rather than maintenance mechanisms. These findings are discussed in the context of behavioral changes elicited in response to drugs of abuse, which differ in adolescent vs. adult rodents and humans. Synapse 45:213–219, 2002. © 2002 Wiley‐Liss, Inc.
Lack of modification of rat hepatocarcinogenesis by fernane‐type triterpenoids, isolated from a Euphorbia genus
Authors: Karim Rezaul , Iwai Shuji , Morimura Keiichirou , Wanibuchi Hideki , Tanaka Reiko , Matsunaga Shunyo , Yoshitake Akira , Fukushima Shoji
Published: October 2002

Inhibitors of topoisomerases, enzymes that produce an unusual type of DNA damage, are considered as antitumor agents. Recently it has been reported that the fernane‐type triterpenoid EC‐2 and its hydroxyl derivative, isolated from Euphorbia, are potent topoisomerase II inhibitors. In this study, the modifying effects of EC‐2 and EC‐4 on the development of putative preneoplastic lesions, glutathione S‐transferase placental form (GST‐P)‐positive foci, in the liver of rats were investigated using a medium‐term bioassay system. Fisher 344 male, 6‐week‐old rats were given a single intraperitoneal injection (200 mg/kg b.w.) of diethylnitrosamine or saline at the beginning of the experiment and subjected to 2/3 partial hepatectomy at the 3rd week. The test compounds were administered five times/week by i.g. gavage at a dose of 1 mg/kg b.w. from 2 to 8 weeks. Quantitation of the numbers and areas per cm2 of induced GST‐P positive foci did not demonstrated any significant differences among the groups and no variation in cell proliferation as indicated by 5‐bromo‐ 2′‐deoxyuridine (BrdU) labeling. Our results suggest that EC‐2 and EC‐4 have no modifying effects on rat hepatocarcinogenesis. © 2002 Wiley‐Liss, Inc.
Protective effect of tenuazonic acid against dimethyl benz(a)antracene‐Induced skin carcinogenesis in mice
Authors: Antony Mary , Shukla Yogeshwer , Janardhanan K.K.
Published: October 2002

Anticarcinogenic potential of tenuazonic acid (TA), a mycotoxin isolated from a fungus, Alternaria alternata, on skin tumorigenesis induced by 7,12‐dimethyl benz(a) antracene (DMBA) was investigated. Female Swiss albino mice were exposed topically to 100 nmole of DMBA twice weekly for 20 weeks. Another group of animals was treated with 250 μg TA in acetone daily for a period of 1 week, followed by the same dose of TA prior to every application of DMBA. At the end of 14 weeks, all the animals in the group that was exposed to DMBA alone developed tumors, while 40% of the animals in TA‐treated group were found to be tumor free. After 20 weeks, there was no further increase in the number of tumor‐bearing animals. Results indicated that prior application of TA significantly delayed the onset of tumorigenesis and also reduced the cumulative number of tumors per tumor‐bearing animals. The present studies reveal the antitumor and protective potential of TA against polycyclic aromatic hydrocarbon induced skin carcinogenesis. © 2002 Wiley‐Liss, Inc.
Interview: United Parcel Service's Director of Electronic Commerce, Alan Amling, on the opportunities and challenges of global electronic commerce
Authors: Wan William P.
Published: October 2002

The development of global electronic commerce presents many opportunities as well as challenges for companies

worldwide. Alan Amling, director of electronic commerce for United Parcel Service (UPS), discusses

various aspects of electronic commerce, its global implications, and UPS's effort in enabling its global

development. Mr. Amling emphasizes that the key success factor for e‐commerce is building relationships

with customers and suppliers. For companies engaging in global e‐commerce, he suggests the importance of

“Thinking Global, Acting Local.” Furthermore, Mr. Amling provides critical insights as to why UPS has

been able to stay at the forefront in the development of e‐commerce and how UPS is positioning itself to

enhance global e‐commerce's growth. © 2002 Wiley Periodicals, Inc.
[ADMAdda5]‐microcystins in Planktothrix agardhii strain PH‐123 (cyanobacteria)— importance for monitoring of microcystins in the environment
Authors: Laub Jesper , Henriksen Peter , Brittain Scott M. , Wang Jim , Carmichael Wayne W. , Rinehart Kenneth L. , Moestrup Øjvind
Published: October 2002

Two major and two minor microcystins (MCYST) were isolated from a hepatotoxic Danish strain of Planktothrix agardhii (Gomont) Anagnostidis et Komárek by reversed‐phase high‐performance liquid chromatography. The microcystins were characterized by UV spectroscopy, amino acid analysis, fast atom bombardment mass spectrometry (FABMS), and high‐resolution FABMS. The major microcystins were further analysed by collisionally induced tandem electrospray ionization MS. The microcystins were found to be demethylated variants of MCYST‐HtyR (homotyrosine‐arginine) and MCYST‐LR (leucine‐arginine). The two major microcystins contained an acetyl‐demethyl variant (ADMAdda) of 3‐amino‐9‐acetoxy‐2,6,8‐trimethyl‐10‐phenyldeca‐4,6‐dienoic acid (Adda). This is the first report of [ADMAdda5]‐microcystins in Planktothrix. The two [ADMAdda5]‐microcystins inhibited protein phosphatase activity but showed low cross‐reactivity with antibodies of an enzyme‐linked immunosorbent assay (ELISA), emphasizing the potential underestimation of the toxicity of natural blooms dominated by Planktothrix when microcystin content is quantified using only an ELISA. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 351–357, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10042
Response of the charophyte Nitellopsis obtusa to heavy metals at the cellular, cell membrane, and enzyme levels
Authors: Manusadžianas Levonas , Maksimov Gemir , Darginavičienė Jūratė , Jurkonienė Sigita , Sadauskas Kazys , Vitkus Rimantas
Published: October 2002

The responses of the freshwater macroalga Nitellopsis obtusa to heavy metal (HM) salts of Hg, Cd, Co, Cu, Cr, and Ni were assessed at different levels: whole‐cell mortality (96‐h LC50), in vivo cell membrane (45‐min depolarization of resting potential, EC50), and enzyme in plasma membrane preparations (K+, Mg2+‐specific H+‐ATPase inhibition, IC50). To measure ATPase activity, a novel procedure for isolation of plasma membrane–enriched vesicles from charophyte cells was developed. The short‐term ATPase inhibition assay (IC50 from 6.0 × 10−7 to 4.6 × 10−4 M) was slightly more sensitive than the cell mortality test (LC50 from 1.1 × 10−6 to 2.6 × 10−3 M), and the electrophysiological test with the end point of 45‐min depolarization of resting potential was characterized by less sensitivity for HMs (EC50 from 1.1 × 10−4 to 2.2 × 10−2 M). The variability of IC50 values assessed for HMs in the ATPase assays was close to that of LC50 values in the mortality tests (CVs from 33.5 to 83.5 and from 12.4% to 57.7%, respectively), whereas the EC50 values in the electrophysiological tests were characterized by CVs generally below 30%. All three end points identified two separate HM groups according to their toxicity to N. obtusa: Co, Ni, and Cr comprised a group of less toxic metals, whereas Hg, Cu, and Cd comprised a group of more toxic metals. However, the adverse effects within each group were discriminated differently. For example, the maximum difference between the highest and lowest LC50 for the group of less toxic metals in the long‐term mortality test was approximately 60% of the response range, whereas the corresponding difference in IC50 values in the ATPase assay was 30%. In contrast, the LC50 values of the more toxic metals occupied only 10% of the response range, whereas the IC50 values were spread over 70%. Further investigation should be done of the underlying mechanism or mechanisms responsible for the observed differences in the dynamic range of a particular end point of the groups of toxicants of varying strength. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 275–283, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10058
Impact of selenium and other trace elements on the endangered adult razorback sucker
Authors: Hamilton Steven J. , Holley Kathy M. , Buhl Kevin J. , Bullard Fern A. , Weston L. Ken , McDonald Susan F.
Published: October 2002

A study was conducted with endangered the razorback sucker (Xyrauchen texanus) to determine if environmental exposure to selenium in flooded bottomland sites affected survival, growth, and egg‐hatching success. Adults were stocked at three sites adjacent to the Colorado River near Grand Junction, Colorado, in July 1996: hatchery ponds at Horsethief Canyon State Wildlife Area (referred to here as Horsethief; the reference site), a diked tertiary channel at Adobe Creek, and North Pond at Walter Walker State Wildlife Area (WWSWA). Fish were collected in April 1997 and spawned. After two spawnings adults from the three sites were held at Horsethief for an 86‐day selenium depuration period. Selenium concentrations at Horsethief were 1.4–3.0 μg/L in water, 0.8–0.9 μg/g in sediment, 4.5 μg/g in muscle plug, and 6.0 μg/g in eggs; at Adobe Creek, <0.7–4.5 μg/L in water, 1.2–2.5 μg/g in sediment, 16–20 μg/g in zooplankton, 9.6 μg/g in muscle plug, and 40 μg/g in eggs; and at North Pond, 3.2–17 μg/L in water, 16–94 μg/g in sediment, 32–48 μg/g in zooplankton, 14 μg/g in muscle plug, and 55 μg/g in eggs. During the depuration period, when adults from Adobe Creek and North Pond were held at Horsethief, the fish lost 7%–13% of their selenium burden in 59 days and 14%–21% in 86 days. Larvae from North Pond adults had the most deformities, followed by Adobe Creek adults, with the fewest deformities found in the Horsethief adults. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 297–323, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10064
Growth animation of human organs
Authors: Ďurikovič Roman , Czanner Silvester , Inoue Hirofumi
Published: October 2002

The growth of the organs of the human embryo changes significantly over a short period of time in the mother's body. The shape of the human organs is organic and has many folds that are difficult to model or animate using conventional techniques. Convolution surface and function representation are a good choice in modelling such organs as human embryo stomach and brain. Two approaches are proposed for animating organ growth: the first uses a simple line segment skeleton demonstrated on a stomach model and the other method uses a tubular skeleton calculated automatically from a 2D object outline. Growth speed varies with the position within the organ and thus the model is divided into multiple geometric primitives that are later glued by a blending operation. Animation of both the embryo stomach and brain is shown. Copyright © 2002 John Wiley & Sons, Ltd.
Lung metastasis detection and visualization on CT images: a knowledge‐based method
Authors: Archip Neculai , Erard Pierre‐Jean , Haefliger Jean‐Marie , Germond Jean‐Francois
Published: October 2002

A solution to the problem of lung metastasis detection on computed tomography (CT) scans of the thorax is presented. A knowledge‐based top‐down approach for image interpretation is used. The method is inspired by the manner in which a radiologist and radiotherapist interpret CT images before radiotherapy is planned. A two‐dimensional followed by a three‐dimensional analysis is performed. The algorithm first detects the thorax contour, the lungs and the ribs, which further help the detection of metastases. Thus, two types of tumors are detected: nodules and metastases located at the lung extremities. A method to visualize the anatomical structures segmented is also presented. The system was tested on 20 patients (988 total images) from the Oncology Department of La Chaux‐de‐Fonds Hospital and the results show that the method is reliable as a computer‐aided diagnostic tool for clinical purpose in an oncology department. Copyright © 2002 John Wiley & Sons, Ltd.
Comparative material characterization of historical and industrial samples by using a compact micro‐XRF spectrometer
Authors: Bichlmeier S. , Janssens K. , Heckel J. , Hoffmann P. , Ortner H. M.
Published: October 2002

An experimental micro‐XRF set‐up was used for investigations in different application fields. In the archaeometric field, valuable 7th century gold objects were analysed with the aim of obtaining concentration data on well‐defined metal areas. The results revealed an insight into the gold manufacturing habits of early medieval times. In the industrial field, piezoelectric ceramics were investigated in order to identify small inclusions in the material. The aim was to identify possible contamination sources in the manufacturing process. Copyright © 2002 John Wiley & Sons, Ltd.