bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software quality improvement in France telecom research center
Authors: Moreau Bernard , Lassudrie Claire , Nicolas Bertrand , I'Homme Odile , d'Anterroches Cécile , Gall Gilbert Le 
Published: August 2004

AbstractThe needs and business goals of France Telecom R&D are centered around achieving enhanced customer satisfaction and greater competitiveness. These key management concerns become drivers that initiate software process improvement with goals of higher software quality, lower development and maintenance costs, shorter time to market, and increased predictability and control of software products and processes.Software process improvement is considered as a continuous process; France Telecom R&D moves continually around a stabilization cycle, Standardize Do Check Act (SDCA) and an improvement cycle, Plan Do Check Act(PDCA). Within these cycles, in a series of steps of specific improvement, actions such as introducing new or improved practices into software processes are accomplished.The software process model is based on the ISO/IEC 12207 standard ‘Software Life‐Cycle Processes’, and the assessment method uses the ISO/IEC 15504 standard ‘Software process Assessment’. Some new processes are defined and used in the area of software engineering. Copyright © 2004 John Wiley & Sons, Ltd.
Towards software excellence—informal self‐assessment for software developers
Authors: Daily K. , Dresner D. 
Published: August 2004

Abstract‘Towards Software Excellence’ (TSE) is a web‐based facility established by the UK's National Computing Centre (NCC), a not‐for‐profit organisation dedicated to helping IT users and providers implement effective information technology. TSE provides software developers with a simple and easy‐to‐use means of self‐assessing their development processes. Its users can understand the practices expected by TSE, identify the ‘strengths and weaknesses’ of their current practice, and then use this knowledge to improve.TSE is especially suited to small‐ and medium‐sized enterprises (SMEs) and development teams or groups within larger organisations. It can provide a first step towards more formal Capability Maturity Model (CMM) or SPICE‐based assessments. TSE's definition of best practice is based on the ISO15504 standard. Once registered, users can log on to the website as many times as they wish to complete their assessment—they don't have to enter all the information at once or cover all processes and practices. Explanations of TSE's best practices can be examined and a ‘gap analysis’ report for the user's assessment can be produced.With financial support from the UK government and promotional support from trade and professional associations, over 1500 users have performed TSE assessments during 2002. As well as helping its users to identify process improvements, the TSE initiative has started to create overall profiles of the strengths and weaknesses of the practices declared by its users.Analysis of the initial set of TSE assessments has identified the generally best and worst performing processes and practices of its users and also those practices that have generated the most and least interest. For example, good performing topics include problem resolution and project management, while low performing topics include verification and measurement. TSE users are most interested in assessing the performance of their development and acquisition practices and least interested in assessing their improvement and legal practices. As use builds up, it is hoped that regular comparison of overall strengths and weaknesses of development practice declared by users will become possible, and the general improvement of process capability for software development can be tracked. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluating the SPICE rating scale with regard to the internal consistency of capability measures
Authors: Jung Ho‐Won , Hunter Robin 
Published: August 2004

AbstractThe international SPICE (Software Process Improvement and Capability dEtermination) project mounted a series of trials to validate the emerging international standard ISO/IEC 15504 against the goals and requirements defined at the start of the project and to verify the consistency and usability of its component parts. This study aims to evaluate the SPICE rating scale with regard to the internal consistency (reliability) of capability measures. For this purpose, this study analyzed 691 process instances assessed during the Phase 2 SPICE Trials (between September 1996 and June 1998). Our findings indicate that the current four‐category rating scale gave a higher internal consistency of capability level than two‐ or three‐category rating scales. Since the current version of ISO/IEC 15504, due to become an International Standard scheduled for publication (Part 2) in 2003, still uses the four‐category rating scale, the results in this article are still valid for the current version. Copyright © 2004 John Wiley & Sons, Ltd.
Genetics and variability in opioid response
Authors: Stamer Ulrike M. , Bayerer Bettina , Stüber Frank 
Published: August 2004

AbstractThe human genome project has revealed data on genomic variation which may influence the pharmacological responses. In pain therapy, the genetic background influencing the efficacy of opioid therapy is of special interest. Screening for variations in expression of drug metabolizing enzymes has been suggested as a potential tool for improving patient therapy. CYP2D6 genetic variability is supposed to be a major factor of adverse drug reaction, possibly influencing hospital stay and total costs. Further candidate genes involved in pain perception, pain processing and pain management like opioid receptors, transporters and other targets of pharmacotherapy are under investigation. Aspects of genetic differences influencing efficacy, side effects and adverse outcome of pharmacotherapy will be of importance for future pain management.
Heparin normalizes allergen‐induced nitric oxide deficiency and airway hyperresponsiveness
Authors: Maarsingh Harm , De Boer Jacob , Kauffman Henk F , Zaagsma Johan , Meurs Herman 
Published: August 2004

It has been established that polycations cause airway hyperresponsiveness (AHR) to methacholine by inducing a deficiency of constitutive nitric oxide synthase (cNOS)‐derived bronchodilating nitric oxide (NO). Since a deficiency of cNOS‐derived NO also contributes to allergen‐induced AHR after the early asthmatic reaction (EAR) and since this AHR is associated with the release of polycationic proteins from infiltrated eosinophils in the airways, we hypothesized that endogenous polycations underlie or at least contribute to the allergen‐induced NO deficiency and AHR.
Using a guinea‐pig model of allergic asthma, we addressed this hypothesis by examining the effect of the polyanion heparin, acting as a polycation antagonist, on the responsiveness to methacholine of isolated perfused tracheae from unchallenged control animals and from animals 6 h after ovalbumin challenge, that is, after the EAR.
A 2.0‐fold AHR (P<0.001) to intraluminal administration of methacholine was observed in airways from allergen‐challenged animals compared to control. Incubation of these airways with 250 U ml−1 heparin completely normalized the observed hyperresponsiveness (P<0.001), whereas the responsiveness to methacholine of airways from unchallenged control animals was not affected.
The effect of heparin on airways from allergen‐challenged guinea‐pigs was dose‐dependently (0.1 and 1.0 mM) reversed by the NOS inhibitor L‐NAME (P<0.01).
These results indicate that endogenous (presumably eosinophil‐derived) polycations are involved in allergen‐induced NO deficiency and AHR after the EAR, probably by inhibition of L‐arginine transport.

British Journal of Pharmacology (2004) 142, 1293–1299. doi:10.1038/sj.bjp.0705848
Effects of dietary lectins on ion transport in epithelia
Authors: Kunzelmann Karl , Sun J , Schreiber R , König Jens 
Published: August 2004

Phytohemagglutinins are widely distributed in common food items. They constitute a heterogeneous group of proteins, which are often resistant to proteolysis in the gastrointestinal tract. Upon binding to the luminal membrane of intestinal cells, they can interfere with digestive, protective or secretory functions of the intestine.
Phytohemagglutinins present in red kidney beans and jackbeans have been shown to induce diarrhea and hypersecretion in human airways, but the underlying mechanisms remain obscure. We examined how agglutinins from wheat germ (WGA), soy bean (SBA), red kidney beans (Pha‐E, Pha‐L), and jackbeans (Con‐A) affect ion transport in mouse airways and large intestine using Ussing chamber techniques.
We found that Pha‐E, Pha‐L, and Con‐A but not WGA and SBA inhibit electrogenic Na+ absorption dose dependently in both colon and trachea. The inhibitory effects of Con‐A on Na+ absorption were suppressed by the sugar mannose, by inhibition of phospholipase C (PLC) and protein kinase C (PKC).
Thus, nutritional phytohemagglutinins block salt absorption in a PLC‐ and PKC‐dependent manner, probably by inhibition of the epithelial Na+ channel (ENaC). This effect may be therapeutically useful in patients suffering from cystic fibrosis.

British Journal of Pharmacology (2004) 142, 1219–1226. doi:10.1038/sj.bjp.0705857
Indomethacin potentiates acetylcholine‐induced vasodilation by increasing free radical production
Authors: De Angelis Antonella , Rinaldi Barbara , Capuano Annalisa , Rossi Francesco , Filippelli Amelia 
Published: August 2004

We studied the effects of indomethacin on endothelium‐dependent and ‐independent vascular relaxation in rat thoracic aortic rings and its role in superoxide anion (O2−) production.
We measured isometric force changes in response to acetylcholine (Ach, 1 nM–0.1 mM), sodium nitroprusside (SNP, 0.1 nM–0.1 μM; a nitric oxide (NO) donor) and cromakalim (1 nM–0.1 mM; a KATP‐channel opener) in aorta rings contracted with norepinephrine (NE, 0.1 μM). Indomethacin (10 μM; 20 min) significantly increased Ach‐induced vasodilation (EC50 decreased from 8.99 μM to 16 nM). The free radical scavengers superoxide dismutase and 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl completely reverted these effects. Indomethacin did not affect SNP‐ or cromakalim‐induced vasodilation.
Neither acetylsalicylic acid (ASA, 5–100 μM; 15 min) nor ketoprofen (1−100 μM; 15 min) affected Ach, SNP and cromakalim concentration–response curves.
Incubation of the aorta with Ach (1 μM) rapidly and markedly increased intracellular NO fluorescence in the aorta endothelium. Indomethacin did not affect Ach‐induced NO production.
We measured intracellular O2− in the aorta endothelium with dihydroethidium (DHE) dye. Indomethacin significantly increased O2− fluorescence versus controls. Neither ASA nor ketoprofen affected O2− fluorescence.
Nitrotyrosine staining was increased in indomethacin‐treated aorta sections exposed to Ach, which indicates endogenous formation of peroxynitrite. It was low in aorta sections exposed to Ach alone or with ASA or ketoprofen.
We cannot judge if indomethacin‐induced endothelium‐dependent vasodilation damages or protects the cardiovascular system. Here, we show that indomethacin acts on the cardiovascular system regardless of cyclooxygenase inhibition.

British Journal of Pharmacology (2004) 142, 1233–1240. doi:10.1038/sj.bjp.0705877
Methyllycaconitine, α‐bungarotoxin and (+)‐tubocurarine block fast ATP‐gated currents in rat dorsal root ganglion cells
Authors: Lalo Ulyana , Pankratov Yuri , Krishtal Oleg , Alan North R 
Published: August 2004

The effects of nicotinic acetylcholine receptor antagonists were studied on currents evoked by application of ATP to rat isolated dorsal root ganglion cells, and human embryonic kidney 293 cells expressing rat P2X3 and P2X2/3 receptors.
The rapidly desensitising (within 100 ms) current in dorsal root ganglion cells was inhibited by methyllycaconitine, α‐bungarotoxin and (+)‐tubocurarine (concentrations giving half‐maximal inhibition were approximately 40, 60 and 800 nM, respectively), but not by hexamethonium (100 μM) or mecamylamine (100 μM). The sustained (>250 ms) current in dorsal root ganglion cells was inhibited by (+)‐tubocurarine (80% by 10 μM), but not by methyllycaconitine (200 nM), α‐bungarotoxin (200 nM), mecamylamine (100 μM) or hexamethonium (100 μM).
Rapidly desensitising currents evoked by α,βmethylene‐ATP in human embryonic kidney cells expressing P2X3 receptors were inhibited by methyllycaconitine and α‐bungarotoxin, at concentrations similar to those effective in dorsal root ganglion cells.
The results indicate that some nicotinic acetylcholine receptor antagonists are potent blockers of P2X receptors on neurons, particularly the homo‐oligomeric P2X3 receptor. This finding suggests that these drugs should be used with care to discriminate between P2X and neuronal acetylcholine receptor types.

British Journal of Pharmacology (2004) 142, 1227–1232. doi:10.1038/sj.bjp.0705878
Ranolazine: Ion‐channel‐blocking actions and in vivo electrophysiological effects
Authors: Schram Gernot , Zhang Liming , Derakhchan Katayoun , Ehrlich Joachim R , Belardinelli Luiz , Nattel Stanley 
Published: August 2004

Ranolazine is a novel anti‐ischemic drug that prolongs the QT interval. To evaluate the potential mechanisms and consequences, we studied: (i) Ranolazine's effects on HERG and IsK currents in Xenopus oocytes with two‐electrode voltage clamp; (ii) effects of ranolazine, compared to D‐sotalol, on effective refractory period (ERP), QT interval and ventricular rhythm in a dog model of acquired long QT syndrome; and (iii) effects on selected native currents in canine atrial myocytes with whole‐cell patch‐clamp technique.
Ranolazine inhibited HERG and IsK currents with different potencies. HERG was inhibited with an IC50 of 106 μmol l−1, whereas the IC50 for IsK was 1.7 mmol l−1.
D‐Sotalol caused reverse use‐dependent ERP and QT interval prolongation, whereas ranolazine produced modest, nonsignificant increases that plateaued at submaximal doses. Neither drug affected QRS duration. D‐Sotalol had clear proarrhythmic effects, with all D‐sotalol‐treated dogs developing torsades de pointes (TdP) ventricular tachyarrhythmias, of which they ultimately died. In contrast, ranolazine did not generate TdP.
Effects on IKr and IKs were similar to those on HERG and IsK. Ranolazine blocked ICa with an IC50 of ∼300 μmol l−1. INa was unaffected.
We conclude that ranolazine inhibits IKr by blocking HERG currents, inhibits ICa at slightly larger concentrations, and has modest and self‐limited effects on the QT interval. Unlike D‐sotalol, ranolazine does not cause TdP in a dog model. The greater safety of ranolazine may be due to its ability to inhibit ICa at concentrations only slightly larger than those that inhibit IKr, thus producing offsetting effects on repolarization.

British Journal of Pharmacology (2004) 142, 1300–1308. doi:10.1038/sj.bjp.0705879
Evidence for gender differences in electrophysiological properties of canine Purkinje fibres
Authors: Abi‐Gerges Najah , Small Ben G , Lawrence Chris L , Hammond Tim G , Valentin Jean‐Pierre , Pollard Chris E 
Published: August 2004

Women are more prone to develop torsades de pointes, a rare life‐threatening polymorphic ventricular tachycardia, than are men during administration of medicines that have the potential to block IKr (rapid delayed rectifier cardiac K+ current) and to prolong the QT interval. Blockade of IKr, hypokalaemia and extreme bradycardia were used to evaluate whether there are gender differences in cardiac repolarisation in canine Purkinje fibres (PFs). Microelectrode techniques were employed to measure action potential (AP) parameters in PFs from adult female and male dogs.
Under control conditions, fibres from female animals in normal or low K+ conditions exhibited significantly longer AP durations at 50% (APD50) and 90% (APD90) of repolarisation as compared with APDs of fibres from male animals.
Gender‐related difference to rate adaptation was also present in APD90 of fibres from female animals compared to males.
At a stimulation rate of 0.2 Hz, but not at 1.0 Hz, dofetilide elicited a significantly higher increase in APD90, incidence of early afterdepolarisations, triggered and sustained‐triggered activities (TAs) in fibres from female animals compared to males in either normal or low K+ conditions. The sustained TAs were reversed by raising the concentration of [K+]0 in Purkinje preparations from both male (one out of one) and female (12 out of 12) dogs.
In conclusion, our data provide experimental evidence pointing to gender differences in canine AP repolarisation. PFs from female dogs can be used in safety pharmacology studies as a sensitive model for evaluating the potential proarrhythmic events in vitro of a new medicinal product.

British Journal of Pharmacology (2004) 142, 1255–1264. doi:10.1038/sj.bjp.0705880
Efficacy in CB1 receptor‐mediated signal transduction
Authors: Howlett Allyn C 
Published: August 2004

CB1 receptor cellular signal transduction is dependent on the expression of G proteins to which the receptor couples, the potential for precoupling of particular G proteins to the receptors either by scaffolding mechanisms or colocalization in lipid raft domains, and the effector mechanisms that these transducer molecules regulate. This discourse will evaluate studies of efficacy for CB1 receptor‐Gi/o activation at the molecular level. Evidence for brain regional differences in CB1 receptor signal transduction efficacy and agonist selectivity for G proteins will be summarized. The possibility that CB1 receptors interact with Gs or Gq will be evaluated, and questions with regard to the constitutive activity and G protein sequestration will be posed.British Journal of Pharmacology (2004) 142, 1209–1218. doi:10.1038/sj.bjp.0705881
Role of different brain structures in the behavioural expression of WIN 55,212‐2 withdrawal in mice
Authors: Castañé Anna , Maldonado Rafael , Valverde Olga 
Published: August 2004

We have evaluated several responses induced by the cannabinoid agonist WIN 55,212‐2 related to its addictive properties, including rewarding effects and the development of physical dependence in mice. Moreover, we have studied the specific involvement of several brain regions with high density of CB1 cannabinoid receptors, such as striatum, hippocampus, amygdala and cerebellum, in the behavioural expression of SR 141716A‐precipitated WIN 55,212‐2 withdrawal.
The systemic administration of the CB1 receptor antagonist SR 141716A (10 mg kg−1, s.c.) precipitated behavioural signs of withdrawal in mice chronically treated with WIN 55,212‐2 (1 and 2 mg kg−1, intraperitoneal (i.p.)), revealing the development of physical dependence.
The microinjection of SR 141716A (1.5 and 3 μg) into the cerebellum induced severe manifestations of abstinence in mice dependent on WIN 55,212‐2 (1 mg kg−1, i.p.). Out of 10 signs evaluated, seven were statistically significant: wet dog shakes, body tremor, paw tremor, piloerection, mastication, genital licks and sniffing. When the cannabinoid antagonist was administered into the hippocampus and the amygdala, a moderate but significant withdrawal syndrome was also observed. However, no signs of abstinence were induced when SR 141716A was microinjected into the striatum.
WIN 55,212‐2 produced rewarding effects in the place‐conditioning paradigm in mice pre‐exposed to a priming injection of the drug.
These results show a reliable behavioural model to reveal rewarding effects and physical dependence induced by the repeated administration of WIN 55,212‐2 in mice. The cerebellum and to a lesser extent the hippocampus and the amygdala participate in the behavioural expression of cannabinoid withdrawal.

British Journal of Pharmacology (2004) 142, 1309–1317. doi:10.1038/sj.bjp.0705882
Matrix metalloproteinase expression and activity in human airway smooth muscle cells
Authors: Elshaw Shona R , Henderson Neil , Knox Alan J , Watson Susan A , Buttle David J , Johnson Simon R 
Published: August 2004

Airway remodelling is a feature of chronic asthma comprising smooth muscle hypertrophy and deposition of extracellular matrix (ECM) proteins. Matrix metalloproteinases (MMPs) breakdown ECM, are involved in tissue remodelling and have been implicated in airway remodelling. Although mesenchymal cells are an important source of MMPs, little data are available on airway smooth muscle (ASM) derived MMPs. We therefore investigated MMP and tissue inhibitor of metalloproteinase (TIMP) production and activity in human ASM cells.
MMPs and TIMPs were examined using quantitative real‐time RT–PCR, Western blotting, zymography and a quench fluorescence (QF) assay of total MMP activity.
The most abundant MMPs were pro‐MMP‐2, pro‐ MMP‐3, active MMP‐3 and MT1‐MMP. TIMP‐1 and TIMP‐2 expression was low in cell lysates but high in conditioned medium. High TIMP secretion was confirmed by the ability of ASM‐conditioned medium to inhibit recombinant MMP‐2 in a QF assay. Thrombin increased MMP activity by activation of pro‐MMP‐2 independent of the conventional smooth muscle thrombin receptors PAR 1 and 4.
In conclusion, ASM cells express pro‐MMP‐2, pro and active MMP‐3, MMP‐9 and MT1‐MMP. Unstimulated cells secrete excess TIMP 1 and 2, preventing proteolytic activity. MMP‐2 can be activated by thrombin which may contribute to airway remodelling.

British Journal of Pharmacology (2004) 142, 1318–1324. doi:10.1038/sj.bjp.0705883
Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP‐ and thrombin‐induced human platelet activation
Authors: Nylander Sven , Mattsson Christer , Ramström Sofia , Lindahl Tomas L 
Published: August 2004

The objective of this study was to investigate if there is a synergistic effect of a combination of P2Y12 and P2Y1 inhibition and P2Y12 and thrombin inhibition, on ADP‐ and thrombin‐induced platelet activation, respectively. The rationale being that these combinations will cause a concurrent inhibition of both Gαq and Gαi signalling.
Blood from healthy volunteers was preincubated with AR‐C69931MX, a reversible P2Y12 antagonist; MRS2179, a reversible P2Y1 antagonist; or melagatran, a direct reversible thrombin inhibitor; alone or in various combinations prior to activation with ADP or thrombin. Platelet function in whole blood was assessed by flow cytometry using the antibody PAC‐1 to estimate the expression of active αIIbβ3 (the fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing the concentrations in the different combinations with those of corresponding equipotent concentrations of each single inhibitor alone. The equipotent single concentrations were experimentally obtained from concentration response curves performed in parallel.
A synergistic effect regarding inhibition of ADP‐induced platelet activation (10 μM) was obtained with different combinations of AR‐C69931MX and MRS2179.
Inhibition of thrombin‐induced platelet activation (2 nM) with combinations of AR‐C69931MX and the thrombin inhibitor melagatran did also result in a strong synergistic effect.
To our knowledge, this is the first time that data supporting a synergistic effect has been published for the inhibitor combinations described.
Whether this synergistic effect in vitro also results in an improved antithrombotic effect in vivo with or without an increased risk of bleeding remains to be studied in well‐conducted clinical studies.

British Journal of Pharmacology (2004) 142, 1325–1331. doi:10.1038/sj.bjp.0705885