bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consistent database sampling as a database prototyping approach
Authors: Bisbal Jesús , Grimson Jane 
Published: January 2003

AbstractRequirements elicitation has been reported to be the stage of software development when errors have the most expensive consequences. Users usually find it difficult to articulate a consistent and complete set of requirements at the beginning of a development project. Prototyping is considered a powerful technique to ease this problem by exposing a partial implementation of the software system to the user, who can then identify required modifications. When prototyping data‐intensive applications a so‐called prototype database is needed.This paper investigates how a prototype database can be built. Two different approaches are analysed, namely test databases and sample databases; the former populates the resulting database with synthetic values, while the latter uses data values from an existing database. The application areas that require prototype databases, in addition to requirements analysis, are also identified. The paper reports on existing research into the construction of both types of prototype databases, and indicates to which type of application area each is best suited. This paper advocates for the use of sample databases when an operational database is available, as is commonly the case in software maintenance and evolution. Domain‐relevant data values and integrity constraints will produce a prototype database which will support the information system development process better than synthetic data. The process of extracting a sample database is also investigated. Copyright © 2002 John Wiley & Sons, Ltd.
Pedicular fixation in the osteoporotic spine: a pilot in vivo study on long‐term ovariectomized sheep
Authors: Nicoli Aldini N. , Fini M. , Giavaresi G. , Giardino R. , Greggi T. , Parisini P. 
Published: January 2003

AbstractSpinal instrumentation success is greatly affected by the presence of osteoporosis. To date, however, no data exist on in vivo investigations on biomaterial and surgical techniques in the osteoporotic spine. In the present study 24 uncoated and 24 HA‐coated screws were implanted in the L3, L4 and L5 pedicles of eight sheep (four ovariectomized, OVX Group; four sham‐operated, Control Group). At four months, uncoated screws showed a significant decrease of about −22% in the extraction torque of the OVX Group as compared to the Control Group (p < 0.005). The extraction torque of HA‐coated screws significantly (p < 0.0005) improved in both groups when compared to that of uncoated screws and showed increases ranging from 133% to 157%. Pedicle trabecular bone of OVX sheep showed a significant decrease in BV/TV (−30%; p < 0.05) and Tb.Th (−33%; p < 0.01). The affinity index (AI) results revealed significant (p < 0.0005) differences between uncoated and HA‐coated screws for both groups: values were lower for uncoated than HA‐coated screws by about −35%. A significant difference was also found for the AI data of uncoated screws between the OVX and Control Groups ( − 13%, p < 0.005). The current findings have demonstrated that long‐term ovariectomized sheep can be used to study in vivo osteointegration in the osteoporotic spine. The HA coating has proven to improve bone purchase and bone‐screw interface strength in healthy and osteopenic animals.© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells
Authors: Wang Mark L. , Nesti Leon J. , Tuli Richard , Lazatin Jovin , Danielson Keith G. , Sharkey Peter F. , Tuan Rocky S. 
Published: January 2003

AbstractLong‐term stability of arthroplasty prosthesis depends on the integration between osseous tissue and the implant biomaterial. Integrity of the osseous tissue requires the contribution of mesenchymal stem cells and their continuous differentiation into an osteoblastic phenotype. This study aims to investigate the hypothesis that exposure to wear debris particles derived from orthopaedic biomaterials affects the osteoblastic differentiation of human mesenchymal stem cells (hMSC). Upon in vitro culture in the presence of osteogenic supplements (OS), we observe that cultures of hMSCs isolated from femoral head bone marrow are capable of osteogenic differentiation, expressing alkaline phosphatase, osteocalcin, and bone sialoprotein (BSP), in addition to producing collagen type I and BSP accompanied by extracellular matrix mineralization. Exposure of OS‐treated hMSCs to submicron commercially pure titanium (cpTi) particles suppresses BSP gene expression, reduces collagen type I and BSP production, decreases cellular proliferation and viability, and inhibits matrix mineralization. In comparison, exposure to zirconium oxide (ZrO2) particles of similar size did not alter osteoblastic gene expression and resulted in only a moderate decrease in cellular proliferation and mineralization. Confocal imaging of cpTi‐treated hMSC cultures revealed patchy groups of cells displaying disorganized cyto‐skeletal architecture and low levels of extracellular BSP. These in vitro findings suggest that chronic exposure of marrow cells to titanium wear debris in vivo may contribute to decreased bone formation at the bone/implant interface by reducing the population of viable hMSCs and compromising their differentiation into functional osteoblasts. Understanding the nature of hMSC bioreactivity to orthopaedic wear debris should provide additional insights into mechanisms underlying aseptic loosening.Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society.
Acetylcholine‐induced vasodilation may depend entirely upon NO in the femoral artery of young piglets
Authors: Støen Ragnhild , Lossius Kristin , Karlsson Jan Olof G 
Published: January 2003

To characterize agonist‐induced relaxation in femoral artery rings from young piglets, we compared the effect of a NOS‐inhibitor Nω‐nitro‐L‐arginine (L‐NOARG), an NO‐inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)‐inhibitor 1H‐[1,2,4]Oxadiazolo‐[4,3,‐α]quinoxalin‐1‐one (ODQ) on acetylcholine(ACh)‐induced relaxation. The involvement of K+ channel activation was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine 3′5′ cyclic monophosphate (cGMP) analogue 8‐Br‐cGMP.
Full reversal of phenylephrine‐mediated precontraction was induced by ACh (1 nM–1 μM) (pD2 8.2±0.01 and Rmax 98.7±0.3%). L‐NOARG (100 μM) partly inhibited relaxation (pD2 7.4±0.02 and Rmax 49.6±0.8%). The L‐NOARG/indomethacin(IM)‐resistant response displayed characteristics typical for endothelium‐derived hyperpolarizing factor (EDHF), being sensitive to a combination of the K+ channel blockers charybdotoxin (CTX) (0.1 μM) and apamin (0.3 μM).
ODQ (10 μM) abolished relaxations induced by ACh and SNP. L‐NOARG/IM‐resistant relaxations to ACh were abolished by HbO (20 μM).
Ouabain (1 μM) significantly inhibited ACh‐induced L‐NOARG/IM‐resistant relaxations and relaxations induced by SNP (10 μM) and 8‐Br‐cGMP (0.1 mM). A combination of ouabain and Ba2+ (30 μM) almost abolished L‐NOARG/IM‐resistant ACh‐induced relaxation (Rmax 7.7±2.5% vs 23.4±6.4%, with and without Ba2+, respectively, P<0.05).
The present study demonstrates that in femoral artery rings from young piglets, despite an L‐NOARG/IM‐resistant component sensitive to K+ channel blockade with CTX and apamin, ACh‐induced relaxation is abolished by sGC‐inhibition or a combination of L‐NOARG and HbO. These findings suggest that relaxation can be fully explained by the NO/cGMP pathway.

British Journal of Pharmacology (2003) 138, 39–46. doi:10.1038/sj.bjp.0705001
Pharmacological profiles of presynaptic nociceptin/orphanin FQ receptors modulating 5‐hydroxytryptamine and noradrenaline release in the rat neocortex
Authors: Marti Matteo , Stocchi Sara , Paganini Francesca , Mela Flora , Risi Carmela De , Calo' Girolamo , Guerrini Remo , Barnes Timothy A , Lambert David G , Beani Lorenzo , Bianchi Clementina , Morari Michele 
Published: January 2003

The pharmacological profiles of presynaptic nociceptin/orphanin FQ (N/OFQ) peptide receptors (NOP) modulating 5‐hydroxytryptamine (5‐HT) and noradrenaline (NE) release in the rat neocortex were characterized in a preparation of superfused synaptosomes challenged with 10 mM KCl.
N/OFQ concentration‐dependently inhibited K+‐evoked [3H]‐5‐HT and [3H]‐NE overflow with similar potency (pEC50 ∼7.9 and ∼7.7, respectively) and efficacy (maximal inhibition ∼40%).
N/OFQ (0.1 μM) inhibition of [3H]‐5‐HT and [3H]‐NE overflow was antagonized by selective NOP receptor antagonists of peptide ([Nphe1]N/OFQ(1‐13)NH2 and UFP‐101; 10 and 1 μM, respectively) and non‐peptide (J‐113397 and JTC‐801; both 0.1 μM) nature. Antagonists were routinely applied 3 min before N/OFQ. However, a 21 min pre‐application time was necessary for J‐113397 and JTC‐801 to prevent N/OFQ inhibition of [3H]‐NE overflow.
The NOP receptor ligand [Phe1ψ(CH2‐NH)Gly2]N/OFQ(1‐13)NH2 ([F/G]N/OFQ(1‐13)NH2; 3 μM) did not affect K+‐evoked [3H]‐NE but inhibited K+‐evoked [3H]‐5‐HT overflow in a UFP‐101 sensitive manner. [F/G]N/OFQ(1‐13)NH2 antagonized N/OFQ actions on both neurotransmitters.
The time‐dependency of JTC‐801 action was studied in CHO cells expressing human NOP receptors. N/OFQ inhibited forskolin‐stimulated cAMP accumulation and JTC‐801, tested at different concentrations (0.1–10 μM) and pre‐incubation times (0, 40 and 90 min), antagonized this effect in a time‐dependent manner. The Schild‐type analysis excluded a competitive type of antagonism.
We conclude that presynaptic NO receptors inhibiting 5‐HT and NE release in the rat neocortex have similar pharmacological profiles. Nevertheless, they can be differentiated pharmacologically on the basis of responsiveness to [F/G]N/OFQ(1‐13)NH2 and time‐dependent sensitivity towards non‐peptide antagonists.

British Journal of Pharmacology (2003) 138, 91–98. doi:10.1038/sj.bjp.0705005
Bradykinin inhibits development of myocardial infarction through B2 receptor signalling by increment of regional blood flow around the ischaemic lesions in rats
Authors: Ito Hiroshi , Hayashi Izumi , Izumi Tohru , Majima Masataka 
Published: January 2003

To identify the roles of endogenous kinins in prevention of myocardial infarction (MI), we performed the permanent ligation of coronary artery in rats.
The size of MI 12, 24, and 48 h after coronary ligation in kininogen‐deficient Brown Norway Katholiek (BN‐Ka) rats was significantly larger (49.7±0.2%, 49.6±2%, and 51.1±1%, respectively) than that of kinin‐replete Brown Norway Kitasato (BN‐Ki) rats (42±2%, 38.5±4%, and 41.5±1%).
Hoe140, a bradykinin (BK) B2 receptor antagonist injected (1.0 mg kg−1, i.v.) half an hour before, and every 8 h after, coronary ligation, significantly increased the size of MI in Sprague‐Dawley rats. Aprotinin, a kallikrein inhibitor, which was infused intravenously (10,000 Units kg−1 h−1) with an osmotic mini‐pump, significantly increased the size of an MI 24 h after ligation.
When evaluated using microspheres, the regional myocardial blood flow around the necrotic lesion in BN‐Ka rats 6 h after ligation was reduced more than that in BN‐Ki rats with MI by 41–46%. The same was true in Hoe140‐treated BN‐Ki rats.
FR190997, a nonpeptide B2 agonist, which was infused (10 μg kg−1 h−1) into the vena cava of BN‐Ka rats for 24 h with an osmotic mini‐pump, caused significant reduction in the size of MI (38±3%), in comparison with the size in vehicle solution‐treated rats (51±3%). The size of MI in FR190997‐treated BN‐Ka rats was the same as in BN‐Ki rats.
These results suggested that endogenous kinin has the capacity to reduce the size of MI via B2 receptor signalling because of the increase in regional myocardial blood flow around the ischaemic lesion.

British Journal of Pharmacology (2003) 138, 225–233. doi:10.1038/sj.bjp.0705013
Evidence against β3‐adrenoceptors or low affinity state of β1‐adrenoceptors mediating relaxation in rat isolated aorta
Authors: Brahmadevara Nataraj , Shaw Angus M , MacDonald Allan 
Published: January 2003

The presence of β3‐adrenoceptors and the low affinity state of the β1‐adrenoceptor (formerly ‘putative β4‐adrenoceptor’) was investigated in ring preparations of rat isolated aorta preconstricted with phenylephrine or prostaglandin F2α (PGF2α). Relaxant responses to isoprenaline, selective β3‐adrenoceptor agonists (BRL 37344, SR 58611A, CL 316243) and non‐conventional partial agonists (CGP 12177A, cyanopindolol, pindolol) were obtained.
In phenylephrine‐constricted, but not PGF2α‐constricted rings, relaxations to isoprenaline showed a propranolol‐resistant component.
In phenylephrine‐constricted rings, relaxations to BRL 37344 (pEC50, 4.64) and SR 58611A (pEC50, 4.94) were not antagonized by the selective β3‐adrenoceptor antagonist SR 59230A (1 μM). CL 316243 (100 μM) failed to produce relaxation. In PGF2α‐constricted rings only SR 58611A produced relaxation, which was not affected by SR 59230A (3 μM).
Non‐conventional partial agonists produced relaxation in phenylephrine‐constricted but not PGF2α‐constricted rings. The relaxation to CGP 12177A was unaffected by SR 59230A (1 μM) or by CGP 20712A (10 μM), reported to block the low affinity state of the β1‐adrenoceptor.
β‐adrenoceptor antagonists also produced relaxation in phenylephrine‐constricted rings with an order of potency of (pEC50 values): bupranolol (5.5)∼38;SR 59230A (5.47)∼38;cyanopindolol (5.47)>pindolol (5.30)>alprenolol (5.10)>propranolol (4.83)>ICI 118551 (4.60)>CGP 12177A (4.38)∼38;CGP 20712A (4.35). Bupranolol (100 μM), alprenolol (30 μM), propranolol (100 μM) and SR 59230A (10 μM) produced no relaxation in PGF2α‐constricted rings.
These results provide no evidence for the presence of functional β3‐adrenoceptors or the low affinity state of the β1‐adrenoceptor in rat aorta.

British Journal of Pharmacology (2003) 138, 99–106. doi:10.1038/sj.bjp.0705017
α1‐Adrenoceptor effects mediated by protein kinase C α in human cultured prostatic stromal cells
Authors: Preston A , Haynes J M 
Published: January 2003

We have investigated the effects of α1‐adrenoceptor stimulation upon contractility, Ca2+ influx, inositol phosphate production, and protein kinase C (PKC) translocation in human cultured prostatic stromal cells (HCPSC).
The α1‐adrenoceptor selective agonist phenylephrine elicited contractile responses of HCPSC, i.e. a maximal cell shortening of 45±6% of initial cell length, with an EC50 of 1.6±0.1 μM. The α1‐adrenoceptor selective antagonists prazosin (1 μM) and terazosin (1 μM) both blocked contractions to phenylephrine (10 μM). The L‐type calcium channel blocker nifedipine (10 μM), and the PKC inhibitors Gö 6976 (1 μM) and bisindolylmaleimide (1 μM) also inhibited phenylephrine‐induced contractions.
Phenylephrine caused a concentration dependent increase in inositol phosphate production (EC50 119±67 nM). This response was blocked by terazosin (1 μM).
Phenylephrine caused the translocation of the PKC α isoform, but not the β, δ, γ, ε or λ isoforms, from the cytosolic to the particulate fraction of HCPSC, with an EC50 of 5.7±0.5 μM.
In FURA‐2AM (5 μM) loaded cells, phenylephrine elicited concentration dependent increases in [Ca2+]i, with an EC50 of 3.9±0.4 μM. The response to phenylephrine (10 μM) was blocked by prazosin (1 μM), bisindolymaleimide (1 μM), and nifedipine (10 μM).
In conclusion, this study has shown that HCPSC express functional α1‐adrenoceptors, and that the intracellular pathways responsible for contractility may be largely dependent upon protein kinase C activation and subsequent opening of L‐type calcium channels.

British Journal of Pharmacology (2003) 138, 218–224. doi:10.1038/sj.bjp.0705021
Activation and potentiation of the NO/cGMP pathway by NG‐hydroxyl‐L‐arginine in rabbit corpus cavernosum under normoxic and hypoxic conditions and ageing
Authors: Angulo Javier , Cuevas Pedro , Fernández Argentina , Gabancho Sonia , Allona Antonio , Martín‐Morales Antonio , Moncada Ignacio , Tejada Iñigo Sáenz de 
Published: January 2003

When nitric oxide synthase (NOS) produces NO from NG‐hydroxy‐L‐arginine (OH‐arginine) instead of L‐arginine, the total requirement of molecular oxygen and NADPH to form NO is reduced. The aim of this work was to evaluate the effects of OH‐arginine on the contractility of rabbit corpus cavernosum (RCC) and to compare the capacities of L‐arginine and OH‐arginine to enhance NO‐mediated responses under normoxic and hypoxic conditions and in ageing, as models of defective NO production.
OH‐arginine, but not L‐arginine, was able to relax phenylephrine‐contracted rabbit trabecular smooth muscle. OH‐arginine‐induced relaxation was inhibited by the NOS‐inhibitor, L‐NNA (300 μM), and by the guanylyl cyclase inhibitor, ODQ (20 μM), while it was not affected by the cytochrome P450 oxygenase inhibitor, miconazole (0.1 mM). Administration of OH‐arginine, but not L‐arginine, produced a significant increment of cGMP accumulation in RCC tissue.
Relaxation elicited by OH‐arginine (300 μM) was still observed at low oxygen tension. The increase of cGMP levels induced by ACh (30 μM) in RCC was significantly enhanced by addition of OH‐arginine (300 μM) in normoxic conditions, as well as under hypoxia, while L‐arginine did not alter the effects of ACh on cGMP accumulation.
Endothelium‐dependent and nitrergic nerve‐mediated relaxations were both significantly reduced in RCC from aged animals (>20‐months‐old) when compared with young adult rabbits (5‐months‐old). Treatment with OH‐arginine (300 μM) significantly potentiated endothelium‐dependent and neurogenic relaxation in corpus cavernosum from aged rabbits, while L‐arginine (300 μM) did not have significant effects.
Results show that OH‐arginine promotes NO‐mediated relaxation of RCC and potentiates the NO‐mediated responses induced by stimulation of endogenous NO generation in hypoxic and aged tissues. We propose that the use of OH‐arginine could be of interest in the treatment of erectile dysfunction, at least in those secondary to defective NO production.

British Journal of Pharmacology (2003) 138, 63–70. doi:10.1038/sj.bjp.0705027
Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine
Authors: Charbit Beny , Becquemont Laurent , Lepère Bénédicte , Peytavin Gilles , Funck‐Brentano Christian 
Published: January 2003

BackgroundHalofantrine, an antimalarial drug that prolongs the QT interval, is metabolized into N‐debutyl‐halofantrine by cytochrome P450 (CYP) 3A4. Grapefruit juice increases the bioavailability of several orally administered CYP3A4 substrates by inhibiting CYP3A4 at the enterocyte level and could therefore increase the risk of halofantrine‐induced QT interval prolongation. We studied the effect of grapefruit juice on halofantrine bioavailability and on QT interval prolongation associated with its oral administration.MethodsTwelve healthy male and female volunteers received 500 mg of halofantrine with 250 mL of water, orange juice, or grapefruit juice (250 mL once a day of regular strength for 3 days and once at 12 hours before halofantrine administration), in a random order, during a crossover study. Plasma pharmacokinetics of halofantrine and N‐debutyl‐halofantrine and QTc interval duration were studied during the following 168 hours.ResultsCompared with water, grapefruit juice increased halofantrine area under the plasma concentration versus time curve (AUC) and peak plasma concentration by 2.8‐fold ± 1.5‐fold (P < .0001) and 3.2‐fold ± 1.3‐fold (P < .0001), respectively. There was a concomitant 2.4‐fold ± 1.6‐fold decrease in N‐debutyl‐halofantrine AUC (P < .01) but no significant change in halofantrine elimination half‐life. Maximum QTc interval prolongation increased from 17 ± 6 ms when halofantrine was administered with water to 31 ± 12 ms when it was administered with grapefruit juice (P < .0005). Multiple regression analysis showed that QTc interval prolongation was better correlated with halofantrine (partial r = 0.432; P < .0001) than with N‐debutyl‐halofantrine (partial r = 0.117; P < .01) concentrations. There was no significant difference between the water and orange juice study periods.ConclusionsGrapefruit juice increases halofantrine bioavailability and halofantrine‐induced QT interval prolongation. Grapefruit juice should be contraindicated during administration of halofantrine.Clinical Pharmacology & Therapeutics (2002) 72, 514–523; doi: 10.1067/mcp.2002.128148
Music education in Taiwan: the dynamics and dilemmas of globalization, localization and sinophilia
Authors: Ho Wai‐Chung , Law Wing‐Wah 
Published: January 2003

ABSTRACTThe article examines the complicated interplay of globalization, localization and sinophilia that, along with associated social changes, determines reforms in Taiwanese music education today. Students are expected not only to be tri‐lingual, in so far as they are obliged to learn English, Mandarin and a local language, such as Southern Fujianese, Hakka or an aboriginal dialect, but they must also become tri‐cultural with respect to western classical music, traditional Chinese music and indigenous Taiwanese music. The findings of our questionnaires suggest that the processes of globalization, localization and sinophilia are unequal determinants in the transformation of Taiwanese music education. The survey, which was conducted among 2596 primary and secondary school students (1309 from Tainan and 1287 from Taipei) between May and November 2000, shows that schools are less inclined than the Taiwanese government to promote local music. Students in the survey much prefer western classical and popular music to local Taiwanese and traditional Chinese styles. They show little interest in promoting Chinese culture or in singing Taiwan's national anthem. By examining the major concerns of music education from the perspective of the complex dynamics of globalization, this study illuminates the tensions and dilemmas facing the music curriculum of Taiwan today.
Differential expression and upregulation of interleukin‐1α, interleukin‐1β and interleukin‐6 by freshly isolated human small intestinal epithelial cells
Authors: Madrigal-Estebas Laura , Doherty Derek G. , O′Donoghue Diarmuid P. , Feighery Conleth , O′Farrelly Cliona 
Published: January 2003

Background: Small intestinal epithelial cells (SIEC) may contribute to local immune regulation.Aim: To examine production of interleukin (IL)‐1α , IL‐1β and IL‐6 by freshly isolated human SIEC.Methods: IL‐1α and IL‐1β mRNA in epithelial layers (EL) prepared from small intestine and in intestinal epithelial cell (EC) lines were examined by reverse transcription‐polymerase chain reaction. IL‐1α, IL‐1β and IL‐6 protein expression by SIEC was examined by flow cytometry before and after activation with lipopolysaccharide and epithelial growth factor.Results: IL‐1α and IL‐1β mRNA was detected in EL and EC lines. Background expression of IL‐1α and IL‐1β protein by SIEC was observed, which did not increase even following activation. IL‐6 protein was expressed by SIEC, in a proportion that increased in two out of three samples following activation.Conclusions: IL‐6 expression and the presence of IL‐1α and IL‐1β mRNA suggest a role for SIEC in the regulation of local inflammation.