bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical analysis of the geometry of the inclined stitch as a structural element of interlacings
Authors: Charalambus A.
Published: November 2002

The geometry of interlacing with different stages and ways of greating are technically investigated. The theoretical lengthening of the fiber in the inclined stitches is defined by different conditions. Preconditions are searched, by which the values of this lengthening are within various limits and do not affect the quality of the used yarns and the ready knitting.
Garment's pressure sensation (2): the psychophysical mechanism for the sensation
Authors: You F. , Wang J.M. , Luo X.N. , Li Y. , Zhang X.
Published: November 2002

Relationships have been investigated between subjective pressure sensation and objective pressure measured, for knit garments of different sizes and fabrics with different extensibilities. Fechner's logarithmic law is used to investigate the relations. Equations are obtained for describing the Psychophysical mechanism of clothing pressure perception under certain conditions. Objective pressure measuring had high predictive power with regard to subjective pressure sensation only under those conditions. Wearing pressure comfort has a negative correlation with feelings of fetter, scratchy, heavy and pressure, and has a poor correlation with feelings of softness and smoothness. Using factor analysis with principal factor solutions and rotated by the Varimax method, we obtained factor matrices.
The theoretical foundation of supply chain management
Authors: Svensson Göran
Published: November 2002

Supply chain management (SCM) emerged in the early 1980s as a result of the rapidly changing and challenging business environments in many industries. SCM is a consequence of the increased necessity for holistic considerations in, between and across companies’ business activities and resources in and between marketing channels, in order to improve the overall performance towards the ultimate consumer in the marketplace. SCM’s generic theoretical foundations are derived from time‐, functional‐, and relationship‐dependencies in, between and across companies’ business activities in marketing channels. There are major similarities and minor differences in the theoretical boundaries between SCM and Alderson’s interpretation of a functionalist theory of marketing. The author argues that the theoretical origin of SCM is derived from, and underpinned by, a part of this functionalist theory of marketing. Furthermore, there is a need for a generic re‐definition and expansion of the theoretical boundaries of SCM towards the incorporation of horizontal dependencies between marketing channels in the marketplace.
Internal supply chain planning determinants in small and medium‐sized manufacturers
Authors: Huin S.F. , Luong L.H.S. , Abhary K.
Published: November 2002

In the manufacturing industry, there are a large number of small and medium‐sized manufacturers (M‐SMEs) which provide specialty manufacturing and support services to large corporations. M‐SMEs form the biggest group of manufacturing entities in many newly industrialized economies. The needs and operating requirements of these M‐SMEs are very different from those of large companies. Much research has been carried out in the area of mechanisms, techniques, heuristic designs, modeling, and usage of fuzzy logic in production planning, scheduling and production control. However, most research only addresses a particular area of the enterprise planning process. In addition, the majority of the large‐scale enterprise resources planning (ERP) systems created for large corporations’ manufacturers are sometimes ineffective in M‐SMEs. This research highlights the organizational, structural, operational and supply chain related interdependencies impacting the planning and management of the internal supply chain in M‐SMEs in the Southeast Asia region. Similar to the deployment of management and manufacturing information systems, the need to fully comprehend the operational dynamics of M‐SMEs is crucial for the successful implementation of ERP systems to manage the internal supply chain. The deployment of ERP systems in M‐SMEs is simpler in some aspects compared to large corporations, but can be more complicated in others.
Distribution and logistics development in China
Authors: Jiang Bin , Prater Edmund
Published: November 2002

Prior to the economic reform movement, China’s centrally planned, three‐tier system dominated the distribution sector. After the 1980s, this system gradually shifted away from the socialist mode to the free market mode. Today, China’s distribution system lies somewhere between these two modes. Since the reform, China’s government has been encouraging export‐oriented foreign firms’ investments in free trade zones along the coast. Foreign firms do not enjoy the same inland distribution and logistics rights as their Chinese counterparts. However, the distribution puzzle is not only faced by foreign firms, but also by Chinese firms that operate nationwide. China’s undeveloped infrastructure, government regulations, and regional protectionism fragment distribution channels throughout China. However, there are three main forces that are changing and modernizing China’s distribution and logistics system. These are the booming economy, entering the WTO and e‐commerce. The inevitable revolution of China’s distribution and logistics system is on the way.
Towards maturity of information security maturity criteria: six lessons learned from software maturity criteria
Authors: Siponen Mikko
Published: November 2002

Traditionally, information security management standards listing generic means of protection have received a lot of attention in the field of information security management. In the background a few information security management‐oriented maturity criteria have been laid down. These criteria can be regarded as the latest promising innovations on the information security checklist‐standard family tree. Whereas information security maturity criteria have so far received inadequate attention in information security circles, software maturity endeavours have been the focus of constructive debate in software engineering circles. Aims to analyze what the alternative maturity criteria for developing secure information systems (IS) and software can learn from these debates on software engineering maturity criteria. First, advances a framework synthesized from the information systems (IS) and software engineering literatures, including six lessons that information security maturity criteria can learn from. Second, pores over the existing information security maturity criteria in the light of this framework. Third, presents, on the basis of results of this analysis, implications for practice and research.
Information flow analysis on role‐based access control model
Authors: Zhang Chang N. , Yang Cungang
Published: November 2002

Information flow analysis is a necessary step to determine the information security for a given system. In this paper, we introduce an object oriented role‐based access control model (ORBAC) and illustrate that the confinement problem may occur on the ORBAC based system. In order to deal with the problem, a technique called information flow analysis is proposed. Moreover, under the principle of mandatory access control (MAC) security policy, a role set assignment method is developed and proved to solve the confinement problem on ORBAC.
Security of personal data across national borders
Authors: Tran Elizabeth , Atkinson MaryAnne
Published: November 2002

Rapid technological advancements present many opportunities in the way people work, communicate and conduct business. That growth is especially prevalent in the World Wide Web. In the last five years, the Internet has expanded the market place to a global arena. More and more companies are conducting business online. Multinational corporations are becoming extremely dependent on the exchange of information across the Internet. As information flows across national borders, the concern for data security increases. Accordingly, personal data and business transactions collected by international companies are no longer safe once they enter the realm of the Internet. This paper addresses privacy concerns of e‐commerce customers, the security regulations imposed on multinational companies transferring data across international boundaries, and the risks of not complying with data protection regulations.
Integrating search engines with data mining for customer‐oriented information search
Authors: France Tim , Yen Dave , Wang Jyun‐Cheng , Chang Chia‐Ming
Published: November 2002

In recent years, the World Wide Web (WWW) has become incredibly popular in homes and offices alike. Consumers need to search for relevant information to help solve purchasing problems on various Web sites. Although there is no question that great numbers of WWW users will continue using search engines for information retrieval, consumers still hesitate before making a final decision, often because only rough and limited information about the products is made available. Consequently, consumers need the help of data mining in order to help them make informed decisions. Herein we propose a new approach to integrating a search engine with data mining in an effort to help support customer‐oriented information search action. This approach also illustrates how to reduce the consumer’s information search perplexity.
An intelligent approach to prevent distributed systems attacks
Authors: Abouzakhar Nasser S. , Manson Gordon A.
Published: November 2002

In today’s society, information and communications technology (ICT) is the force that drives prosperity and provides a higher standard of living. All other e‐services and infrastructures tend to play a major role in our daily life and global economy. The growing dependence on such systems, however, has increased their vulnerability to cyber attacks. Any failure to these systems typically would lead to a huge impact, not only on businesses, but also human life, that depends on such interconnected systems. The growing potential for telecommunications network infrastructures problems stems from their nature of openness. A successful attempt for a network attack to a particular organization’s network could have devastating effects on the security of the organisation. In this paper we propose an innovative way to counteract distributed protocols attacks such as distributed denial of service (DDoS) attacks using intelligent fuzzy agents.
Formal strategic planning
Authors: O’Regan Nicholas , Ghobadian Abby
Published: November 2002

The literature contends that the lack of strategic business planning is a major drawback in the implementation of business process initiatives such as total quality management. In addition, it is evident that strategic planning firms achieve better performance than other firms. However, strategic planning often fails due to problems or barriers encountered at the implementation stage. It is unclear from the limited research carried out to date what actions, if any, firms can take to minimise or eliminate these barriers. This paper examines the concept of strategic planning and identifies the barriers to its implementation. It considers the suitability of formal strategic planning as the key to eliminating or reducing implementation barriers by comparing the extent to which the barriers are experienced in formal and non‐formal planning firms. The paper also examines the extent to which the barriers are experienced by high and low performing firms.
Change management at Mobil Oil Australia
Authors: Martin Ian , Cheung Yen
Published: November 2002

To remain competitive many businesses in the 1990s have undertaken business process reengineering projects reorganising one or more parts of their operations. This paper results from a case study of the enterprise‐wide review of Mobil Oil Australia Limited to increase profitability and change the culture of the organisation. A radical (to the oil industry) business unit organisation structure was designed, populated and implemented. The project was an immediate financial success and reenergized the company. Income after tax was six times higher after the reorganisation than in the previous year, notwithstanding a continuing recession and the uncertainty caused by the restructuring. Return on capital employed increased from 2 percent to 7 percent. Lessons can be learnt from the way the project was initiated and developed, the deployment of the project management structure and improvement methodology, the approach to the implementation of the new structure and the findings of the post implementation review.
The promotion of strategic community management utilizing video‐based information networks
Authors: Kodama Mitsuru
Published: November 2002

This paper describes the importance of strategic community creation as a new management style. It verifies that video‐based information networks utilizing information and multimedia technologies enhance the quality of competencies and knowledge possessed by strategic communities, and it also verifies, through case studies, these networks are valid as organizational learning support systems within the strategic communities. Innovations in the area of veterinary medicine utilizing video‐based information networks over the past four years in Japan are taken as examples. This paper describes how knowledge and competencies within strategic communities comprising “industry, government, and academia” are enhanced, how the new virtual methods of telemedicine and distance learning are incorporated into the business process, and how “concepts of regionally linked cooperative bodies” are realized.
Quantitative risk level estimation of business process reengineering efforts
Authors: Crowe Thomas J. , Meghan Fong Pekying , Bauman Todd A. , Zayas‐Castro José L.
Published: November 2002

With risk defined as the possibility of deviation in the results from the expected goals, business process reengineering (BPR) initiatives clearly involve risk taking. However, due to the high expected returns of such efforts, the acceptable risk levels of BPR will tend to be greater than those of less ambitious projects. This research reports the development of a tool to quantitatively estimate the potential risk level of a BPR effort before an organization commits its resources to that effort. The underlying research employed a survey of BPR‐experienced organizations to collect assessment information in order to build a BPR risk estimation model. The developed tool uses triangular fuzzy numbers to approximate the degree of success/failure of proposed BPR initiatives. The tool can be applied by any organization contemplating BPR, thus giving such organizations a heretofore unavailable estimate of the risk level of proposed BPR efforts. Validation was performed based upon an 18‐month BPR project conducted at the Missouri Lottery.
Effects of annual fertilization and complete competition control on current annual increment, foliar development, and growth efficiency of different aged Pinus taeda stands
Authors: Will Rodney E , Munger Gregory T , Zhang Yujia , Borders Bruce E
Published: November 2002

The effects that competing vegetation and nitrogen limitation have on the current annual increment (CAI), leaf biomass, and growth efficiency (GE) of different aged loblolly pine (Pinus taeda L.) stands planted on a Piedmont and lower Coastal Plain location in Georgia, U.S.A. were determined by measuring stands receiving a factorial combination of complete interspecific competition control and annual nitrogen fertilization. At the Piedmont location, CAI increased with age (5, 10, and 12 years) as well as fertilization (7.39.2 Mg·ha1) and competition control (6.89.6 Mg·ha1). The effects of fertilization on leaf biomass increased with stand age (no difference at age 5 to 1.5 Mg·ha1 difference at age 12), while the effects of competition control on leaf biomass decreased with stand age (difference of 2.5 Mg·ha1 at age 5 to difference of 1.6 Mg·ha1 at age 12). At the Coastal Plain location, fertilization increased CAI from 10.3 to 14.8 Mg·ha1. Leaf biomass increased with competition control (4.95.5 Mg·ha1) and fertilization (4.46.0 Mg·ha1). Leaf biomass increased with stand age for the fertilized stands (5.37.0 Mg·ha1 between age 7 and 13) and decreased with stand age for nonfertilized stands (4.94.0 Mg·ha1 between age 7 and 13). At the Coastal Plain location, fertilization increased the GE of the age-7 stands from 2.34 to 2.86 but decreased the GE of the age-13 stands from 2.32 to 2.14. In general, GE decreased as mean tree size increased indicating that changes in GE related to treatments may be confounded with changes in tree size. Results of this experiment emphasize the importance of nutrition on stand growth as fertilization increased leaf biomass and may increase stem production per unit of foliage at early stages of development.
Radial variations in cation exchange capacity and base saturation rate in the wood of pedunculate oak and European beech
Authors: Herbauts J , Penninckx V , Gruber W , Meerts P
Published: November 2002

In a mixed forest stand on an ochreous brown earth in the Belgian Ardennes, pedunculate oak (Quercus robur L.) and European beech (Fagus sylvatica L.) have outwardly decreasing cation concentration profiles in wood. To test if these profiles can be ascribed to endogenous factors or to decreased availability of cations in the soil, radial profiles of water-soluble, exchangeable, and total cations and of cation exchange capacity (CEC) of wood were determined. In both species, [Formula: see text]75% of K is in the water-soluble form so is of little use for dendrochemical monitoring. About 80% of Mg is adsorbed on wood exchange sites. For Ca, 30 (beech) to 60% (oak) of total content cannot be extracted by SrCl2 and is, thus, relatively immobile in wood. Wood CEC decreases from pith to bark in European beech and from pith to outer heartwood in pedunculate oak. Decreasing profiles of exchangeable Ca and Mg in pedunculate oak and exchangeable Ca in European beech are strongly constrained by CEC and, thus, are not related to environmental change. Base cation saturation rate shows no consistent radial change in either species. European beech maintained much higher base cation saturation rate than pedunculate oak, although both species had similar CEC. In conclusion, the results do not provide convincing evidence for a significant change in nutritional status of pedunculate oak and European beech in the Belgian Ardennes due to atmospheric pollution.
Effects of simulated post-harvest light availability and soil compaction on deciduous forest herbs
Authors: Small Christine J , McCarthy Brian C
Published: November 2002

To better understand the response of eastern deciduous forest herbs to microenvironmental changes associated with logging, the effects of experimental light and soil compaction treatments were examined in six herbaceous plant species characteristic of varying successional stages. We found severe growth reductions and increased mortality of Osmorhiza claytonii (Michx.) C.B. Clarke, a shade-tolerant forest perennial, when grown in full sun and greater soil compaction. Deeply shaded conditions, similar to those beneath regenerating forests, resulted in reduced growth of early successional species such as Galium aparine L., and Eupatorium rugosum Houtt. Growth of other species such as Geum canadense Jacq., and Elymus hystrix L. appeared to increase in the patchy, intermediate light treatment mimicking mature eastern deciduous forests. Soil compaction caused severe reductions in height and biomass of Eupatorium rugosum and O. claytonii, early- and late-successional species, respectively. While harvested stands experience relatively uniform light environments, canopy gaps and sunflecks in mature eastern deciduous forests create heterogeneous light environments often correlated with recruitment, growth, and diversity of understory herbs. Therefore, management approaches that minimize alteration of forest environments and mimic natural disturbance patterns may be important to the maintenance and regeneration of forest herbs.
Missing growth rings at the trunk base in suppressed balsam fir saplings
Authors: Parent Sylvain , Morin Hubert , Messier Christian
Published: November 2002

Numerous researchers have suggested a causal relationship between low leaf biomass in suppressed trees and the lack of radial growth at the base of the trunk. The objective of this study was to verify this relationship with suppressed balsam fir (Abies balsamea (L.) Mill.) saplings found growing in an old-growth fir stand. A total of 29 saplings varying in height from 67 to 183 cm were uprooted. All saplings had adventitious roots. All terminal bud scars (TBS) found between the apex of the terminal leader and the trunk base (first adventitious root) as well as those found below ground were localized, and rings were counted between TBS along the aboveground trunk. Various morphological traits and the ratio of photosynthetic tissue dry mass (P, needles) to non-photosynthetic tissue dry mass (nP, aboveground stem) were used as an indicator of tree vigour. Between 3 and 33 rings counted along the aboveground trunk were missing at the trunk base. The number of missing rings at the base of the trunk was correlated with total height (r = 0.41), height growth (r = 0.51), radial growth (r = 0.44), the P/nP ratio (r = 0.73), and the proportion of live crown (r = 0.62). Moreover, from 2 to 35 additional rings, missing at the trunk base, were found in the belowground section of trunk and these missing rings were associated with the adventitious roots phenomenon. In conclusion, suppressed firs had missing rings at the base of the trunk. When all of the missing rings were added to the number of rings counted at the base of the trunk, age estimates provided a different temporal pattern of recruitment compared with that obtained by solely counting rings at the base of the trunk. Stem analysis on the entire trunk is the best aging method for suppressed balsam fir saplings.
How long do trees take to reach breast height after fire in northeastern Ontario?
Authors: Vasiliauskas Stan , Chen Han YH
Published: November 2002

Accurate determination of stand establishment ages is important in developing growth and yield models and in studying stand dynamics of fire-origin stands. The study objective was to determine time to reach breast height for black spruce (Picea mariana (Mill.) BSP), jack pine (Pinus banksiana Lamb.), trembling aspen (Populus tremuloides Michx.), and white birch (Betula papyrifera Marsh.) from fire origin stands under different site conditions in northeastern Ontario. Stands were randomly selected from burns with known fire dates. In each stand, three to six dominant and codominant trees of a selected species were cored at breast height (1.3 m above the ground level) to determine time to reach breast height. Trembling aspen and white birch did not differ for time to reach breast height after fire, taking 6 or 7 years, jack pine took marginally longer (8 years), whereas black spruce took the longest (18 years). While time to reach breast height did not vary among site conditions as described by soil texture and moisture regime, it was positively related to time since fire. The results of this study indicate that stand establishment dates and total tree ages can be substantially underestimated if breast height age is used as the stand age, resulting in misinterpretations of growth and yield and forest succession.
Nonparametric estimation of stand volume using spectral and spatial features of aerial photographs and old inventory data
Authors: Anttila Perttu
Published: November 2002

The forest management planning inventories for private forests in Finland are currently carried out in stand-level field inventories. To decrease the amount of fieldwork, aerial photographs and old inventory data could be utilized. The main objectives were to test the accuracy of a method based on these data sources and the effect of stand shape on the accuracy. Median pixel values, semivariances, and old inventory data were extracted for each of the 577 stands in the study. These data were applied as indicator attributes in k-nearest-neighbor estimation of stand volume. Stand-level estimates were computed as weighted means of k most similar neighbors. When all the stands were used, a root mean square error of 29.9% was obtained. Old inventory data proved to be valuable auxiliary information. It was also found that exclusion of stands with tortuous boundaries and small area decreased the error. The accuracy of mean volume estimation just met the requirements for stand-level inventory, but the method still needs further research before the final conclusion of the applicability for management planning.
Habitat associations of black-backed and three-toed woodpeckers in the boreal forest of Alberta
Authors: Hoyt Jeff S , Hannon Susan J
Published: November 2002

Recent studies suggest that black-backed (Picoides arcticus) and three-toed woodpeckers (Picoides tridactylus) might decrease in abundance because of habitat loss from fire suppression and short-rotation logging in landscapes managed for forestry. We examined black-backed and three-toed woodpecker occupancy of stands in a 2-year post-fire forest, mature and old-growth spruce and pine forests, and six post-fire coniferous forests of different ages. Three-toeds were detected in old stands and in the 2-year-old burn, and their probability of occupancy of burned forests decreased between 3 and 8 years post-fire. Within 50 km of the 2-year-old burn, black-backs were only detected in the burn and not in old-growth or mature conifer stands. However, they did occupy old coniferous stands located 75 and 150 km from the recent burn. They had a similar probability of occupying stands in the 3-, 4-, and 8-year-old burns but were not detected in the 16-year-old burn. The persistence of three-toed woodpeckers in boreal Alberta will likely depend on the presence of both old-growth and recently burned coniferous forests or forests with old-growth structural characteristics. Black-backed woodpeckers appear to be more burn dependent than three-toeds, and their long-term persistence may depend on the frequency of recently burned forests within their dispersal range.
Cardiovascular effects of peptide kinin B2 receptor antagonists in rats
Authors: Carini F , Guelfi M , Lecci A , Tramontana M , Meini S , Giuliani S , Montserrat X , Pascual J , Fabbri G , Ricci R , Quartara L , Maggi C A
Published: November 2002

Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate (HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B2 receptor antagonist, namely icatibant (0.11 µmol/kg as a bolus) and MEN11270 (0.11 µmol/kg as a bolus or 1 µmol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 µmol/kg did not change BP but at 0.1 µmol/kg increased HR at 30 min from administration. MEN11270 at 0.1 or 0.3 µmol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 µmol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 µmol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN11270 at 1 µmol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN11270 (1 µmol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN11270 (0.1 µmol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN11270 was more rapid than that of icatibant. These results indicate that kinin B2 receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN11270 could be putatively attributed to kinetic characteristics.Key words: icatibant, MEN11270, bradykinin, blood pressure, heart rate.
Expression of tissue kallikrein mRNA in developing rat brains
Authors: Iwadate Hiromoto , Kudo Motoshige , Kizuki Kazuyuki
Published: November 2002

Immunoreactive kallikrein has been demonstrated in the neurons of both prenatal and adult rat brains. However, the preferential site is quite different between the prenatal and adult brains, i.e., the former is mainly in the nuclei, and the latter is in the cell bodies and processes. In this study, the intensity of kallikrein mRNA expression was investigated in prenatal and postnatal rat brains by reverse transcription polymerase chain reaction (RT-PCR). A marked progressive increase in kallikrein mRNA expression was observed during the prenatal and early postnatal stage, with the maximum level at postnatal days 0 and 1 (P0 to P1). This helps to explain the previous immunohistochemical findings in which a strong immuno-intensity of kallikrein in the neurons of prenatal and newborn rat brains was found as compared with adult rats. The function(s) of kallikrein expressed in the neurons in the developing stages is unclear, but the role(s) must be different from that of the adult because of the unequivocal difference in its location between them. It is thus possible that kallikrein has certain unknown important role(s) in the neuronal physiology acting on nuclear protein(s) in the developing stages, although the possibility of function via kinin receptors cannot be excluded at present.Key words: kallikrein, kinin receptor, brain, neuron, mRNA.
Preliminary mutational analysis of the human kinin B2receptor for nonpeptide antagonist ligands recognition
Authors: Meini Stefania , Cucchi Paola , Zappitelli Sabrina , Rotondaro Luigi , Quartara Laura , Giolitti Alessandro , Maggi Carlo Alberto
Published: November 2002

FR173657, LF16,0335, and LF16,0687 are nonpeptide antagonists, endowed with high affinity and selectivity for the human kinin B2receptor. The kinin B2receptor belongs to the family of G-protein-coupled receptors with seven transmembrane (TM) helices. In the present study, we aimed, through computer-assisted modeling and mutagenesis, to identify residues in the human B2receptor (hB2R) amino acid sequence that are involved in nonpeptide antagonist binding in order to build up experimental data as a first step towards a molecular model of nonpeptide ligands binding site. Fourteen amino acid residues within the TM segments were mutated to alanine. The wild type and mutant receptors were stably expressed in Chinese hamster ovary (dhfr) cells and tested for their ability to bind agonist ([3H]bradykinin) and peptide antagonist ([3H]MEN11270) radioligands. The affinity of nonpeptide ligands was determined by heterologous competition experiments using the above radioligands. We found that some mutations in TM2 (W86A) and TM7 (Y295A, N297A) impair the binding affinity of the three nonpeptide antagonists. On the other hand, some mutated residues in TM3 (S117A) and TM6 (W256A) reduce the affinity of LF16,0335 and LF16,0687 only. Results are discussed in order to build up a hypothesis for the likely different interactions of various nonpeptide ligands with the B2receptor.Key words: binding, bradykinin B2receptor, G-protein-coupled receptor, mutagenesis, nonpeptide.
B2receptor activation reduces Erk1 and Erk2 phosphorylation induced by insulin-like growth factor-1, platelet-derived growth factor-BB, and high glucose in rat isolated glomeruli
Authors: Cellier Eric , Duchêne Johan , Pécher Christiane , Alric Céline , Bascands Jean-Loup , Schanstra Joost Peter , Girolami Jean-Pierre
Published: November 2002

Several experimental data document an activation of the mitogen-activated protein kinases Erk1 and Erk2 by bradykinin (BK), an agonist of the kinin B2receptor (B2R). In contrast, other reports showed an inhibitory modulation of mitogenesis by BK. Therefore, we explored in the isolated glomeruli the effect of B2R activation on the signaling of insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-BB (PDGF-BB), and high glucose (HG), three factors that are believed to be involved in the development of glomerulosclerosis via the phosphorylation of Erk1 and Erk2. We observed that the activation of B2R negatively modulates the phosphorylation of Erk1 and Erk2 induced by IGF-1, PDGF-BB, and HG in the glomerulus. These effects are consistent with the hypothesis of a protective role for BK in the kidney during development of glomerulosclerosis and renal pathologies associated with a hyperproliferative state.Key words: bradykinin, kinin B2receptors, growth factors, hyperglycemia, glomerulosclerosis.
Bradykinin B2receptor gene polymorphism is associated with altered urinary albumin/creatinine values in diabetic patients
Authors: Maltais Isabelle , Bachvarova Magdalena , Maheux Pierre , Perron Patrice , Marceau Francois , Bachvarov Dimcho
Published: November 2002

Diabetic nephropathy (DN) is an important microvascular complication of both insulin-dependent and non-insulin-dependent diabetes mellitus. Considerable evidence exists that genetic predisposition is a major determinant in the development of DN. Progress in the understanding of the kinin receptor gene expression indicates their relevance in nephrology and renal pathology. In order to investigate whether clinically relevant polymorphisms of the kinin receptor genes contribute to the genetic predetermination of the renal complication of diabetes, we have initiated a retrospective study with a mixed population of 49 type 1 and 112 type 2 diabetic patients who have been followed for several years by an endocrinologist and (or) nephrologist with periodical functional tests relevant to DN (microalbuminuria, serum and urinary creatinine). The allelic frequencies of four kinin receptor polymorphisms, including three B2R polymorphisms (the C/T58promoter polymorphism, the exon 2 and exon 1 polymorphisms, all of them with assumed clinical significance) and the putative nephroprotective (G/C699) B1R promoter polymorphism, were analyzed in all recruited diabetic patients. Our results indicate a significant association of the B2R exon 1 (+/) genotype with increased urinary albumin/creatinine values (P = 0.026) and serum creatinine levels (P = 0.028). More importantly, the (+) allele of B2R exon 1 polymorphism was associated very significantly with lower albumin/creatinine values in these patients (P = 0.0087). Thus, the B2R exon 1 polymorphism may represent a susceptibility marker for nephropathy progression in diabetic patients.Key words: kinin receptors, gene polymorphisms, diabetic nephropathy.
ACE inhibition and atherogenesis
Authors: Schölkens Bernward A , Landgraf Wolfgang
Published: November 2002

Recent clinical studies such as HOPE, SECURE, and APRES show that angiotensin-converting enzyme (ACE) inhibitors like ramipril improve the prognosis of patients with a high risk of atherothrombotic cardiovascular events. Atherosclerosis, as a chronic inflammatory condition of the vascular system, can turn into an acute clinical event through the rupture of a vulnerable atherosclerotic plaque followed by thrombosis. ACE inhibition has a beneficial effect on the atherogenic setting and on fibrinolysis. Endothelial dysfunction is the end of a common process in which cardiovascular risk factors contribute to inflammation and atherogenesis. By inhibiting the formation of angiotensin II, ACE inhibitors prevent any damaging effects on endothelial function, vascular smooth muscle cells, and inflammatory vascular processes. An increase in the release of NO under ACE inhibition has a protective effect. Local renin-angiotensin systems in the tissue are involved in the inflammatory processes in the atherosclerotic plaque. Circulating ACE-containing monocytes, which adhere to endothelial cell lesions, differentiate within the vascular wall to ACE-containing macrophages or foam cells with increased local synthesis of ACE and angiotensin II. Within the vascular wall, angiotensin II decisively contributes to the instability of the plaque by stimulating growth factors, adhesion molecules, chemotactic proteins, cytokines, oxidized LDL, and matrix metalloproteinases. Suppression of the increased ACE activity within the plaque can lead to the stabilization and deactivation of the plaque by reducing inflammation in the vascular wall, thus lessening the risk of rupture and thrombosis and the resultant acute clinical cardiovascular events. The remarkable improvement in the long-term prognosis of atherosclerotic patients with increased cardiovascular risk might be the clinical result of the contribution made by ACE inhibition in the vascular wall.Key words: ACE inhibition, angiotensin II, atherosclerotic plaque, cardiovascular prognosis.
A bradykinin antagonist and a caspase inhibitor prevent severe pulmonary hypertension in a rat model
Authors: Taraseviciene-Stewart Laimute , Gera Lajos , Hirth Peter , Voelkel Norbert F , Tuder Rubin M , Stewart John M
Published: November 2002

Chronically hypoxic rats (exposed to 5000 m elevation for 3 weeks) develop pulmonary hypertension (PH) that is reversed upon return to normoxia and is blocked by bradykinin (BK) antagonist B9430 treatment (100 µg/kg s.c. three times per week). Treatment of rats with both the synthetic VEGF receptor-1/2 antagonist 3-[(2,4-dimethylpyrrol- 5-yl)methylidenyl]-indolin-2-one (SU5416) (200 mg/kg, single s.c. injection) and hypoxia (3 weeks) causes irreversible severe PH characterized by marked elevation of pulmonary artery pressure (PAP), right ventricular hypertrophy, and obliteration of pulmonary arteries by proliferating endothelial cells (EC). Between weeks 1 and 2 of treatment, there is increased apoptotic EC death and caspase-3 activity. The combination of hypoxia with VEGFR-1 and -2 blockade appears to cause death of normal lung EC and proliferation of an apoptosis-resistant proliferating EC phenotype. Cotreatment with BK antagonist B9430 and (or) the broad caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp) (2 mg/kg three times per week) prevented development of severe PH and caused significant reduction of PAP: 39.7 ± 4.6 mmHg in Z-Asp + SU5416, 37.1 ± 1.2 mmHg in BK antagonist B9430 + SU5416, 27.2 ± 0.7 mmHg in Z-Asp alone, and 36.6 ± 3.0 mmHg in BK antagonist alone versus 48 ± 1.7 mmHg in SU5416-treated rats and 32.8 ± 1.4 mmHg in vehicle-treated controls. The PAP correlated with the right ventricular mass. Pulmonary arteries of rats treated with Z-Asp and BK antagonist B9430 had a marked reduction of intravascular EC, yet there was still evidence of medial muscular hypertrophy, similar to that observed in chronically hypoxic rats not treated with SU5416. We conclude that EC death induced by VEGFR-2 blockade with SU5416 may trigger an EC selection process that allows for the expansion of apoptosis-resistant EC, possibly driven by mechanisms independent of VEGF and VEGFR-2.Key words: bradykinin antagonist, severe pulmonary hypertension, vascular endothelial growth factor receptors, apoptosis.
The bradykinin B1 receptor antagonist B9858 inhibits a nociceptive spinal reflex in rabbits
Authors: Mason Glenn S , Cumberbatch Michael J , Hill Raymond G , Rupniak Nadia MJ
Published: November 2002

There are two bradykinin receptor subtypes, designated B1 and B2. Whilst both have been implicated in nociception, it is believed that there is a low level of constitutive expression of B1 receptors and that their expression is induced by inflammation or tissue damage. The present study investigated the role of B1 receptors in spinal nociceptive processing using an in vivo electrophysiological assay in decerebrate, spinalized rabbits, a species that shares close B1 receptor homology with the human receptor. Inflammation was induced in the paw by an injection of complete Freund's adjuvant at least 1 h before recording single motor unit activity of the semitendinous/biceps femoris muscle in response to a noxious pinch of the foot. Control animals received an intraplantar injection of saline. The peptide B1 receptor antagonist B9858 was administered i.v. and caused dose-dependent and complete inhibition of the nociceptive spinal reflex (ID50 = 1 mg·kg1). In control animals without paw inflammation, B9858 had no effect. These findings are consistent with other evidence that peptide B1 receptor antagonists inhibit spinal nociceptive reflexes only after induction of B1 receptors by inflammation and support the potential therapeutic utility of B1 receptor antagonists as analgesic and anti-inflammatory drugs.Key words: bradykinin B1 receptor, inflammation, spinal reflex, rabbit.
Autoradiographic detection of kinin receptors in the human medulla of control, hypertensive, and diabetic donors
Authors: Buck Hudson de Sousa , Ongali Brice , Thibault Gaétan , Lindsey Charles J , Couture Réjean
Published: November 2002

Kinins have been elected to the status of central neuromediators. Their effects are mediated through the activation of two G-protein-coupled receptors, denoted B1 and B2. Functional and binding studies suggested that B1 and B2 receptors are upregulated in the medulla and spinal cord of hypertensive and diabetic rats. The aim of this study was to localize and quantify kinin receptors in post-mortem human medulla obtained from normotensive, hypertensive, and diabetic subjects, using in vitro receptor autoradiography with the radioligands [125I]HPP-HOE140 (B2 receptor) and [125I]HPP[des-Arg10]-HOE140 (B1 receptor). Data showed specific binding sites for B2 receptor (0.41.5 fmol/mg tissue) in 11 medullary nuclei from 4 control specimens (paratrigeminal > ambiguus > cuneate, gelatinous layer of the caudal spinal trigeminal nucleus > caudal and interpolar spinal trigeminal, external cuneate, solitary tract > hypoglossal > gracile > inferior olivary nuclei). Increased density of B2 receptor binding sites was observed in seven medullary nuclei of four hypertensive specimens (paratrigeminal > external cuneate > interpolar and caudal spinal trigeminal, gracile, inferior olivary > hypoglossal nuclei). B2 receptor binding sites were seemingly increased in the same medullary nuclei of two diabetic specimens. Specific binding sites for B1 receptor (1.05 and 1.36 fmol/mg tissue) were seen only in the inferior olivary nucleus in two out of the ten studied specimens. The present results support a putative role for kinins in the regulation of autonomic, nociceptive, and motor functions at the level of the human medulla. Evidence is also provided that B2 receptors are upregulated in medullary cardiovascular centers of subjects afflicted of cardiovascular diseases.Key words: bradykinin, hypertension, diabetes, human brain.
Kinin B1 receptor antagonists with multi-enzymatic resistance properties
Authors: Neugebauer Witold , Blais Paul A , Hallé Stephanie , Filteau Catherine , Regoli Domenico , Gobeil, Jr. Fernand
Published: November 2002

The kinin B1 receptor has been implicated in a variety of pathological states; therefore, potent, selective, and specific antagonists with prolonged duration of action in vivo are needed. Using R-715 (AcLys[D-β-Nal7,Ile8] desArg9BK) as a template, new peptides containing α-MePhe in position 5, Oic in position 2, and AcOrn instead of AcLys at the N-terminal were prepared and tested for their antagonist potency, their selectivity, and their specificity for the kinin B1 receptor. In vitro metabolic stabilities toward aminopeptidase M (from human plasma), aminopeptidase P (from human platelets), and angiotensin-converting enzyme (purified from rabbit lung) were also investigated. The results of this study indicate that the three modifications applied separately are as well tolerated as they are when present conjointly in the template R-715. Indeed, pA2 values of R-715 (ranging from 8.40 to 8.5) do not differ significantly from the analogues R-954 and R-955 (both ranging from 8.4 to 8.6) when measured at kinin B1 receptors from rabbit aortas and human umbilical veins. Moreover, the chemical modifications utilized in the peptides R-954 and R-955 have provided resistance against aminopeptidases M and P, as well as the angiotensin-converting enzyme, unlike the early (e.g., Lys[Leu8]desArg9BK) and more recent (e.g., R-715, B-9858) generations of B1 receptor antagonists. Ongoing in vivo assays will validate the assumption that the analogues R-954 and R-955 have a prolonged duration of action.Key words: bradykinin, antagonists, B1 receptors, peptidases, metabolism.
Mechanisms underlying the contraction induced by bradykinin in the guinea pig epithelium-denuded trachea
Authors: Schlemper Valfredo , Calixto João B
Published: November 2002

This study investigates some of the mechanisms by which bradykinin (BK) triggers contraction of epithelium-denuded strips of guinea pig trachea (GPT). Cumulative or single additions of BK, T-BK, L-BK, or ML-BK in the presence of captopril (30 µM) produced graded GPT contractions with the following rank order of potency (EC50level): T-BK (31.3 nM) > BK (40.0 nM) > L-BK (56.0 nM) > ML-BK (77.0 nM). BK-induced contraction (100 nM) in GPT was completely inhibited by either HOE 140 or NPC 17731 with mean IC50values of 17 and 217 nM, respectively. Addition of BK (100 nM) at 30 min intervals, induced progressive tachyphylaxis, which was complete after 4 h. The tachyphylaxis induced by BK was unaffected by L-NOARG (nitric oxide synthase inhibitor, 100 µM) or valeryl salicylate (a cyclooxygenase-1 (COX-1) inhibitor, 30 µM), but was prevented by a low concentration of indomethacin, diclofenac (non-selective COX inhibitors, 3 nM each) or by NS 398 (a COX-2 inhibitor, 10 nM). Furthermore, higher concentrations of indomethacin, diclofenac, phenidone (a lypooxygenase (LOX) and COX inhibitor), or NS 398, caused graded inhibition of BK-induced contraction, with mean IC50values of 0.28, 0.08, 46.37, and 0.15 µM, respectively. Together, these results suggest that BK-induced contraction in GPT involves activation of B2receptors and release of prostanoids from COX-2 pathway. Furthermore, the tachyphylaxis induced by BK was insensitive to the nitric oxide and COX-1 inhibitors, but was prevented by non-selective and selective COX-2 inhibitors, indicating a mediation via COX-2-derived arachidonic acid metabolites.Key words: guinea pig trachea, bradykinin, B2receptors, desensitization, prostaglandins.
COHERENCE RESONANCE: ON THE USE AND ABUSE OF THE FANO FACTOR
Authors: SHUAI J. W. , ZENG S. , JUNG P.
Published: November 2002

Coherence resonance describes a phenomenon in excitable systems in which a suitable dose of noise generates excitation-events that maximizes its periodicity or coherence. The Fano-factor, defined as the ratio of the standard deviation of the time-intervals between successive events and the average time interval, exhibits a minimum at this optimal noise level. It is shown here that a decreasing Fano factor is a necessary but not a sufficient criterion to indicate enhanced coherence of a signal.