Protease-activated receptor-2 peptides activate neurokinin-1 receptors in the mouse isolated trachea

Protective roles for protease-activated receptor-2 (PAR2) in the airways including activation of epithelial chloride (Cl-) secretion are based on the use of presumably PAR(2)-selective peptide agonists. To determine whether PAR(2) peptide-activated Cl- secretion from mouse tracheal epithelium is dependent on PAR(2), changes in ion conductance across the epithelium [short-circuit current (I-SC)] to PAR(2) peptides were measured in Ussing chambers under voltage clamp. In addition, epithelium and endothelium-dependent relaxations to these peptides were measured in two established PAR(2) bioassays, isolated ring segments of mouse trachea and rat thoracic aorta, respectively. Apical application of the PAR(2) peptide SLIGRL caused increases in I-SC, which were inhibited by three structurally different neurokinin receptor-1 (NK1R) antagonists and inhibitors of Cl- channels but not by capsaicin, the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37), or the nonselective cyclooxygenase inhibitor indomethacin. Only high concentrations of trypsin caused an increase in I-SC but did not affect the responses to SLIGRL. Relaxations to SLIGRL in the trachea and aorta were unaffected by the NK1R antagonist nolpitantium (SR 140333) but were abolished by trypsin desensitization. The rank order of potency for a range of peptides in the trachea I-SC assay was 2-furoyl-LIGRL > SLCGRL > SLIGRL > SLIGRT > LSIGRL compared with 2-furoyl-LIGRL > SLIGRL > SLIGRT > SLCGRL (LSIGRL inactive) in the aorta relaxation assay. In the mouse trachea, PAR(2) peptides activate both epithelial NK1R coupled to Cl- secretion and PAR(2) coupled to prostaglandin E-2-mediated smooth muscle relaxation. Such a potential lack of specificity of these commonly used peptides needs to be considered when roles for PAR(2) in airway function in health and disease are determined.

The effect of larval age on morphology and gene expression during ascidian metamorphosis

Metamorphosis is both an ecological and a developmental genetic transition that an organism undergoes as a normal part of ontogeny. Many organisms have the ability to delay metamorphosis when conditions are unsuitable. This strategy carries obvious benefits, but may also result in severe consequences for older larvae that run low on energy. In the marine environment, some lecithotrophic larvae that have prolonged periods in the plankton may begin forming postlarval and juvenile structures that normally do not appear until after settlement and the initiation of metamorphosis. This precocious activation of the postlarval developmental program may reflect an adaptation to increase the survival of older, energy-depleted larvae by allowing them to metamorphose more quickly. In the present study, we investigate morphological and genetic consequences of delay of metamorphosis in larvae of Herdmania momus (a solitary stolidobranch ascidian). We observe significant morphological and genetic changes during prolonged larval life, with older larvae displaying significant changes in RNA levels, precocious migration of mesenchyme cells, and changes in larval shape including shortening of the tail. While these observations suggest that the older H. momus larvae are functionally different from younger larvae and possibly becoming more predisposed to undergo metamorphosis, we did not find any significant differences in gene expression levels between postlarvae arising from larvae that metamorphosed as soon as they were competent and postlarvae developing from larvae that postponed metamorphosis. This recalibration, or convergence, of transcript levels in the early postlarva suggests that changes that occur during prolonged larval life of H. momus are not necessarily associated with early activation of adult organ differentiation. Instead, it suggests that an autonomous developmental program is activated in H. momus upon the induction of metamorphosis regardless of the history of the larva.

Analytical electron microscopy of proton exchange membrane fuel cells

Microtome sections of proton exchange membrane cells produce a wide range of information ranging from macroscopic distribution of components through specimens in which the detailed distribution of catalyst particles can be observed. Using modern data management practices it is possible to combine information at different scales and correlate processing and performance data. Analytical electron microscopy reveals the compositional variations across used cells at the electrolyte/electrode interface. In particular analytical techniques indicate that sulphur concentrations are likely to diminish at the interface Nafion/anode interface. © 2006 Elsevier B.V. All rights reserved.

Examining the role of networking capability in small and medium firm internationalization

While research on SME internationalization has increased, there remains a lack of relevant theory on the SME internationalization process. The literature reports that small firms overcome their resource poverty-based constraints to internationalization by developing network relationships. Networking enables SMEs to acquire much needed internationalization process knowledge, and knowledge for the development of innovative products and services for this internationalization. However, networking activity has not yet been conceptualized and measured as a competitive capability in internationalization research. Drawing on the capability-based theory of competitive strategy, this paper conjectures that internationally entrepreneurial SMEs build and nurture distinctive networking capabilities, enabling them to acquire new knowledge. These learning capabilities enable them to pursue innovation thereby facilitating nternationalization. Data from Australian firms largely supports the conceptual framework. Implications for theory and practice are presented.

Business education in operations management

This paper examines trends in the practice of Operations Management and in teaching the field in major Business Schools. Operations Management has been defined as the design and management of transformation processes that create value for society. The operations function is the one function directly involved in that transformation, and hence is directly responsible for the activities that justify the existence of the firm, both economically and as a value-creating organization in society. The top rated schools in Operations Management are the top-rated research-intensive Business Schools in the world. Operations Management is an area that has been undergoing rapid change in response to changes in business practices worldwide. It is at the heart of changes of which the AACSB report Management Education at Risk, August 2002 (p 20), comments of Business Schools in general: ‘With regard to global relevance (of Business Schools), the complex opportunities and challenges that emanate from the world scope of operations, outsourcing, supply chains, partnerships, and financial and consumer markets – all linked in real time through the Internet – are not reflected adequately in curricula and learning approaches.’ Products, and even services, depend increasingly on advanced technology. This is true globally and especially so for countries in South East and East Asia, from which Australian Universities draw a significant number of students. Services operations management has become much more important, while there are both educational and industrial needs in management science or operations research.

A comparison of sales response predictions from demand models applied to store-level versus panel data

In order to generate sales promotion response predictions, marketing analysts estimate demand models using either disaggregated (consumer-level) or aggregated (store-level) scanner data. Comparison of predictions from these demand models is complicated by the fact that models may accommodate different forms of consumer heterogeneity depending on the level of data aggregation. This study shows via simulation that demand models with various heterogeneity specifications do not produce more accurate sales response predictions than a homogeneous demand model applied to store-level data, with one major exception: a random coefficients model designed to capture within-store heterogeneity using store-level data produced significantly more accurate sales response predictions (as well as better fit) compared to other model specifications. An empirical application to the paper towel product category adds additional insights. This article has supplementary material online.

Staying on track

Rick Delbridge and Francesca Mariotti states that efforts to regulate and impose budgetary restrictions on the Formula One (F1) motorsport industry in the UK can have significant adverse effects on engineering professionals. It is expected that these efforts will adversely affect innovations in the engineering industry. These engineers rely on the F1 motorsport industry to introduce new innovations. The motorsport industry has enabled these professionals to combine engineering capability, design creativity, and innovation to develop new technologies and products. The motorsport industry and engineering professionals have worked jointly to conduct extensive research and develop the latest technologies, materials, and products. It is expected that potential regulatory and budgetary restrictions on the motorsport industry will minimize opportunities for engineers to be involved in innovations.

Overcoming network overload and redundancy in inter-organizational networks:the roles of potential and latent ties

This paper builds on Granovetter's distinction between strong and weak ties [Granovetter, M. S. 1973. The strength of weak ties. Amer. J. Sociol. 78(6) 1360–1380] in order to respond to recent calls for a more dynamic and processual understanding of networks. The concepts of potential and latent tie are deductively identified, and their implications for understanding how and why networks emerge, evolve, and change are explored. A longitudinal empirical study conducted with companies operating in the European motorsport industry reveals that firms take strategic actions to search for potential ties and reactivate latent ties in order to solve problems of network redundancy and overload. Examples are given, and their characteristics are examined to provide theoretical elaboration of the relationship between the types of tie and network evolution. These conceptual and empirical insights move understanding of the managerial challenge of building effective networks beyond static structural contingency models of optimal network forms to highlight the processes and capabilities of dynamic relationship building and network development. In so doing, this paper highlights the interrelationship between search and redundancy and the scope for strategic action alongside path dependence and structural influences on network processes.

Racing for radical innovation

How motorsport companies harness network diversity for discontinuous innovation.

Racing for radical innovation:how motorsport companies harness network diversity for discontinuous innovation

The motorsport industry is a significant part of the UK economy. According to industry estimates approximately 4,500 companies are involved in the UK Motorsport and Performance Engineering Industry and its wide-ranging support activities. The industry has an annual turnover of £6.0 billion, and contributes £3.6 billion worth of exports. The Motorsport Industry Association estimates that the support side of the sector alone "involving events management, public relations, marketing, sponsorship and a host of other support functions" accounts for approximately £1.7 billion of the yearly industry total. And in terms of employment, UK Motorsport supports 38,500 full and part-time jobs, including 25,000 engineers.

Networks of learning : how motorsport companies collaborate and share knowledge:evidence from the UK and Italian motorsport industries

The motorsport industry is a high value-added and highly innovative business sector. The UK’s leading racing car manufacturers are world class centres of research, development and engineering. However, individual firms in the sector do not have the range and depth of capabilities to compete independently in motorsport’s dynamic and competitive environment. Industry attention has therefore progressively focused on how networks of collaborating firms can work together to develop new products, improve business processes and reduce costs. This report presents findings from a three year Cardiff Business School study which examined the ways in which firms collaborate as part of wider networks. The research involved gathering data from over 120 firms in the UK and Italian motorsport sectors.

Estimating the SCAN*PRO model of store sales: HB, FM or just OLS?

In this paper we investigate whether consideration of store-level heterogeneity in marketing mix effects improves the accuracy of the marketing mix elasticities, fit, and forecasting accuracy of the widely-applied SCAN*PRO model of store sales. Models with continuous and discrete representations of heterogeneity, estimated using hierarchical Bayes (HB) and finite mixture (FM) techniques, respectively, are empirically compared to the original model, which does not account for store-level heterogeneity in marketing mix effects, and is estimated using ordinary least squares (OLS). The empirical comparisons are conducted in two contexts: Dutch store-level scanner data for the shampoo product category, and an extensive simulation experiment. The simulation investigates how between- and within-segment variance in marketing mix effects, error variance, the number of weeks of data, and the number of stores impact the accuracy of marketing mix elasticities, model fit, and forecasting accuracy. Contrary to expectations, accommodating store-level heterogeneity does not improve the accuracy of marketing mix elasticities relative to the homogeneous SCAN*PRO model, suggesting that little may be lost by employing the original homogeneous SCAN*PRO model estimated using ordinary least squares. Improvements in fit and forecasting accuracy are also fairly modest. We pursue an explanation for this result since research in other contexts has shown clear advantages from assuming some type of heterogeneity in market response models. In an Afterthought section, we comment on the controversial nature of our result, distinguishing factors inherent to household-level data and associated models vs. general store-level data and associated models vs. the unique SCAN*PRO model specification.