Evolutionary agglomeration theory: increasing returns, diminishing returns, and the industry life cycle

According to Marshall’s agglomeration theory, Krugman’s New Economic Geography models, and Porter’s cluster policies, firms should receive increasing returns from a trinity of agglomeration economies: a local pool of skilled labour, local supplier linkages, and local knowledge spillovers. Recent evolutionary theories suggest that whether agglomeration economies generate increasing returns or diminishing returns depends on time, and especially the evolution of the industry life cycle. At the start of the twenty-first century, we re-examine Marshall’s trinity of agglomeration economies in the city-region where he discovered them. The econometric results from our multivariate regression models are the polar opposite of Marshall’s. During the later stages of the industry life cycle, Marshall’s agglomeration economies decrease the economic performance of firms and create widespread diminishing returns for the economic development of the city-region, which has evolved to become one of the poorest city-regions in Europe.

PAR-2 Regulates Dental Pulp Inflammation Associated with Caries

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Drivers of Supply Network Governance: An Explorative Study of the Dutch Chemical Industry.

The authors identify a number of drivers of supply network governance, a widely appraised governance form aimed at reaping the benefits of both vertical integration and market exchange. Case studies conducted in the Dutch chemical industry are used to explore these drivers. The findings identify interdependence of organizational activities and asset-specific investments as the key drivers of supply network governance in the chemical industry. Firms enjoy relational rents and tend to share knowledge in supply network relationships, however these factors seem to strengthen supply network relationships rather than create them.

Human Dental Pulp Fibroblasts Express the “Cold-sensing” Transient Receptor Potential Channels TRPA1 and TRPM8

Introduction: Transient receptor potential (TRP) channels comprise a group of nonselective calcium-permeable cationic channels, which are polymodal sensors of environmental stimuli such as thermal changes and chemicals. TRPM8 and TRPA1 are cold-sensing TRP channels activated by moderate cooling and noxious cold temperatures, respectively. Both receptors have been identified in trigeminal ganglion neurones, and their expression in nonneuronal cells is now the focus of much interest. The aim of this study was to investigate the molecular and functional expression of TRPA1 and TRPM8 in dental pulp fibroblasts.
Methods: Human dental pulp fibroblasts were derived from healthy molar teeth. Gene and protein expression was determined by polymerase chain reaction and Western blotting. Cellular localization was investigated by immunohistochemistry, and TRP functionality was determined by Ca2+ microfluorimetry.
Results: Polymerase chain reaction and Western blotting showed gene and protein expression of both TRPA1 and TRPM8 in fibroblast cells in culture. Immunohistochemistry studies showed that TRPA1 and TRPM8 immunoreactivity co-localized with the human fibroblast surface protein. In Ca2+ microfluorimetry studies designed to determine the functionality of TRPA1 and TRPM8 in pulp fibroblasts, we showed increased intracellular calcium ([Ca2+]i) in response to the TRPM8 agonist menthol, the TRPA1 agonist cinnamaldehyde, and to cool and noxious cold stimuli, respectively. The responses to agonists and thermal stimuli were blocked in the presence of specific TRPA1 and TRPM8 antagonists.
Conclusions: Human dental pulp fibroblasts express TRPA1 and TRPM8 at the molecular, protein, and functional levels, indicating a possible role for fibroblasts in mediating cold responses in human teeth.

A comparison of four extraction methods for substance P, neurokinin A and calcitonin gene-related peptide from human dental pulp tissue

Measuring neuropeptides in biological tissues by radioimmunoassay requires efficient extraction that maintains their immunoreactivity. Many different methods for extraction have been described, but there is little information on optimal extraction methods for individual neuropeptides from human dental pulp tissue. The aim was therefore to identify an effective extraction procedure for three pulpal neuropeptides: substance P. neurokinin A and calcitonin gene-related peptide. Tissue was obtained from 20 pulps taken from teeth freshly extracted for orthodontic reasons. The pulp samples were divided into four equal groups and different extraction methods were used for each group. Boiling whole pulp in acetic acid gave the highest overall yield and, in addition, offered an easy and rapid means of pulp tissue processing. The use of protease inhibitors did not increase the recovery of the immunoreactive neuropeptides but did provide the best combination of maximal recoveries and minimal variability. These results should be useful for planning the extraction of these neuropeptides from human pulp tissue in future studies. (C) 1999 Elsevier Science Ltd. All rights reserved.