Transglutaminase and vascular biology: physiopathologic implications and perspectives for therapeutic interventions

Consistent clinical and experimental evidence points to the involvement of two enzymatic systems (the matrix metalloproteinases-MMPs and the protein crosslinking enzymes transglutaminases) in prominent physiologic roles of endothelium in the maintenance of vascular wall integrity, regulation of blood flow and clotting, and exchange of molecules and cells between the extra- and the intravascular space. These issues are briefly discussed in relation to differentiation of the endothelium within the vascular system, mechanisms of molecular regulation and the effects of their disruption in pathology. While the roles of MMPs are now understood in detail and represent a promising target for pharmacological interventions, much less is known on the roles of transglutaminases in vascular biology. These last enzymes are expressed at extremely high levels in endothelial cells and are involved in cell matrix interactions important to angiogenesis and apoptosis/cell death of endothelial cells, in the control of blood clotting and and in the transfer of molecules and cells across the vascular walls. On the clinical side, these properties are relevant in vascular inflammatory processes, atherosclerosis and tumor metastasis. We summarise the large body of evidence available in this perspective and discuss its implications for the development of new therapeutic strategies.

Evaluation and development of drainage and pipeline construction processes

In 1974 Dr D M Bramwell published his research work at the University of Aston a part of which was the establishment of an elemental work study data base covering drainage construction. The Transport and Road Research Laboratory decided to, extend that work as part of their continuing research programme into the design and construction of buried pipelines by placing a research contract with Bryant Construction. This research may be considered under two broad categories. In the first, site studies were undertaken to validate and extend the data base. The studies showed good agreement with the existing data with the exception of the excavation trench shoring and pipelaying data which was amended to incorporate new construction plant and methods. An inter-active on-line computer system for drainage estimating was developed. This system stores the elemental data, synthesizes the standard time of each drainage operation and is used to determine the required resources and construction method of the total drainage activity. The remainder of the research was into the general topic of construction efficiency. An on-line command driven computer system was produced. This system uses a stochastic simulation technique, based on distributions of site efficiency measurements to evaluate the effects of varying performance levels. The analysis of this performance data quantities the variability inherent in construction and demonstrates how some of this variability can be reconciled by considering the characteristics of a contract. A long term trend of decreasing efficiency with contract duration was also identified. The results obtained from the simulation suite were compared to site records collected from current contracts. This showed that this approach will give comparable answers, but these are greatly affected by the site performance parameters.

The evolution and design of safety management systems

Research in safety management has been inhibited by lack of consensus as to the definitions of the terms with which it is concerned and, in general, the lack of an agreed theoretical framework within which to collate and contrast empirical findings. This thesis sets out definitions of key terms (hazard, risk, accident, incident and safety) and provides a theoretical framework. This framework has been informed by many sources but especially the Management Oversight and Risk Tree (MORT), cybernetics and the Viable System Model (VSM). Fieldwork designs are proposed for the empirical development of an analytical framework and its use to assist study of the development of safety management in organisations.

Compressed orally disintegrating tablets:excipients evolution and formulation strategies

Introduction: Orally disintegrating tablets (ODTs) have emerged as one of the novel solid oral dosage forms with a potential to deliver a wide range of drug candidates to both paediatric and geriatric patient populations. Of the plethora of available technologies, compression of excipients offers a cost-effective and translatable methodology for the manufacture of ODTs. Areas covered: The review is a modest endeavour from the authors to assemble literature published over the last couple of decades on formulation development of compressed ODT. It describes the main ODT excipients used since the introduction of this dosage form in the 1990s and explores the switch from cellulose-based excipients towards sugar/polyols. Furthermore, it unfolds the key properties of ODT fillers, binders and disintegrants with an emphasis on their advantages and drawbacks. The review also provides a critical assessment of the various strategies employed for performance enhancement of compressed ODT with a focus on the underlying mechanisms for fast disintegration and acceptable mechanical strength. Expert opinion: Recent increase in the total number of compression-based technologies for ODT development promises to reduce the manufacturing cost of this dosage form in the future. However, some of the developed methods may affect the stability of tablets due to susceptibility to moisture, collapse of pores or the generation of less stable polymorphs which require rigorous testing prior to commercialization. © 2013 Informa UK, Ltd.

Regional evolution and waves of growth:a knowledge-based perspective

The evolution of a regional economy and its competitiveness capacity may involve multiple independent trajectories, through which different sets of resources and capabilities evolve together. However, there is a dearth of evidence concerning how these trends are occurring across the globe. This paper seeks to present evidence in relation to the recent development of the globe’s most productive regions from the viewpoint of their growth trajectories, and the particular form of growth they are experiencing. The aim is to uncover the underlying structure of the changes in knowledge-based resources, capabilities and outputs across regions, and offer an analysis of these regions according to an uncovered set of key trends. The analysis identifies three key trends by which the economic evolution and growth patterns of these regions are differentiated—namely the Fifth Wave Growth, the Third & Fourth Wave Growth, and Government-led Third Wave Growth. Overall, spectacular knowledge-based growth of leading Chinese regions is evident, highlighting a continued shift of knowledge-based resources to Asia. In addition, a superstructure is observed at the global scale, consisting of two separate continuums that explicitly distinguish Chinese regions from the rest in terms of regional growth trajectories.

Regional evolution and waves of growth:a knowledge-based perspective

The evolution of a regional economy and its competitiveness capacity may involve multiple independent trajectories through which different sets of resources and capabilities evolve together. However, there is a dearth of evidence concerning how these trends are occurring across the globe. Based on the underlying tenets of the streams of research relating to regional competitiveness, knowledge cities/regions, and knowledge-based urban development, this paper seeks to present an empirical approach to establishing such evidence in relation to the recent development of the globe’s most productive regions from the viewpoint of their growth trajectories and the particular form of growth they are experiencing. The aim is to uncover the underlying structure of the changes in knowledge-based resources, capabilities and outputs across regions, and offer an analysis of these regions according to an uncovered set of key trends. The analysis identifies three key trends by which the economic evolution and growth patterns of these regions are differentiated – namely the Fifth Wave Growth, the Third & Fourth Wave Growth, and Government-led Third Wave Growth. Overall, spectacular knowledge-based growth of leading Chinese regions is evident, highlighting a continued shift of knowledge-based resources to Asia. In addition, a superstructure is observed at the global scale, consisting of two separate continuums that explicitly distinguish Chinese regions from the rest in terms of regional growth trajectories. © 2014 Elsevier Ltd. All rights reserved. © 2014 Elsevier Ltd. All rights reserved.

Network evolution and the spatiotemporal dynamics of knowledge sourcing

Knowledge accessing from external organisations is important to firms, especially entrepreneurial ones which often cannot generate internally all the knowledge necessary for innovation. There is, however, a lack of evidence concerning the association between the evolution of firms and the evolution of their networks. The aim of this paper is to begin to fill this gap by undertaking an exploratory analysis of the relationship between the vintage of firms and their knowledge sourcing networks. Drawing on an analysis of firms in the UK, the paper finds some evidence of a U-shaped relationship existing between firm age and the frequency of accessing knowledge from certain sources. Emerging entrepreneurial firms tend to be highly active with regard to accessing knowledge for a range of sources and geographic locations, with the rate of networking dropping somewhat during the period of peak firm growth. For instance, it is found that firms tend to less frequently access knowledge sources such as universities and research institutes in their own region during a stage of peak turnover growth. Overall, the results suggest a complex relationship between the lifecycle of the firm and its networking patterns. It is concluded that policymakers need to become more aware that network formation and utilisation by firms is likely to vary dependent upon their lifecycle position.