The cellular response to transglutaminase-cross-linked collagen

Collagen, type I, is a highly abundant natural protein material which has been cross-linked by a variety of methods including chemical agents, physical heating and UV irradiation with the aim of enhancing its physical characteristics such as mechanical strength, thermal stability, resistance to proteolytic breakdown, thus increasing its overall biocompatibility. However, in view of the toxicity of residual cross-linking agents, or impracticability at large scales, it would be more useful if the collagen could be cross-linked by a milder, efficient and more practical means by using enzymes as biological catalysts. We demonstrate that on treating native collagen type I (from bovine skin) with both tissue transglutaminase (TG2; tTG) and microbial transglutaminase (mTG; Streptoverticillium mobaraense) leads to an enhancement in cell attachment, spreading and proliferation of human osteoblasts (HOB) and human foreskin dermal fibroblasts (HFDF) when compared to culture on native collagen. The transglutaminase-treated collagen substrates also showed a greater resistance to cell-mediated endogenous protease degradation than the native collagen. In addition, the HOB cells were shown to differentiate at a faster rate than on native collagen when assessed by measurement of alkaline phosphatase activity and osteopontin expression. © 2005 Elsevier Ltd. All rights reserved.

Alzheimer's disease: Are cellular neurofibrillary tangles linked to beta/A4 formation at the projection sites?

The density of senile plaques (SP) and cellular neurofibrillary tabgles (NFT) revealed by the Glees and Gallyas stains; and beta/A4 deposits revealed by immunocytochemical staining, was estimated in the hippocampus and adjacent gyri in Alzheimer's disease (AD). Stepwise multiple regression was used to detemine whether the density of cellular NFT was related to the density of SP or beta/A4 deposits totalled over the projection sites. Cellular NFT density was only weakly correlated with the density of Glees SP and beta/A4 deposits at some of the projection sites. However, beta/A4 deposit density in a tissue was strongly correlated with the density of beta/A4 deposits at the projection sites suggesting that the lesions could spread through the brain. Hence, although there is a strong correlation between the density of beta/A4 deposits in different parts of the hippocampal formation there is little association between SP or beta/A4 and cellular NFT. These results do not provide strong evidence that beta/A4 protein is the cause of the neuritc changes in AD.

Stabilisation of isocyanate cross linked polybutadiene binder

Isocyanate cross-linked hydroxy terminated polybutadiene is used as a binder for solid rocket propellant. Rocket motors containing this propellant require a storage life of at least 20 years. During storage it has been found that the important rubbery properties of the binder can be lost due to oxidative cross-linking of the polybutadiene chains. This could cause catastrophic failure when the rocket motor is required. At present the bis-hindered phenol Calco 2246 is used as a thermal oxidative stabiliser, but it's performance is only adequate. This has led to the search for a more efficient stabiliser system. To hasten the evaluation of new antioxidant systems the use of dynamic thermal analysis was investigated. Results showed that a tentative relationship existed between predictions by thermal analysis and the long term oven ageing for simple single antioxidant systems. But for more complex systems containing either autosynergistic or mixed antioxidants no relationship was observed suggesting that results for such an "accelerated" technique cannot be used for the purpose of extrapolation for long term performance. This was attributed to the short time and more aggressive condition used (hjgher temperature and oxygen rich atmosphere in thermal analysis) altering the mechanism of action of the antioxidants and not allowing time for co-operative effect of the combined antioxidant system to form. One potential problem for the binder system is the use of an diisocyanate as a cross-linking agent. This reacts with the hydroxyl hydrogen on the polymer as well as other active hydrogens such as those contained in a number of antioxidants, affecting both cross-linking and antioxidant effectiveness. Studies in this work showed that only antioxidants containing amine moieties have a significant affect on binder preparation, with the phenolic antioxidants not reacting. This is due to the greater nucleophilicity of the amines. Investigation of a range of antioxidant systems, including potentially homo, hetero and autosynergistic systems, has highlighted a number of systems which show considerably greater effectiveness than the currently used antioxidant Calco 2246. The only single antioxidant which showed improvement was the partially unhindered phenol y-Tocopherol. Of the mixed systems combinations of the sulphur containing antioxidants e.g. DLTP with higher levels of chain-breaking antioxidants, especially Calco 2246, were the most promising. Also the homosynergistic mix of an aromatic amine and a phenol was seen to be very effective but the results were inconsistent. This inconsistency could be explained by the method of sample preparation used. It was shown that the efficiency of a number of antioxidant.s could be dramatically improved by the use of ultrasound during the mixing stage of preparation. The reason for this increase in performance is unclear but in the case of the homosynergistic amine/phenol mix both more efficient mixing and/or the production of a novel mechanism of action are suggested

The effect of cis-5,8,11,14,17-eicosapentaenoic acid upon the contractile mechanisms linked to calcium influx and the mobilisation of intracellular calcium in aortic smooth muscle

Epidemiological studies previously identified cis-5,8,11,14,17-eicosapentaenoic acid (EPA) as the biologically active component of fish oil of benefit to the cardiovascular system. Although clinical investigations demonstrated its usefulness in surgical procedures, its mechanism of action still remained unclear. It was shown in this thesis, that EPA partially blocked the contraction of aortic smooth muscle cells to the vasoactive agents KCl and noradrenaline. The latter effect was likely caused by reducing calcium influx through receptor-operated channels, supporting a recent suggestion by Asano et al (1997). Consistently, EPA decreased noradrenaline-induced contractures in aortic tissue, in support of previous reports (Engler, 1992b). The observed effect of EPA on cell contractions to KCl was not simple due to blocking calcium influx through L-type channels, consistent with a previous suggestion by Hallaq et al (1992). Moreover, EPA caused a transient increase in [Ca2+]i in the absence of extracellular calcium. To resolve this it was shown that EPA increased inositol phosphate formation which, it is suggested, caused the release of calcium from an inositol phosphate-dependent internal binding site, possibly that of an intracellular membrane or superficial sarcoplasmic reticulum, producing the transient increase in [Ca2+]i. As it was shown that the cellular contractile filaments were not desensitised to calcium by EPA, it is suggested that the transient increase in [Ca2+]i subsequently blocks further cell contraction to KCl by activating membrane-associated potassium channels. Activation of potassium channels induces the cellular efflux of potassium ions, thereby hyperpolarising the plasma membrane and moving the membrane potential farther from the activation range for calcium channels. This would prevent calcium influx in the longer term and could explain the initial observed effect of EPA to block cell contraction to KCl.

GIS linked environmental process models

In recent years there has been a great effort to combine the technologies and techniques of GIS and process models. This project examines the issues of linking a standard current generation 2½d GIS with several existing model codes. The focus for the project has been the Shropshire Groundwater Scheme, which is being developed to augment flow in the River Severn during drought periods by pumping water from the Shropshire Aquifer. Previous authors have demonstrated that under certain circumstances pumping could reduce the soil moisture available for crops. This project follows earlier work at Aston in which the effects of drawdown were delineated and quantified through the development of a software package that implemented a technique which brought together the significant spatially varying parameters. This technique is repeated here, but using a standard GIS called GRASS. The GIS proved adequate for the task and the added functionality provided by the general purpose GIS - the data capture, manipulation and visualisation facilities - were of great benefit. The bulk of the project is concerned with examining the issues of the linkage of GIS and environmental process models. To this end a groundwater model (Modflow) and a soil moisture model (SWMS2D) were linked to the GIS and a crop model was implemented within the GIS. A loose-linked approach was adopted and secondary and surrogate data were used wherever possible. The implications of which relate to; justification of a loose-linked versus a closely integrated approach; how, technically, to achieve the linkage; how to reconcile the different data models used by the GIS and the process models; control of the movement of data between models of environmental subsystems, to model the total system; the advantages and disadvantages of using a current generation GIS as a medium for linking environmental process models; generation of input data, including the use of geostatistic, stochastic simulation, remote sensing, regression equations and mapped data; issues of accuracy, uncertainty and simply providing adequate data for the complex models; how such a modelling system fits into an organisational framework.

Accessibility indices and linked trips: a case study of the elderly

The confusion over the concept of accessibility in transport planning and the deficiencies of existing accessibility indices are examined by developing a conceptual framework of accessibility with a fundamental distinction being drawn between the, often conflicting, theoretical and practical dimensions. The theoretical validity of alternative indices is assessed with reference to the problems and assumptions implicit in defining, measuring, valuing and aggregating the variables and components comprising accessibility. The major deficiencies of existing indices are identified as the inability of indices to take account of the potential to link trips between more than one activity location and the level of assumptions implicit in valuing and aggregating accessibility information. In this context, it is argued that accessibility information is more appropriately expressed on a comparative basis in the form of a profile rather than as a composite single-unit index and that the present confines of accessibility measurement must be extended in line with current developments in disaggregate travel and activity modelling. The sensitivity of accessibility levels to the use of alternative value judgements, alternative forms and levels of aggregation and the inclusion of information on the potential to link trips is examined by undertaking a case study. Accessibility profiles are developed for 23 zones in the London Borough of Hammersmith and Fulham showing the accessibility of the elderly to post offices and grocers. In a practical context, the profiles assist in identifying areas and individuals with relatively poor accessibility. The incidence and nature of linked trip-making and its significance and implications for accessibility measurement are explored further by analysing the results of a survey of the elderly's travel patterns. It is concluded that future accessibility analysis should be undertaken at a disaggregate level, taking account of the potential opportunity available from nonhome as well as home origins.

The stabilisation of purified, reconstituted P-glycoprotein by freeze drying with disaccharides

The drug efflux pump P-glycoprotein (P-gp) (ABCB1) confers multidrug resistance, a major cause of failure in the chemotherapy of tumours, exacerbated by a shortage of potent and selective inhibitors. A high throughput assay using purified P-gp to screen and characterise potential inhibitors would greatly accelerate their development. However, long-term stability of purified reconstituted ABCB1 can only be reliably achieved with storage at -80 °C. For example, at 20 °C, the activity of ABCB1 was abrogated with a half-life of <1 day. The aim of this investigation was to stabilise purified, reconstituted ABCB1 to enable storage at higher temperatures and thereby enable design of a high throughput assay system. The ABCB1 purification procedure was optimised to allow successful freeze drying by substitution of glycerol with the disaccharides trehalose or maltose. Addition of disaccharides resulted in ATPase activity being retained immediately following lyophilisation with no significant difference between the two disaccharides. However, during storage trehalose preserved ATPase activity for several months regardless of the temperature (e.g. 60% retention at 150 days), whereas ATPase activity in maltose purified P-gp was affected by both storage time and temperature. The data provide an effective mechanism for the production of resilient purified, reconstituted ABCB1.

Absorptive capacity and the benefits from global reservoirs of knowledge:evidence from a linked China-OECD dataset

This paper investigates the role of absorptive capacity in the diffusion of global technology with sector and firm heterogeneity. We construct the FDI-intensity weighted global R&D stock for each industry and link it to Chinese firm-level panel data relating to 53,981 firms over the period 2001-2005. Non-parametric frontier analysis is employed to explore how absorptive capacity affects technical change and catch-up in the presence of global knowledge spillovers. We find that R&D activities and training at individual firms serve as an effective source of absorptive capability. The contribution of absorptive capacity varies according to the type of FDI and the extent of openness.

Linked data for the 21st Century enterprise:from silos to supply chains

Six actions for collation collective intelligence to inform and accelerate change

Linked data flows in multi-player games for servitisation

The increased data complexity and task interdependency associated with servitization represent significant barriers to its adoption. The outline of a business game is presented which demonstrates the increasing complexity of the management problem when moving through Base, Intermediate and Advanced levels of servitization. Linked data is proposed as an agile set of technologies, based on well established standards, for data exchange both in the game and more generally in supply chains.

Scaling up question-answering to linked data

Linked Data semantic sources, in particular DBpedia, can be used to answer many user queries. PowerAqua is an open multi-ontology Question Answering (QA) system for the Semantic Web (SW). However, the emergence of Linked Data, characterized by its openness, heterogeneity and scale, introduces a new dimension to the Semantic Web scenario, in which exploiting the relevant information to extract answers for Natural Language (NL) user queries is a major challenge. In this paper we discuss the issues and lessons learned from our experience of integrating PowerAqua as a front-end for DBpedia and a subset of Linked Data sources. As such, we go one step beyond the state of the art on end-users interfaces for Linked Data by introducing mapping and fusion techniques needed to translate a user query by means of multiple sources. Our first informal experiments probe whether, in fact, it is feasible to obtain answers to user queries by composing information across semantic sources and Linked Data, even in its current form, where the strength of Linked Data is more a by-product of its size than its quality. We believe our experiences can be extrapolated to a variety of end-user applications that wish to scale, open up, exploit and re-use what possibly is the greatest wealth of data about everything in the history of Artificial Intelligence. © 2010 Springer-Verlag.

Overcoming schema heterogeneity between linked semantic repositories to improve coreference resolution

Schema heterogeneity issues often represent an obstacle for discovering coreference links between individuals in semantic data repositories. In this paper we present an approach, which performs ontology schema matching in order to improve instance coreference resolution performance. A novel feature of the approach is its use of existing instance-level coreference links defined in third-party repositories as background knowledge for schema matching techniques. In our tests of this approach we obtained encouraging results, in particular, a substantial increase in recall in comparison with existing sets of coreference links.

Self-assembly of cross-linked β-cyclodextrin nanocapsules

Stirring of perthiolated β-cyclodextrin in water yields cross-linked hollow capsules ca. 50 nm in diameter, which can be used for encapsulation and controlled release of large molecules as shown using Reichardt's dye. © 2009 The Royal Society of Chemistry.

LEAPS:a semantic web and linked data framework for the Algal biomass domain

In this paper we present, LEAPS, a Semantic Web and Linked data framework for searching and visualising datasets from the domain of Algal biomass. LEAPS provides tailored interfaces to explore algal biomass datasets via REST services and a SPARQL endpoint for stakeholders in the domain of algal biomass. The rich suite of datasets include data about potential algal biomass cultivation sites, sources of CO2, the pipelines connecting the cultivation sites to the CO2 sources and a subset of the biological taxonomy of algae derived from the world's largest online information source on algae.

Consuming linked data in supply chains:enabling data visibility via linked pedigrees

The performance of a supply chain depends critically on the coordinating actions and decisions undertaken by the trading partners. The sharing of product and process information plays a central role in the coordination and is a key driver for the success of the supply chain. In this paper we propose the concept of "Linked pedigrees" - linked datasets, that enable the sharing of traceability information of products as they move along the supply chain. We present a distributed and decentralised, linked data driven architecture that consumes real time supply chain linked data to generate linked pedigrees. We then present a communication protocol to enable the exchange of linked pedigrees among trading partners. We exemplify the utility of linked pedigrees by illustrating examples from the perishable goods logistics supply chain.