The importance of the tissue transglutaminase-fibronectin heterocomplex in the RGD-independent cell adhesion and fibronectin matrix deposition

Tissue transglutaminase (TG2) has been reported as a wound response protein. Once over-expressed by cells under stress such as during wound healing or following tissue damage, TG2 can be secreted and deposited into extracellular matrix, where it forms a heterocomplex (TG-FN) with the abundant matrix protein fibronectin (FN). A further cellular response elicited after tissue damage is that of matrix remodelling leading to the release of the Arg-Gly-Asp (RGD) containing matrix fragments by matrix matelloproteinases (MMPs). These peptides are able to block the interaction between integrin cell surface receptors and ECM proteins, leading to the loss of cell adhesion and ultimately Anoikis. This study provides a mechanism for TG2, as a stress-induced matrix protein, in protecting the cells from the RGD-dependent loss of cell adhesion and rescuing the cells from Anoikis. Mouse fibroblasts were used as a major model for this study, including different types of cell surface receptor knockout mouse embryonic fibroblasts (MEFs) (such as syndecan-4, a5, ß1 or ß3 integrins). In addition specific syndecan-2 targetting siRNAs, ß1 integrin and a4ß1 integrin functional blocking antibodies, and a specific targeting peptide against a5ß1 integrin A5-1 were used to investigate the involvement of these receptors in the RGD-independent cell adhesion on TG-FN. Crucial for TG-FN to compensate the RGD-independent cell adhesion and actin cytoskeleton formation is the direct interaction between the heparan sulfate chains of syndecan-4 and TG2, which elicits the inside-out signalling of a5ß1 integrin and the intracellular activation of syndecan-2 by protein kinase C a (PKCa). By using specific inhibitors, a cell-permeable inhibiting peptide and the detection of the phosphorylation sites for protein kinases and/or the translocation of PKCa via Western blotting, the activation of PKCa, focal adhesion kinase (FAK), ERK1/2 and Rho kinase (ROCK) were confirmed as downstream signalling molecules. Importantly, this study also investigated the influence of TG-FN on matrix turnover and demonstrated that TG-FN can restore the RGD-independent FN deposition process via an a5ß1 integrin and syndecan-4/2 co-signalling pathway linked by PKCa in a transamidating-independent manner. These data provide a novel function for TG2 in wound healing and matrix turnover which is a key event in a number of both physiological and pathological processes.

Management role in employee participation:a comparative study of multi-national enterprises in India and the U.K.

This research is an Anglo-Indian comparative case study. It studies managerial action in the participation arena of two British multi-nationals i.e. Cadbury Limited and ICI plc. The research was carried out in matched pairs of factories of the above named companies, located in the Midlands of the UK and in Bombay in India. The data for this research was collected through semi-structured interviews with managers and non-management actors, study of company documents and non-participant observation of some participation forums. The research conceptualises the idea of a `participation arena' consisting of the structures, processes, purposes and dynamics of participation. This arena is visualised as broadly reflecting the organisation structure and can be divided into corporate, unit and shopfloor level. Managerial action in this arena is examined in terms of interaction between three sets of factors i.e. company business objectives, strategies and policies; managerial values of power and control; and the responses of unions. Similarities and differences between management action in the home and host plants of the two multi-national companies are also examined. The major findings of the research are as follows. There is significant difference between the participation arena of the parent and the subsidiary company. The latter is marked by absence of higher level participation forums and lack of opportunity for employees to discuss, let alone influence, key decisions. This results from parent company control over key activities of the subsidiary. The similarities in management action in the participation arenas of the two companies in both countries can be attributed to the operation of the three sets of factors mentioned above. Nevertheless, the particular circumstances of each company are a greater influence on managerial action than the national context. Finally, future areas of research in this field are explored.

Innovation in the pharmaceutical industry:a study of the effects of regulation on the U.K. pharmaceutical industry

A history of government drug regulation and the relationship between the pharmaceutical companies in the U.K. and the licensing authority is outlined. Phases of regulatory stringency are identified with the formation of the Committees on Safety of Drugs and Medicines viewed as watersheds. A study of the impact of government regulation on industrial R&D activities focuses on the effects on the rate and direction of new product innovation. A literature review examines the decline in new chemical entity innovation. Regulations are cited as a major but not singular cause of the decline. Previous research attempting to determine the causes of such a decline on an empirical basis is given and the methodological problems associated with such research are identified. The U.K. owned sector of the British pharmaceutical industry is selected for a study employing a bottom-up approach allowing disaggregation of data. A historical background to the industry is provided, with each company analysed or a case study basis. Variations between companies regarding the policies adopted for R&D are emphasised. The process of drug innovation is described in order to determine possible indicators of the rate and direction of inventive and innovative activity. All possible indicators are considered and their suitability assessed. R&D expenditure data for the period 1960-1983 is subsequently presented as an input indicator. Intermediate output indicators are treated in a similar way and patent data are identified as a readily-available and useful source. The advantages and disadvantages of using such data are considered. Using interview material, patenting policies for most of the U.K. companies are described providing a background for a patent-based study. Sources of patent data are examined with an emphasis on computerised systems. A number of searches using a variety of sources are presented. Patent family size is examined as a possible indicator of an invention's relative importance. The patenting activity of the companies over the period 1960-1983 is given and the variation between companies is noted. The relationship between patent data and other indicators used is analysed using statistical methods resulting in an apparent lack of correlation. An alternative approach taking into account variations in company policy and phases in research activity indicates a stronger relationship between patenting activity, R&D Expenditure and NCE output over the period. The relationship is not apparent at an aggregated company level. Some evidence is presented for a relationship between phases of regulatory stringency, inventive and innovative activity but the importance of other factors is emphasised.

Matrix-assisted diffusion-ordered spectroscopy:mixture resolution by NMR using SDSmicelles

Diffusion-ordered spectroscopy (DOSY) is a powerful technique for mixture analysis, but in its basic form it cannot separate the component spectra for species with very similar diffusion coefficients. It has been recently demonstrated that the component spectra of a mixture of isomers with nearly identical diffusion coefficients (the three dihydroxybenzenes) can be resolved using matrix-assisted DOSY (MAD), in which diffusion is perturbed by the addition of a co-solute such as a surfactant [R. Evans, S. Haiber, M. Nilsson, G. A. Morris, Anal. Chem. 2009, 81, 4548-4550]. However, little is known about the conditions required for such a separation, for example, the concentrations and concentration ratios of surfactant and solutes. The aim of this study was to explore the concentration range over whichmatrix-assisted DOSY using the surfactant SDS can achieve diffusion resolution of a simple model set of isomers, the monomethoxyphenols. The results show that the separation is remarkably robust with respect to both the concentrations and the concentration ratios of surfactant and solutes, supporting the idea that MAD may become a valuable tool formixture analysis. © 2010 John Wiley & Sons, Ltd.

A multiple pheromone ant clustering algorithm

Ant colony optimisation algorithms model the way ants use pheromones for marking paths to important locations in their environment. Pheromone traces are picked up, followed, and reinforced by other ants but also evaporate over time. Optimal paths attract more pheromone and less useful paths fade away. The main innovation of the proposed Multiple Pheromone Ant Clustering Algorithm (MPACA) is to mark objects using many pheromones, one for each value of each attribute describing the objects in multidimensional space. Every object has one or more ants assigned to each attribute value and the ants then try to find other objects with matching values, depositing pheromone traces that link them. Encounters between ants are used to determine when ants should combine their features to look for conjunctions and whether they should belong to the same colony. This paper explains the algorithm and explores its potential effectiveness for cluster analysis. © 2014 Springer International Publishing Switzerland.

Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan

Study Design. Coculture assays of the migration and interaction of human intervertebral disc cells and chick sensory nerves on alternate substrata of collagen and aggrecan. Objective. To examine the effects of aggrecan on disc cell migration, how disc cells and sensory nerves interact, and whether disc cells affect previously reported inhibitory effects of aggrecan on sensory nerve growth. Summary of Background Data. Human intervertebral disc aggrecan is inhibitory to sensory nerve growth in vitro, suggesting that a loss of aggrecan from the disc may have a role in the increased innervation seen in disc degeneration. Endothelial cells that appear to co-migrate with nerves into degenerated intervertebral disc express neurotrophic factors, but the effects of disc cells on nerve growth are not known. Methods. Human disc cells were seeded onto tissue culture plates that had been coated with type I collagen and human intervertebral disc aggrecan. Explants of chick dorsal root ganglions (DRGs) were subsequently added to the plates and sensory neurite outgrowth stimulated by the addition of nerve growth factor. Time-lapse video and fluorescence microscopy were used to examine the migration and interaction of the disc cells and sensory neurites, in the context of the different matrix substrata. The effects of disc cell conditioned medium on nerve growth were also examined. Results. Disc cells spread and migrated on collagen until they encountered the aggrecan substrata, where some cells, but not all, were repelled. In coculture, DRG neurites extended onto the collagen/disc cells until they encountered the aggrecan, where, like the disc cells, many were repelled. However, in the presence of disc cells, some neurites were able to cross onto this normally inhibitory substratum. The number of neurite crossings onto aggrecan correlated significantly with the number of disc cells present on the aggrecan. In control experiments using DRG alone, all extending neurites were repelled at the collagen/aggrecan border. Conditioned medium from disc cell cultures stimulated DRG neurite outgrowth on collagen but did not increase neurite crossing onto aggrecan substrata. Conclusions. Human disc cells migrate across aggrecan substrata that are repellent to sensory DRG neurites. Disc cells synthesize neurotrophic factors in vitro that promote neurite outgrowth. Furthermore, the presence of disc cells in coculture with DRG partially abrogates the inhibitory effects of aggrecan on nerve growth. These findings have important implications for the regulation of nerve growth into the intervertebral disc, but whether disc cells promote nerve growth in vivo remains to be determined.

Crack closure and residual stress effects in fatigue of a particle-reinforced metal matrix composite

A study of the influence of macroscopic quenching stresses on long fatigue crack growth in an aluminium alloy-SiC composite has been made. Direct comparison between quenched plate, where high residual stresses are present, and quenched and stretched plate, where they have been eliminated, has highlighted their rôle in crack closure. Despite similar strength levels and identical crack growth mechanisms, the stretched composite displays faster crack growth rates over the complete range of ΔK, measured at R = 0.1, with threshold being displaced to a lower nominal ΔK value. Closure levels are dependent upon crack length, but are greater in the unstretched composite, due to the effect of surface compressive stresses acting to close the crack tip. These result in lower values of ΔKeff in the unstretched material, explaining the slower crack growth rates. Effective ΔKth values are measured at 1.7 MPa√m, confirmed by constant Kmax testing. In the absence of residual stress, closure levels of approximately 2.5 MPa√m are measured and this is attributed to a roughness mechanism.

In situ studies of structure-reactivity relations in biodiesel synthesis over nanocrystalline MgO

High temperature processing of solvothermally synthesised MgO nanoparticles promotes striking changes in their morphology, and surface chemical and electronic structure. As-prepared NanoMgO comprised ∼4 nm cubic periclase nanocrystals, interspersed within an amorphous Mg(OH)(OCH3) matrix. These crystallites appear predominantly (1 0 0) terminated, and the overall material exhibits carbonate and hydroxyl surface functionalities of predominantly weak/moderate base character. Heating promotes gradual crystallisation and growth of the MgO nanoparticles, and concomitant loss of Mg(OH)(OCH3). In situ DRIFTS confirms the residual precursor and surface carbonate begin to decompose above 300 °C, while in situ XPS shows these morphological changes are accompanied by the disappearance of surface hydroxyl/methoxide species and genesis of O- centres which enhance both the surface density and basicity of the resulting stepped and defective MgO nanocrystals. The catalytic performance in tributyrin transesterification with methanol is directly proportional to the density of strong surface base sites. © 2010 Elsevier B.V. All rights reserved.

The multiple pheromone Ant clustering algorithm

Ant Colony Optimisation algorithms mimic the way ants use pheromones for marking paths to important locations. Pheromone traces are followed and reinforced by other ants, but also evaporate over time. As a consequence, optimal paths attract more pheromone, whilst the less useful paths fade away. In the Multiple Pheromone Ant Clustering Algorithm (MPACA), ants detect features of objects represented as nodes within graph space. Each node has one or more ants assigned to each feature. Ants attempt to locate nodes with matching feature values, depositing pheromone traces on the way. This use of multiple pheromone values is a key innovation. Ants record other ant encounters, keeping a record of the features and colony membership of ants. The recorded values determine when ants should combine their features to look for conjunctions and whether they should merge into colonies. This ability to detect and deposit pheromone representative of feature combinations, and the resulting colony formation, renders the algorithm a powerful clustering tool. The MPACA operates as follows: (i) initially each node has ants assigned to each feature; (ii) ants roam the graph space searching for nodes with matching features; (iii) when departing matching nodes, ants deposit pheromones to inform other ants that the path goes to a node with the associated feature values; (iv) ant feature encounters are counted each time an ant arrives at a node; (v) if the feature encounters exceed a threshold value, feature combination occurs; (vi) a similar mechanism is used for colony merging. The model varies from traditional ACO in that: (i) a modified pheromone-driven movement mechanism is used; (ii) ants learn feature combinations and deposit multiple pheromone scents accordingly; (iii) ants merge into colonies, the basis of cluster formation. The MPACA is evaluated over synthetic and real-world datasets and its performance compares favourably with alternative approaches.

The Matrix Method of Determining the Fault Tolerance Degree of a Computer Network Topology

This work presents a theoretical-graph method of determining the fault tolerance degree of the computer network interconnections and nodes. Experimental results received from simulations of this method over a distributed computing network environment are also presented.

Key Agreement Protocol Using Elliptic Curve Matrix Power Function

* Work is partially supported by the Lithuanian State Science and Studies Foundation.

A Basis for Z-Graded Identities of Matrices over Infinite Fields

2000 Mathematics Subject Classification: 16R10, 16R20, 16R50

Involution Matrix Algebras – Identities and Growth

2000 Mathematics Subject Classification: 16R50, 16R10.

A Statistical Approach for Multilingual Document Clustering and Topic Extraction from Clusters

2000 Mathematics Subject Classification: 62H30

Cayley-Hamilton Theorem for Matrices over an Arbitrary Ring

2000 Mathematics Subject Classification: 15A15, 15A24, 15A33, 16S50.