Development of an in-vitro model system to investigate the mechanism of muscle protein catabolism induced by proteolysis-inducing factor

The mechanism of muscle protein catabolism induced by proteolysis-inducing factor, produced by cachexia-inducing murine and human tumours has been studied in vitro using C2C12 myoblasts and myotubes. In both myoblasts and myotubes protein degradation was enhanced by proteolysis-inducing factor after 24 h incubation. In myoblasts this followed a bell-shaped dose-response curve with maximal effects at a proteolysis-inducing factor concentration between 2 and 4 nM, while in myotubes increased protein degradation was seen at all concentrations of proteolysis-inducing factor up to 10 nM, again with a maximum of 4 nM proteolysis-inducing factor. Protein degradation induced by proteolysis-inducing factor was completely attenuated in the presence of cycloheximide (1 μM), suggesting a requirement for new protein synthesis. In both myoblasts and myotubes protein degradation was accompanied by an increased expression of the α-type subunits of the 20S proteasome as well as functional activity of the proteasome, as determined by the 'chymotrypsin-like' enzyme activity. There was also an increased expression of the 19S regulatory complex as well as the ubiquitin-conjugating enzyme (E214k), and in myotubes a decrease in myosin expression was seen with increasing concentrations of proteolysis-inducing factor. These results show that proteolysis-inducing factor co-ordinately upregulates both ubiquitin conjugation and proteasome activity in both myoblasts and myotubes and may play an important role in the muscle wasting seen in cancer cachexia. © 2002 Cancer Research UK.

Complementary methods to investigate the development of clogging within a horizontal sub-surface flow tertiary treatment wetland

A combination of experimental methods was applied at a clogged, horizontal subsurface flow (HSSF) municipal wastewater tertiary treatment wetland (TW) in the UK, to quantify the extent of surface and subsurface clogging which had resulted in undesirable surface flow. The three dimensional hydraulic conductivity profile was determined, using a purpose made device which recreates the constant head permeameter test in-situ. The hydrodynamic pathways were investigated by performing dye tracing tests with Rhodamine WT and a novel multi-channel, data-logging, flow through Fluorimeter which allows synchronous measurements to be taken from a matrix of sampling points. Hydraulic conductivity varied in all planes, with the lowest measurement of 0.1 md1 corresponding to the surface layer at the inlet, and the maximum measurement of 1550 md1 located at a 0.4m depth at the outlet. According to dye tracing results, the region where the overland flow ceased received five times the average flow, which then vertically short-circuited below the rhizosphere. The tracer break-through curve obtained from the outlet showed that this preferential flow-path accounted for approximately 80% of the flow overall and arrived 8 h before a distinctly separate secondary flow-path. The overall volumetric efficiencyof the clogged system was 71% and the hydrology was simulated using a dual-path, dead-zone storage model. It is concluded that uneven inlet distribution, continuous surface loading and high rhizosphere resistance is responsible for the clog formation observed in this system. The average inlet hydraulic conductivity was 2 md1, suggesting that current European design guidelines, which predict that the system will reach an equilibrium hydraulic conductivity of 86 md1, do not adequately describe the hydrology of mature systems.

An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P and Ca ions in the surrounding soft tissue after implantation of a calcium phosphate-mullite ceramic composite in a rabbit animal model

Synthetic calcium phosphates, despite their bioactivity, are brittle. Calcium phosphate-mullite composites have been suggested as potential dental and bone replacement materials which exhibit increased toughness. Aluminium, present in mullite, has however been linked to bone demineralisation and neurotoxicity: it is therefore important to characterise the materials fully in order to understand their in vivo behaviour. The present work reports the compositional mapping of the interfacial region of a calcium phosphate-20 wt% mullite biocomposite/soft tissue interface, obtained from the samples implanted into the long bones of healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X-ray micro-fluorescence was used to map simultaneously the distribution of Al, P, Si and Ca across the ceramic-soft tissue interface. A well defined and sharp interface region was present between the ceramic and the surrounding soft tissue for each time period examined. The concentration of Al in the surrounding tissue was found to fall by two orders of magnitude, to the background level, within similar to 35 mu m of the implanted ceramic.

Using discrete event simulation to investigate road delivery policies to UK retailers

Retail customers provide a number of significant challenges to the efficiency and effectiveness of distribution systems. These challengers include shorter delivery windows, fluctuating volumes and a wider product mix. This paper demonstrates the use of discrete-event simulation to investigate policy issues regarding the incorporation of retail customers in a road delivery network from the spoke terminal of a hub and spoke distribution system. In particular a comparison of a mixed (retail and non-retail) delivery policy with a dedicated retail delivery run is made.

A Conceptual Foresight Model to Investigate the Adoption of Radio Frequency Identification Technology in the English National Health Service

Radio Frequency Identification Technology (RFID) adoption in healthcare settings has the potential to reduce errors, improve patient safety, streamline operational processes and enable the sharing of information throughout supply chains. RFID adoption in the English NHS is limited to isolated pilot studies. Firstly, this study investigates the drivers and inhibitors to RFID adoption in the English NHS from the perspective of the GS1 Healthcare User Group (HUG) tasked with coordinating adoption across private and public sectors. Secondly a conceptual model has been developed and deployed, combining two of foresight’s most popular methods; scenario planning and technology roadmapping. The model addresses the weaknesses of each foresight technique as well as capitalizing on their individual, inherent strengths. Semi structured interviews, scenario planning workshops and a technology roadmapping exercise were conducted with the members of the HUG over an 18-month period. An action research mode of enquiry was utilized with a thematic analysis approach for the identification and discussion of the drivers and inhibitors of RFID adoption. The results of the conceptual model are analysed in comparison to other similar models. There are implications for managers responsible for RFID adoption in both the NHS and its commercial partners, and for foresight practitioners. Managers can leverage the insights gained from identifying the drivers and inhibitors to RFID adoption by making efforts to influence the removal of inhibitors and supporting the continuation of the drivers. The academic contribution of this aspect of the thesis is in the field of RFID adoption in healthcare settings. Drivers and inhibitors to RFID adoption in the English NHS are compared to those found in other settings. The implication for technology foresight practitioners is a proof of concept of a model combining scenario planning and technology roadmapping using a novel process. The academic contribution to the field of technology foresight is the conceptual development of foresight model that combines two popular techniques and then a deployment of the conceptual foresight model in a healthcare setting exploring the future of RFID technology.