Invention, innovation and inspiration: optimisation and resolving technological change in the Sri Lankan archaeological record

Reproduced with permission of the publisher. Details of the publication are available at: http://www.archetype.co.uk/publication-details.php?id=174Abstract not availableThe project was supported by the British Government (Overseas Development Agency) and the Japanese (Kumagi-Hazima-Kagima) and British (Sir Alexander Gibb and Partners, and Balfour Beatty) developers of the Samanalawewa Hydro-Electric scheme. Logistical and financial support were also given by the British Council and the British High Commission, Colombo

Geochemical survey and metalworking: a case study from Exmoor, southwest Britain

Reproduced with permission of the publisher.A series of geochemical surveys were undertaken on Exmoor as part of a multilayered investigation into the rich ironworking history of this landscape. Exmoor was created by semi-metamorphosed sedimentary lithologies, which contain a range of iron ore sources. The Romano-British iron smelting site at Sherracombe Ford was one of several production complexes to exploit these ores and excavation demonstrated evidence of iron smelting and primary iron smithing. Site investigation strategies utilised a range of techniques including geochemical survey, gradiometer survey and excavation. This paper describes one geochemical survey applied at an intra-site level to investigate a large compacted smithing floor and a multiple-use furnace location. Discussion is given to how geochemical survey can be conducted on sites with archaeometallurgical remains and how such data can be analysed and interpreted. Significantly, geochemical and gradiometer surveys are compared and the datasets integrated, the resulting plot indicating a significant potential for the application of these technologies on ironworking sites.English Heritag

Pioneering Metallurgy: The origins of iron and steel making in the Southern Indian subcontinent Telangana Field Survey Interim Report 2011

A chapter from this report ("From the macroscopic to the microscopic: some scientific insights") is in ORE: http://hdl.handle.net/10871/17744British Council UKIER

Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts

RNA virus populations within samples are highly heterogeneous, containing a large number of minority sequence variants which can potentially be transmitted to other susceptible hosts. Consequently, consensus genome sequences provide an incomplete picture of the within- and between-host viral evolutionary dynamics during transmission. Foot-and-mouth disease virus (FMDV) is an RNA virus that can spread from primary sites of replication, via the systemic circulation, to found distinct sites of local infection at epithelial surfaces. Viral evolution in these different tissues occurs independently, each of them potentially providing a source of virus to seed subsequent transmission events. This study employed the Illumina Genome Analyzer platform to sequence 18 FMDV samples collected from a chain of sequentially infected cattle. These data generated snap-shots of the evolving viral population structures within different animals and tissues. Analyses of the mutation spectra revealed polymorphisms at frequencies >0.5% at between 21 and 146 sites across the genome for these samples, while 13 sites acquired mutations in excess of consensus frequency (50%). Analysis of polymorphism frequency revealed that a number of minority variants were transmitted during host-to-host infection events, while the size of the intra-host founder populations appeared to be smaller. These data indicate that viral population complexity is influenced by small intra-host bottlenecks and relatively large inter-host bottlenecks. The dynamics of minority variants are consistent with the actions of genetic drift rather than strong selection. These results provide novel insights into the evolution of FMDV that can be applied to reconstruct both intra- and inter-host transmission routes

Interactions of foot-and-mouth disease virus with cells in organised lymphoid tissue influence innate and adaptive immune responses

Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV „carrier state‟ and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. The aim of this thesis was to study the interaction between FDMV and cells in lymphoid tissue in the natural bovine host, in order to improve our understanding of the protective immune response. Using laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborated by in situ hybridization, it is shown that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. Maintenance of non-replicating FMDV in these sites may represent a source of persisting infectious virus and also contribute to the generation of long-lasting antibody responses against neutralising epitopes of the virus. The role of T-lymphocyte subsets in recovery from FMDV infection in calves was investigated by administering subset-specific mouse monoclonal antibodies. Depletion of circulating CD4+ or WC1+ γδ T cells was achieved for a period extending from before challenge to after resolution of viraemia and peak clinical signs, whereas CD8+ cell depletion was only partial. Depletion of CD4+ cells was also confirmed by analysis of lymph node biopsies 5 days post-challenge. Depletion with anti-WC1 and anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs and immune responses following FMDV infection. Three of the four CD4+ T-cell-depleted calves failed to generate an antibody response to the non-structural polyprotein 3ABC, but generated a neutralising antibody response similar to that in the controls, including rapid isotype switching to IgG antibody. These data suggest that antibody responses to sites on the surface of the virus capsid are T cell-independent whereas those directed against the non-structural proteins are T cell-dependent. CD4 depletion was found to substantially inhibit antibody responses to the G-H peptide loop VP1135-156 on the viral capsid, indicating that responses to this particular site, which has a more mobile structure than other neutralising sites on the virus capsid, are T cell-dependent. Depletion of CD4+ T cells had no adverse effect on the magnitude or duration of clinical signs or clearance of virus from the circulation. In conclusion, CD4+ T-cell-independent antibody responses play a major role in the resolution of primary infection with FMDV in cattle

Early iron objects of southwest China: a case study of iron objects excavated from Qiaogoutou cemetery site, Sichuan Province

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.Iron objects excavated from the Qiaogoutou cemetery site provides an opportunity to study iron-making technology during the late Warring States period and the early Western Han dynasty in southwest China. Five metallographic samples were prepared and analysed. The results are discussed in relation to other studies of iron objects discovered in southwest China

An infectious recombinant foot-and-mouth disease virus expressing a fluorescent marker protein

Foot-and-mouth disease virus (FMDV) is one of the most extensively studied animal pathogens because it remains a major threat to livestock economies worldwide. However, the dynamics of FMDV infection are still poorly understood. The application of reverse genetics provides the opportunity to generate molecular tools to further dissect the FMDV life cycle. Here, we have used reverse genetics to determine the capsid packaging limitations for a selected insertion site in the FMDV genome. We show that exogenous RNA up to a defined length can be stably introduced into the FMDV genome, whereas larger insertions are excised by recombination events. This led us to construct a recombinant FMDV expressing the fluorescent marker protein, termed iLOV. Characterization of infectious iLOV-FMDV showed the virus has a plaque morphology and rate of growth similar to the parental virus. In addition, we show that cells infected with iLOV-FMDV are easily differentiated by flow cytometry using the inherent fluorescence of iLOV and that cells infected with iLOV-FMDV can be monitored in real-time with fluorescence microscopy. iLOV-FMDV therefore offers a unique tool to characterize FMDV infection in vitro, and its applications for in vivo studies are discussed

Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis.

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. FMD virus (FMDV) shows a strong tropism for epithelial cells, and FMD is characterised by cell lysis and the development of vesicular lesions in certain epithelial tissues (for example, the tongue). By contrast, other epithelial tissues do not develop lesions, despite being sites of viral replication (for example, the dorsal soft palate). The reasons for this difference are poorly understood, but hypotheses are difficult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial differential equation model of FMDV infection in bovine epithelial tissues and used it to explore a range of hypotheses about epithelium structure which could be driving differences in lytic behaviour observed in different tissues. Our results demonstrate that, based on current parameter estimates, epithelial tissue thickness and cell layer structure are unlikely to be determinants of FMDV-induced cell lysis. However, differences in receptor distribution or viral replication amongst cell layers could influence the development of lesions, but only if viral replication rates are much lower than current estimates.This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant code: BBS/E/I/00001397], http://www.bbsrc.ac.uk/home/home.aspx. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013857

Advanced producer services and urban growth.

Service industries have traditionally been viewed as secondary to, and at best supportive of, manufacturing industries. This thesis is designed to challenge this view with regard to a particular group of services, advanced producer services. It contends that this group makes both direct and indirect contributions to economic growth at urban region level by operating in two ways: firstly, by providing intermediate inputs into the production of finished products and secondly, in its own right, selling its services to clients outside of the region. This contradicts the expectations of theoretical models of urban growth such as export base theory which cast services in an entirely dependent role. Analysis of the spatial distribution of advanced producer services reveals a significant degree of regional inequality in their provision which given the contribution they make to growth has potentially serious implications for the economic regeneration of many of Britain's depressed areas