83 research outputs found

    Stonemasons and craft mobility in the Bronze Age eastern Mediterranean

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    This chapter considers the evidence for craft mobility and cultural learning amongst stonemasons in the Bronze Age eastern Mediterranean. It draws on a range of cross-cultural comparative evidence, as well as placing particular emphasis on case studies from Egypt and the Aegean in the 3rd and 2nd millennium BC

    Modelling diffusion of innovation curves using radiocarbon data

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    Archaeological data provide a potential to investigate the diffusion of technological and cultural traits. However, much of this research agenda currently needs more formal quantitative methods to address small sample sizes and chronological uncertainty. This paper introduces a novel Bayesian framework for inferring the shape of diffusion curves using radiocarbon data associated with the presence/absence of a particular innovation. We developed two distinct approaches: 1) a hierarchical model that enables the fitting of an s-shaped diffusion curve whilst accounting for inter-site variations in the probability of sampling the innovation itself, and 2) a non-parametric model that can estimate the changing proportion of the innovation across user-defined time-blocks. The robustness of the two approaches was first tested against simulated datasets and then applied to investigate three case studies, the first pair on the diffusion of farming in prehistoric Japan and Britain and the third on cycles of changes in the burial practices of later prehistoric Britain

    NMR structure of Hsp12, a protein induced by and required for dietary restriction-induced lifespan extension in yeast.

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    Dietary restriction (DR) extends lifespan in yeast, worms, flies and mammals, suggesting that it may act via conserved processes. However, the downstream mechanisms by which DR increases lifespan remain unclear. We used a gel based proteomic strategy to identify proteins whose expression was induced by DR in yeast and thus may correlate with longevity. One protein up-regulated by DR was Hsp12, a small heat shock protein induced by various manipulations known to retard ageing. Lifespan extension by growth on 0.5% glucose (DR) was abolished in an hsp12Δ strain, indicating that Hsp12 is essential for the longevity effect of DR. In contrast, deletion of HSP12 had no effect on growth under DR conditions or a variety of environmental stresses, indicating that the effect of Hsp12 on lifespan is not due to increased general stress resistance. Unlike other small heat shock proteins, recombinant Hsp12 displayed negligible in vitro molecular chaperone activity, suggesting that its cellular function does not involve preventing protein aggregation. NMR analysis indicated that Hsp12 is monomeric and intrinsically unfolded in solution, but switches to a 4-helical conformation upon binding to membrane-mimetic SDS micelles. The structure of micelle-bound Hsp12 reported here is consistent with its recently proposed function as a membrane-stabilising 'lipid chaperone'. Taken together, our data suggest that DR-induced Hsp12 expression contributes to lifespan extension, possibly via membrane alterations

    Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in lifespan extension

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    Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including replicative lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were downregulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was upregulated by DR and that overexpression of Hsp26 extended yeast replicative lifespan. As overexpression of sHSPs in Caenorhabditis elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity

    Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25<sup>th </sup>gestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10<sup>th </sup>centile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p

    The Landscape of the Gibbet

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    From the Murder Act of 1752 until the Anatomy Act of 1832 it was forbidden to bury the bodies of executed murderers unless they had first been anatomised or ‘hung in chains’ (gibbeted). This paper considers some of the observations of the Wellcome-funded project ‘Harnessing the Power of the Criminal Corpse’ as they relate to the practice of gibbeting. The nature of hanging in chains is briefly described before an extensive discussion of the criteria by which gibbets, which often remained standing for many decades, were selected. These are: proximity to the scene of crime, visibility, and practicality. Exceptions, in the forms of those sentenced by the Admiralty Courts, and those sentenced in and around London, are briefly considered. Hanging in chains was an infrequent punishment (anatomical dissection was far more frequently practised) but it was the subject of huge public interest and attracted thousands of people. There was no specified time for which a body should remain hanging, and the gibbet often became a known landmark and a significant place in the landscape. There is a remarkable contrast between anatomical dissection, which obliterates and anonymises the body of the individual malefactor, and hanging in chains, which leaves a highly personalised and enduring imprint on the actual and imaginative landscape
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