583 research outputs found

    Gesture politics and the art of ambiguity: the Iron Age statue from Hirschlanden

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    NoThe discovery of the extraordinary Hirschlanden figure was reported in this journal in 1964. Since then the statue has featured in numerous discussions of Iron Age art and society, to the extent that it has become one of the iconic images of the European Iron Age. It has become almost taken for granted that the Hirschlanden figure is an `intensely masculineÂż warrior statue representing the heroised dead. However, certain aspects of the figure suggest a rather deeper, more ambiguous symbolism. The authors use their up-to-date critique to raise questions about the eclectic character of Iron Age spirituality

    Syntheses and rearrangement reactions of some tertiary phosphine complexes of ruthenium

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    p53 and responses to DNA damage in small airway epithelium

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    Acute lung injury is implicated in many respiratory diseases, including lung adenocarcinoma and emphysema. In this thesis, the hypothesis that the stress protein p53 is important in acute lung injury was investigated. p53 is a short-lived, latent transcription factor which is activated and stabilised in response to a wide range of cellular stresses, including DNA damage. In certain cell types, wild type p53 protein mediates a variety of DNA damage responses and transcriptionally modulates a battery of downstream genes involved in DNA repair, growth control, and apoptosis.The effects of p53 were investigated in a mouse model of acute lung injury and in short-term primary cultures of isolated Clara cells. Gene targeted mice, germline deficient in p53, were exposed to y-irradiation and compared to wild type controls. The in vivo response to DNA damage was characterised in terms of growth arrest, apoptosis, morphology, and gene expression. An acute stress response was observed in vivo, and localised to a subpopulation of the lung epithelium, the bronchiolar cells. p53 was stabilised in this population and was associated with transcriptional induction of Bax, but not other bcl-2 family members. p53 deficient mice did not display this rapid accumulation of Bax transcripts, as assessed by RNase Protection Assay. Within wild type and p53 null mice, y-irradiation did not induce apoptosis in lung epithelial cells at any timepoints studied, as assessed by morphology, but did induce strand breaks that were detectable by TUNEL. Cell cycle activity, as assessed by BrdU incorporation, was infrequent in the lung at all timepoints, regardless of p53 status, and hence an effect of p53 on cell cycle progression was not detected in vivo.The effects of p53-deficiency were additionally investigated in short-term primary cultures of murine bronchiolar Clara cells. Culturing of Clara cells allowed an assessment of the functional consequences of p53 deficiency in proliferating cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. Baseline proliferation rates, as determined by BrdU incorporation, were similar irrespective of p53 status. p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells maintained expression of the Clara cell marker CC10, and were proficient in S phase DNA synthesis, as determined by BrdU incorporation. Nucleation defects in p53 -/- Clara cells associated with abnormalities in mitosis and cytokinesis, as documented by timelapse videomicroscopy, and with increased centrosome number, determined by confocal microscopy. Defects in centrosome homeostasis, mitotic fidelity, and cytokinesis in p53-null Clara cells may reflect a novel role of p53 in preserving genomic integrity in lung epithelium.Effects of p53-deficiency were also studied following exposure to DNA damage. A p53-dependent reduction in the BrdU index was observed in Clara cells following ionizing radiation. The reduction in BrdU index in wild type cells displayed serumdependency, and occurred only in the absence of serum. Apoptosis was infrequent in both genotypes, as determined by time-lapse videomicroscopy. Taken together, these findings demonstrate that in murine primary Clara cell culture, growth arrest but not apoptosis is a p53-mediated response to DNA damage, and that extracellular factors, such as serum, influence this response.In addition, a transgenic model employing lung-specific Cre/lox technology was evaluated. The Cre/lox recombinase system evolved within bacteriophage PI as a mechanism to maintain correct unit copy segregation of the prophage within host cells. This thesis reports application of this system to regulate gene expression in murine lung epithelial cells in vivo, with the eventual goal of generating improved mouse models of acute lung injury. Transgenic mice expressing Cre from the lungspecific promoter human SP-C were crossed to a Floxed DNA Ligase I line, and transgene stability and function assessed by PCR and Southern blot methodologies. The SP-C Cre transgene was demonstrated as stable, but of low copy-number. Excision of the floxed allele, as determined by PCR, was specific to the lung, and was not observed in other tissues. However, the level of excision was poor as assessed by Southern analysis of the excision event. Furthermore, Cre expression was undetectable by RT-PCR. Low expression levels of Cre may reflect the low copy-number of the SP-C/Cre transgene.In summary, this thesis reports on the role of p53 in lung epithelial cells, and on the feasibility of using Cre/lox technologies to regulate gene expression in the lung epithelium of transgenic mice. Bax mRNA induction, but not apoptosis, is a DNA damage response of small airway epithelial cells. Transactivation of Bax was p53- dependent in irradiated lung, as determined by RNase protection assay, and did not occur in p53-/- mice. To further investigate the role of p53 in the lung, a method for extracting, isolating, and culturing Clara cells, a progenitor cell of the lung, was established and incorporated into this analysis. Absence of p53 favours multinucleation and loss of cell cycle arrest in primary Clara cell culture, and highlight additional roles of p53 in cell division and growth control. In addition, this thesis explored the feasibility of using Cre/lox technologies to regulate gene expression in murine lung epithelium. SP-C/Cre mice were assessed in their ability to excise a Floxed DNA Ligase I cassette in the tissues of double transgenic mice. Cre-mediated excision was specific to lung epithelium, but infrequent

    Later prehistoric settlement in the Western Isles of Scotland

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    This study aims to establish an understanding of the nature of settlement development in the Western Isles in the period from c. 1000 BC - 800 AD. A new classification of the sites is formulated to deal with the specific Hebridean context and with the restrictions of the available evidence. This provides a framework for analysis and replaces previous schemes, imported from elsewhere in Scotland, which have tended to confuse the settlement patterns and the settlement development of the area. The large number of older excavations are reassessed in the light of both new approaches to classification and interpretation, and the evidence of recent survey and excavation. A coherent settlement sequence can be seen to emerge, showing a development of monumental architecture in the mid-lst millennium BC from a background of non-monumental domestic settlement: this monumentality persists for several centuries in the form of the atlantic roundhouses and wheelhouses before being gradually replaced by non-monumental, cellular and linear structures in the 1st millennium AD. Structural, locational and spatial analyses combine to demonstrate patterns of settlement development which show the progressive adaptation of Hebridean populations to the changing socioÂŹ economic context. The development of architecture is shown to be linked to contemporary social and economic processes. The environmental context of settlement development is shown to be of great significance in shaping broad trends of settlement development, while the specific responses of human groups indicate the importance of social factors. The final part of the study proposes possible models for the interpretation of settlement change. Material culture, including architecture, can be seen to be used actively in the negotiation of social relationships, both within the islands and between the islanders and the emerging states of Scotland in the 1st millennium AD

    Death and Display in the North Atlantic: The Bronze and Iron Age Human Remains from Cnip, Lewis, Outer Hebrides

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    YesThis paper revisits the series of disarticulated human remains discovered during the 1980s excavations of the Cnip wheelhouse complex in Lewis. Four fragments of human bone, including two worked cranial fragments, were originally dated to the 1st centuries BC/AD based on stratigraphic association. Osteoarchaeological reanalysis and AMS dating now provide a broader cultural context for these remains and indicate that at least one adult cranium was brought to the site more than a thousand years after the death of the individual to whom it had belonged

    Le Castellan (Istres, Bouches-du-RhĂ´ne) : resultats de prospections gĂŠophysique

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    YesTwo seasons of geophysical prospection (magnetic, resistance and ground-penetrating radar) were conducted at the Iron Age oppidum of Le Castellan, Istres, Bouches-du-RhĂ´ne, in order to determine the utility of these techniques for sites in this region. The survey revealed numerous strong anomalies, of which many ran parallel or perpendicular to one another. These are the sorts of responses one might expect from the remains of buried stone wall foundations; this interpretation is supported by the presence, on the west side of the site, of exposed walls on the same alignment as certain of the geophysical anomalies. Overall, the evidence suggests a network of buried buildings and road-ways across the oppidum. One particularly substantial building was identified towards the centre of the site, through the presence of a strong resistance anomaly of distinctly rectilinear form. It appears to represent the remains of a buried stone building with three rooms. In conclusion, the results provide strong encouragement for the further application of geophysical survey in this regio
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