143 research outputs found

    Local festivals, social capital and sustainable destination development: experiences in East London

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    This paper explores the nature of social capital arising from engagement in local festivals and the implications of this for the social sustainability of an emerging destination. Two case studies are developed from a longitudinal research project which investigates local festivals staged in the Hackney Wick and Fish Island area adjacent to Queen Elizabeth Olympic Park in East London, UK between 2008 and 2014. This area has been directly affected by extensive development and regeneration efforts associated with the staging of the London 2012 Olympic Games. The two festivals considered here respond to the challenges and opportunities arising for local people as the area changes. One festival aims to foster a sense of community by creating shared experiences and improving communication across diverse groups. The other draws together the cultural community, links them to the opportunities arising as the area emerges as a destination, and attracts visitors. These festivals increase social capital in the area, but its distribution is very uneven. The accrual of social capital exacerbates existing inequalities within the host community, favouring the “haves” at the expense of the “have nots”. There are tensions between the development of social capital and social sustainability in this emerging destination

    Early warning signals of simulated Amazon rainforest dieback

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    Copyright © The Author(s) 2013. This article is published with open access at Springerlink.comWe test proposed generic tipping point early warning signals in a complex climate model (HadCM3) which simulates future dieback of the Amazon rainforest. The equation governing tree cover in the model suggests that zero and non-zero stable states of tree cover co-exist, and a transcritical bifurcation is approached as productivity declines. Forest dieback is a non-linear change in the non-zero tree cover state, as productivity declines, which should exhibit critical slowing down. We use an ensemble of versions of HadCM3 to test for the corresponding early warning signals. However, on approaching simulated Amazon dieback, expected early warning signals of critical slowing down are not seen in tree cover, vegetation carbon or net primary productivity. The lack of a convincing trend in autocorrelation appears to be a result of the system being forced rapidly and non-linearly. There is a robust rise in variance with time, but this can be explained by increases in inter-annual temperature and precipitation variability that force the forest. This failure of generic early warning indicators led us to seek more system-specific, observable indicators of changing forest stability in the model. The sensitivity of net ecosystem productivity to temperature anomalies (a negative correlation) generally increases as dieback approaches, which is attributable to a non-linear sensitivity of ecosystem respiration to temperature. As a result, the sensitivity of atmospheric CO2 anomalies to temperature anomalies (a positive correlation) increases as dieback approaches. This stability indicator has the benefit of being readily observable in the real world.NERCJoint DECC/Defra Met Office Hadley Centre Climate ProgrammeUniversity of Exete

    Stellar Archaeology: a Keck Pilot Program on Extremely Metal-Poor Stars from the Hamburg/ESO Survey. II. Abundance Analysis

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    We present a detailed abundance analysis of 8 stars selected as extremely metal poor candidates from the Hamburg/ESO Survey (HES). For comparison, we have also analysed 3 extremely metal-poor candidates from the HK survey, and 3 additional bright metal-poor stars. With this work, we have doubled the number of extremely metal-poor stars ([Fe/H]≀3.0\le 3.0) with high-precision abundance analyses. Our sample of extremely metal-poor candidates from the HES contains 3 stars with [Fe/H] ≀−3.0\le -3.0, 3 more with [Fe/H]≀−2.8\le -2.8, and 2 stars that are only slightly more metal rich. Thus, the chain of procedures that led to the selection of these stars from the HES successfully provides a high fraction of extremely metal-poor stars. We verify that our stellar parameters, derived in Paper I, lead to acceptable ionization and excitation balances for Fe, ruling out substantial non-LTE effects in Fe. For the α−\alpha-elements Mg, Si, Ca, Ti, the light element Al, the iron-peak elements Sc, Cr, Mn, and the neutron capture elements Sr and Ba, we find trends in abundance ratios [X/Fe] similar to those found by previous studies. However,the scatter in most of these ratios, even at [Fe/H]≀−3.0\le -3.0 dex, is surprisingly small. Only Sr and Ba show scatter larger than the expected errors. Future work (the 0Z project) will provide much stronger constraints on the scatter (or lack thereof) in abundances for a greater number of stars. We discuss the implications of these results for the early chemical evolution of the Galaxy, including such issues as the number of contributing SN, and the sizes of typical fragments in which they were born. In addition, we have identified a very metal poor star that appears to be the result of the s-process chain, operating in a very metal-poor environment, with extremely enhanced C, Ba, and Pb, and somewhat enhanced Sr.Comment: 36 pages, 9 tables, 14 figures included; accepted for publication in the July 2002 issue of The Astronomical Journa

    MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV

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    A novel human coronavirus, SARS-CoV, emerged suddenly in 2003, causing approximately 8000 human cases and more than 700 deaths worldwide. Since most animal models fail to faithfully recapitulate the clinical course of SARS-CoV in humans, the virus and host factors that mediate disease pathogenesis remain unclear. Recently, our laboratory and others developed a recombinant mouse-adapted SARS-CoV (rMA15) that was lethal in BALB/c mice. In contrast, intranasal infection of young 10-week-old C57BL/6 mice with rMA15 results in a nonlethal infection characterized by high titer replication within the lungs, lung inflammation, destruction of lung tissue, and loss of body weight, thus providing a useful model to identify host mediators of protection. Here, we report that mice deficient in MyD88 (MyD88−/−), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to rMA15 infection. The genetic absence of MyD88 resulted in enhanced pulmonary pathology and greater than 90% mortality by day 6 post-infection. MyD88−/− mice had significantly higher viral loads in lung tissue throughout the course of infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue and recruitment of inflammatory monocytes/macrophages to the lung was severely impaired in MyD88−/− mice compared to wild-type mice. Furthermore, mice deficient in chemokine receptors that contribute to monocyte recruitment to the lung were more susceptible to rMA15-induced disease and exhibited severe lung pathology similar to that seen in MyD88−/−mice. These data suggest that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection

    Molecular mechanisms of toxicity of silver nanoparticles in zebrafish embryos.

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    addresses: Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK. [email protected]: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. http://pubs.acs.org/doi/abs/10.1021/es401758d. Please cite the published version© 2013 American Chemical SocietySupporting Information: Further details on the methodology and results for the characterization of the silver particles used for the exposures, mortality curves, sequencing analysis, and a number of supporting figures and tables. This material is available free of charge via the Internet at http://pubs.acs.org.Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk-, and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24 h of exposure, but with a recovery at 48 h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24 h, but not at 48 h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms.Natural Environment Research Council (NERC)NERC Biomolecular Analysis FacilityUK Environment AgencySystems Biology Seed fund, University of Exete

    A method for detergent-free isolation of membrane proteins in their local lipid environment.

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    Despite the great importance of membrane proteins, structural and functional studies of these proteins present major challenges. A significant hurdle is the extraction of the functional protein from its natural lipid membrane. Traditionally achieved with detergents, purification procedures can be costly and time consuming. A critical flaw with detergent approaches is the removal of the protein from the native lipid environment required to maintain functionally stable protein. This protocol describes the preparation of styrene maleic acid (SMA) co-polymer to extract membrane proteins from prokaryotic and eukaryotic expression systems. Successful isolation of membrane proteins into SMA lipid particles (SMALPs) allows the proteins to remain with native lipid, surrounded by SMA. We detail procedures for obtaining 25 g of SMA (4 d); explain the preparation of protein-containing SMALPs using membranes isolated from Escherichia coli (2 d) and control protein-free SMALPS using E. coli polar lipid extract (1-2 h); investigate SMALP protein purity by SDS-PAGE analysis and estimate protein concentration (4 h); and detail biophysical methods such as circular dichroism (CD) spectroscopy and sedimentation velocity analytical ultracentrifugation (svAUC) to undertake initial structural studies to characterize SMALPs (∌2 d). Together, these methods provide a practical tool kit for those wanting to use SMALPs to study membrane proteins

    The Chemical Composition of Carbon-Rich, Very Metal-Poor Stars: A New Class of Mildly Carbon-Rich Objects Without Excess of Neutron-Capture Elements

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    We report on an analysis of the chemical composition of five carbon-rich, very metal-poor stars based on high-resolution spectra. One star, CS22948-027, exhibits very large overabundances of carbon, nitrogen, and the neutron-capture elements, as found in the previous study of Hill et al.. This result may be interpreted as a consequence of mass transfer from a binary companion that previously evolved through the asymptotic giant branch stage. By way of contrast, the other four stars we investigate exhibit no overabundances of barium ([Ba/Fe]<0), while three of them have mildly enhanced carbon and/or nitrogen ([C+N]+1). We have been unable to determine accurate carbon and nitrogen abundances for the remaining star (CS30312-100). These stars are rather similar to the carbon-rich, neutron-capture-element-poor star CS22957-027 discussed previously by Norris et al., though the carbon overabundance in this object is significantly larger ([C/Fe]=+2.2). Our results imply that these carbon-rich objects with ``normal'' neutron-capture element abundances are not rare among very metal-deficient stars. One possible process to explain this phenomenon is as a result of helium shell flashes near the base of the AGB in very low-metallicity, low-mass (M~< 1M_sun) stars, as recently proposed by Fujimoto et al.. The moderate carbon enhancements reported herein ([C/Fe]+1) are similar to those reported in the famous r-process-enhanced star CS22892-052. We discuss the possibility that the same process might be responsible for this similarity, as well as the implication that a completely independent phenomenon was responsible for the large r-process enhancement in CS22892-052.Comment: 53 pages, 8 figures, to appear in Ap

    The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

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    <p>Abstract</p> <p>Background</p> <p>Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or Caucasian-American (CAU) breast tissue would affect the tumorigenicity of cancer cells <it>in vitro </it>and <it>in vivo</it>. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women.</p> <p>Methods</p> <p>The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested <it>in vitro </it>via soft agar and invasion assays, and <it>in vivo </it>via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry.</p> <p>Results</p> <p>Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER)<sup>-</sup>, progesterone receptor (PR)/PR<sup>- </sup>cells were significantly more aggressive when in contact with AA ECM, as were ER<sup>+</sup>/PR<sup>+ </sup>cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER<sup>+</sup>/PR<sup>+ </sup>cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1,759 of approximately 8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CAU unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CAU breast tissue.</p> <p>Conclusions</p> <p>This study details normal premenopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities.</p
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