348 research outputs found

    Flood inundation uncertainty: the case of a 0.5% annual probability flood event

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    Aging coastal defences around the UK are challenging managers to redesign schemes to be resilient to extreme events and climate change, be cost-effective, and have minimal or beneficial environmental impact. To enable effective design, reduced uncertainty in the assessment of flood risk due to natural variability within the coastal forcing is required to focus on conditions that pose highest threat. The typical UK standard of protection for coastal defences is to withstand a 0.5% annual probability event, historically also known as a 1 in 200 year return period event. However, joint wave-water level probability curves provide a range of conditions that meet this criterion. We examine the Dungeness and Romney Marsh coastal zone, a region of high value in terms of habitat and energy assets, to quantify the uncertainty in flood depth and extent generated by a 0.5% probability event, and to explore which combinations of wave and water levels generate the greatest threat

    Physical and economic impacts of sea-level rise and low probability flooding events on coastal communities

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    Conventionally flood mapping typically includes only a static water level (e.g. peak of a storm tide) in coastal flood inundation events. Additional factors become increasingly important when increased water-level thresholds are met during the combination of a storm tide and increased mean sea level. This research incorporates factors such as wave overtopping and river flow in a range of flood inundation scenarios of future sea-level projections for a UK case study of Fleetwood, northwest England. With increasing mean sea level it is shown that wave overtopping and river forcing have an important bearing on the cost of coastal flood events. The method presented converts inundation maps into monetary cost. This research demonstrates that under scenarios of joint extreme surge-wave-river events the cost of flooding can be increased by up to a factor of 8 compared with an increase in extent of up to a factor of 3 relative to “surge alone” event. This is due to different areas being exposed to different flood hazards and areas with common hazard where flood waters combine non-linearly. This shows that relying simply on flood extent and volume can under-predict the actual economic impact felt by a coastal community. Additionally, the scenario inundation depths have been presented as “brick course” maps, which represent a new way of interpreting flood maps. This is primarily aimed at stakeholders to increase levels of engagement within the coastal community

    Protecting Energy Infrastructure against the Uncertainty of Future Climate Change: A Real Options Approach

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    The coastal impacts of climate change, including flooding and erosion due to storms and sea-level rise, and the possible adaptation responses have been studied using very different approaches; from very detailed site-specific, process-based investigations and interventions to global macroeconomic assessments of coastal zone vulnerability. This paper presents a flood defence real option analysis methodology that values potential investment decisions made in the building and maintaining of flood defences around electricity infrastructure at local spatial scales for a large region. Real option analysis embraces uncertainty in future climate conditions and flexibility in the management of investment projects to produce a more precise optimal outcome than attained with traditional discount cash flow analysis alone. The method uses high-level analysis from flood inundation models to assess the cost of flooding for energy infrastructure at the present-day up to the highest plausible sea-level rise for the UK in 2100 known as the H++ scenario, which projects a sea-level rise of 1.8 m. These costs feed into a real option valuation model able to identify which energy infrastructure will benefit from investment, and when. This northwest UK study identifies two infrastructure sites that, today, would benefit from flood defence investment over discount cash flow analysis, increasing to an additional 14 in 2050. Using this method has identified 46 sites that would benefit from deferring flood defence investment now, reducing to 35 sites in 2050. This method of project valuation can be applied to any feature within the floodplain, e.g. infrastructure or residential housing, making it an adaptable and useful tool in identifying vulnerable features that require investment to ensure they stay resilient to extreme flood events in the future. This work is the result of an inter-disciplinary collaboration between hydrodynamic modelling, flood risk assessment and economics. The outputs of which are ideal to be fed into a decision-support tool, allowing stakeholders to interrogate and disseminate information about the spatial locations they are interested in

    Culture and collective action: Japan, Germany and the United States after 11 September 2001

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    In order to put a lens on the issue of international security cooperation after 11 September 2001, this article examines the question of how collective action in International Relations becomes possible. The author maintains that a fair amount of inter-state collective action can be understood, even explained, by analysing the culture of the international system. Using discourse analysis as a tool, the analysis addresses the underlying ideas, norms and identities that constitute the relationship between the United States and Japan, on the one hand, and Germany and the United States, on the other, as it has evolved since September 2001. The method exposes how some ideas are privileged over others, how norms are maintained, reformulated and abandoned, how identity is constructed and how power is legitimized in the 'war on terror'

    Expression of the ???6 integrin promotes migration and invasion in squamous carcinoma cells

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    The integrin αvβ6 is a fibronectin receptor whose expression is not detectable on normal oral epithelium but is increased significantly in healing and in oral epithelial dysplasia and oral squamous cell carcinoma, suggesting it may promote changes associated with tumor development. To study whether αvβ6 may drive invasive behavior we have used transfection and retroviral infection to create a panel of epithelial cell lines expressing various levels of αvβ6. We report that increased expression of αvβ6 in malignant keratinocytes promotes invasion and leads to an increased capacity for migration towards fibronectin. αvβ6 expression may have a significant role in contributing to the malignant behavior of epithelial cells

    Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat

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    Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo

    MitoNeoD:a mitochondria-targeted superoxide probe

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    Mitochondrial superoxide (O2⋅−) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2⋅−, but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2⋅− probe, MitoNeoD, which can assess O2⋅− changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2⋅−-sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2⋅− over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria. We demonstrated that MitoNeoD was a versatile and robust probe to assess changes in mitochondrial O2⋅− from isolated mitochondria to animal models, thus offering a way to examine the many roles of mitochondrial O2⋅−production in health and disease

    A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo

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    Coenzyme Q (CoQ) is an essential cofactor, primarily found in the mitochondrial inner membrane where it functions as an electron carrier in the respiratory chain, and a lipophilic antioxidant. The redox state of the CoQ pool is the ratio of its oxidised (ubiquinone) and reduced (ubiquinol) forms, and is a key indicator of mitochondrial bioenergetic and antioxidant status. However, the role of CoQ redox state in vivo is poorly understood, because determining its value is technically challenging due to redox changes during isolation, extraction and analysis. To address these problems, we have developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay that enables us to extract and analyse both the CoQ redox state and the magnitude of the CoQ pool with negligible changes to redox state from small amounts of tissue. This will enable the physiological and pathophysiological roles of the CoQ redox state to be investigated in vivo

    A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo.

    Get PDF
    Coenzyme Q (CoQ) is an essential cofactor, primarily found in the mitochondrial inner membrane where it functions as an electron carrier in the respiratory chain, and as a lipophilic antioxidant. The redox state of the CoQ pool is the ratio of its oxidised (ubiquinone) and reduced (ubiquinol) forms, and is a key indicator of mitochondrial bioenergetic and antioxidant status. However, the role of CoQ redox state in vivo is poorly understood, because determining its value is technically challenging due to redox changes during isolation, extraction and analysis. To address these problems, we have developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay that enables us to extract and analyse both the CoQ redox state and the magnitude of the CoQ pool with negligible changes to redox state from small amounts of tissue. This will enable the physiological and pathophysiological roles of the CoQ redox state to be investigated in vivo

    Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

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    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two
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