105 research outputs found

    Impacts of Competitive Seabed Allocation for Offshore Wind Energy: A cash flow analysis of implemented allocation scheme designs, results, and impacts

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    This is the final version. Available from AURES II via the link in this recordExecutive Summary Offshore wind is an important part of the accelerating transition to green energy sources in many maritime countries. To develop offshore wind projects, private developers require access to and tenure over the seabed, which is a scarce and valuable resource controlled and managed by governments. In this report we describe the currently implemented seabed allocation schemes for offshore wind around the world and analyse the economic effects of the fees embedded in the seabed lease agreements. We describe the allocation schemes for seabed including pre-qualification, fees, and method of competition for the examples of UK (England, Wales, and Northern Ireland), UK (Scotland), the United States and the Netherlands. Then, we use a discounted cash flow analysis to assess and compare the timeline and magnitude of the fees. We show that the costs embedded in the seabed lease agreements can be extensive and have been trending upward over time.Economic and Social Research Council (ESRC)European Union Horizon 202

    A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions

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    The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanismin the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events

    CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

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    One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC. © 2014 Huang et al

    Auctions for Renewable Energy Support II - First insights and results of the Horizon2020 project AURES II

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    This is the final version. Available from Funcas via the link in this recordThe Horizon2020 project AURES II aims at ensuring the effective implementation of auctions for renewable energies in the EU Member States (MS). In recent years, auction schemes for the allocation of support for renewable electricity sources (RES) have been advancing rapidly across Europe. Auctions are considered to have brought down support levels and increased planning capability for RES deployment and state budgets. In some unfortunate cases, they have, however, also resulted in delayed or unrealised projects and increased uncertainty for project developers. A variety of auction designs are still being tested and introduced in EU MS, as well as foreseen by European legislation. Therefore, there is still a need for further assessment and improvement of national auction design and implementation to ensure the future success of RES auctions in Europe. Applying different qualitative and quantitative methods in the various work packages (WPs), the AURES II project partners have already drafted and published a large number of reports and studies. This article aims at comprehensively presenting these results and provide a first overview.European Union Horizon 202

    α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

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    Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo
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