22 research outputs found

    The experimental power of FR900359 to study Gq-regulated biological processes.

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    Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq

    Identifying and Mitigating Bias in Machine Learning Applications

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    This study addresses the existence of bias in machine learning applications and examines techniques for identifying and mitigating bias using scholarly literature published between 2012 and 2019. The intended audience is machine learning engineers, system analysts, and data analysts of any industry. This study is significant because there may be considerable ethical implications caused by machine learning bias; identifying and mitigating these biases is key to the development and deployment of effective machine learning algorithms

    Perché indagare la lotta al terrorismo italiano in chiave transnazionale. Nuove ipotesi e percorsi di ricerca

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    With this article, we aim at drawing attention to a hitherto less studied perspective in the history of Italian counterterrorism: the international cooperation in order to tackle the transnational threat of terrorism. Departing from the observation of several similar phenomena of political violence in the second half of the 20th century, we understand the Italian “storia della lotta al terrorismo” as embedded in its global context. However, this does not mean neglecting national particularities. Firstly, we explain which are the most important aspects of a transnational history of the fight against terrorism. Secondly, we argue that the investigation of these aspects can enrich the Italian history of counterterrorism in manifold ways. Thirdly, we propose manners and methods to open up Italian contemporary historiography on the topic towards a broader field of historical analysis, intertwined with the histories of international relations and European Integration. Concluding, we claim that the histories of Italian and of European antiterrorism efforts complement each other and that the links between both of them can help to better understand a complex history of diplomatic duties, legal frameworks, and institutional structure

    What drives environmental impacts of fertilizers produced from fish wastes?

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    The worldwide fish consumption has more than doubled between 1961 (9 kg per capita) and 2019 (20.5 kg) (FAO, 2022) The production in the EU amounted to 5.7 million tonnes of products from catches and aquaculture in 2018 (European Commission, 2020). Of this amount, approximately 25% – 35% is discarded as waste with variable nutrient composition and water content without further valorisation (Villamil et al., 2017). To evaluate the feasibility of producing bio-based fertilizers from the macro nutrients contained in these wastes, the Horizon2020 project Sea2Land piloted different technologies. Their environmental performance was analysed with a cradle to factory gate life cycle assessment (LCA) at two stages of production: pilot stage and industrial stage. The sidestreams were assumed to be burden-free. First results identify the main environmental hotspots, at both stages, to be the implemented concentration and drying processes such as membrane filtration or spray drying, the transport of the raw materials and the packaging of the final product. On the other hand, machines do generally not contribute much to environmental impacts and factory buildings’ contribution is mainly at pilot level and with regard to mineral resources use. To lower the environmental impacts of bio-based fertilisers from fish waste, the concentration of sidestreams should be improved by using of more efficient technologies (e.g. with heat recovery) or alternative energy sources. Secondly, the production needs to be in close geographic distance of the source of the fish waste generation and the amount of packaging materials should be minimized
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