Broadening out and opening up technology assessment: Approaches to enhance international development, co-ordination and democratisation

Technology assessment (TA) has a strong history of helping to identify priorities and improve environmental sustainability, cost-effectiveness and wider benefits in the technology policies and innovation strategies of nation-states. At international levels, TA has the potential to enhance the roles of science, technology and innovation towards achieving the Millennium Development Goals, effectively implementing the UN Framework on Climate Change and fostering general global transitions to ‘green economies’. However, when effectively recommending single ostensibly ‘best’ technologies or strategies, TA practices can serve unjustifiably to ‘close down’ debate, failing adequately to address technical uncertainties and social ambiguities, reducing scope for democratic accountability and co-ordination across scales and contexts. This paper investigates ways in which contrasting processes ‘broadening out’ and ‘opening up’ TA can enhance both rigour and democratic accountability in technology policy, as well as facilitating social relevance and international cooperation. These methods allow TA to illuminate options, uncertainties and ambiguities and so inform wider political debates about how the contending questions, values and knowledges of different social interests often favour contrasting innovation pathways. In this way TA can foster both technical robustness and social legitimacy in subsequent policy-making. Drawing on three empirical case studies (at local, national and international levels), the paper discusses detailed cases and methods, where recent TA exercises have contributed to this ‘broadening out’ and ‘opening up’. It ends by exploring wider implications and challenges for national and international technology assessment processes that focus on global sustainable development challenges.ESR

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CRISPR-screen identifies ZIP9 and dysregulated Zn2+ homeostasis as a cause of cancer-associated changes in glycosylation

IntroductionIn epithelial cancers, truncated O-glycans, such as the Thomson-nouveau antigen (Tn) and its sialylated form (STn), are upregulated on the cell surface and associated with poor prognosis and immunological escape. Recent studies have shown that these carbohydrate epitopes facilitate cancer development and can be targeted therapeutically; however, the mechanism underpinning their expression remains unclear.MethodsTo identify genes directly influencing the expression of cancer-associated O-glycans, we conducted an unbiased, positive-selection, whole-genome CRISPR knockout-screen using monoclonal antibodies against Tn and STn.Results and ConclusionsWe show that knockout of the Zn2+-transporter SLC39A9 (ZIP9), alongside the well-described targets C1GALT1 (C1GalT1) and its molecular chaperone, C1GALT1C1 (COSMC), results in surface-expression of cancer-associated O-glycans. No other gene perturbations were found to reliably induce O-glycan truncation. We furthermore show that ZIP9 knockout affects N-linked glycosylation, resulting in upregulation of oligo-mannose, hybrid-type, and α2,6-sialylated structures as well as downregulation of tri- and tetra-antennary structures. Finally, we demonstrate that accumulation of Zn2+ in the secretory pathway coincides with cell-surface presentation of truncated O-glycans in cancer tissue, and that over-expression of COSMC mitigates such changes. Collectively, the findings show that dysregulation of ZIP9 and Zn2+ induces cancer-like glycosylation on the cell surface by affecting the glycosylation machinery.Proteomic