The term responsible (research and) innovation has gained increasing EU policy relevance in the last two years, in particular within the European Commission's Science in Society programme, in the context of the Horizon 2020 Strategy. We provide a brief historical overview of the concept, and identify three distinct features that are emerging from associated discourses. The first is an emphasis on the democratic governance of the purposes of research and innovation and their orientation towards the 'right impacts'. The second is responsiveness, emphasising the integration and institutionalisation of established approaches of anticipation, reflection and deliberation in and around research and innovation, influencing the direction of these and associated policy. The third concerns the framing of responsibility itself in the context of research and innovation as collective activities with uncertain and unpredictable consequences. Finally, we reflect on possible motivations for responsible innovation itself. Copyright The Author 2012. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com, Oxford University Press.
In response to the challenges of policy issues of risk and the environment, a new type of science-‘post-normal’-is emerging. This is analysed in contrast to traditional problem-solving strategies, including core science, applied science, and professional consultancy. We use the two attributes of systems uncertainties and decision stakes to distinguish among these. Postnormal science is appropriate when either attribute is high; then the traditional methodologies are ineffective. In those circumstances, the quality assurance of scientific inputs to the policy process requires an ‘extended peer community’, consisting of all those with a stake in the dialogue on the issue. Post-normal science can provide a path to the democratization of science, and also a response to the current tendencies to post-modernity. Science always evolves, responding to its leading challenges as they change through history. After centuries of triumph and optimism, science is now called on to remedy the pathologies of the global industrial system of which it forms the basis. Whereas science was previously understood as steadily advancing in the certainty of our knowledge and control of the natural world, now science is seen as coping with many uncertainties in policy issues of risk and the environment. In response, new styles of scientific activity are being developed. The reductionist, analytical worldview which divides systems into ever smaller elements, studied by ever more esoteric specialism, is being replaced by a systemic, synthetic and humanistic approach. The old dichotomies of facts and values, and of knowledge and ignorance, are being transcended. Natural systems are recognized as dynamic and complex; those involving interactions with humanity are ‘emergent’, including properties of reflection and contradiction. The science appropriate to this new condition will be based on the assumptions of unpredictability, incomplete control, and a plurality of legitimate perspectives. At present, there is no agreed description of what the future will bring, but
Este artigo explora a aplicação de métodos probabilísticos na análise da fiabilidade e no dimensionamento do reforço de taludes rochosos sujeitos a mecanismos de rotura planar. O estudo incide no caso de um maciço rochoso intersetado por uma família de descontinuidades paralela à face do talude. O volume com potencial de instabilização é idealizado como um modelo de blocos, para o qual se desenvolve uma formulação em sistemas de componentes. Como termo de comparação, analisa-se igualmente um modelo simplificado que considera o mesmo volume como um bloco único. Os resultados evidenciam a influência da inclinação do plano de deslizamento. Verifica-se que o modelo constituído por múltiplos blocos conduz a índices de fiabilidade inferiores. Contudo, a sua utilização para o dimensionamento probabilístico do reforço tem vantagens apenas para inclinações baixas do plano de deslizamento. A análise sugere ainda que o modelo de blocos múltiplos pode ser adequadamente representado por um modelo simplificado de dois blocos.
Geology, Engineering geology. Rock mechanics. Soil mechanics. Underground construction
AbstractNeuroinflammation is initiated in response to ischemic stroke, generally with the hallmarks of microglial activation and collateral brain injury contributed by robust inflammatory effects. Triggering receptor expressed on myeloid cells (TREM)-1, an amplifier of the innate immune response, is a critical regulator of inflammation. This study identified that microglial TREM-1 expression was upregulated following cerebral ischemic injury. After pharmacologic inhibition of TREM-1 with synthetic peptide LP17, ischemia-induced infarction and neuronal injury were substantially alleviated. Moreover, blockade of TREM-1 can potentiate cellular proliferation and synaptic plasticity in hippocampus, resulting in long-term functional improvement. Microglial M1 polarization and neutrophil recruitment were remarkably abrogated as mRNA levels of M1 markers, chemokines, and protein levels of myeloperoxidase and intracellular adhesion molecule-1 (ICAM-1) were decreased by LP17. Mechanistically, both in vivo and in vitro, we delineated that TREM-1 can activate downstream pro-inflammatory pathways, CARD9/NF-κB, and NLRP3/caspase-1, through interacting with spleen tyrosine kinase (SYK). In addition, TREM-1-induced SYK initiation was responsible for microglial pyroptosis by elevating levels of gasdermin D (GSDMD), N-terminal fragment of GSDMD (GSDMD-N), and forming GSDMD pores, which can facilitate the release of intracellular inflammatory factors, in microglia. In summary, microglial TREM-1 receptor yielded post-stroke neuroinflammatory damage via associating with SYK.
Bell's inequality is derived from three assumptions: measurement independence, outcome independence, and parameter independence. Among these, measurement independence, often taken for granted, holds that hidden variables are statistically uncorrelated with measurement settings. Under this assumption, the violation of Bell's inequality implies that either outcome independence or parameter independence fails to hold, meaning that local hidden variables do not exist. In this paper, we refer to this interpretive stance as the nonfactorizable position. In contrast, superdeterminism represents the view that measurement independence does not hold. Despite its foundational role, this assumption has received relatively little philosophical scrutiny. This paper offers a philosophical reassessment of measurement independence through three major frameworks in the philosophy of science: de Regt's contextual theory of scientific understanding, Kuhn's criteria for theory choice, and Lakatos's methodology of scientific research programmes. Using these lenses, we evaluate the two major responses to the violation of Bell's inequality, the nonfactorizable position and superdeterminism, and argue that the nonfactorizable position currently fares better across all three criteria. Beyond this binary, we introduce a spectrum of intermediate positions that allow for partial violations of measurement independence, modeled via mutual information. These positions modify the ``positive heuristic'' of superdeterminism, a crucial component in Lakatos's definition of research programmes, offering avenues for progressive research. This analysis reframes the debate surrounding Bell's inequality and illustrates how methodological tools can effectively guide theory evaluation in physics.
Sophia Daum, Lilith Decristoforo, Mira Mousa
et al.
Abstract The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in the progression of non-small cell lung cancer (NSCLC). In general, endothelial cells exhibit diverse immunomodulatory properties, influencing immune cell recruitment, antigen presentation, and regulation of immune checkpoint expression. Understanding the multifaceted roles of TECs as well as assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development of therapeutic interventions, particularly in the context of advanced immunotherapy and anti-angiogenic treatments. This review provides insights into the complex interplay between TECs and the immune system in NSCLC including discussion of potential optimized therapeutic opportunities.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens