Grounding knowledge and normative valuation in agent-based action and scientific commitment

Philosophical investigation in synthetic biology has focused on the knowledge-seeking questions pursued, the kind of engineering techniques used, and on the ethical impact of the products produced. However, little work has been done to investigate the processes by which these epistemological, metaphysical, and ethical forms of inquiry arise in the course of synthetic biology research. An attempt at this work relying on a particular area of synthetic biology will be the aim of this chapter. I focus on the reengineering of metabolic pathways through the manipulation and construction of small DNA-based devices and systems synthetic biology. Rather than focusing on the engineered products or ethical principles that result, I will investigate the processes by which these arise. As such, the attention will be directed to the activities of practitioners, their manipulation of tools, and the use they make of techniques to construct new metabolic devices. Using a science-in-practice approach, I investigate problems at the intersection of science, philosophy of science, and sociology of science. I consider how practitioners within this area of synthetic biology reconfigure biological understanding and ethical categories through active modelling and manipulation of known functional parts, biological pathways for use in the design of microbial machines to solve problems in medicine, technology, and the environment. We might describe this kind of problem-solving as relying on what Helen Longino referred to as “social cognition” or the type of scientific work done within what Hasok Chang calls “systems of practice”. My aim in this chapter will be to investigate the relationship that holds between systems of practice within metabolic engineering research and social cognition. I will attempt to show how knowledge and normative valuation are generated from this particular network of practitioners. In doing so, I suggest that the social nature of scientific inquiry is ineliminable to both knowledge acquisition and ethical evaluations

A Comparison of U. S. and European University-Industry Relations in the Life Sciences

We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U. S. system is based on much closer integration of basic science and clinical development

Knowledge politics and new converging technologies: a social epistemological perspective

The “new converging technologies” refers to the prospect of advancing the human condition by the integrated study and application of nanotechnology, biotechnology, information technology and the cognitive sciences - or “NBIC”. In recent years, it has loomed large, albeit with somewhat different emphases, in national science policy agendas throughout the world. This article considers the political and intellectual sources - both historical and contemporary - of the converging technologies agenda. Underlying it is a fluid conception of humanity that is captured by the ethically challenging notion of “enhancing evolution”

A systematic review of biomarkers among hospitalized patients with COVID-19 predictive of venous thromboembolism: A communication from the Predictive and Diagnostic Variables Scientific and Standardization Committee of the ISTH

Background Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures

Systemic chemokine levels, coronary heart disease, and ischemic stroke events: The PRIME Study

OBJECTIVES: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. METHODS: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. RESULTS: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). CONCLUSIONS: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors

Synthetic biology: Building the language for a new science brick by metaphorical brick

Changes in the biosciences and their relations to society over the last decades provide a unique opportunity to examine whether or not such changes leave traces in the language we use to talk about them. In this article we examine metaphors used in English-speaking press coverage to conceptualize a new type of (interdisciplinary) bioscience: synthetic biology. Findings show that three central metaphors were used between 2008 and May 2010. They exploit social and cultural knowledge about books, computers and engines and are linked to knowledge of three revolutions in science and society (the printing, information and industrial revolutions). These three central metaphors are connected to each other through the concepts of reading/writing, designing and mass production and they focus on science as a revolutionary process rather than on the end results or products of science. Overall, we observed the use of a complex bricolage of mixed metaphors and chains of metaphors that root synthetic biology in historical events and achievements, while at the same time extolling its promises for the future. © 2011 Copyright Taylor and Francis Group, LLC

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV