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The roles digital media-technologies play in raising public issues relating to emerging technologies and their potential for engaging publics with science and policy assessments is a lively field of inquiry in Science and Technology Studies (STS). This paper presents an analysis of controversies over proposals for the large-scale removal of atmospheric carbon dioxide (CDR). The study combines a digital method (web-querying) with document analysis to map debates about two CDR approaches: bioenergy with carbon capture and storage (BECCS) and afforestation. In the first step, we locate actors using the web to engage with BECCS and afforestation and map their alignments in relation to competing framings of CDR. In a second step, we examine the devices deployed by UK-based actors to evidence and contest the feasibility of BECCS and afforestation. Our analysis shows that policy distinctions between "natural" and "engineered" CDR are used flexibly in practice and do not map neatly onto actor engagement with BECCS and afforestation. We highlight the predominance of cross-cutting techno-economic expertise and argue that framings of CDR as a solution to governing climate change may contribute to public disengagement from climate policy processes. The paper reflects on methods for studying controversies, publics, and issues emerging around processes of technoscientific assessment. [ABSTRACT FROM AUTHOR]

Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous [CD8.sup.+] T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation--pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with [CD4.sup.+] T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy., Instruction Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) that predominantly affect young adults and cause considerable morbidity. UC typically presents with bloody [...]

Follicular helper ([T.sub.FH]) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of [T.sub.FH] numbers maintains self tolerance. We describe a population of [Foxp3.sup.+] [Blimp-1.sup.+] [CD4.sup.+] T cells constituting 10-25% of the CXCR5 high [PD-1.sup.high] [CD4.sup.+] T cells found in the germinal center after immunization with protein antigens. These follicular regulatory T ([T.sub.FR]) cells share phenotypic characteristics with [T.sub.FH] and conventional [Foxp3.sup.+] regulatory T ([T.sub.reg]) cells yet are distinct from both. Similar to [T.sub.FH] cells, [T.sub.FR] cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, [T.sub.FR] cells originate from thymic-derived [Foxp3.sup.+] precursors, not naive or [T.sub.FH] cells. [T.sub.FR] cells are suppressive in vitro and limit [T.sub.FH] cell and germinal center B cell numbers in vivo. In the absence of [T.sub.FR] cells, an outgrowth of non--antigen-specific B cells in germinal centers leads to fewer antigen- specific cells. Thus, the [T.sub.FH] differentiation pathway is co-opted by [T.sub.reg] cells to control the germinal center response., Germinal centers are clusters of rapidly dividing B cells formed in secondary lymphoid tissues in response to T-dependent antigens. Within the germinal center, mutation of the B receptor cell V-region [...]

Researchers expect under-reaction in climate policy. However, this might differ depending on the access of different interest groups to a political system. To explore the relationship between entrenched patterns of domestic politics and proportionality of climate policy, we compare two renewables policies which financially support new renewable electricity in the UK. Drawing on the literature on policy styles and related opportunity structures, this article shows that UK political parties have responded to growing public concern and NGO pressure by, at times, trying to out-green one another to win votes. However, powerful industry actors have been influential in shaping UK renewables policies, in particular when political competition about the individual policies has been low. The findings suggest that an over-reaction in terms of exceeding the marginal costs of renewable electricity production is equally likely under conditions of high or low political competition. [ABSTRACT FROM AUTHOR]

Abstract Background Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. Results We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. Conclusion MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML.

Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes. Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity. [ABSTRACT FROM AUTHOR]

Prospective approaches for large‐scale greenhouse gas removal (GGR) are now central to the post‐2020 international commitment to pursue efforts to limit the global temperature increase to 1.5°C. However, the feasibility of large‐scale GGR has been repeatedly questioned. Most systematic analyses focus only on the physical, technical, and economic challenges of deploying it at scale. However, social and political dimensions will be just as important, if not more so, to how possible futures play out. We conduct one of the first reviews of the international peer‐reviewed literature pertaining to the social and political dimensions of large‐scale GGR, with a specific focus on two predominant approaches: Biomass energy with carbon capture and storage (BECCS) and afforestation/reforestation (AR). Our analysis of 78 studies proposes two important insights. First, it shows how six key social and political dimensions of GGR feasibility–namely economics and incentives; innovation; societal engagement; governance; complexity and uncertainty; and ethics, equity, and justice–are identifiable and are emphasized to varying degrees in the literature. Second, there are three contested ways in which BECCS and AR and their feasibility are being framed in the literature: (a) a techno‐economic framing; (b) a social and political acceptability framing; and (c) a responsible development framing. We suggest this third frame will, and indeed should, become increasingly pertinent to the assessment, innovation, and governance of climate futures. This article is categorized under: The Carbon Economy and Climate Mitigation > Policies, Instruments, Lifestyles, Behavior. [ABSTRACT FROM AUTHOR]

Appraisal is defined as a variety of ex ante techniques and procedures that seek to predict and evaluate the consequences of certain human actions that is afforded an increasingly important role in environmental policy. The nature of appraisal and its role in the political process that is inadequately conceptualized is discussed.

This article defines six core elements of hacker paradigm leadership – a style of leadership required in agile, lean, and collaborative design environments. Hacker paradigm leaders start with human connection, creating a foundation of trust and ownership in teams. They give people a sense of purpose. They cultivate a tribal mindset, focused on shared potential and rewards. They challenge teams to identify unverified assumptions and resolve unknowns through experiments. They spur teams to create value for customers and to work collaboratively to sustain a generative space where life is good and great things get done. Hackers have a bad reputation. Thanks to the high profile Distributed Denial of Service (DDoS) attacks of hacktivist groups like Anonymous, political hacks like attempts to interfere with voter registration databases in the 2016 US election, and criminal hacks like the Sony cyber-attack of 2014, in which hackers stole over 100 terabytes of data and planted malware to erase content from the company’s servers, many people have a dim view of hacking. Hacking is seen as a subversive, immoral activity. Films like Hackers (1995) and the HBO series Mr Robot portray hackers as lonely outsiders who fight governments and corporations. When hackers appear in the media, the article is typically headed with a shot of a shadowy figure hunched over a keyboard, looking like the Grim Reaper in a hoodie. While the media’s depiction of hackers is not factually incorrect, it is a partial and misleading view, focused exclusively on ‘black hat hackers’, or file breakers. Steven Levy’s seminal book, Hackers: Heroes of the Computer Revolution (1984), offers a different perspective on hacking that is vital for understanding the broader impact and influence of hacking today. Levy’s account focuses on the True Hackers, a tradition that started at Massachusetts University of Technology (MIT) in the 1960s, where a ragtag band of young electronics engineers volunteered their passion, knowledge, and coding skills to write software for the first generation of userprogrammable computers. These hackers created a culture of open, collaborative, exploratory coding (Levy, 2010). In subsequent decades, this tradition fueled the rise of personal computing (and Apple Computers), inspired the free and open source software (FOSS) movement, and contributed massively to the culture and technical infrastructure of the internet. It continues to shape the world of technology today. In the wake of the dot.com crash of 2001-2002, a new generation of tech entrepreneurs emerged inspired by the practices and principles of hacking. Entrepreneurs like Facebook’s CEO Mark Zuckerberg and Twitter’s Jack Dorsey cut their teeth on open source hacking. The success of their companies helped drive a new wave of interest in fast, cheap, exploratory approaches to product design and small business development. This interest subsequently cohered around three methods: agile development, lean startup and design thinking. These methods, used today by developers, entrepreneurs, and designers internationally, are deeply indebted to the positive tradition of hacking that started at MIT (Rayner, 2018). Today, hacking is a ubiquitous approach to innovation, a way of solving problems through collaborative, iterated sprints. It is not just for programmers. Anyone can be a hacker, assuming an experimental mindset and a willingness to get hands on, build and learn. [ABSTRACT FROM AUTHOR]

The impact of renewables on the energy markets-falling wholesale electricity prices and lower investment stability-are apparently creating a shortage of energy project financing, which in future could lead to power supply shortages. Governments have responded by introducing payments for capacity, alongside payments for energy being sold. The increasing use of capacity mechanisms (CMs) in the EU has created tensions between the European Commission, which encourages cross-country cooperation, and Member States that favour backup solutions such as capacity markets and strategic reserves. We seek to trace the influence of the European Commission on national capacity markets as well as learning between Member States. Focusing on the United Kingdom, France and Poland, the analysis shows that energy security concerns have been given more emphasis than the functioning of markets by Member States. Policy developments have primarily been domestically driven, but the European Commission has managed to impose certain elements, most importantly a uniform methodology to assess future supply security, as well as specific requirements for national capacity markets: interconnectors to neighbouring countries, demand side responses and continuous revision of CMs. Learning from other Member States' experiences also play a role in policy decisions. [ABSTRACT FROM AUTHOR]

Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. Here we measure allele-specific transcription factor binding occupancy of three liver-specific transcription factors between crosses of two inbred mouse strains to elucidate the regulatory mechanisms underlying transcription factor binding variations in mammals. Our results highlight the pre-eminence of cis-acting variants on transcription factor occupancy divergence. Transcription factor binding differences linked to cis-acting variants generally exhibit additive inheritance, while those linked to trans-acting variants are most often dominantly inherited. Cis-acting variants lead to local coordination of transcription factor occupancies that decay with distance; distal coordination is also observed and may be modulated by long-range chromatin contacts. Our results reveal the regulatory mechanisms that interplay to drive transcription factor occupancy, chromatin state, and gene expression in complex mammalian cell states. [ABSTRACT FROM AUTHOR]