377 research outputs found

    A genome blogger manifesto

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    Cheap prices for genomic testing have revolutionized consumers’ access to personal genomics. Exploration of personal genomes poses significant challenges for customers wishing to learn beyond provider customer reports. A vibrant community has spontaneously appeared blogging experiences and data as a way to learn about their personal genomes. No set of values has publicly been described to date encapsulating ideals and code of conduct for this community. Here I present a first attempt to address this vacuum based on my own personal experiences as genome blogger

    An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

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    Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

    Machine Learning Interatomic Potentials as Emerging Tools for Materials Science.

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    Atomic-scale modeling and understanding of materials have made remarkable progress, but they are still fundamentally limited by the large computational cost of explicit electronic-structure methods such as density-functional theory. This Progress Report shows how machine learning (ML) is currently enabling a new degree of realism in materials modeling: by "learning" electronic-structure data, ML-based interatomic potentials give access to atomistic simulations that reach similar accuracy levels but are orders of magnitude faster. A brief introduction to the new tools is given, and then, applications to some select problems in materials science are highlighted: phase-change materials for memory devices; nanoparticle catalysts; and carbon-based electrodes for chemical sensing, supercapacitors, and batteries. It is hoped that the present work will inspire the development and wider use of ML-based interatomic potentials in diverse areas of materials research.Academy of Finland under project #310574. The authors are thankful for generous allocation of computational resources on the ARCHER UK National Supercomputing Service (EPSRC grants EP/K014560/1 and EP/P022596/1) and by CSC ‐ IT Center for Science, Finland, which supported some of the work discussed herein. V.L.D. and M.A.C. are grateful for mutual HPC‐Europa3 exchange visits (funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 730897), during one of which this manuscript was finalized

    Binding of EphrinA5 to RET receptor tyrosine kinase : An in vitro study

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    Eph/Ephrin signaling pathways are crucial in regulating a large variety of physiological processes during development, such as cell morphology, proliferation, migration and axonal guidance. EphrinA (efn-A) ligands, in particular, can be activated by EphA receptors at cellcell interfaces and have been proposed to cause reverse signaling via RET receptor tyrosine kinase. Such association has been reported to mediate spinal motor axon navigation, but conservation of the interactive signaling pathway and the molecular mechanism of the interaction are unclear. Here, we found Danio rerio efn-A5b bound to Mus musculus EphA4 with high affinity, revealing structurally and functionally conserved EphA/efn-A signaling. Interestingly, we observed no interaction between efn-A5b and RET from zebrafish, unlike earlier cell-based assays. Their lack of association indicates how complex efn-A signaling is and suggests that there may be other molecules involved in efn-A5-induced RET signaling.Peer reviewe

    Introduction: looking beyond the walls

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    In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

    Hacking events: project development practices and technology use at hackathons

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    Hackathons are techno-creative events during which participants get together in a physical location. They may be hosted by civic communities, corporations or public institutions. Working individually or in teams, usually for several days, participants develop projects such as hardware or software prototypes. Based on a digital ethnography of two events in the Netherlands and Denmark, this article investigates project development practices at hackathons. In particular, it analyses how participants organized their project work and which technologies were used in support of their creative endeavours. Hackathons are increasingly competitive rather than collaborative events, involving time pressure, inducements such as prizes, and requiring efficient skills utilization. I argue that this facilitates the following tendencies: Firstly, strategic effort is put into final presentations. Projects need to be convincingly presented, and persuasively pitching an idea becomes crucial. Secondly, there is only limited time for personal learning, since participants’ existing skills need to be efficiently applied if a team wants to stay competitive. This encourages division of labour within groups: a tendency which seems especially problematic given that IT skills biases are often expressed in terms of gender. Thirdly, participants are more inclined to use technologies that are proprietary but appear ‘open enough’. In light of this observation and by drawing on the concept of technology as resource and opportunity, I discuss the techno-political implications of utilized technologies. With this analysis, I aim at contributing to the critical debate on hackathons as productive but likewise ideologically significant fields of ‘hacking cultures’
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