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

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

Cultivating resilience by empirically revealing response diversity

201

Hacking events: project development practices and technology use at hackathons

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’

Introduction: looking beyond the walls

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

Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations

10.1371/journal.pone.0074040PLoS ONE89-POLN

Can filesharers be triggered by economic incentives? Results of an experiment

Illegal filesharing on the internet leads to considerable financial losses for artists and copyright owners as well as producers and sellers of music. Thus far, measures to contain this phenomenon have been rather restrictive. However, there are still a considerable number of illegal systems, and users are able to decide quite freely between legal and illegal downloads because the latter are still difficult to sanction. Recent economic approaches account for the improved bargaining position of users. They are based on the idea of revenue-splitting between professional sellers and peers. In order to test such an innovative business model, the study reported in this article carried out an experiment with 100 undergraduate students, forming five small peer-to-peer networks.The networks were confronted with different economic conditions.The results indicate that even experienced filesharers hold favourable attitudes towards revenue-splitting.They seem to be willing to adjust their behaviour to different economic conditions

How can contributors to open-source communities be trusted? On the assumption, inference, and substitution of trust

Open-source communities that focus on content rely squarely on the contributions of invisible strangers in cyberspace. How do such communities handle the problem of trusting that strangers have good intentions and adequate competence? This question is explored in relation to communities in which such trust is a vital issue: peer production of software (FreeBSD and Mozilla in particular) and encyclopaedia entries (Wikipedia in particular). In the context of open-source software, it is argued that trust was inferred from an underlying 'hacker ethic', which already existed. The Wikipedian project, by contrast, had to create an appropriate ethic along the way. In the interim, the assumption simply had to be that potential contributors were trustworthy; they were granted 'substantial trust'. Subsequently, projects from both communities introduced rules and regulations which partly substituted for the need to perceive contributors as trustworthy. They faced a design choice in the continuum between a high-discretion design (granting a large amount of trust to contributors) and a low-discretion design (leaving only a small amount of trust to contributors). It is found that open-source designs for software and encyclopaedias are likely to converge in the future towards a mid-level of discretion. In such a design the anonymous user is no longer invested with unquestioning trust