Principles of Antifragile Software

The goal of this paper is to study and define the concept of "antifragile software". For this, I start from Taleb's statement that antifragile systems love errors, and discuss whether traditional software dependability fits into this class. The answer is somewhat negative, although adaptive fault tolerance is antifragile: the system learns something when an error happens, and always imrpoves. Automatic runtime bug fixing is changing the code in response to errors, fault injection in production means injecting errors in business critical software. I claim that both correspond to antifragility. Finally, I hypothesize that antifragile development processes are better at producing antifragile software systems.Comment: see https://refuses.github.io

On the mean value of the energy for resonant states

In this work we discuss possible definitions of the mean value of the energy for a resonant (Gamow) state. The mathematical and physical aspects of the formalism are reviewed. The concept of rigged Hilbert space is used as a supportive tool in dealing with Gamow-resonances.Comment: 9 page

EMMIE and engineering: What works as evidence to improve decisions?

While written by a proponent of realism, this article argues in favour of a pragmatic approach to evaluation. It argues that multiple sources of evidence collected using diverse research methods can be useful in conducting informative evaluations of programmes, practices and policies. It argues in particular that methods, even if their assumptions appear incommensurable with one another, should be chosen to meet the evidence needs of decision-makers. These evidence needs are captured in the acronym, EMMIE, which refers to Effect size, Mechanism, Moderator (or context), Implementation and Economic impact. Finally the article questions evidence hierarchies that are inspired by clinical trials, and suggests instead that, notwithstanding the clear differences in the physical and social worlds, engineering may provide a superior model for evaluators to try to emulate. And engineering is, above all, a pragmatic field

A Generic Platform for Cellular Screening Against Ubiquitin Ligases

Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class

Challenges of mainstreaming green infrastructure in built environment professions

© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Green infrastructure (GI) has been identified as a promising approach to help cities adapt to climate change through the provision of multiple ecosystem services. However, GI contributions to urban resilience will not be realized until it is more fully mainstreamed in the built environment and design professions. Here, we interrogate five key challenges for the effective implementation of GI: (1) design standards; (2) regulatory pathways; (3) socio-economic considerations; (4) financeability; and (5) innovation. Methods include a literature review, case studies, and interviews with resilience managers. We propose a people-centred and context-dependent approach to advance effective implementation of GI in urban planning. We highlight two underlying currents that run across all of the challenges–(1) the role of political will as a pre-condition for tackling all challenges holistically; and (2) the role of stakeholder engagement in achieving public support, harnessing funding, and maintaining and monitoring GI in the long term. Highlights: • The effective implementation of GI is context-specific and should adhere to the basic principles of appropriate technology. • Continuous community engagement is needed to ensure the inclusivity and multi-functionality of GI. • Challenges to successful GI are intersectional and therefore cannot be addressed singly in isolation

Lentiviral Vpx Accessory Factor Targets VprBP/DCAF1 Substrate Adaptor for Cullin 4 E3 Ubiquitin Ligase to Enable Macrophage Infection

Vpx is a small virion-associated adaptor protein encoded by viruses of the HIV-2/SIVsm lineage of primate lentiviruses that enables these viruses to transduce monocyte-derived cells. This probably reflects the ability of Vpx to overcome an as yet uncharacterized block to an early event in the virus life cycle in these cells, but the underlying mechanism has remained elusive. Using biochemical and proteomic approaches, we have found that Vpx protein of the pathogenic SIVmac 239 strain associates with a ternary protein complex comprising DDB1 and VprBP subunits of Cullin 4–based E3 ubiquitin ligase, and DDA1, which has been implicated in the regulation of E3 catalytic activity, and that Vpx participates in the Cullin 4 E3 complex comprising VprBP. We further demonstrate that the ability of SIVmac as well as HIV-2 Vpx to interact with VprBP and its associated Cullin 4 complex is required for efficient reverse transcription of SIVmac RNA genome in primary macrophages. Strikingly, macrophages in which VprBP levels are depleted by RNA interference resist SIVmac infection. Thus, our observations reveal that Vpx interacts with both catalytic and regulatory components of the ubiquitin proteasome system and demonstrate that these interactions are critical for Vpx ability to enable efficient SIVmac replication in primary macrophages. Furthermore, they identify VprBP/DCAF1 substrate receptor for Cullin 4 E3 ubiquitin ligase and its associated protein complex as immediate downstream effector of Vpx for this function. Together, our findings suggest a model in which Vpx usurps VprBP-associated Cullin 4 ubiquitin ligase to enable efficient reverse transcription and thereby overcome a block to lentivirus replication in monocyte-derived cells, and thus provide novel insights into the underlying molecular mechanism

Architectural Growth of Cu Nanoparticles Through Electrodeposition

Cu particles with different architectures such as pyramid, cube, and multipod have been successfully fabricated on the surface of Au films, which is the polycrystalline Au substrate with (111) domains, using the electrodeposition technique in the presence of the surface-capping reagents of dodecylbenzene sulfonic acid and poly(vinylpyrrolidone). Further, the growth evolution of pyramidal Cu nanoparticles was observed for the first time. We believe that our method might open new possibilities for fabricating nanomaterials of non-noble transition metals with various novel architectures, which can then potentially be utilized in applications such as biosensors, catalysis, photovoltaic cells, and electronic nanodevices