Design: One, but in different forms

This overview paper defends an augmented cognitively oriented generic-design hypothesis: there are both significant similarities between the design activities implemented in different situations and crucial differences between these and other cognitive activities; yet, characteristics of a design situation (related to the design process, the designers, and the artefact) introduce specificities in the corresponding cognitive activities and structures that are used, and in the resulting designs. We thus augment the classical generic-design hypothesis with that of different forms of designing. We review the data available in the cognitive design research literature and propose a series of candidates underlying such forms of design, outlining a number of directions requiring further elaboration

Influence of boundaries on pattern selection in through-flow

The problem of pattern selection in absolutely unstable open flow systems is investigated by considering the example of Rayleigh-B\'{e}nard convection. The spatiotemporal structure of convection rolls propagating downstream in an externally imposed flow is determined for six different inlet/outlet boundary conditions. Results are obtained by numerical simulations of the Navier-Stokes equations and by comparison with the corresponding Ginzburg-Landau amplitude equation. A unique selection process is observed being a function of the control parameters and the boundary conditions but independent of the history and the system length. The problem can be formulated in terms of a nonlinear eigen/boundary value problem where the frequency of the propagating pattern is the eigenvalue. PACS: 47.54.+r, 47.20.Bp, 47.27.Te, 47.20.KyComment: 8 pages, 5 Postscript figures, Physica D 97, 253-263 (1996

Pattern selection as a nonlinear eigenvalue problem

A unique pattern selection in the absolutely unstable regime of driven, nonlinear, open-flow systems is reviewed. It has recently been found in numerical simulations of propagating vortex structures occuring in Taylor-Couette and Rayleigh-Benard systems subject to an externally imposed through-flow. Unlike the stationary patterns in systems without through-flow the spatiotemporal structures of propagating vortices are independent of parameter history, initial conditions, and system length. They do, however, depend on the boundary conditions in addition to the driving rate and the through-flow rate. Our analysis of the Ginzburg-Landau amplitude equation elucidates how the pattern selection can be described by a nonlinear eigenvalue problem with the frequency being the eigenvalue. Approaching the border between absolute and convective instability the eigenvalue problem becomes effectively linear and the selection mechanism approaches that of linear front propagation. PACS: 47.54.+r,47.20.Ky,47.32.-y,47.20.FtComment: 18 pages in Postsript format including 5 figures, to appear in: Lecture Notes in Physics, "Nonlinear Physics of Complex Sytems -- Current Status and Future Trends", Eds. J. Parisi, S. C. Mueller, and W. Zimmermann (Springer, Berlin, 1996

Self-tuning experience weighted attraction learning in games

Self-tuning experience weighted attraction (EWA) is a one-parameter theory of learning in games. It addresses a criticism that an earlier model (EWA) has too many parameters, by fixing some parameters at plausible values and replacing others with functions of experience so that they no longer need to be estimated. Consequently, it is econometrically simpler than the popular weighted fictitious play and reinforcement learning models. The functions of experience which replace free parameters “self-tune” over time, adjusting in a way that selects a sensible learning rule to capture subjects’ choice dynamics. For instance, the self-tuning EWA model can turn from a weighted fictitious play into an averaging reinforcement learning as subjects equilibrate and learn to ignore inferior foregone payoffs. The theory was tested on seven different games, and compared to the earlier parametric EWA model and a one-parameter stochastic equilibrium theory (QRE). Self-tuning EWA does as well as EWA in predicting behavior in new games, even though it has fewer parameters, and fits reliably better than the QRE equilibrium benchmark

Pattern selection in the absolutely unstable regime as a nonlinear eigenvalue problem: Taylor vortices in axial flow

A unique pattern selection in the absolutely unstable regime of a driven, nonlinear, open-flow system is analyzed: The spatiotemporal structures of rotationally symmetric vortices that propagate downstream in the annulus of the rotating Taylor-Couette system due to an externally imposed axial through-flow are investigated for two different axial boundary conditions at the in- and outlet. Unlike the stationary patterns in systems without through-flow the spatiotemporal structures of propagating vortices are independent of parameter history, initial conditions, and system's length. They do, however, depend on the axial boundary conditions, the driving rate of the inner cylinder and the through-flow rate. Our analysis of the amplitude equation shows that the pattern selection can be described by a nonlinear eigenvalue problem with the frequency being the eigenvalue. Approaching the border between absolute and convective instability the eigenvalue problem becomes effectively linear and the selection mechanism approaches that one of linear front propagation. PACS:47.54.+r,47.20.Ky,47.32.-y,47.20.FtComment: 15 pages (LateX-file), 8 figures (Postscript

Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility

High-resolution spatial modelling of greenhouse gas emissions from land-use change to energy crops in the United Kingdom

Funded by Energy Technologies Institute EPSRC-Supergen. Grant Number: EP/M013200/1Peer reviewedPublisher PD

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

Interferon-ß regulates the production of IL-10 by toll-like receptor-activated microglia

Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression. In this context, the anti-inflammatory cytokine interleukin (IL)-10 appears as an attractive target. In this study, we investigated how activation of microglia by TLRs with distinct roles in MS impacts on IL-10 production. We found that activation of TLR2, TLR4, and TLR9 induced the production of IL-10 to a greater extent than activation of TLR3. This was surprising as both TLR3 and IL-10 play protective roles in animal models of MS. Interestingly, combination of TLR3 triggering with the other TLRs, enhanced IL-10 through the modulation of its transcription, via interferon (IFN)-beta, but independently of IL-27. Thus, in addition to the modulation of inflammatory responses of the periphery described for the axis TLR3/IFN-beta, we now report a direct modulation of microglial responses. We further show that the presence of IFN-gamma in the microenvironment abrogated the modulation of IL-10 by TLR3, whereas that of IL-17 had no effect. Considering the therapeutic application of IFN-beta in MS, our study bears important implications for the understanding of the cytokine network regulating microglia responses in this setting.Portuguese Foundation for Science and Technology (FCT), Grant/Award Numbers: SFRH/BD/88081/2012 and SFRH/BPD/72710/2010; FEDER - Competitiveness Factors Operational Programme (COMPETE), Grant/Award Numbers: POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; Norte Portugal Regional Operational Programme, PORTUGAL 2020, European Regional Development Fund (ERDF), Grant/Award Number: NORTE 2020; FCT-ANR, Grant/Award Number: FCT-ANR/BIM-MEC/0007/2013; FEDER - Fundo Europeu de Desenvolvimento Regional; COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; Institute for Research and Innovation in Health Sciences, Grant/Award Number: POCI-01-0145-FEDER-007274info:eu-repo/semantics/publishedVersio

Reorientation-effect measurement of the first 2+ state in 12C : Confirmation of oblate deformation

A Coulomb-excitation reorientation-effect measurement using the TIGRESS γ−ray spectrometer at the TRIUMF/ISAC II facility has permitted the determination of the 〈21 +‖E2ˆ‖21 +〉 diagonal matrix element in 12C from particle−γ coincidence data and state-of-the-art no-core shell model calculations of the nuclear polarizability. The nuclear polarizability for the ground and first-excited (21 +) states in 12C have been calculated using chiral NN N4LO500 and NN+3NF350 interactions, which show convergence and agreement with photo-absorption cross-section data. Predictions show a change in the nuclear polarizability with a substantial increase between the ground state and first excited 21 + state at 4.439 MeV. The polarizability of the 21 + state is introduced into the current and previous Coulomb-excitation reorientation-effect analyses of 12C. Spectroscopic quadrupole moments of QS(21 +)=+0.053(44) eb and QS(21 +)=+0.08(3) eb are determined, respectively, yielding a weighted average of QS(21 +)=+0.071(25) eb, in agreement with recent ab initio calculations. The present measurement confirms that the 21 + state of 12C is oblate and emphasizes the important role played by the nuclear polarizability in Coulomb-excitation studies of light nuclei