55 research outputs found

    Key settings for successful Open Innovation Arena

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    The purpose of this paper is to examine settings for the Open Innovation Arena. In greater depth, this paper aims to analyse and reveal which factors influence the formation of an appropriate arena for doing open innovation and furthermore to prescribe how a firm can create an effective arena to gain access to external knowledge. This paper presents a review on open innovation literature with the purpose of examining the current understanding of factors influencing a firm’s capacity to embrace and practice open innovation as well as understanding what is critical when fitting outside systems. It presents the results of a survey conducted among 25 researchers from INESC TEC, the Portuguese Institute for Systems and Computer Engineering, Technology, and Science. The study concludes that conditions, namely culture, leadership and strategy, are the main drivers to an open innovation arena, highlighting culture as the most important one.info:eu-repo/semantics/publishedVersio

    The effects of symmetry on the dynamics of antigenic variation

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    In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

    Clinical trials in amyotrophic lateral sclerosis:a systematic review and perspective

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    Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of phase II, phase II/III and phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15000 people with amyotrophic lateral sclerosis. 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis

    Parametric variation of a coupled pendulum-oscillator system using real-time dynamic substructuring

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    In this paper, we present results from real-time dynamic substructuring tests used to model the dynamics of a coupled pendulum–oscillator system. The substructuring technique is particularly suitable for systems where the nonlinear and linear parts of the system can be separated. The nonlinear part is built full size and tested physically (the substructure) while the linear part is simulated numerically. Then, in order to replicate the dynamics of the complete system the substructure and the numerical model must be coupled in real time. In this study, we demonstrate how real-time dynamic substructure testing can be used to model systems with strongly nonlinear behaviour using parametric variation. We show that the substructuring results give good qualitative and quantitative agreement with purely numerical simulations of the complete system for a range of parameters values. This includes single parameter bifurcation diagrams, some of which cannot be obtained from a full physical experiment. We also briefly discuss the effects of delay and noise on the stability of the substructured system, and how these effects can be mitigated. Copyright © 2006 John Wiley & Sons, Ltd

    Bifurcation study of a neural field competition model with an application to perceptual switching in motion integration.

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    Perceptual multistability is a phenomenon in which alternate interpretations of a fixed stimulus are perceived intermittently. Although correlates between activity in specific cortical areas and perception have been found, the complex patterns of activity and the underlying mechanisms that gate multistable perception are little understood. Here, we present a neural field competition model in which competing states are represented in a continuous feature space. Bifurcation analysis is used to describe the different types of complex spatio-temporal dynamics produced by the model in terms of several parameters and for different inputs. The dynamics of the model was then compared to human perception investigated psychophysically during long presentations of an ambiguous, multistable motion pattern known as the barberpole illusion. In order to do this, the model is operated in a parameter range where known physiological response properties are reproduced whilst also working close to bifurcation. The model accounts for characteristic behaviour from the psychophysical experiments in terms of the type of switching observed and changes in the rate of switching with respect to contrast. In this way, the modelling study sheds light on the underlying mechanisms that drive perceptual switching in different contrast regimes. The general approach presented is applicable to a broad range of perceptual competition problems in which spatial interactions play a role

    TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis

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    Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. Quiescent LT-HSCs were maintained in infected RAG2 KO mice, but lost following adoptive transfer of IFNγ-sufficient but not IFNγ-deficient CD4+ T cells. Using mixed BM chimeras, we established that IFNγ and TNF signalling pathways converge at the level of CD4+ T cells. Critically, intrinsic TNF signalling is required for the expansion and/or differentiation of pathogenic IFNγ+CD4+ T cells that promote the irreversible loss of BM function. These finding provide new insights into the pathogenic potential of CD4+ T cells that target hematopoietic function in leishmaniasis and perhaps other infectious diseases where TNF expression and BM dysfunction also occur simultaneously
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