Understanding behaviour patterns of multi-agents in digital business ecosystems: an organisational semiotics inspired framework

Digital business ecosystem (DBE) is a collaborative network of organisations, processes and technologies that collectively create value. Thus, value creation in DBEs is jointly undertaken by multiple human and digital agents. To aid appropriate apportionment of work and design of information systems, it is essential to understand behaviour of both human and digital agents. However limited attention has been paid to agents’ behaviour in the extant DBEs literature. Moreover, multi-agent research has also largely focused on technical issues while limited research exists on agents’ behaviour. As such, in this paper, we develop a framework to understand behaviour patterns of multi-agent in DBEs. This framework builds its foundation on the theoretical lens of Organisational Semiotics, a sociotechnical theory towards contribution to DBE research

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations are common in myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during the evolution of acute myeloid leukemia (AML), where we observed stage-specific and diametrically opposite functions for Ezh2 at the early and late stages of disease. During disease maintenance, WT Ezh2 exerts an oncogenic function that may be therapeutically targeted. In contrast, Ezh2 acts as a tumor suppressor during AML induction. Transcriptional analysis explains this apparent paradox, demonstrating that loss of Ezh2 derepresses different expression programs during disease induction and maintenance. During disease induction, Ezh2 loss derepresses a subset of bivalent promoters that resolve toward gene activation, inducing a feto-oncogenic program that includes genes such as Plag1, whose overexpression phenocopies Ezh2 loss to accelerate AML induction in mouse models. Our data highlight the importance of cellular context and disease phase for the function of Ezh2 and its potential therapeutic implications.The Huntly laboratory is funded by CRUK (program C18680/ A25508), the European Research Council (grant 647685 COMAL), the Kay Kendall Leukaemia Fund, the Medical Research Council (MRC), Bloodwise, the Wellcome Trust, and the Cambridge National Institute of Health Research Biomedical Research Centre. F. Basheer is a recipient of a Wellcome Trust PhD for Clinicians award. P. Gallipoli is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the Wellcome Trust/ MRC center grant (097922/Z/11/Z) and support from Wellcome Trust strategic award 100140. Research in the laboratory is also supported by core funding from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. This research was supported by the Cambridge National Institute of Health Research Biomedical Research Centre Cell Phenotyping Hub

Study of the chemotactic response of multicellular spheroids in a microfluidic device

YesWe report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Test-retest stability of cerebral A1 adenosine receptor quantification using [18F]CPFPX and PET

The goal of the present study was to evaluate the reproducibility of cerebral A1 adenosine receptor (A1AR) quantification using [18F]CPFPX and PET in a test-retest design.Eleven healthy volunteers were studied twice. Eight brain regions ranging from high to low receptor binding were examined. [18F]CPFPX was injected as a bolus with subsequent infusion over 120 min. Various outcome parameters were compared based on either metabolite-corrected venous blood sampling [e.g. apparent equilibrium total distribution volume (DVt')] or a reference region [ratio of specific to non-specific distribution volume (BP2)].Test-retest variability was low in the outcome measure BP2 (on average 5.9%) and moderate in DVt' (on average 13.2%). Regarding reproducibility, the outcome parameter BP2 showed an intra-class correlation coefficient (ICC) of 0.94 +/- 0.1. For DVt' the between-subject coefficient of variation (%CV) was similar to the within-subject %CV (around 10%), resulting in a poor ICC of 0.06 +/- 0.2.Our results suggest that quantification of [18F]CPFPX imaging is reproducible and reliable for PET studies of the cerebral A1AR. Among the outcome parameters the non-invasive measures were of superior test-retest stability over the invasive