161 research outputs found

    Neutron tomography in modern archaeology

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    The search for non invasive and non destructive techniques is fundamental when dealing with samples of great historical, cultural and artistic value as well as with samples strongly degraded. Among different techniques, Neutron Tomography NT allows a close analysis of samples of Archaeological interest without damaging them. In what follows, a few cases in which the Neutron Tomography instrument of the BENSC at HMI Berlin has been successfully applied will be show

    Hypoxia up-regulates SERPINB3 through HIF-2\u3b1 in human liver cancer cells.

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    SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells. Exposure of HepG2 and Huh7 cells to hypoxia up-regulated SERPINB3 transcription, protein synthesis and release in the extracellular medium. Hypoxia-dependent SERPINB3 up-regulation was selective (no change detected for SERPINB4) and operated through hypoxia inducible factor (HIF)-2\u3b1 (not HIF-1\u3b1) binding to SERPINB3 promoter, as confirmed by chromatin immuno-precipitation assay and silencing experiments employing specific siRNAs. HIF-2\u3b1-mediated SERPINB3 up-regulation under hypoxic conditions required intracellular generation of ROS. Immuno-histochemistry (IHC) and transcript analysis, performed in human HCC specimens, revealed co-localization of the two proteins in liver cancer cells and the existence of a positive correlation between HIF-2\u3b1 and SERPINB3 transcript levels, respectively. Hypoxia, through HIF-2\u3b1-dependent and redox-sensitive mechanisms, up-regulates the transcription, synthesis and release of SERPINB3, a molecule with a high oncogenic potential

    System architecture of Intelligent Monitoring in multi-domain orchestration

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    Orchestrating a service or resources across multiple administrative domains requires three main high level steps of operation: i) capability detection of other domains ii) placement of the service request across the domains iii) assurance that the service is functioning within the acceptable bounds of the service level agreement (SLA). This paper focuses on the assurance step; in particular, we present a novel architecture and preliminary implementation that supports monitoring of KPIs across multiple administrative domains. The challenges towards realising such an architecture are: i) coordinated monitoring with no direct access to the other domain's infrastructure ii) monitoring over an abstracted (instead of actual) topology that each administrative domain may expose to other domains iii) different domains have different systems for monitoring with different KPIs as well as different ways of measuring those KPI. Our architecture, referred to as IMoS addresses these challenges to provide an end-to-end monitoring as a fundamental functionality for supporting assurance and SLA management for services orchestration across multi-administrative-domains. In addition, the preliminary results are provided from the first proof of concept implementation of an IMoS. The work done in this paper has been developed within the H2020 ICT14 project 5G Exchange

    Rethinking the social impacts of the arts

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    The paper presents a critical discussion of the current debate over the social impacts of the arts in the UK. It argues that the accepted understanding of the terms of the debate is rooted in a number of assumptions and beliefs that are rarely questioned. The paper goes on to present the interim findings of a three‐year research project, which aims to rethink the social impact of the arts, with a view to determining how these impacts might be better understood. The desirability of a historical approach is articulated, and a classification of the claims made within the Western intellectual tradition for what the arts “do” to people is presented and discussed

    Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures: an architectural survey

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    Over the last couple of years, industry operators’ associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This arti- cle provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi- operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation

    PO-145 ERK5 pathway inhibitors inhibit the maintenance of chronic myeloid leukaemia stem cells

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    Introduction Chronic myeloid leukaemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterised by the expression of the constitutively active tyrosine kinase BCR/ABL. CML therapy based on tyrosine kinase inhibitors (TKi) is highly effective in inducing remission but not in targeting leukaemia stem cells (LSC), which sustain the minimal residual disease and are responsible for CML relapse following discontinuation of treatment. Our aim was to address the effects of the inhibition of the ERK5 pathway on the maintenance of CML LSC. Material and methods KCL22 and K562 CML cell lines, patient-derived CML cells or CD34 +peripheral blood cells from healthy donors (informed consent) were incubated in normoxic or hypoxic (0.1% O 2 ) primary cultures (LC1) in the presence or the absence of drugs. At the end of incubation (day 7), cells were analysed on a flow cytometer to determine the expression of stem cell markers or transferred to drug-free normoxic secondary cultures (LC2) to measure LC2 repopulation as a read-out of progenitor/stem cell potential (CRA assay). In the serial Colony Formation Ability (CFA) assay colonies were scored on day 7 of each passage (III passages). In the Long-Term Culture-Initiating Cells (LTC-IC) assay the number of colonies was scored after 14 days. Compounds: XMD8-92 (ERK5 inhibitor) and BIX02189 (MEK5 inhibitor); imatinib and dasatinib (BCR/ABL inhibitors). Results and discussions In CML patient-derived cells and cell lines, we found that the MEK5/ERK5 pathway is active and necessary for optimal proliferation in low oxygen, a condition typical of normal hematopoietic and leukemic stem cell niches. Treatment of primary CML cells with XMD8-92 or BIX02189, but not with TKi, strikingly reduced Culture Repopulation Ability (CRA), serial Colony Formation Ability and Long-Term Culture-Initiating Cells (LTC-IC). Importantly, inhibition of MEK5/ERK5 was effective on CML cells regardless of the presence or absence of imatinib (IM), and did not reduce CRA or LTC-IC of normal CD34 +cells. Interestingly, in hypoxia, combined treatment XMD8-92/IM decreased the expression of genes relevant for stem cell maintenance such as c-MYC, SOX2 and NANOG and the expression of CD26, a CML LSC marker. Conclusion We propose ERK5 pathway inhibitors as a novel therapeutic approach to prevent CML relapse and, in combination with TKi, enhance induction of remission
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