1,126 research outputs found

    Studying the energy consumption of data transfers in Clouds: the Ecofen approach

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    International audienceEnergy consumption is one of the main limiting factors for designing large scale Clouds. Evaluating the energy consumption of Clouds networking architectures and providing multi-level views required by providers and users, is a challenging issue. In this paper, we show how to evaluate and understand network choices (protocols, topologies) in terms of contributions to the energy consumption of the global Cloud infrastructures. By applying the ECOFEN model (Energy Consumption mOdel For End-to-end Networks) and the corresponding simulation framework, we profile and analyze the energy consumption of data transfers in Clouds

    A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models

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    <p>Abstract</p> <p>Background</p> <p>Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.</p> <p>Methods</p> <p>The <it>in-vitro </it>activities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity on <it>in-vitro </it>microtubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compound <it>in vivo</it>. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.</p> <p>Results</p> <p>In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 10<sup>5 </sup>M<sup>-1</sup>, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. These <it>in vitro </it>studies were reinforced by our <it>in vivo </it>investigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.</p> <p>Conclusion</p> <p>These <it>in vitro </it>and <it>in vivo </it>data suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.</p

    Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

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    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease

    European Lung Cancer Working Party Clinical Practice Guidelines. Non-Small Cell Lung Cancer: III. Metastatic disease

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    The present guidelines on the management of advanced non-small cell lung cancer (NS CLC) were formulated by the ELCWP in October 2006. They are designed to answer the following twelve questions: 1) What benefits can be expected from chemotherapy and what are the treatment objectives? 2) What are the active chemotherapeutic drugs for which efficacy has been shown? 3) Which are the most effective platinum-based regimens? 4) Which is the indicated dosage of cisplatin? 5) Can carboplatin be substituted for cisplatin? 6) Which is the optimal number of cycles to be administered? 7) Can non-platinum based regimens be substituted for platinum based chemotherapy as first-line treatment? 8) Is there an indication for sequential chemotherapy? 9) What is the efficacy of salvage chemotherapy and which drugs should be used in that indication? 10) What is the place of targeted therapies? 11) What is the place of chemotherapy in the management of a patient with brain metastases? 12) Which specific drugs can be used for the patient with bone metastases

    EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

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    AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

    ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

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    Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

    International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

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    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

    International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

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    Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

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    Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a ZZ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 <pT<100< p_{\textrm{T}} < 100 GeV and in the pseudorapidity range 2.5<η<42.5 < \eta < 4. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb1^{-1}. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages
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