1,235 research outputs found

    Practical applications of multi-agent systems in electric power systems

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    The transformation of energy networks from passive to active systems requires the embedding of intelligence within the network. One suitable approach to integrating distributed intelligent systems is multi-agent systems technology, where components of functionality run as autonomous agents capable of interaction through messaging. This provides loose coupling between components that can benefit the complex systems envisioned for the smart grid. This paper reviews the key milestones of demonstrated agent systems in the power industry and considers which aspects of agent design must still be addressed for widespread application of agent technology to occur

    Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody

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    Highly selective monoclonal antibodies recognizing the extracellular 3D epitope of G protein-coupled receptors represent valuable tools for elucidating receptor function and localization in the cell and show promise for a range of therapeutic applications. Here we present the structure of a complex between the human serotonin 2B receptor, captured in an active-like state, and an antibody Fab fragment, bound to the extracellular side of the receptor. The structure uncovers the mechanisms of receptor activation and of extracellular receptor recognition by antibodies

    Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding

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    BACKGROUND AND AIM: Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in liver cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic stent-shunt (TIPSS) improves the survival of patients with failure to control OGVB and ACLF. METHODS: From a prospectively maintained ICU registry, data of 174 consecutive eligible patients with failure to control OGVB between 2005 and 2015, were included. Rescue TIPSS was defined as technically successful TIPSS within 72-hours of presentation with failure to control OGVB. Cox proportional hazards regression analyses were applied to explore the impact of ACLF and TIPSS on survival in failure-to-control OGVB. RESULTS: ACLF patients (n=119) were significantly older, had organ failures and higher white cell count compared with patients with acute decompensation (AD, n=55). Mortality at 42-days and 1-year was significantly higher in ACLF (47.9% and 61.3%) as compared to AD patients (9.1% and 12.7%, p<0.001), whereas there was no difference in the number of endoscopies and transfusion requirements between these groups. TIPSS was inserted in 78 patients [AD: 21 (38.2%); ACLF: 57 (47.8%), p=0.41]. In ACLF, rescue TIPSS insertion was an independent favorable prognostic factor for 42-day mortality. In contrast, rescue TIPSS did not impact on the outcome of AD patients. CONCLUSIONS: This study shows for the first time that in patients with failure to control OGVB, the presence and severity of ACLF determines the risk of 42-day and 1-year mortality. Rescue TIPSS is associated with improved survival of ACLF patients

    Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

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    Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

    Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

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    Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra; ArgentinaFil: Vranych, Cecilia VerĂłnica. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra. Universidad Nacional de CĂłrdoba. Instituto de InvestigaciĂłn MĂ©dica Mercedes y MartĂ­n Ferreyra; Argentin

    Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apnea

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    Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some patients with obstructive sleep apnea (OSA). A pooled analysis of two 12-week, randomized, double-blind studies in nCPAP-adherent patients with ES associated with OSA evaluated the effect of armodafinil on wakefulness and cognition. Three hundred and ninety-one patients received armodafinil (150 or 250 mg) and 260 patients received placebo once daily for 12 weeks. Efficacy assessments included the Maintenance of Wakefulness Test (MWT), Cognitive Drug Research cognitive performance battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. Adverse events were monitored. Armodafinil increased mean MWT sleep latency from baseline to final visit by 2.0 min vs a decrease of 1.5 min with placebo (P < 0.0001). Compared with placebo, armodafinil significantly improved quality of episodic secondary memory (P < 0.05) and patients’ ability to engage in activities of daily living (P < 0.0001) and reduced fatigue (P < 0.01). The most common adverse events were headache, nausea, and insomnia. Armodafinil did not adversely affect desired nighttime sleep, and nCPAP use remained high (approximately 7 h/night). Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients’ ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. Armodafinil also reduced patient-reported fatigue and was well tolerated

    Visualization of Glutamine Transporter Activities in Living Cells Using Genetically Encoded Glutamine Sensors

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    Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells) is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET) glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP)1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level

    Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

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    The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≄20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≀pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≀{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  Όb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∌0) correlation that grows rapidly with increasing ÎŁETPb. A long-range “away-side” (Δϕ∌π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ÎŁETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁥2Δϕ modulation for all ÎŁETPb ranges and particle pT
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