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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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3.
  • Adare, A., et al. (author)
  • Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review Letters. - 1079-7114. ; 115:14
  • Journal article (peer-reviewed)abstract
    • We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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4.
  • Adare, A., et al. (author)
  • Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
  • Journal article (peer-reviewed)abstract
    • The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
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5.
  • Adare, A., et al. (author)
  • Measurement of gamma(1S+2S+3S) production in p plus p and Au plus Au collisions at root sNN=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:2
  • Journal article (peer-reviewed)abstract
    • Measurements of bottomonium production in heavy-ion and p + p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three states, (1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au + Au and p + p collisions at root sNN = 200 GeV. The (1S + 2S + 3S) -> e(+)e(-) differential cross section at midrapidity was found to be B(ee)d sigma/dy = 108 +/- 38 (stat) +/- 15 (syst) +/- 11 (luminosity) pb in p + p collisions. The nuclear modification factor in the 30% most central Au + Au collisions indicates a suppression of the total. state yield relative to the extrapolation from p + p collision data. The suppression is consistent with measurements made by STAR at RHIC and at higher energies by the CMS experiment at the Large Hadron Collider.
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6.
  • Adare, A., et al. (author)
  • Systematic study of charged-pion and kaon femtoscopy in Au plus Au collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
  • Journal article (peer-reviewed)abstract
    • We present a systematic study of charged-pion and kaon interferometry in Au + Au collisions at root s(NN) = 200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.
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7.
  • Adare, A., et al. (author)
  • phi meson production in d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:4
  • Journal article (peer-reviewed)abstract
    • The PHENIX Collaboration has measured phi meson production in d + Au collisions at root s(NN) = 200 GeV using the dimuon and dielectron decay channels. The phi meson is measured in the forward (backward) d-going (Au-going) direction, 1.2 < y < 2.2 (-2.2 < y < -1.2) in the transverse-momentum (pT) range from 1-7 GeV/c and at midrapidity vertical bar y vertical bar < 0.35 in the p(T) range below 7 GeV/c. The phi meson invariant yields and nuclear-modification factors as a function of p(T), rapidity, and centrality are reported. An enhancement of phi meson production is observed in the Au-going direction, while suppression is seen in the d-going direction, and no modification is observed at midrapidity relative to the yield in p + p collisions scaled by the number of binary collisions. Similar behavior was previously observed for inclusive charged hadrons and open heavy flavor, indicating similar cold-nuclear-matter effects.
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8.
  • Adare, A., et al. (author)
  • Centrality dependence of low-momentum direct-photon production in Au plus Au collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:6
  • Journal article (peer-reviewed)abstract
    • The PHENIX experiment at RHIC has measured the centrality dependence of the direct photon yield from Au + Au collisions at root s(NN) = 200 GeV down to pT = 0.4 GeV/c. Photons are detected via photon conversions to e(+)e(-) pairs and an improved technique is applied that minimizes the systematic uncertainties that usually limit direct photon measurements, in particular at low pT. We find an excess of direct photons above the N-coll-scaled yield measured in p + p collisions. This excess yield is well described by an exponential distribution with an inverse slope of about 240 MeV/c in the pT range 0.6-2.0 GeV/c. While the shape of the pT distribution is independent of centrality within the experimental uncertainties, the yield increases rapidly with increasing centrality, scaling approximately with N-part(alpha), where alpha = 1.38 +/- 0.03(stat) +/- 0.07(syst).
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9.
  • Adare, A., et al. (author)
  • Measurement of higher cumulants of net-charge multiplicity distributions in Au plus Au collisions at root s(NN)=7.7-200 GeV
  • 2016
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 93:1
  • Journal article (peer-reviewed)abstract
    • We report the measurement of cumulants (C-n,n = 1, ..., 4) of the net-charge distributions measured within pseudorapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(NN) = 7.7-200 GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g., C-1/C-2, C-3/C-1) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of C-1/C-2 and C-3/C-1 can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy. The extracted baryon chemical potentials are in excellent agreement with a thermal-statistical analysis model.
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10.
  • Adare, A, et al. (author)
  • Measurement of Long-Range Angular Correlation and Quadrupole Anisotropy of Pions and (Anti)Protons in Central d+Au Collisions at sqrt[s_{NN}]=200 GeV.
  • 2015
  • In: Physical Review Letters. - 1079-7114. ; 114:19
  • Journal article (peer-reviewed)abstract
    • We present azimuthal angular correlations between charged hadrons and energy deposited in calorimeter towers in central d+Au and minimum bias p+p collisions at sqrt[s_{NN}]=200 GeV. The charged hadron is measured at midrapidity |η|<0.35, and the energy is measured at large rapidity (-3.7<η<-3.1, Au-going direction). An enhanced near-side angular correlation across |Δη|>2.75 is observed in d+Au collisions. Using the event plane method applied to the Au-going energy distribution, we extract the anisotropy strength v_{2} for inclusive charged hadrons at midrapidity up to p_{T}=4.5 GeV/c. We also present the measurement of v_{2} for identified π^{±} and (anti)protons in central d+Au collisions, and observe a mass-ordering pattern similar to that seen in heavy-ion collisions. These results are compared with viscous hydrodynamic calculations and measurements from p+Pb at sqrt[s_{NN}]=5.02 TeV. The magnitude of the mass ordering in d+Au is found to be smaller than that in p+Pb collisions, which may indicate smaller radial flow in lower energy d+Au collisions.
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11.
  • Adare, A., et al. (author)
  • Systematic study of azimuthal anisotropy in Cu plus Cu and Au plus Au collisions at root s(NN)=62.4 and 200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
  • Journal article (peer-reviewed)abstract
    • We have studied the dependence of azimuthal anisotropy nu(2) for inclusive and identified charged hadrons in Au + Au and Cu + Cu collisions on collision energy, species, and centrality. The values of nu(2) as a function of transverse momentum pT and centrality in Au + Au collisions at root s(NN) = 200 and 62.4 GeV are the same within uncertainties. However, in Cu + Cu collisions we observe a decrease in nu(2) values as the collision energy is reduced from 200 to 62.4 GeV. The decrease is larger in the more peripheral collisions. By examining both Au + Au and Cu + Cu collisions we find that nu(2) depends both on eccentricity and the number of participants, N-part. We observe that nu(2) divided by eccentricity (epsilon) monotonically increases with N-part and scales as N-part(1/3). The Cu + Cu data at 62.4 GeV falls below the other scaled nu(2) data. For identified hadrons, nu(2) divided by the number of constituent quarks n(q) is independent of hadron species as a function of transverse kinetic energy K E-T = m(T) - m between 0.1 < K E-T / n(q) < 1 GeV. Combining all of the above scaling and normalizations, we observe a near-universal scaling, with the exception of the Cu + Cu data at 62.4 GeV, of nu(2)/(nq center dot e center dot N-part(1/3)) vs K E-T / n(q) for all measured particles.
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12.
  • Adare, A., et al. (author)
  • Charged-pion cross sections and double-helicity asymmetries in polarized p plus p collisions at root s=200 GeV
  • 2015
  • In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 91:3
  • Journal article (peer-reviewed)abstract
    • We present midrapidity charged-pion invariant cross sections, the ratio of the pi(-) to pi(+) cross sections and the charge-separated double-spin asymmetries in polarized p + p collisions at root s = p + 200 GeV. While the cross section measurements are consistent within the errors of next-to-leading-order (NLO) perturbative quantum chromodynamics predictions (pQCD), the same calculations overestimate the ratio of the charged-pion cross sections. This discrepancy arises from the cancellation of the substantial systematic errors associated with the NLO-pQCD predictions in the ratio and highlights the constraints these data will place on flavor-dependent pion fragmentation functions. The charge-separated pion asymmetries presented here sample an x range of similar to 0.03-0.16 and provide unique information on the sign of the gluon-helicity distribution.
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13.
  • Adare, A., et al. (author)
  • Cross section for b(b)over-bar production via dielectrons in d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:1
  • Journal article (peer-reviewed)abstract
    • We report a measurement of e(+)e(-) pairs from semileptonic heavy-flavor decays in d + Au collisions at root s(NN) = 200 GeV. By exploring the mass and transverse-momentum dependence of the yield, the bottom decay contribution can be isolated from charm, and quantified by comparison to PYTHIA and MC@NLO simulations. The resulting b (b) over bar -production cross section is sigma(dAu)(b (b) over bar) = 1.37 +/- 0.28 (stat) +/- 0.46 (syst) mb, which is equivalent to a nucleon-nucleon cross section of sigma(NN)(b (b) over bar) = 3.4 +/- 0.8 (stat) +/- 1.1 ( syst) mu b.
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14.
  • Adare, A., et al. (author)
  • Heavy-quark production and elliptic flow in Au plus Au collisions at root(NN)-N-S=62.4 GeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:4
  • Journal article (peer-reviewed)abstract
    • We present measurements of electrons and positrons from the semileptonic decays of heavy-flavor hadrons at midrapidity (vertical bar gamma vertical bar < 0.35) in Au + Au collisions at root(NN)-N-S = 62.4 GeV. The data were collected in 2010 by the PHENIX experiment that included the new hadron-blind detector. The invariant yield of electrons from heavy-flavor decays is measured as a function of transverse momentum in the range 1 < p(T)(e) < 5 GeV/c. The invariant yield per binary collision is slightly enhanced above the p + p reference in Au + Au 0%-20%, 20%-40%, and 40%-60% centralities at a comparable level. At this low beam energy this may be a result of the interplay between initial-state Cronin effects, final-state flow, and energy loss in medium. The v(2) of electrons from heavy-flavor decays is nonzero when averaged between 1.3 < p(T)(e) < 2.5 GeV/c for 0%-40% centrality collisions at root(NN)-N-S = 62.4 GeV. For 20%-40% centrality collisions, the v(2) at root(NN)-N-S = 62.4 GeV is smaller than that for heavy-flavor decays at root(NN)-N-S = 200 GeV. The v2 of the electrons from heavy-flavor decay at the lower beam energy is also smaller than v(2) for pions. Both results indicate that the heavy quarks interact with the medium formed in these collisions, but they may not be at the same level of thermalization with the medium as observed at root(NN)-N-S = 200 GeV.
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  • Bousquet, J., et al. (author)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Journal article (peer-reviewed)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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  • Smol, T., et al. (author)
  • MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
  • 2018
  • In: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
  • Journal article (peer-reviewed)abstract
    • Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
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  • Greene, Christopher J., et al. (author)
  • A novel strategy to protect against influenza-induced pneumococcal disease without interfering with commensal colonization
  • 2016
  • In: Infection and Immunity. - 1098-5522. ; 84:6, s. 1693-1703
  • Journal article (peer-reviewed)abstract
    • Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype-replacement with, so-far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virally-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally-induced, pneumococcal disease can be conferred without disturbing the desirable pre-existing commensal colonization of the nasopharynx.
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  • Krishnan, Jerry A., et al. (author)
  • Prevalence and characteristics of asthma-chronic obstructive pulmonary disease overlap in routine primary care practices
  • 2019
  • In: Annals of the American Thoracic Society. - 2325-6621. ; 16:9, s. 1143-1150
  • Journal article (peer-reviewed)abstract
    • Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care. Objectives: To estimate the prevalence and describe characteristics of individuals withACOin primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations. Methods: The Respiratory Effectiveness Group conducted a crosssectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in theUKOptimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only.ACOwas defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) postbronchodilator airflow limitation (forced expiratory volume in 1 second/ forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second. Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P<0.001) or asthma only (14%; P<0.001). Demographic and clinical characteristics of ACO varied across these three source populations. Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.
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  • Åberg, Anna, et al. (author)
  • Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
  • 2017
  • In: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
  • Journal article (peer-reviewed)abstract
    • The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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  • Abellán, F. J., et al. (author)
  • Very Deep inside the SN 1987A Core Ejecta : Molecular Structures Seen in 3D
  • 2017
  • In: Astrophysical Journal Letters. - : Institute of Physics Publishing. - 2041-8205 .- 2041-8213. ; 842:2
  • Journal article (peer-reviewed)abstract
    • Most massive stars end their lives in core-collapse supernova explosions and enrich the interstellar medium with explosively nucleosynthesized elements. Following core collapse, the explosion is subject to instabilities as the shock propagates outward through the progenitor star. Observations of the composition and structure of the innermost regions of a core-collapse supernova provide a direct probe of the instabilities and nucleosynthetic products. SN 1987A in the Large Magellanic Cloud is one of very few supernovae for which the inner ejecta can be spatially resolved but are not yet strongly affected by interaction with the surroundings. Our observations of SN 1987A with the Atacama Large Millimeter/submillimeter Array are of the highest resolution to date and reveal the detailed morphology of cold molecular gas in the innermost regions of the remnant. The 3D distributions of carbon and silicon monoxide (CO and SiO) emission differ, but both have a central deficit, or torus-like distribution, possibly a result of radioactive heating during the first weeks ("nickel heating"). The size scales of the clumpy distribution are compared quantitatively to models, demonstrating how progenitor and explosion physics can be constrained.
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  • Bourgoin, M., et al. (author)
  • Investigation of the small-scale statistics of turbulence in the Modane S1MA wind tunnel
  • 2018
  • In: CEAS Aeronautical Journal. - : Springer. - 1869-5582 .- 1869-5590. ; 9:2, s. 269-281
  • Journal article (peer-reviewed)abstract
    • This article describes the planning, set-up, turbulence characterization and analysis of measurements of a passive grid turbulence experiment that was carried out in the S1MA wind-tunnel from ONERA in Modane, in the context of the ESWIRP European project. This experiment aims at a detailed investigation of the statistical properties of turbulent flows at large Reynolds numbers. The primary goal is to take advantage of the unequaled large-scale dimensions of the ONERA S1MA wind-tunnel facility, to make available to the broad turbulence community high-quality experimental turbulence data with unprecendented resolution (both spatial and temporal) and accuracy (in terms of statistical convergence). With this goal, we designed the largest grid-generated turbulence experiment planned and performed to date. Grid turbulence is a canonical flow known to produce almost perfectly homogeneous and isotropic turbulence (HIT) which remains a unique framework to investigate fundamental physics of turbulent flows. Here, we present a brief description of the measurements, in particular those based on hot-wire diagnosis. By comparing results from classical hot-wires and from a nano-fabricated wire (developed at Princeton University), we show that our goal of resolving down to the smallest dissipative scales of the flow has been achieved. We also present the full characterization of the turbulence here, in terms of turbulent energy dissipation rate, injection and dissipation scales (both spatial and temporal) and Reynolds number.
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  • Bousquet, J. Jean, et al. (author)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Research review (peer-reviewed)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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40.
  • Campbell, Jonathan D., et al. (author)
  • The REal Life EVidence AssessmeNt Tool (RELEVANT) : Development of a novel quality assurance asset to rate observational comparative effectiveness research studies
  • 2019
  • In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Background: Evidence from observational comparative effectiveness research (CER) is ranked below that from randomized controlled trials in traditional evidence hierarchies. However, asthma observational CER studies represent an important complementary evidence source answering different research questions and are particularly valuable in guiding clinical decision making in real-life patient and practice settings. Tools are required to assist in quality appraisal of observational CER to enable identification of and confidence in high-quality CER evidence to inform guideline development. Methods: The REal Life EVidence AssessmeNt Tool (RELEVANT) was developed through a step-wise approach. We conducted an iterative refinement of the tool based on Task Force member expertise and feedback from pilot testing the tool until reaching adequate inter-rater agreement percentages. Two distinct pilots were conducted - the first involving six members of the Respiratory Effectiveness Group (REG) and European Academy of Allergy and Clinical Immunology (EAACI) joint Task Force for quality appraisal of observational asthma CER; the second involving 22 members of REG and EAACI membership. The final tool consists of 21 quality sub-items distributed across seven methodology domains: Background, Design, Measures, Analysis, Results, Discussion/Interpretation, and Conflict of Interest. Eleven of these sub-items are considered critical and named "primary sub-items". Results: Following the second pilot, RELEVANT showed inter-rater agreement ≥ 70% for 94% of all primary and 93% for all secondary sub-items tested across three rater groups. For observational CER to be classified as sufficiently high quality for future guideline consideration, all RELEVANT primary sub-items must be fulfilled. The ten secondary sub-items further qualify the relative strengths and weaknesses of the published CER evidence. RELEVANT could also be applicable to general quality appraisal of observational CER across other medical specialties. Conclusions: RELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation. Developed for a REG-EAACI Task Force quality appraisal of recent asthma CER, RELEVANT also has wider utility to support appraisal of CER literature in general (including pre-publication). It may also assist in manuscript development and in educating relevant stakeholders about key quality markers in observational CER.
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41.
  • Clark, Timothy D., et al. (author)
  • Maximum thermal limits of coral reef damselfishes are size dependent and resilient to near-future ocean acidification
  • 2017
  • In: Journal of Experimental Biology. - : COMPANY OF BIOLOGISTS LTD. - 0022-0949 .- 1477-9145. ; 220:19, s. 3519-3526
  • Journal article (peer-reviewed)abstract
    • Theoretical models predict that ocean acidification, caused by increased dissolved CO2, will reduce the maximum thermal limits of fishes, thereby increasing their vulnerability to rising ocean temperatures and transient heatwaves. Here, we tested this prediction in three species of damselfishes on the Great Barrier Reef, Australia. Maximum thermal limits were quantified using critical thermal maxima (CTmax) tests following acclimation to either presentday or end-of-century levels of CO2 for coral reef environments (similar to 500 or similar to 1000 mu atm, respectively). While species differed significantly in their thermal limits, whereby Dischistodus perspicillatus exhibited greater CTmax (37.88 +/- 0.03 degrees C; N=47) than Dascyllus aruanus (37.68 +/- 0.02 degrees C; N=85) and Acanthochromis polyacanthus (36.58 +/- 0.02 degrees C; N=63), end-of-century CO2 had no effect (D. aruanus) or a slightly positive effect (increase in CTmax of 0.16 degrees C in D. perspicillatus and 0.21 degrees C in A. polyacanthus) on CTmax. Contrary to expectations, early-stage juveniles were equally as resilient to CO2 as larger conspecifics, and CTmax was higher at smaller body sizes in two species. These findings suggest that ocean acidification will not impair the maximum thermal limits of reef fishes, and they highlight the critical role of experimental biology in testing predictions of theoretical models forecasting the consequences of environmental change.
  •  
42.
  • Ferrari, A. C., et al. (author)
  • Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems
  • 2015
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 7:11, s. 4598-4810
  • Journal article (peer-reviewed)abstract
    • We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.
  •  
43.
  • Goldberg, Emily L., et al. (author)
  • beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares
  • 2017
  • In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:9, s. 2077-2087
  • Journal article (peer-reviewed)abstract
    • Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1 beta (IL-1 beta) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases beta-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1 beta in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.
  •  
44.
  • Gruden, M. A., et al. (author)
  • Antibodies to Glutamate Reversed the Amnesic Effects of Proinflammatory S100A9 Protein Fibrils in Aged C57Bl/6 Mice
  • 2017
  • In: Bulletin of experimental biology and medicine. - : SPRINGER. - 0007-4888 .- 1573-8221. ; 162:4, s. 430-432
  • Journal article (peer-reviewed)abstract
    • Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.
  •  
45.
  • Gruden, Marina A, et al. (author)
  • Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
  • 2015
  • In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 279, s. 191-201
  • Journal article (peer-reviewed)abstract
    • Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances.
  •  
46.
  • Gruden, Marina A., et al. (author)
  • S100A9 Protein Aggregates Boost Hippocampal Glutamate Modifying Monoaminergic Neurochemistry : A Glutamate Antibody Sensitive Outcome on Alzheimer-like Memory Decline
  • 2018
  • In: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:3, s. 568-577
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy.
  •  
47.
  • Gruden, Marina A., et al. (author)
  • The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit
  • 2016
  • In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 306, s. 106-116
  • Journal article (peer-reviewed)abstract
    • Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and All antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy.
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