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Measurement of the fraction of jet longitudinal momentum carried by Λ⁺c baryons in pp collisions
(2024)
Recent measurements of charm-baryon production in hadronic collisions have questioned the universality of charm-quark fragmentation across different collision systems. In this work the fragmentation of charm quarks into charm baryons is probed, by presenting the first measurement of the longitudinal jet momentum fraction carried by Λ+c baryons, zch||, in hadronic collisions. The results are obtained in proton-proton (pp) collisions at s√=13 TeV at the LHC, with Λ+c baryons and charged (track-based) jets reconstructed in the transverse momentum intervals of 3≤pΛ+cT<15 GeV/c and 7≤pjetchT<15 GeV/c, respectively. The zch|| distribution is compared to a measurement of D0-tagged charged jets in pp collisions as well as to PYTHIA 8 simulations. The data hints that the fragmentation of charm quarks into charm baryons is softer with respect to charm mesons, in the measured kinematic interval, as predicted by hadronisation models which include colour correlations beyond leading-colour in the string formation.
Observation of abnormal suppression of f₀(980) production in p–Pb collisions at √sNN = 5.02 TeV
(2024)
The dependence of f0(980) production on the final-state charged-particle multiplicity in p−Pb collisions at sNN−−−√=5.02 TeV is reported. The production of f0(980) is measured with the ALICE detector via the f0(980)→π+π− decay channel in a midrapidity region of −0.5<y<0. Particle yield ratios of f0(980) to π and K∗(892)0 are found to be decreasing with increasing charged-particle multiplicity. The magnitude of the suppression of the f0(980)/π and f0(980)/K∗(892)0 yield ratios is found to be dependent on the transverse momentum pT, suggesting different mechanisms responsible for the measured effects. Furthermore, the nuclear modification factor QpPb of f0(980) is measured in various multiplicity ranges. The QpPb shows a strong suppression of the f0(980) production in the pT region up to about 4 GeV/c. The results on the particle yield ratios and QpPb for f0(980) may help to understand the late hadronic phase in p−Pb collisions and the nature of the internal structure of f0(980) particle.
Observation of abnormal suppression of f₀(980) production in p–Pb collisions at √sNN = 5.02 TeV
(2024)
The dependence of f0(980) production on the final-state charged-particle multiplicity in p−Pb collisions at sNN−−−√=5.02 TeV is reported. The production of f0(980) is measured with the ALICE detector via the f0(980)→π+π− decay channel in a midrapidity region of −0.5<y<0. Particle yield ratios of f0(980) to π and K∗(892)0 are found to be decreasing with increasing charged-particle multiplicity. The magnitude of the suppression of the f0(980)/π and f0(980)/K∗(892)0 yield ratios is found to be dependent on the transverse momentum pT, suggesting different mechanisms responsible for the measured effects. Furthermore, the nuclear modification factor QpPb of f0(980) is measured in various multiplicity ranges. The QpPb shows a strong suppression of the f0(980) production in the pT region up to about 4 GeV/c. The results on the particle yield ratios and QpPb for f0(980) may help to understand the late hadronic phase in p−Pb collisions and the nature of the internal structure of f0(980) particle.
K+K− pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons, or directly as non-resonant K+K− pairs. Measurements of K+K− photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon−proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K+K− pairs on lead ions in ultra-peripheral collisions using the ALICE detector, including the first investigation of direct K+K− production. There is significant K+K− production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1<MKK<1.4 GeV/c2 above the ϕ(1020) resonance, for rapidity |yKK|<0.8 and pT,KK<0.1 GeV/c, the measured coherent photoproduction cross section is dσ/dy = 3.37 ± 0.61 (stat.) ± 0.15 (syst.) mb. The center-of-mass energy per nucleon of the photon-nucleus (Pb) system WγPb,n ranges from 33 to 188 GeV, far higher than previous measurements on heavy-nucleus targets. The cross section is larger than expected for ϕ(1020) photoproduction alone. The mass spectrum is fit to a cocktail consisting of ϕ(1020) decays, direct K+K− photoproduction, and interference between the two. The confidence regions for the amplitude and relative phase angle for direct K+K− photoproduction are presented.
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
The correlations between event-by-event fluctuations of symmetry planes are measured in Pb−Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√ = 5.02 TeV recorded by the ALICE detector at the Large Hadron Collider. This analysis is conducted using the Gaussian Estimator technique, which is insensitive to biases from correlations between different flow amplitudes. The study presents, for the first time, the centrality dependence of correlations involving up to five different symmetry planes. The correlation strength varies depending on the harmonic order of the symmetry plane and the collision centrality. Comparisons with measurements from lower energies indicate no significant differences within uncertainties. Additionally, the results are compared with hydrodynamic model calculations. Although the model predictions provide a qualitative explanation of the experimental results, they overestimate the data for some observables. This is particularly true for correlators that are sensitive to the non-linear response of the medium to initial-state anisotropies in the collision system. As these new correlators provide unique information - independent of flow amplitudes - their usage in future model developments can further constrain the properties of the strongly-interacting matter created in ultrarelativistic heavy-ion collisions.
This is an addendum to the article [arXiv:2005.11995] "Dielectron production in proton-proton and proton-lead collisions at sNN−−−√ = 5.02 TeV" published in Phys. Rev. C 102 no. 5, (2020) 055204. We update the extracted charm cross section at midrapidity given in Table 3 and Figure 4 (left) of the original publication with the fragmentation fractions of charm quarks in pp collisions published in Phys. Rev. D 105 (2022) L011103.
Multiplicity-dependent jet modification from di-hadron correlations in pp collisions at √s= 13 TeV
(2024)
Short-range correlations between charged particles are studied via two-particle angular correlations in pp collisions at s√=13 TeV. The correlation functions are measured as a function of the relative azimuthal angle Δφ and the pseudorapidity separation Δη for pairs of primary charged particles within the pseudorapidity interval |η|<0.9 and the transverse-momentum range 1<pT<8 GeV/c. Near-side (|Δφ|<1.3) peak widths are extracted from a generalised Gaussian fitted over the correlations in full pseudorapidity separation (|Δη|<1.8), while the per-trigger associated near-side yields are extracted for the short-range correlations (|Δη|<1.3). Both are evaluated as a function of charged-particle multiplicity obtained by two different event activity estimators. The width of the near-side peak decreases with increasing multiplicity, and this trend is reproduced qualitatively by the Monte Carlo event generators PYTHIA 8, AMPT, and EPOS. However, the models overestimate the width in the low transverse-momentum region (pT<3 GeV/c). The per-trigger associated near-side yield increases with increasing multiplicity. Although this trend is also captured qualitatively by the considered event generators, the yield is mostly overestimated by the models in the considered kinematic range. The measurement of the shape and yield of the short-range correlation peak can help us understand the interplay between jet fragmentation and event activity, quantify the narrowing trend of the near-side peak as a function of transverse momentum and multiplicity selections in pp collisions, and search for final-state jet modification in small collision systems.
The production of inclusive, prompt and non-prompt J/ψ was studied for the first time at midrapidity (−1.37<ycms<0.43) in p−Pb collisions at √sNN =8.16 TeV with the ALICE detector at the LHC. The inclusive J/ψ mesons were reconstructed in the dielectron decay channel in the transverse momentum (pT) interval 0<pT<14 GeV/c and the prompt and non-prompt contributions were separated on a statistical basis for pT>2 GeV/c. The study of the J/ψ mesons in the dielectron channel used for the first time in ALICE online single-electron triggers from the Transition Radiation Detector, providing a data sample corresponding to an integrated luminosity of 689±13μb−1. The proton−proton reference cross section for inclusive J/ψ was obtained based on interpolations of measured data at different centre-of-mass energies and a universal function describing the pT-differential J/ψ production cross sections. The pT-differential nuclear modification factors RpPb of inclusive, prompt, and non-prompt J/ψ are consistent with unity and described by theoretical models implementing only nuclear shadowing.
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Conclusion: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with <nCR after first ASCT were assigned tandem ASCT in both trials. In patients with <nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.
We report inclusive photon measurements about midrapidity ( |y| <0.5 ) from 197 Au + 197 Au collisions at sqrt[sNN ]=130 GeV at RHIC. Photon pair conversions were reconstructed from electron and positron tracks measured with the Time Projection Chamber (TPC) of the STAR experiment. With this method, an energy resolution of Delta E/E ~ 2% at 0.5 GeV has been achieved. Reconstructed photons have also been used to measure the transverse momentum ( pt ) spectra of pi 0 mesons about midrapidity ( |y| <1 ) via the pi 0 --> gamma gamma decay channel. The fractional contribution of the pi 0 --> gamma gamma decay to the inclusive photon spectrum decreases by 20%±5% between pt =1.65 GeV/c and pt =2.4 GeV/c in the most central events, indicating that relative to pi 0 --> gamma gamma decay the contribution of other photon sources is substantially increasing.
We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account.
We present the first large-acceptance measurement of event-wise mean transverse momentum <pt> fluctuations for Au-Au collisions at nucleon-nucleon center-of-momentum collision energy sqrt[sNN] = 130 GeV. The observed nonstatistical <pt> fluctuations substantially exceed in magnitude fluctuations expected from the finite number of particles produced in a typical collision. The r.m.s. fractional width excess of the event-wise <pt> distribution is 13.7±0.1(stat) ±1.3(syst)% relative to a statistical reference, for the 15% most-central collisions and for charged hadrons within pseudorapidity range | eta |<1,2 pi azimuth, and 0.15 <= pt <= 2 GeV/c. The width excess varies smoothly but nonmonotonically with collision centrality and does not display rapid changes with centrality which might indicate the presence of critical fluctuations. The reported <pt> fluctuation excess is qualitatively larger than those observed at lower energies and differs markedly from theoretical expectations. Contributions to <pt> fluctuations from semihard parton scattering in the initial state and dissipation in the bulk colored medium are discussed.
We present STAR measurements of the azimuthal anisotropy parameter v2 and the binary-collision scaled centrality ratio RCP for kaons and lambdas ( Lambda + Lambda -bar) at midrapidity in Au+Au collisions at sqrt[sNN]=200 GeV. In combination, the v2 and RCP particle-type dependencies contradict expectations from partonic energy loss followed by standard fragmentation in vacuum. We establish pT ~ 5 GeV/c as the value where the centrality dependent baryon enhancement ends. The K0S and Lambda + Lambda -bar v2 values are consistent with expectations of constituent-quark-number scaling from models of hadron formation by parton coalescence or recombination.
Pion-kaon correlation functions are constructed from central Au+Au STAR data taken at sqrt[sNN]=130 GeV by the STAR detector at the Relativistic Heavy Ion Collider (RHIC). The results suggest that pions and kaons are not emitted at the same average space-time point. Space-momentum correlations, i.e., transverse flow, lead to a space-time emission asymmetry of pions and kaons that is consistent with the data. This result provides new independent evidence that the system created at RHIC undergoes a collective transverse expansion.
Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[sNN]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.
We report high statistics measurements of inclusive charged hadron production in Au+Au and p+p collisions at sqrt[sNN]=200 GeV. A large, approximately constant hadron suppression is observed in central Au+Au collisions for 5<pT<12 GeV/c. The collision energy dependence of the yields and the centrality and pT dependence of the suppression provide stringent constraints on theoretical models of suppression. Models incorporating initial-state gluon saturation or partonic energy loss in dense matter are largely consistent with observations. We observe no evidence of pT-dependent suppression, which may be expected from models incorporating jet attenuation in cold nuclear matter or scattering of fragmentation hadrons.
The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
We present the results of charged particle fluctuations measurements in Au+Au collisions at sqrt[sNN ]=130 GeV using the STAR detector. Dynamical fluctuations measurements are presented for inclusive charged particle multiplicities as well as for identified charged pions, kaons, and protons. The net charge dynamical fluctuations are found to be large and negative providing clear evidence that positive and negative charged particle production is correlated within the pseudorapidity range investigated. Correlations are smaller than expected based on model-dependent predictions for a resonance gas or a quark-gluon gas which undergoes fast hadronization and freeze-out. Qualitative agreement is found with comparable scaled p+p measurements and a heavy ion jet interaction generation model calculation based on independent particle collisions, although a small deviation from the 1/N scaling dependence expected from this model is observed.
We report measurements of single-particle inclusive spectra and two-particle azimuthal distributions of charged hadrons at high transverse momentum (high pT) in minimum bias and central d+Au collisions at sqrt[sNN]=200 GeV. The inclusive yield is enhanced in d+Au collisions relative to binary-scaled p+p collisions, while the two-particle azimuthal distributions are very similar to those observed in p+p collisions. These results demonstrate that the strong suppression of the inclusive yield and back-to-back correlations at high pT previously observed in central Au+Au collisions are due to final-state interactions with the dense medium generated in such collisions.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Transverse mass and rapidity distributions for charged pions, charged kaons, protons, and antiprotons are reported for sqrt[sNN]=200 GeV pp and Au+Au collisions at Relativistic Heary Ion Collider (RHIC). Chemical and kinetic equilibrium model fits to our data reveal strong radial flow and long duration from chemical to kinetic freeze-out in central Au+Au collisions. The chemical freeze-out temperature appears to be independent of initial conditions at RHIC energies.
Measurements of the production of forward high-energy pi 0 mesons from transversely polarized proton collisions at sqrt[s]=200 GeV are reported. The cross section is generally consistent with next-to-leading order perturbative QCD calculations. The analyzing power is small at xF below about 0.3, and becomes positive and large at higher xF, similar to the trend in data at sqrt[s] <= 20 GeV. The analyzing power is in qualitative agreement with perturbative QCD model expectations. This is the first significant spin result seen for particles produced with pT>1 GeV/c at a polarized proton collider.
We report results on rho (770)0--> pi + pi - production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[sNN]=200 GeV. This is the first direct measurement of rho (770)0--> pi + pi - in heavy-ion collisions. The measured rho 0 peak in the invariant mass distribution is shifted by ~40 MeV/c2 in minimum bias p+p interactions and ~70 MeV/c2 in peripheral Au+Au collisions. The rho 0 mass shift is dependent on transverse momentum and multiplicity. The modification of the rho 0 meson mass, width, and shape due to phase space and dynamical effects are discussed.
We report the first observations of the first harmonic (directed flow, v1) and the fourth harmonic (v4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v2) generated at RHIC. From the correlation of v2 with v1 it is determined that v2 is positive, or in-plane. The integrated v4 is about a factor of 10 smaller than v2. For the sixth (v6) and eighth (v8) harmonics upper limits on the magnitudes are reported.
We present STAR measurements of charged hadron production as a function of centrality in Au+Au collisions at sqrt[sNN ]=130 GeV . The measurements cover a phase space region of 0.2< pT <6.0 GeV/c in transverse momentum and -1< eta <1 in pseudorapidity. Inclusive transverse momentum distributions of charged hadrons in the pseudorapidity region 0.5< | eta | <1 are reported and compared to our previously published results for | eta | <0.5 . No significant difference is seen for inclusive pT distributions of charged hadrons in these two pseudorapidity bins. We measured dN/d eta distributions and truncated mean pT in a region of pT > pcutT , and studied the results in the framework of participant and binary scaling. No clear evidence is observed for participant scaling of charged hadron yield in the measured pT region. The relative importance of hard scattering processes is investigated through binary scaling fraction of particle production.
Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at sqrt[sNN]=200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in p+p at the same energy. The elliptic anisotropy v2 is found to reach its maximum at pt~3 GeV/c, then decrease slowly and remain significant up to pt ~ 7-10 GeV/c. Stronger suppression is found in the back-to-back high-pt particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v2 at intermediate pt is compared to simple models based on jet quenching.
Transverse energy ( ET ) distributions have been measured for Au+Au collisions at sqrt[sNN ]=200 GeV by the STAR Collaboration at RHIC. ET is constructed from its hadronic and electromagnetic components, which have been measured separately. ET production for the most central collisions is well described by several theoretical models whose common feature is large energy density achieved early in the fireball evolution. The magnitude and centrality dependence of ET per charged particle agrees well with measurements at lower collision energy, indicating that the growth in ET for larger collision energy results from the growth in particle production. The electromagnetic fraction of the total ET is consistent with a final state dominated by mesons and independent of centrality.
We present data on e+ e- pair production accompanied by nuclear breakup in ultraperipheral gold-gold collisions at a center of mass energy of 200 GeV per nucleon pair. The nuclear breakup requirement selects events at small impact parameters, where higher-order diagrams for pair production should be enhanced. We compare the data with two calculations: one based on the equivalent photon approximation, and the other using lowest-order quantum electrodynamics (QED). The data distributions agree with both calculations, except that the pair transverse momentum spectrum disagrees with the equivalent photon approach. We set limits on higher-order contributions to the cross section.
The transverse mass spectra and midrapidity yields for Xi s and Omega s are presented. For the 10% most central collisions, the Xi -bar+/h- ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi -/h- stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi , K, p, and Lambda s.
The pseudorapidity asymmetry and centrality dependence of charged hadron spectra in d+Au collisions at sqrt[sNN ]=200 GeV are presented. The charged particle density at midrapidity, its pseudorapidity asymmetry, and centrality dependence are reasonably reproduced by a multiphase transport model, by HIJING, and by the latest calculations in a saturation model. Ratios of transverse momentum spectra between backward and forward pseudorapidity are above unity for pT below 5 GeV/c . The ratio of central to peripheral spectra in d+Au collisions shows enhancement at 2< pT <6 GeV/c , with a larger effect at backward rapidity than forward rapidity. Our measurements are in qualitative agreement with gluon saturation and in contrast to calculations based on incoherent multiple partonic scatterings.
The short-lived K(892)* resonance provides an efficient tool to probe properties of the hot and dense medium produced in relativistic heavy-ion collisions. We report measurements of K* in sqrt[sNN]=200GeV Au+Au and p+p collisions reconstructed via its hadronic decay channels K(892)*0-->K pi and K(892)*±-->K0S pi ± using the STAR detector at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The K*0 mass has been studied as a function of pT in minimum bias p+p and central Au+Au collisions. The K*pT spectra for minimum bias p+p interactions and for Au+Au collisions in different centralities are presented. The K*/K yield ratios for all centralities in Au+Au collisions are found to be significantly lower than the ratio in minimum bias p+p collisions, indicating the importance of hadronic interactions between chemical and kinetic freeze-outs. A significant nonzero K*0 elliptic flow (v2) is observed in Au+Au collisions and is compared to the K0S and Lambda v2. The nuclear modification factor of K* at intermediate pT is similar to that of K0S but different from Lambda . This establishes a baryon-meson effect over a mass effect in the particle production at intermediate pT (2<pT <= 4GeV/c).
Midrapidity open charm spectra from direct reconstruction of D0(D0-bar)-->K± pi ± in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at sqrt[sNN]=200 GeV are reported. The D0(D0-bar) spectrum covers a transverse momentum (pT) range of 0.1<pT<3 GeV/c, whereas the electron spectra cover a range of 1<pT<4 GeV/c. The electron spectra show approximate binary collision scaling between p+p and d+Au collisions. From these two independent analyses, the differential cross section per nucleon-nucleon binary interaction at midrapidity for open charm production from d+Au collisions at BNL RHIC is d sigma NNcc-bar/dy=0.30±0.04(stat)±0.09(syst) mb. The results are compared to theoretical calculations. Implications for charmonium results in A+A collisions are discussed.
Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (| eta | <= 1) and azimuth(full 2 pi ) in bins of transverse momentum (pt) from 0.14 <= pt <= 2.1GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to minijet fragmentation is observed. It evolves with collision centrality and pt in a way not seen before, which suggests strong dissipation of minijet fragmentation in the longitudinally expanding medium.
Azimuthally sensitive Hanbury Brown-Twiss interferometry in Au+Au collisions at sqrt[sNN]=200 GeV
(2004)
We present the results of a systematic study of the shape of the pion distribution in coordinate space at freeze-out in Au+Au collisions at BNL RHIC using two-pion Hanbury Brown-Twiss (HBT) interferometry. Oscillations of the extracted HBT radii versus emission angle indicate sources elongated perpendicular to the reaction plane. The results indicate that the pressure and expansion time of the collision system are not sufficient to completely quench its initial shape.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (nonflow correlations). Using data for Au + Au collisions at sqrt[sNN]=130 GeV from the STAR time projection chamber, it is found that four-particle correlation analyses can reliably separate flow and nonflow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of 2. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
We report the first observation of K*(892)0--> pi K in relativistic heavy ion collisions. The transverse momentum spectrum of (K*0+K*0)/2 from central Au+Au collisions at sqrt[sNN]=130 GeV is presented. The ratios of the K*0 yield derived from these data to the yields of negative hadrons, charged kaons, and phi mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable e+e-, pp, and p-barp results. The data indicate no dramatic reduction of K*0 production in relativistic heavy ion collisions despite expected losses due to rescattering effects.
The STAR Collaboration reports the first observation of exclusive rho 0 photoproduction, AuAu-->AuAu rho 0, and rho 0 production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au [star] Au [star] rho 0, in ultraperipheral heavy-ion collisions. The rho 0 have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[sNN]=130 GeV agree with theoretical predictions treating rho 0 production and Coulomb excitation as independent processes.
We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.
Inclusive transverse momentum distributions of charged hadrons within 0.2<pT<6.0 GeV/c have been measured over a broad range of centrality for Au+Au collisions at sqrt[sNN]=130 GeV. Hadron yields are suppressed at high pT in central collisions relative to peripheral collisions and to a nucleon-nucleon reference scaled for collision geometry. Peripheral collisions are not suppressed relative to the nucleon-nucleon reference. The suppression varies continuously at intermediate centralities. The results indicate significant nuclear medium effects on high-pT hadron production in heavy-ion collisions at high energy.
We report the first measurement of strange ( Lambda ) and antistrange ( Lambda -bar) baryon production from sqrt[sNN]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda -bar hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda -bar hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.
Two-pion correlation functions in Au+Au collisions at sqrt[sNN] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in sqrt[sNN].
The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d-bar and 3He-bar are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the 3He-bar freeze-out volume is smaller than the d-bar freeze-out volume.
We present the first measurement of midrapidity vector meson phi production in Au+Au collisions at RHIC (sqrt[sNN]=130 GeV) from the STAR detector. For the 11% highest multiplicity collisions, the slope parameter from an exponential fit to the transverse mass distribution is T=379±50(stat)±45(syst) MeV, the yield dN/dy=5.73±0.37(stat)±0.69(syst) per event, and the ratio N phi /Nh- is found to be 0.021±0.001(stat)±0.004(syst). The measured ratio N phi /Nh- and T for the phi meson at midrapidity do not change for the selected multiplicity bins.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h-) in Au+Au interactions at sqrt[sNN] = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/d eta | eta = 0 = 280±1(stat)±20(syst), an increase per participant of 38% relative to pp-bar collisions at the same energy. The mean transverse momentum is 0.508±0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pperp. The pseudorapidity distribution is almost constant within | eta |<1.
We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<pperp<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
From July 2002 to March 2004 the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European Space Agency´s Environmental Satellite (Envisat) measured nearly continuously mid infrared limb radiance spectra. These measurements are utilised to retrieve the global distribution of the chlorofluorocarbon CFC-11 by applying a new fast forward model for Envisat MIPAS and an accompanying optimal estimation retrieval processor. A detailed analysis shows that the total retrieval errors of the individual CFC-11 volume mixing ratios are typically below 10% in the altitude range 10 to 25 km and that the systematic components dominate. Contribution of a priori information to the retrieval results are less than 5 to 10% and the vertical resolution of the observations is about 3 to 4 km in the same vertical range. The data are successfully validated by comparison with several other space experiments, an air-borne in-situ instrument, measurements from ground-based networks, and independent Envisat MIPAS analyses. The retrieval results from 425 000 Envisat MIPAS limb scans are compiled to provide a new climatological data set of CFC-11. The climatology shows significantly lower CFC-11 abundances in the lower stratosphere compared with the Reference Atmospheres for MIPAS (RAMstan V3.1) climatology. Depending on the atmospheric conditions the differences between the climatologies are up to 30 to 110 ppt (45 to 150%) at 19 to 27 km altitude. Additionally, time series of CFC-11 mean abundance and variability for five latitudinal bands are presented. The observed CFC-11 distributions can be explained by the residual mean circulation and large-scale eddy-transports in the upper troposphere and lower stratosphere. The new CFC-11 data set is well suited for further scientific studies.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
The results from the STAR Collaboration on directed flow (v1), elliptic flow (v2), and the fourth harmonic (v4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrt[sNN]=200GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a blast-wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v2, scaling with the number of constituent quarks and parton coalescence are discussed. For v4, scaling with v22 and quark coalescence are discussed.
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
(2018)
Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
We present a systematic analysis of two-pion interferometry in Au+Au collisions at sqrt[sNN]=200GeV using the STAR detector at Relativistic Heavy Ion Collider. We extract the Hanbury-Brown and Twiss radii and study their multiplicity, transverse momentum, and azimuthal angle dependence. The Gaussianness of the correlation function is studied. Estimates of the geometrical and dynamical structure of the freeze-out source are extracted by fits with blast-wave parametrizations. The expansion of the source and its relation with the initial energy density distribution is studied.
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
The international research project RECONCILE has addressed central questions regarding polar ozone depletion, with the objective to quantify some of the most relevant yet still uncertain physical and chemical processes and thereby improve prognostic modelling capabilities to realistically predict the response of the ozone layer to climate change. This overview paper outlines the scope and the general approach of RECONCILE, and it provides a summary of observations and modelling in 2010 and 2011 that have generated an in many respects unprecedented dataset to study processes in the Arctic winter stratosphere. Principally, it summarises important outcomes of RECONCILE including (i) better constraints and enhanced consistency on the set of parameters governing catalytic ozone destruction cycles, (ii) a better understanding of the role of cold binary aerosols in heterogeneous chlorine activation, (iii) an improved scheme of polar stratospheric cloud (PSC) processes that includes heterogeneous nucleation of nitric acid trihydrate (NAT) and ice on non-volatile background aerosol leading to better model parameterisations with respect to denitrification, and (iv) long transient simulations with a chemistry-climate model (CCM) updated based on the results of RECONCILE that better reproduce past ozone trends in Antarctica and are deemed to produce more reliable predictions of future ozone trends. The process studies and the global simulations conducted in RECONCILE show that in the Arctic, ozone depletion uncertainties in the chemical and microphysical processes are now clearly smaller than the sensitivity to dynamic variability.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular, we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here, we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.
In the upcoming years, the internet of things (IoT)will enrich daily life. The combination of artificial intelligence(AI) and highly interoperable systems will bring context-sensitive multi-domain services to reality. This paper describesa concept for an AI-based smart living platform with open-HAB, a smart home middleware, and Web of Things (WoT) askey components of our approach. The platform concept con-siders different stakeholders, i.e. the housing industry, serviceproviders, and tenants. These activities are part of the Fore-Sight project, an AI-driven, context-sensitive smart living plat-form.
We present the measured correlation functions for pi+ pi-, pi- pi- and pi+ pi+ pairs in central S+Ag collisions at 200 GeV per nucleon. The Gamov function, which has been traditionally used to correct the correlation functions of charged pions for the Coulomb interaction, is found to be inconsistent with all measured correlation functions. Certain problems which have been dominating the systematic uncertainty of the correlation analysis are related to this inconsistency. It is demonstrated that a new Coulomb correction method, based exclusively on the measured correlation function for pi+ pi- pairs, may solve the problem.
The transverse momentum and rapidity distributions of negative hadrons and participant protons have been measured for central 32S+ 32S collisions at plab=200 GeV/c per nucleon. The proton mean rapidity shift < Delta y>~1.6 and mean transverse momentum <pT>~0.6 GeV/c are much higher than in pp or peripheral AA collisions and indicate an increase in the nuclear stopping power. All pT spectra exhibit similar source temperatures. Including previous results for K0s Lambda , and Lambda -bar, we account for all important contributions to particle production.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice-nucleating particles. However, an intercomparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nuclei Research Unit), we distributed an illite-rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. A total of 17 measurement methods were involved in the data intercomparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while 10 other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing data set was evaluated using the ice nucleation active surface-site density, ns, to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers 9 orders of magnitude in ns.
In general, the 17 immersion freezing measurement techniques deviate, within a range of about 8 °C in terms of temperature, by 3 orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency expressed in ns of illite NX particles is relatively independent of droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature dependence and weak time and size dependence of the immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns(T) spectra and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. While the agreement between different instruments was reasonable below ~ −27 °C, there seemed to be a different trend in the temperature-dependent ice nucleation activity from the suspension and dry-dispersed particle measurements for this mineral dust, in particular at higher temperatures. For instance, the ice nucleation activity expressed in ns was smaller for the average of the wet suspended samples and higher for the average of the dry-dispersed aerosol samples between about −27 and −18 °C. Only instruments making measurements with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −27 and −18 °C is discussed. Multiple exponential distribution fits in both linear and log space for both specific surface area-based ns(T) and geometric surface area-based ns(T) are provided. These new fits, constrained by using identical reference samples, will help to compare IN measurement methods that are not included in the present study and IN data from future IN instruments.
Rezensionen [2017]
(2017)
156 Ansari, Christine (Hrsg.): Adoleszenz in Medienkontexten. Literaturrezeption, Medienwirkung und Jugendmedienschutz (judith mathez)
158 Bachmann, Christian A. / Emans, Laura / Schmitz-Emans, Monika (Hrsg.): Bewegungsbücher. Spielformen, Poetiken, Konstellationen (gundel mattenklott)
160 Ballis, Anja /Schlachter, Birgit (Hrsg.): Schätze der Kinder- und Jugendliteratur wiederentdeckt. Frühe Lektüreerfahrung und Kanonbildung im akademischen Kontext (ernst seibert)
162 Benner, Julia: Federkrieg. Kinder- und Jugendliteratur gegen den Nationalsozialismus 1933 – 1945 (linde storm)
164 Born, Stefan: Allgemeinliterarische Adoleszenzromane. Untersuchungen zu Herrndorf, Regener, Strunk, Kehlmann und anderen (lena hoffmann)
166 Börnchen, Stefan: Poetik der Linie. Wilhelm Busch, Max und Moritz und die Tradition (lukas sarvari)
168 Burwitz-Melzer, Eva /O’Sullivan, Emer (Hrsg.): Einfachheit in der Kinder- und Jugendliteratur. Ein Gewinn für den Fremdsprachenunterricht (roland alexander issler)
169 Emde, Oliver /Möller, Lukas /Wicke, Andreas (Hrsg.): Von »Bibi Blocksberg« bis »TKKG«. Kinderhörspiele aus gesellschafts- und kulturwissenschaftlicher Perspektive (anika ullmann)
171 Ferstl, Paul /Walach, Thomas / Zahlmann, Stefan (Hrsg.): Fantasy Studies (maren bonacker)
173 Giesa, Felix: Graphisches Erzählen von Adoleszenz. Deutschsprachige Autorencomics nach 2000 (michael staiger)
175 Hahn, Heidi / Laudenberg, Beate / Rösch, Heidi (Hrsg.): »Wörter raus!?« Zur Debatte um eine diskriminierungsfreie Sprache im Kinderbuch (julia benner)
177 Haug, Christine / Frimmel, Johannes (Hrsg.): Schulbücher um 1800. Ein Spezialmarkt zwischen staatlichem, volksaufklärerischem und konfessionellem Auftrag (ortwin beisbart)
179 Hollerweger, Elisabeth /Stemmann, Anna (Hrsg.): Narrative Delikatessen. Kulturelle Dimensionen von Ernährung (sonja loidl)
180 Hopp, Margarete: Sterben, Tod und Trauer im Bilderbuch seit 1945 (iris schäfer)
182 Huemer, Georg: Mira Lobe. Doyenne der österreichischen Kinder- und Jugendliteratur (andreas schumann)
183 Josting, Petra (Hrsg.): Andreas Steinhöfel, Bielefelder Poet in Residence 2014 (heinke kilian)
185 Josting, Petra /Roeder, Caroline /Dettmar, Ute (Hrsg.): Immer Trouble mit Gender. Genderperspektiven in Kinder- und Jugendliteraturforschung und -medien (jana mikota)
187 Kurwinkel, Tobias /Schmerheim, Philipp /Sevi, Annika (Hrsg.): Michael Ende intermedial. Von Lokomotivführern, Glücksdrachen und dem (phantastischen) Spiel mit Mediengrenzen (michael stierstorfer)
188 Mikota, Jana / Pecher, Claudia Maria / von Glasenapp, Gabriele (Hrsg.): Literarisch-kulturelle Begegnungen mit dem Judentum. Beiträge zur kinderliterarischen Fachöffentlichkeit (susanne blumesberger)
190 Müller, Karla / Decker, Jan-Oliver / Krah, Hans / Schilcher, Anita (Hrsg.): Genderkompetenz mit Kinder- und Jugendliteratur entwickeln: Grundlagen – Analysen – Modelle (annette kliewer)
192 Nikolajeva, Maria: Reading for Learning. Cognitive Approaches to Children’s Literature (sabine fuchs)
194 Paul, Lissa / Johnston, Rosemary R. / Short, Emma (Hrsg.):Children’s Literature and Culture of the First World War.(julia benner)
195 Payrhuber, Franz-Josef / Meier, Bernhard(Hrsg.): Franz, Kurt: Kinderlyrik. Geschichte, Formen, Rezeption(ludger scherer)
197 Payrhuber, Franz-Josef:Gedichte entdecken. Wege zu Gedichten in der ersten bis sechsten Klasse (andreas schumann)
198 Pohlmann, Carola (Hrsg): Kinder- und Jugendliteratur. Sammeln und Erwerben (wolfgang wangerin)
200 Pompe, Anja (Hrsg): Kind und Gedicht. Wie wir lesen lernen (heinz-jürgen kliewer)
202 Preindl, Nadia:Russische Kinderliteratur im europäischen Exil der Zwischenkriegszeit (verena rutschmann)
204 Richter, Karin: Die Kinder- und Jugend-literatur der DDR. Entwicklungslinien – Themen und Genres. Autorenporträts und Textanalysen (maria becker)
206 Riemhofer, Andra:Interkulturelle Kinder- und Jugendliteratur in Deutschland. Lesen auf eigene Gefahr (roger meyer)
208Roeder, Caroline (Hrsg.): Himmel und Hölle. Raumerkundungen – interdisziplinär & in schulischer Praxis (claudia blei-hoch)
210 Ruzicka Kenfel, Vejka (Hrsg.): New Trends in Children’s Literature Research. Twenty-first Century Approaches (2000–2012) from the University of Vigo (Spain) (susanne blumesberger)
212 Schäfer, Iris:Von der Hysterie zur Magersucht. Adoleszenz und Krankheit in Romanen und Erzählungen der Jahrhundert- und der Jahrtausendwende (philipp schmerheim)
214 Scherer, Gabriela / Volz, Steffen (Hrsg.): Im Bildungsfokus: Bilderbuchrezeptions-forschung (margarete hopp)
216 Schmitt, Susann Sophie:Nachwuchs für die Literatur. Kinder- und Jugendprogramme ausgewählter Literaturhäuser Deutschlands, Österreichs und der Schweiz (renate grubert)
217 Seelinger Trites, Roberta:Literary Conceptu-alizations of Growth. Metaphors and Cogni-tion in Adolescent Literature (iris schäfer)
219 Seifert, Martina:Die Bilderfalle. Kanada in der deutschsprachigen Kinder- und Jugend-literatur: Produktion und Rezeption (sabine planka)
222 Stein, Daniel / Thon, Jan-Noël (Hrsg.): From Comic Strips to Graphic Novels. Contributions to the Theory and History of Graphic Narrative (anna stemmann)
223 Tomberg, Markus (Hrsg.): Alle wichtigen Bücher handeln von Gott. Religiöse Spuren in aktueller Kinder- und Jugendliteratur (martin anker)
Background: In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision.
Methods: Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP.
Results: The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs’ decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48–0.59; ORs per country 0.11–1.78).
Conclusions: Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.
Anderer Fehler sind gute Lehrer « – so lautet ein nur wenig bekanntes altes deutsches Sprichwort. Für medizinische Fehler galt das die längste Zeit nicht: entweder totgeschwiegen oder als »Kunstfehler « in das Licht der Öffentlichkeit gezerrt, entzogen sich ärztliche Fehler einer systematischen Analyse. Damit hat die Medizin lange eine wichtige Chance vertan. Am Institut für Allgemeinmedizin der Universität Frankfurt beschäftigt sich seit einigen Jahren ein Team unter Leitung von Prof. Dr. Ferdinand Gerlach intensiv mit der Fehlerforschung. ...
Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice nucleating particles (INPs). However, an inter-comparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nucleation research UnIT), we distributed an illite rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. Seventeen measurement methods were involved in the data inter-comparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while ten other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing dataset was evaluated using the ice nucleation active surface-site density (ns) to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers nine orders of magnitude in ns.
Our inter-comparison results revealed a discrepancy between suspension and dry-dispersed particle measurements for this mineral dust. While the agreement was good below ~ −26 °C, the ice nucleation activity, expressed in ns, was smaller for the wet suspended samples and higher for the dry-dispersed aerosol samples between about −26 and −18 °C. Only instruments making measurement techniques with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −26 and −18 °C is discussed. In general, the seventeen immersion freezing measurement techniques deviate, within the range of about 7 °C in terms of temperature, by three orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency (i.e., ns) of illite NX particles is relatively independent on droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature-dependence and weak time- and size-dependence of immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns (T) spectra, and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. A multiple exponential distribution fit is expressed as ns(T) = exp(23.82 × exp(−exp(0.16 × (T + 17.49))) + 1.39) based on the specific surface area and ns(T) = exp(25.75 × exp(−exp(0.13 × (T + 17.17))) + 3.34) based on the geometric area (ns and T in m−2 and °C, respectively). These new fits, constrained by using an identical reference samples, will help to compare IN measurement methods that are not included in the present study and, thereby, IN data from future IN instruments.
Background: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH4+) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome.
Methods: Detailed information of 17 patients (born between 1994 and 2012) with confirmed diagnosis of UCD and neonatal hyperammonemic encephalopathy were collected from the original medical records.
Results: The initially suspected diagnosis was neonatal sepsis in all patients, but was not confirmed in any of them. Unlike neonatal sepsis and not previously reported blood pressure increased above the 95th percentile in 13 (81%) of UCD patients before emergency treatment was started. Respiratory alkalosis was found in 11 (65%) of UCD patients, and in 14 (81%) plasma NH4+concentrations further increased despite initiation of metabolic therapy.
Conclusion: Detection of high blood pressure could be a valuable parameter for distinguishing neonatal sepsis from neonatal manifestation of UCD. Since high blood pressure is not typical for neonatal sepsis, other reasons such as encephalopathy and especially hyperammonemic encephalopathy (caused by e.g. UCD) should be searched for immediately. However, our result that the majority of newborns with UCD initially present with high blood pressure has to be evaluated in larger patient cohorts.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine
(2017)
Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer.
Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by γH2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs.
Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762.
Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy.
Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au + Au collisions at √sNN = 130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are K+/π− = 0.161± 0.002(stat) ± 0.024(syst) and K−/π− = 0.146± 0.002(stat) ± 0.022(syst) for the most central collisions. The K+/π− ratio is lower than the same ratio observed at the SPS while the K−/π− is higher than the SPS result. The ratios are enhanced by about 50% relative to p + p and p¯ + p collision data at similar energies.
Cryo-electron tomography (CryoET) resolves individual macromolecules inside living cells. However, the complex composition and high density of cells challenge the faithful identification of features in tomograms. Here, we capitalize on recent advances in electron tomography and demonstrate that 3D template matching (TM) localizes a wide range of structures inside crowded eukaryotic cells with confidence 10 to 100-fold above the noise level. We establish a TM pipeline with systematically tuned parameters for automated, objective and comprehensive feature identification. High-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, lipid membranes and microtubules, and individual subunits, demonstrate that TM is generic. We resolve ~100-kDa proteins, connect the functional states of complexes to their cellular localization, and capture vaults carrying ribosomal cargo in situ. By capturing individual molecular events inside living cells with defined statistical confidence, high-confidence TM greatly speeds up the CryoET workflow and sets the stage for visual proteomics.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.