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Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. These measurements are performed as a function of multiplicity in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus--nucleus collisions in the same multiplicity range. Using the novel subevent method, v2 measured in pp and p-Pb collisions with four-particle cumulants is found to be compatible with that from six-particle cumulants. The symmetric cumulants SC(m,n) calculated with the subevent method which evaluate the correlation strength between v2n and v2m are also presented. The presented data, which add further support to the existence of long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions, can neither be described by PYTHIA8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
We present the first measurements of femtoscopic correlations between the K0 S and K± particles in pp collisions at √s = 7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at √s = 7 TeV by ALICE andwith a K0 SK± measurement in Pb–Pb collisions at √sNN = 2.76 TeV. Combined with the Pb–Pb results, our pp analysis is found to be compatible with th e interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at √s=13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT > 1.7 GeV/c are σmπ0 = 4.56 ± 0.03 MeV/c2 and σmη = 15.3 ± 1.0 MeV/c2, respectively.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at s√=13 TeV. After applying all corrections, the achieved mass resolution of π0 and η mesons for pT>1.7 GeV/c is σπ0m=4.56±0.03 MeV/c2 and σηm=15.3±1.0 MeV/c2.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at s√ = 13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT>1.7 GeV/c are σπ0m=4.56±0.03 MeV/c2 and σηm=15.3±1.0 MeV/c2, respectively.
Two-particle correlations in high-energy collision experiments enable the extraction of particle source radii by using the Bose-Einstein enhancement of pion production at low relative momentum q ∝ 1/R. It was previously observed that in pp collisions at s√ = 7TeV the average pair transverse momentum kT range of such analyses is limited due to large background correlations which were attributed to mini-jet phenomena. To investigate this further, an event-shape dependent analysis of Bose-Einstein correlations for pion pairs is performed in this work. By categorizing the events by their transverse sphericity ST into spherical (ST > 0:7) and jet-like (ST < 0:3) events a method was developed that allows for the determination of source radii for much larger values of kT for the first time. Spherical events demonstrate little or no background correlations while jet-like events are dominated by them. This observation agrees with the hypothesis of a mini-jet origin of the non-femtoscopic background correlations and gives new insight into the physics interpretation of the kT dependence of the radii. The emission source size in spherical events shows a substantially diminished kT dependence, while jet-like events show indications of a negative trend with respect to kT in the highest multiplicity events. Regarding the emission source shape, the correlation functions for both event sphericity classes show good agreement with an exponential shape, rather than a Gaussian one.
Two-particle correlations in high-energy collision experiments enable the extraction of particle source radii by using the Bose-Einstein enhancement of pion production at low relative momentum q∝1/R. It was previously observed that in pp collisions at s√=7 TeV the average pair transverse momentum kT range of such analyses is limited due to large background correlations which were attributed to mini-jet phenomena. To investigate this further, an event-shape dependent analysis of Bose-Einstein correlations for pion pairs is performed in this work. By categorizing the events by their transverse sphericity ST into spherical (ST>0.7) and jet-like (ST<0.3) events a method was developed that allows for the determination of source radii for much larger values of kT for the first time. Spherical events demonstrate little or no background correlations while jet-like events are dominated by them. This observation agrees with the hypothesis of a mini-jet origin of the non-femtoscopic background correlations and gives new insight into the physics interpretation of the kT dependence of the radii. The emission source size in spherical events shows a substantially diminished kT dependence, while jet-like events show indications of a negative trend with respect to kT in the highest multiplicity events. Regarding the emission source shape, the correlation functions for both event sphericity classes show good agreement with an exponential shape, rather than a Gaussian one.
Two-particle correlations in high-energy collision experiments enable the extraction of particle source radii by using the Bose-Einstein enhancement of pion production at low relative momentum q∝1/R. It was previously observed that in pp collisions at s√=7 TeV the average pair transverse momentum kT range of such analyses is limited due to large background correlations which were attributed to mini-jet phenomena. To investigate this further, an event-shape dependent analysis of Bose-Einstein correlations for pion pairs is performed in this work. By categorizing the events by their transverse sphericity ST into spherical (ST>0.7) and jet-like (ST<0.3) events a method was developed that allows for the determination of source radii for much larger values of kT for the first time. Spherical events demonstrate little or no background correlations while jet-like events are dominated by them. This observation agrees with the hypothesis of a mini-jet origin of the non-femtoscopic background correlations and gives new insight into the physics interpretation of the kT dependence of the radii. The emission source size in spherical events shows a substantially diminished kT dependence, while jet-like events show indications of a negative trend with respect to kT in the highest multiplicity events. Regarding the emission source shape, the correlation functions for both event sphericity classes show good agreement with an exponential shape, rather than a Gaussian one.
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from −25 ∘C to 25 ∘C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward.
In the past two decades, pions created in the high density regions of heavy ion collisions have been predicted to be sensitive at high densities to the symmetry energy term in the nuclear equation of state, a property that is key to our understanding of neutron stars. In a new experiment designed to study the symmetry energy, the multiplicities of negatively and positively charged pions have been measured with high accuracy for central 132Sn+124Sn, 112Sn+124Sn, and 108Sn+112Sn collisions at E/A = 270 MeV with the SπRIT Time Projection Chamber. While individual pion multiplicities are measured to 4% accuracy, those of the charged pion multiplicity ratios are measured to 2% accuracy. We compare these data to predictions from seven major transport models. The calculations reproduce qualitatively the dependence of the multiplicities and their ratios on the total neutron and proton number in the colliding systems. However, the predictions of the transport models from different codes differ too much to allow extraction of reliable constraints on the symmetry energy from the data. This finding may explain previous contradictory conclusions on symmetry energy constraints obtained from pion data in Au+Au system. These new results call for still better understanding of the differences among transport codes, and new observables that are more sensitive to the density dependence of the symmetry energy.
New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)1,2,3,4. However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles—comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO3–H2SO4–NH3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Background and Aim. Spontaneous bacterial peritonitis (SBP) is one of the most common complications of liver cirrhosis. Antibiotics are the main treatment regimen of SBP. Traditional Chinese medicine Xuebijing injection has been used in such patients. Our study aimed to overview the efficacy of Xuebijing injection combined with antibiotics for the treatment of SBP.
Method. We searched the PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang databases. The search items included "Xuebijing", "peritonitis", "liver cirrhosis", and "random" to identify all relevant randomized controlled trials (RCTs). The Cochrane risk of bias tool was used to assess the study quality. The odd ratios (ORs) with 95% confidence intervals (CIs) were calculated by using a random-effect model. Heterogeneity was also calculated.
Results. A total of 9 RCTs were included. The study quality was unsatisfied. The overall (OR = 2.95, 95% CI = 1.97–4.42, p<0.00001) and complete (OR = 2.18, 95% CI = 1.57–3.04, p<0.00001) responses were significantly higher in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. The incidence of cirrhosis related complications, including hepatic encephalopathy and hepatorenal syndrome, was lower in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. No significant heterogeneity was observed among studies.
Conclusion. Additional use of Xuebijing injection may improve the efficacy of antibiotics for the treatment of SBP in liver cirrhosis. However, due to a low level of current evidence, we did not establish any recommendation regarding the use of Xuebijing injection for the treatment of SBP.
Background: Denosumab treatment for up to 8 years in the FREEDOM study and Extension was associated with low fracture incidence. It was not clear whether subjects who discontinued during the study conduct had a higher risk of fracture than those who remained enrolled, thereby underestimating the true fracture risk for the entire trial cohort. Thus, we explored the influence of early withdrawals on nonvertebral fracture incidence during the Extension study.
Methods: To understand the potential effect of depletion of susceptible subjects on fracture incidence, we first evaluated subject characteristics in patients who were enrolled in the Extension vs those who were not. We subsequently employed a Kaplan-Meier multiple imputation (KMMI) approach to consider subjects who discontinued as if they remained enrolled with a 0%, 20%, 50%, and 100% increase in fracture risk compared with participants remaining on study.
Results: Extension enrollees were generally similar to nonparticipants in median age (71.9 and 73.1 years, respectively), mean total hip bone mineral density T-score (–1.9 and –2.0, respectively), and probability of fracture risk by Fracture Risk Assessment Tool (FRAX®) at FREEDOM baseline (16.9% and 17.7% for major osteoporotic fracture and 6.7% and 7.4% for hip fracture, respectively). When we assumed a doubled fracture risk (100% increase) after discontinuation in KMMI analyses, nonvertebral fracture rate estimates were only marginally higher than the observed rates for both the crossover group (10.32% vs 9.16%, respectively) and the long-term group (7.63% vs 6.63%, respectively).
Conclusion: The observation of continued denosumab efficacy over 8 years of treatment was robust and does not seem to be explained by depletion of susceptible subjects.
Trial registration: ClincalTrials.gov registration number NCT00523341; registered August 30, 2007
Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Périgord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries.
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.