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Institute
A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog, but how it occurs in cities is often puzzling. If the growth rates of urban particles are similar to those found in cleaner environments (1–10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below −15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid–base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms.
Triple differential cross sections d3 sigma /dp3 for charged pions produced in symmetric heavy-ion collisions were measured with the KaoS magnetic spectrometer at the heavy-ion synchrotron facility SIS at GSI. The correlations between the momentum vectors of charged pions and the reaction plane in 197Au+197Au collisions at an incident energy of 1 GeV/nucleon were determined. We observe, for the first time, an azimuthally anisotropic distribution of pions, with enhanced emission perpendicular to the reaction plane. The anisotropy is most pronounced for pions of high transverse momentum in semicentral collisions.
The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±,Ξ(1530)0) produced in p–Pb collisions at √sNN = 5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content.
During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the CLOUD1 experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm−3s−1, and growth rates between 2 and 37 nm h−1. The corresponding H2SO4 concentrations were typically around 106 cm−3 or less. The experimentally-measured formation rates and H2SO4 concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1°C).
Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.
The disruption in blood supply due to myocardial infarction is a critical determinant for infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin β4 (TMSB4) and Prothymosin α (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.
Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.
Results: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p<0.001). Median time to resolution of grade 3/4 cytopenias to grade ≤2 was 2.0 (95% CI 1.87 to 2.23) months for neutropenia, 2.4 (95% CI 1.97 to 3.68) months for lymphopenia, 2.0 (95% CI 1.87 to 2.27) months for leukopenia, 1.9 (95% CI 1.74 to 2.10) months for thrombocytopenia, and 1.0 (95% CI 0.95 to 1.87) month for anemia. All patients who achieved complete remission (CR)/CR with incomplete hematologic recovery experienced B cell aplasia; however, as nearly all responders also received immunoglobulin replacement, few grade 3/4 infections occurred >1 year postinfusion.
Conclusions: This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.
During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the Cosmics Leaving OUtdoor Droplets (CLOUD) experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm -3 s -1, and growth rates between 2 and 37 nm h -1. The corresponding H2O concentrations were typically around 106 cm -3 or less. The experimentally-measured formation rates and htwosofour concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1 °C)
Seven new euptychiine (Lepidoptera: Nymphalidae: Satyrinae) taxa are described and named herein, namely Harjesia argentata Nakahara, Zacca and Lamas, n. sp., Orotaygetis Nakahara and Zacca, n. gen., O. surui Nakahara, Zacca and Lamas, n. sp., Euptychoides sanmarcos Nakahara and Lamas, n. sp., Pseudeuptychia cuzquenya Nakahara and Lamas, n. sp., P. languida austrina Nakahara and Lamas, n. ssp., and Godartiana astronesthes Lamas and Nakahara, n. sp. A revisional note is provided for Harjesia Forster, 1964 and Pseudeuptychia Forster, 1964, and as a result, Taygetis vrazi Kheil, 1896 is removed from Harjesia and a new taxonomic arrangement, Pseudodebis vrazi n. comb., is proposed based on both morphology and molecular data.
The differential charged jet cross sections, jet fragmentation distributions, and jet shapes are measured in minimum bias proton-proton collisions at centre-of-mass energy s√=7 TeV using the ALICE detector at the LHC. Jets are reconstructed from charged particle momenta in the mid-rapidity region using the sequential recombination kT and anti-kT as well as the SISCone jet finding algorithms with several resolution parameters in the range R=0.2 to 0.6. Differential jet production cross sections measured with the three jet finders are in agreement in the transverse momentum (pT) interval 20<pjet,chT<100 GeV/c. They are also consistent with prior measurements carried out at the LHC by the ATLAS collaboration. The jet charged particle multiplicity rises monotonically with increasing jet pT, in qualitative agreement with prior observations at lower energies. The transverse profiles of leading jets are investigated using radial momentum density distributions as well as distributions of the average radius containing 80% (⟨R80⟩) of the reconstructed jet pT. The fragmentation of leading jets with R=0.4 using scaled pT spectra of the jet constituents is studied. The measurements are compared to model calculations from event generators (PYTHIA, PHOJET, HERWIG). The measured radial density distributions and ⟨R80⟩ distributions are well described by the PYTHIA model (tune Perugia-2011). The fragmentation distributions are better described by HERWIG.
We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian PID approach for charged pions, kaons and protons in the central barrel of ALICE is studied. PID is performed via measurements of specific energy loss (dE/dx) and time-of-flight. PID efficiencies and misidentification probabilities are extracted and compared with Monte Carlo simulations using high-purity samples of identified particles in the decay channels K0S→π−π+, ϕ→K−K+, and Λ→pπ− in p-Pb collisions at sNN−−−√=5.02 TeV. In order to thoroughly assess the validity of the Bayesian approach, this methodology was used to obtain corrected pT spectra of pions, kaons, protons, and D0 mesons in pp collisions at s√=7 TeV. In all cases, the results using Bayesian PID were found to be consistent with previous measurements performed by ALICE using a standard PID approach. For the measurement of D0→K−π+, it was found that a Bayesian PID approach gave a higher signal-to-background ratio and a similar or larger statistical significance when compared with standard PID selections, despite a reduced identification efficiency. Finally, we present an exploratory study of the measurement of Λ+c→pK−π+ in pp collisions at s√=7 TeV, using the Bayesian approach for the identification of its decay products.
The multi-strange baryon yields in PbPb collisions have been shown to exhibit an enhancement relative to pp reactions. In this work, Ξ and Ω production rates have been measured with the ALICE experiment as a function of transverse momentum, pT, in pPb collisions at a centre-of-mass energy of sNN=5.02 TeV. The results cover the kinematic ranges 0.6 GeV/c<pT<7.2 GeV/c and 0.8 GeV/c<pT<5 GeV/c, for Ξ and Ω respectively, in the common rapidity interval −0.5<yCMS<0. Multi-strange baryons have been identified by reconstructing their weak decays into charged particles. The pT spectra are analysed as a function of event charged-particle multiplicity, which in pPb collisions ranges over one order of magnitude and lies between those observed in pp and PbPb collisions. The measured pT distributions are compared to the expectations from a Blast-Wave model. The parameters which describe the production of lighter hadron species also describe the hyperon spectra in high multiplicity pPb collisions. The yield of hyperons relative to charged pions is studied and compared with results from pp and PbPb collisions. A continuous increase in the yield ratios as a function of multiplicity is observed in pPb data, the values of which range from those measured in minimum bias pp to the ones in PbPb collisions. A statistical model qualitatively describes this multiplicity dependence using a canonical suppression mechanism, in which the small volume causes a relative reduction of hadron production dependent on the strangeness content of the hyperon.
The multi-strange baryon yields in Pb--Pb collisions have been shown to exhibit an enhancement relative to pp reactions. In this work, Ξ and Ω production rates have been measured with the ALICE experiment as a function of transverse momentum, pT, in p-Pb collisions at a centre-of-mass energy of sNN−−−√ = 5.02 TeV. The results cover the kinematic ranges 0.6 GeV/c<pT<7.2 GeV/c and 0.8 GeV/c<pT< 5 GeV/c, for Ξ and Ω respectively, in the common rapidity interval -0.5 <yCMS< 0. Multi-strange baryons have been identified by reconstructing their weak decays into charged particles. The pT spectra are analysed as a function of event charged-particle multiplicity, which in p-Pb collisions ranges over one order of magnitude and lies between those observed in pp and Pb-Pb collisions. The measured pT distributions are compared to the expectations from a Blast-Wave model. The parameters which describe the production of lighter hadron species also describe the hyperon spectra in high multiplicity p-Pb. The yield of hyperons relative to charged pions is studied and compared with results from pp and Pb-Pb collisions. A statistical model is employed, which describes the change in the ratios with volume using a canonical suppression mechanism, in which the small volume causes a species-dependent relative reduction of hadron production. The calculations, in which the magnitude of the effect depends on the strangeness content, show good qualitative agreement with the data.
The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±, Ξ(1530)0) produced in p-Pb collisions at sNN−−−√=5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content.
The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±, Ξ(1530)0) produced in p-Pb collisions at sNN−−−√=5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content.
The ALICE collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y|<0.8 and transverse momentum 1<pT<10 GeV/c, in pp collisions at s√= 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD calculations agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e=3.47±0.40(stat)+1.12−1.33(sys)±0.07(norm)μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) predictions to obtain the total bb¯ production cross section, σbb¯=130±15.1(stat)+42.1−49.8(sys)+3.4−3.1(extr)±2.5(norm)±4.4(BR)μb.
The ALICE collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y|<0.8 and transverse momentum 1<pT<10 GeV/c, in pp collisions at s√= 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD calculations agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e=3.47±0.40(stat)+1.12−1.33(sys)±0.07(norm)μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) predictions to obtain the total bb¯ production cross section, σbb¯=130±15.1(stat)+42.1−49.8(sys)+3.4−3.1(extr)±2.5(norm)±4.4(BR)μb.
The production of K∗(892)0 and ϕ(1020) mesons has been measured in p-Pb collisions at sNN−−−√ = 5.02 TeV. K∗0 and ϕ are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range −0.5<y<0. The transverse momentum spectra, measured as a function of the multiplicity, have pT range from 0 to 15 GeV/c for K∗0 and from 0.3 to 21 GeV/c for ϕ. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at s√ = 7 TeV and Pb-Pb collisions at sNN−−−√ = 2.76 TeV. In Pb-Pb and p-Pb collisions, K∗0 and ϕ probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-ϕ ratio are discussed as a function of the multiplicity of the event. The short-lived K∗0 is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.
The production of K∗(892)0 and ϕ(1020) mesons has been measured in p-Pb collisions at sNN−−−√ = 5.02 TeV. K∗0 and ϕ are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range −0.5<y<0. The transverse momentum spectra, measured as a function of the multiplicity, have pT range from 0 to 15 GeV/c for K∗0 and from 0.3 to 21 GeV/c for ϕ. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at s√ = 7 TeV and Pb-Pb collisions at sNN−−−√ = 2.76 TeV. In Pb-Pb and p-Pb collisions, K∗0 and ϕ probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-ϕ ratio are discussed as a function of the multiplicity of the event. The short-lived K∗0 is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.
Due to massive energetic investments in woody support structures, trees are subject to unique physiological, mechanical, and ecological pressures not experienced by herbaceous plants. Despite a wealth of studies exploring trait relationships across the entire plant kingdom, the dominant traits underpinning these unique aspects of tree form and function remain unclear. Here, by considering 18 functional traits, encompassing leaf, seed, bark, wood, crown, and root characteristics, we quantify the multidimensional relationships in tree trait expression. We find that nearly half of trait variation is captured by two axes: one reflecting leaf economics, the other reflecting tree size and competition for light. Yet these orthogonal axes reveal strong environmental convergence, exhibiting correlated responses to temperature, moisture, and elevation. By subsequently exploring multidimensional trait relationships, we show that the full dimensionality of trait space is captured by eight distinct clusters, each reflecting a unique aspect of tree form and function. Collectively, this work identifies a core set of traits needed to quantify global patterns in functional biodiversity, and it contributes to our fundamental understanding of the functioning of forests worldwide.