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The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s√=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (dNch/dη∼26) as measured in p–Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p–Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM).
The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s√=13 TeV using the ALICE experiment. Thanks to the large accumulated integrated luminosity, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (dNch/dη∼26) as measured in p-Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p-Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and Statistical Hadronisation Models (SHM).
We report here the nuclear magnetic resonance 19F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess the druggability of RNAs. Our RNA targets include representative bacterial riboswitches that naturally bind with nanomolar affinity and high specificity to cellular metabolites of low molecular weight. Based on counter-screens against five DNAs and five proteins, we can show that RNA can be specifically targeted. To demonstrate the quality of the initial fragment library that has been designed for easy follow-up chemistry, we further show how to increase binding affinity from an initial fragment hit by chemistry that links the identified fragment to the intercalator acridine. Thus, we achieve low-micromolar binding affinity without losing binding specificity between two different terminator structures.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
One of the big challenges for nuclear physics today is to understand, starting from first principles, the effective interaction between hadrons with different quark content. First successes have been achieved utilizing techniques to solve the dynamics of quarks and gluons on discrete space-time lattices. Experimentally, the dynamics of the strong interaction have been studied by scattering hadrons off each other. Such scattering experiments are difficult or impossible for unstable hadrons and hence, high quality measurements exist only for hadrons containing up and down quarks. In this work, we demonstrate that measuring correlations in the momentum space between hadron pairs produced in ultrarelativistic proton–proton collisions at the CERN LHC provides a precise method to obtain the missing information on the interaction dynamics between any pair of unstable hadrons. Specifically, we discuss the case of the interaction of baryons containing strange quarks (hyperons). We demonstrate for the first time how, using precision measurements of p–Ω− correlations, the effect of the strong interaction for this hadron–hadron pair can be studied and compared with predictions from lattice calculations.
Background: Brodalumab is a fully human monoclonal immunoglobulin IgG2 antibody that binds to the human IL-17 receptor subunit A and by that inhibits the biologic action of IL-17A, IL-17F, IL-17C and IL-17E. Therapy with fumaric acid esters (FAE) is a well established and widely used first-line systemic treatment for subjects with moderate-to-severe plaque psoriasis. Objectives: To compare brodalumab to FAE in terms of clinical efficacy, patient-reported outcomes and safety in subjects with moderate-to-severe plaque psoriasis who were naïve to systemic treatment. Methods: Eligible subjects were randomized 1 : 1 to 210 mg brodalumab injections or oral FAE according to product label in this 24-week, open-label, assessor-blinded, multi-centre, head-to-head phase 4 trial. The primary endpoints were having PASI75 and having sPGA score of 0 or 1 (sPGA 0/1). Subjects with missing values for the primary endpoints were considered non-responders. Results: A total of 210 subjects were randomized. 91/105 subjects completed brodalumab treatment and 58/105 subjects completed FAE treatment. At Week 24, significantly more subjects in the brodalumab group compared to the FAE group had PASI75 (81.0% vs. 38.1%, P < 0.001) and sPGA 0/1 (64.8% vs. 20.0%, P < 0.001). In the brodalumab group, the median time to both PASI75 and to PASI90 was significantly shorter than in the FAE group (4.1 weeks vs. 16.4 weeks, and 7.4 weeks vs. 24.4 weeks, respectively, P < 0.0001 for both). The rate of adverse events was lower in subjects treated with brodalumab compared to subjects treated with FAE (616.4 vs. 1195.8 events per 100 exposure years). No new safety signals were detected for brodalumab. Conclusions: Brodalumab was associated with rapid and significant improvements in signs and symptoms of moderate-to-severe plaque psoriasis, with a superior efficacy profile to what was observed with FAE in systemic-naïve subjects over 24 weeks.
Accurate measurement of the standard 235U(n,f) cross section from thermal to 170 keV neutron energy
(2020)
An accurate measurement of the 235U(n,f) cross section from thermal to 170 keV of neutron energy has recently been performed at n_TOF facility at CERN using 6Li(n,t)4He and 10B(n,α)7Li as references. This measurement has been carried out in order to investigate a possible overestimation of the 235U fission cross section evaluation provided by most recent libraries between 10 and 30 keV. A custom experimental apparatus based on in-beam silicon detectors has been used, and a Monte Carlo simulation in GEANT4 has been employed to characterize the setup and calculate detectors efficiency. The results evidenced the presence of an overestimation in the interval between 9 and 18 keV and the new data may be used to decrease the uncertainty of 235U(n,f) cross section in the keV region.
Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promising pre-clinical results in the therapy of several inflammatory diseases. Since inflammation is a main driver of disease progression in alcoholic hepatitis, we investigated the impact of endogenous ALOX15-dependent lipid mediators and exogenously applied LXA4 on AH development. A mouse model for alcoholic steatohepatitis (NIAAA model) was tested in Alox12/15+/+ and Alox12/15−/− mice, with or without supplementation of LXA4. Absence of Alox12/15 aggravated parameters of liver disease, increased hepatic immune cell infiltration in AH, and elevated systemic neutrophils as a marker for systemic inflammation. Interestingly, i.p. injections of LXA4 significantly lowered transaminase levels only in Alox12/15−/− mice and reduced hepatic immune cell infiltration as well as systemic inflammatory cytokine expression in both genotypes, even though steatosis progressed. Thus, while LXA4 injection attenuated selected parameters of disease progression in Alox12/15−/− mice, its beneficial impact on immunity was also apparent in Alox12/15+/+ mice. In conclusion, pro-resolving lipid mediators may be beneficial to reduce inflammation in alcoholic hepatitis.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
The measurement of the azimuthal-correlation function of prompt D mesons with charged particles in pp collisions at s√=5.02 TeV and p–Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC is reported. The D0, D+, and D∗+ mesons, together with their charge conjugates, were reconstructed at midrapidity in the transverse momentum interval 3<pT<24 GeV/c and correlated with charged particles having pT>0.3 GeV/c and pseudorapidity |η|<0.8. The properties of the correlation peaks appearing in the near- and away-side regions (for Δφ≈0 and Δφ≈π, respectively) were extracted via a fit to the azimuthal correlation functions. The shape of the correlation functions and the near- and away-side peak features are found to be consistent in pp and p–Pb collisions, showing no modifications due to nuclear effects within uncertainties. The results are compared with predictions from Monte Carlo simulations performed with the PYTHIA, POWHEG+PYTHIA, HERWIG, and EPOS 3 event generators.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
1. Recent research highlights the ecological importance of individual variation in behavioural predictability. Individuals may not only differ in their average expression of a behavioural trait (their behavioural type) and in their ability to adjust behaviour to changing environmental conditions (individual plasticity), but also in their variability around their average behaviour (predictability). However, quantifying behavioural predictability in the wild has been challenging due to limitations of acquiring sufficient repeated behavioural measures.
2. We here demonstrate how common biologging data can be used to detect individual variation in behavioural predictability in the wild and reveal the coexistence of highly predictable individuals along with unpredictable individuals within the same population.
3. We repeatedly quantified two behaviours—daily movement distance and diurnal activity—in 62 female brown bears Ursus arctos tracked across 187 monitoring years. We calculated behavioural predictability over the short term (50 consecutive monitoring days within 1 year) and long term (across monitoring years) as the residual intra-individual variability (rIIV) of behaviour around the behavioural reaction norm. We tested whether predictability varies systematically across average behavioural types and whether it is correlated across functionally distinct behaviours, that is, daily movement distance and amount of diurnal activity.
4. Brown bears showed individual variation in behavioural predictability from predictable to unpredictable individuals. For example, the standard deviation around the average daily movement distance within one monitoring year varied up to fivefold from 1.1 to 5.5 km across individuals. Individual predictability for both daily movement distance and diurnality was conserved across monitoring years. Individual predictability was correlated with behavioural type where individuals which were on average more diurnal and mobile were also more unpredictable in their behaviour. In contrast, more nocturnal individuals moved less and were more predictable in their behaviour. Finally, individual predictability in daily movement distance and diurnality was positively correlated, suggesting that individual predictability may be a quantitative trait in its own regard that could evolve and is underpinned by genetic variation.
5. Unpredictable individuals may cope better with stochastic events and unpredictability may hence be an adaptive behavioural response to increased predation risk.
The inclusive J/ψ meson production in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision of sNN−−−√ = 5.02 TeV at midrapidity (|y| < 0.9) is reported by the ALICE Collaboration. The measurements are performed in the dielectron decay channel, as a function of event centrality and J/ψ transverse momentum pT, down to pT = 0 GeV/c. The J/ψ mean transverse momentum ⟨pT⟩ and rAA ratio, defined as ⟨p2T⟩PbPb/⟨p2T⟩pp, are evaluated. Both observables show a centrality dependence decreasing towards central (head-on) collisions. The J/ψ nuclear modification factor RAA exhibits a strong pT dependence with a large suppression at high pT and an increase to unity for decreasing pT. When integrating over the measured momentum range pT < 10 GeV/c, the J/ψ RAA shows a weak centrality dependence. Each measurement is compared with results at lower center-of-mass energies and with ALICE measurements at forward rapidity, as well as to theory calculations. All reported features of the J/ψ production at low pT are consistent with a dominant contribution to the J/ψ yield originating from charm quark (re)combination.
The inclusive J/ψ meson production in Pb–Pb collisions at a center-of-mass energy per nucleon–nucleon collision of sNN=5.02 TeV at midrapidity (|y|<0.9) is reported by the ALICE Collaboration. The measurements are performed in the dielectron decay channel, as a function of event centrality and J/ψ transverse momentum pT, down to pT=0. The J/ψ mean transverse momentum 〈pT〉 and rAA ratio, defined as 〈pT2〉PbPb/〈pT2〉pp, are evaluated. Both observables show a centrality dependence decreasing towards central (head-on) collisions. The J/ψ nuclear modification factor RAA exhibits a strong pT dependence with a large suppression at high pT and an increase to unity for decreasing pT. When integrating over the measured momentum range pT<10 GeV/c, the J/ψ RAA shows a weak centrality dependence. Each measurement is compared with results at lower center-of-mass energies and with ALICE measurements at forward rapidity, as well as to theory calculations. All reported features of the J/ψ production at low pT are consistent with a dominant contribution to the J/ψ yield originating from charm quark (re)combination.
The inclusive production of the J/ψ and ψ(2S) charmonium states is studied as a function of centrality in p-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=8.16 TeV at the LHC. The measurement is performed in the dimuon decay channel with the ALICE apparatus in the centre-of-mass rapidity intervals −4.46<ycms<−2.96 (Pb-going direction) and 2.03<ycms<3.53 (p-going direction), down to zero transverse momentum (pT). The J/ψ and ψ(2S) production cross sections are evaluated as a function of the collision centrality, estimated through the energy deposited in the zero degree calorimeter located in the Pb-going direction. The pT-differential J/ψ production cross section is measured at backward and forward rapidity for several centrality classes, together with the corresponding average ⟨pT⟩ and ⟨p2T⟩ values. The nuclear effects affecting the production of both charmonium states are studied using the nuclear modification factor. In the p-going direction, a suppression of the production of both charmonium states is observed, which seems to increase from peripheral to central collisions. In the Pb-going direction, however, the centrality dependence is different for the two states: the nuclear modification factor of the J/ψ increases from below unity in peripheral collisions to above unity in central collisions, while for the ψ(2S) it stays below or consistent with unity for all centralities with no significant centrality dependence. The results are compared with measurements in p-Pb collisions at sNN−−−√=5.02 TeV and no significant dependence on the energy of the collision is observed. Finally, the results are compared with theoretical models implementing various nuclear matter effects.
Coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb–Pb collisions at √sNN = 5.02 TeV
(2020)
Cross sections for the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb-Pb collisions at sNN−−−√=5.02 TeV are reported. The measurements, which rely on the π+π− decay channel, are presented in three regions of rapidity covering the range |y|<0.8. For each rapidity interval, cross sections are shown for different nuclear-breakup classes defined according to the presence of neutrons measured in the zero-degree calorimeters. The results are compared with predictions based on different models of nuclear shadowing. Finally, the observation of a coherently produced resonance-like structure with a mass around 1.7 GeV/c2 and a width of about 140 MeV/c2 is reported and compared with similar observations from other experiments.
Coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb–Pb collisions at √sNN = 5.02 TeV
(2020)
Cross sections for the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb-Pb collisions at sNN−−−√=5.02 TeV are reported. The measurements, which rely on the π+π− decay channel, are presented in three regions of rapidity covering the range |y|<0.8. For each rapidity interval, cross sections are shown for different nuclear-breakup classes defined according to the presence of neutrons measured in the zero-degree calorimeters. The results are compared with predictions based on different models of nuclear shadowing. Finally, the observation of a coherently produced resonance-like structure with a mass around 1.7 GeV/c2 and a width of about 140 MeV/c2 is reported and compared with similar observations from other experiments.
Coherent photoproduction of ρ⁰ vector mesons in ultra-peripheral Pb-Pb collisions at √sNN = 5.02 TeV
(2020)
Cross sections for the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb-Pb collisions at sNN−−−√ = 5.02 TeV are reported. The measurements, which rely on the π+π− decay channel, are presented in three regions of rapidity covering the range |y| < 0.8. For each rapidity interval, cross sections are shown for different nuclear-breakup classes defined according to the presence of neutrons measured in the zero-degree calorimeters. The results are compared with predictions based on different models of nuclear shadowing. Finally, the observation of a coherently produced resonance-like structure with a mass around 1.7 GeV/c2 and a width of about 140 MeV/c2 is reported and compared with similar observations from other experiments.
Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa). Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed. Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy. Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance.
Systematic studies of charge-dependent two- and three-particle correlations in Pb-Pb collisions at sNN−−−√ = 2.76 and 5.02 TeV used to probe the Chiral Magnetic Effect (CME) are presented. These measurements are performed for charged particles in the pseudorapidity (η) and transverse momentum (pT) ranges |η| < 0.8 and 0.2 < pT < 5 GeV/c. A significant charge-dependent signal that becomes more pronounced for peripheral collisions is reported for the CME-sensitive correlators γ1, 1 = 〈cos(φα + φβ − 2Ψ2)〉 and γ1, − 3 = 〈cos(φα − 3φβ + 2Ψ2)〉. The results are used to estimate the contribution of background effects, associated with local charge conservation coupled to anisotropic flow modulations, to measurements of the CME. A blast-wave parametrisation that incorporates local charge conservation tuned to reproduce the centrality dependent background effects is not able to fully describe the measured γ1,1. Finally, the charge and centrality dependence of mixed-harmonics three-particle correlations, of the form γ1, 2 = 〈cos(φα + 2φβ − 3Ψ3)〉, which are insensitive to the CME signal, verify again that background contributions dominate the measurement of γ1,1.