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The ALICE Collaboration has made the first measurement at the LHC of J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at sNN=2.76 TeV. The J/ψ is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 μb−1. The cross section for coherent J/ψ production in the rapidity interval −3.6<y<−2.6 is measured to be dσJ/ψcoh/dy=1.00±0.18(stat)−0.26+0.24(syst) mb. The result is compared to theoretical models for coherent J/ψ production and found to be in good agreement with those models which include nuclear gluon shadowing.
The first study of ϕ-meson production in p-Pb collisions at forward and backward rapidity, at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02~TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass, the integrated luminosity amounting to 5.01±0.19~nb−1 and 5.81±0.20~nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4 for a 78±3~nb−1 integrated luminosity sample.
The first study of ϕ-meson production in p-Pb collisions at forward and backward rapidity, at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02~TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass, the integrated luminosity amounting to 5.01±0.19~nb−1 and 5.81±0.20~nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4 for a 78±3~nb−1 integrated luminosity sample.
Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti‐angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin‐2 (Ang‐2) as a potential target in both naive and bevacizumab‐treated glioblastoma. Ang‐2 expression was absent in normal human brain endothelium, while the highest Ang‐2 levels were observed in bevacizumab‐treated GBM. In a murine GBM model, VEGF blockade resulted in endothelial upregulation of Ang‐2, whereas the combined inhibition of VEGF and Ang‐2 leads to extended survival, decreased vascular permeability, depletion of tumor‐associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. CD206+ (M2‐like) macrophages were identified as potential novel targets following anti‐angiogenic therapy. Our findings imply a novel role for endothelial cells in therapy resistance and identify endothelial cell/myeloid cell crosstalk mediated by Ang‐2 as a potential resistance mechanism. Therefore, combining VEGF blockade with inhibition of Ang‐2 may potentially overcome resistance to bevacizumab therapy.
Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma
(2020)
Aims: Changes in metabolism are known to contribute to tumour phenotypes. If and how metabolic alterations in brain tumours contribute to patient outcome is still poorly understood. Epigenetics impact metabolism and mitochondrial function. The aim of this study is a characterisation of metabolic features in molecular subgroups of isocitrate dehydrogenase mutant (IDHmut) and isocitrate dehydrogenase wildtype (IDHwt) gliomas. Methods: We employed DNA methylation pattern analyses with a special focus on metabolic genes, large-scale metabolism panel immunohistochemistry (IHC), qPCR-based determination of mitochondrial DNA copy number and immune cell content using IHC and deconvolution of DNA methylation data. We analysed molecularly characterised gliomas (n = 57) for in depth DNA methylation, a cohort of primary and recurrent gliomas (n = 22) for mitochondrial copy number and validated these results in a large glioma cohort (n = 293). Finally, we investigated the potential of metabolic markers in Bevacizumab (Bev)-treated gliomas (n = 29). Results: DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours. Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under anti-angiogenic therapy. Conclusion: A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities.
Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5<|η|<4.0) and associated particles in the central range (|η|<1.0) are measured with the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The trigger particles are reconstructed using the muon spectrometer, and the associated particles by the central barrel tracking detectors. In high-multiplicity events, the double-ridge structure, previously discovered in two-particle angular correlations at midrapidity, is found to persist to the pseudorapidity ranges studied in this Letter. The second-order Fourier coefficients for muons in high-multiplicity events are extracted after jet-like correlations from low-multiplicity events have been subtracted. The coefficients are found to have a similar transverse momentum (pT) dependence in p-going (p-Pb) and Pb-going (Pb-p) configurations, with the Pb-going coefficients larger by about 16±6%, rather independent of pT within the uncertainties of the measurement. The data are compared with calculations using the AMPT model, which predicts a different pT and η dependence than observed in the data. The results are sensitive to the parent particle v2 and composition of reconstructed muon tracks, where the contribution from heavy flavour decays are expected to dominate at pT>2 GeV/c.
Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5<|η|<4.0) and associated particles in the central range (|η|<1.0) are measured with the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The trigger particles are reconstructed using the muon spectrometer, and the associated particles by the central barrel tracking detectors. In high-multiplicity events, the double-ridge structure, previously discovered in two-particle angular correlations at midrapidity, is found to persist to the pseudorapidity ranges studied in this Letter. The second-order Fourier coefficients for muons in high-multiplicity events are extracted after jet-like correlations from low-multiplicity events have been subtracted. The coefficients are found to have a similar transverse momentum (pT) dependence in p-going (p-Pb) and Pb-going (Pb-p) configurations, with the Pb-going coefficients larger by about 16±6%, rather independent of pT within the uncertainties of the measurement. The data are compared with calculations using the AMPT model, which predicts a different pT and η dependence than observed in the data. The results are sensitive to the parent particle v2 and composition of reconstructed muon tracks, where the contribution from heavy flavour decays are expected to dominate at pT>2 GeV/c.
Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5<|η|<4.0) and associated particles in the central range (|η|<1.0) are measured with the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The trigger particles are reconstructed using the muon spectrometer, and the associated particles by the central barrel tracking detectors. In high-multiplicity events, the double-ridge structure, previously discovered in two-particle angular correlations at midrapidity, is found to persist to the pseudorapidity ranges studied in this Letter. The second-order Fourier coefficients for muons in high-multiplicity events are extracted after jet-like correlations from low-multiplicity events have been subtracted. The coefficients are found to have a similar transverse momentum (pT) dependence in p-going (p-Pb) and Pb-going (Pb-p) configurations, with the Pb-going coefficients larger by about 16±6%, rather independent of pT within the uncertainties of the measurement. The data are compared with calculations using the AMPT model, which predicts a different pT and η dependence than observed in the data. The results are sensitive to the parent particle v2 and composition of reconstructed muon tracks, where the contribution from heavy flavour decays are expected to dominate at pT>2 GeV/c.
Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5<|η|<4.0) and associated particles in the central range (|η|<1.0) are measured with the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The trigger particles are reconstructed using the muon spectrometer, and the associated particles by the central barrel tracking detectors. In high-multiplicity events, the double-ridge structure, previously discovered in two-particle angular correlations at midrapidity, is found to persist to the pseudorapidity ranges studied in this Letter. The second-order Fourier coefficients for muons in high-multiplicity events are extracted after jet-like correlations from low-multiplicity events have been subtracted. The coefficients are found to have a similar transverse momentum (pT) dependence in p-going (p-Pb) and Pb-going (Pb-p) configurations, with the Pb-going coefficients larger by about 16±6%, rather independent of pT within the uncertainties of the measurement. The data are compared with calculations using the AMPT model, which predicts a different pT and η dependence than observed in the data. The results are sensitive to the parent particle v2 and composition of reconstructed muon tracks, where the contribution from heavy flavour decays are expected to dominate at pT>2 GeV/c.
We have has performed the first measurement of the coherent ψ(2S) photo-production cross section in ultra-peripheral Pb-Pb collisions at the LHC. This charmonium excited state is reconstructed via the ψ(2S) →l+l− and ψ(2S) → J/ψπ+π− decays, where the J/ψ decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 μb−1. The cross section for coherent ψ(2S) production in the rapidity interval −0.9<y<0.9 is dσcohψ(2S)/dy=0.83±0.19(stat+syst) mb. The ψ(2S) to J/ψ coherent cross section ratio is 0.34+0.08−0.07(stat+syst). The obtained results are compared to predictions from theoretical models.