Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

IntroductionHistotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects.MethodsTo measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.ResultsUnilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge.DiscussionWe propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death

Symmetry plane correlations in Pb–Pb collisions at √sNN = 2.76 TeV

A newly developed observable for correlations between symmetry planes, which characterize the direction of the anisotropic emission of produced particles, is measured in Pb-Pb collisions at sNN−−−√=2.76 TeV with ALICE. This so-called Gaussian Estimator allows for the first time the study of these quantities without the influence of correlations between different flow amplitudes. The centrality dependence of various correlations between two, three and four symmetry planes is presented. The ordering of magnitude between these symmetry plane correlations is discussed and the results of the Gaussian Estimator are compared with measurements of previously used estimators. The results utilizing the new estimator lead to significantly smaller correlations than reported by studies using the Scalar Product method. Furthermore, the obtained symmetry plane correlations are compared to state-of-the-art hydrodynamic model calculations for the evolution of heavy-ion collisions. While the model predictions provide a qualitative description of the data, quantitative agreement is not always observed, particularly for correlators with significant non-linear response of the medium to initial state anisotropies of the collision system. As these results provide unique and independent information, their usage in future Bayesian analysis can further constrain our knowledge on the properties of the QCD matter produced in ultrarelativistic heavy-ion collisions

Measurement of the radius dependence of charged-particle jet suppression in Pb–Pb collisions at sNN=5.02\sqrt{s_{\rm NN}} = 5.02 TeV

The ALICE Collaboration reports a new differential measurement of inclusive jet suppression using pp and Pb–Pb collision data at center-of-mass energy per nucleon–nucleon collision $\sqrt{s_{\rm NN}} = 5.02$ TeV. Charged-particle jets are reconstructed using the anti-$k_{\rm T}$ algorithm with resolution parameters $R$ = 0.2, 0.3, 0.4, 0.5, and 0.6 in pp collisions and $R$ = 0.2, 0.4, 0.6 in central (0–10\%), semi-central (30–50\%), and peripheral (60–80\%) Pb–Pb collisions. The analysis uses a novel approach based on machine learning to mitigate the influence of jet background in central heavy-ion collisions, which enables measurements of inclusive jet suppression for jet $p_{\rm T} \ge 40$ GeV/$c$ in central collisions at a resolution parameter of $R$ = 0.6. This is the lowest value of jet $p_{\rm T}$ achieved for inclusive jet measurements at $R$ = 0.6 at the LHC, and is an important step for discriminating different models of jet quenching in the quark-gluon plasma. The transverse momentum spectra, nuclear modification factors, and derived cross section and nuclear modification factor ratios for different jet resolution parameters of charged-particle jets are presented and compared to model predictions. A mild dependence of the nuclear modification factor ratios on collision centrality and resolution parameter is observed. The results are compared to a variety of jet quenching models with varying levels of agreement, demonstrating the effectiveness of this observable to discriminate between models.The ALICE Collaboration reports a new differential measurement of inclusive jet suppression using pp and Pb$-$Pb collision data at center-of-mass energy per nucleon-nucleon collision $\sqrt{s_{\rm NN}} = 5.02$ TeV. Charged-particle jets are reconstructed using the anti-$k_{\rm T}$ algorithm with resolution parameters $R =$ 0.2, 0.3, 0.4, 0.5, and 0.6 in pp collisions and $R =$ 0.2, 0.4, 0.6 in central (0$-$10%), semi-central (30$-$50%), and peripheral (60$-$80%) Pb$-$Pb collisions. The analysis uses a novel approach based on machine learning to mitigate the influence of jet background in central heavy-ion collisions, which enables measurements of inclusive jet suppression for jet $p_{\rm T} \geq 40$ GeV/$c$ in central collisions at a resolution parameter of $R = 0.6$. This is the lowest value of jet $p_{\rm T}$ achieved for inclusive jet measurements at $R=0.6$ at the LHC, and is an important step for discriminating different models of jet quenching in the quark-gluon plasma. The transverse momentum spectra, nuclear modification factors, and derived cross section and nuclear modification factor ratios for different jet resolution parameters of charged-particle jets are presented and compared to model predictions. A mild dependence of the nuclear modification factor ratios on collision centrality and resolution parameter is observed. The results are compared to a variety of jet quenching models with varying levels of agreement, demonstrating the effectiveness of this observable to discriminate between models

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at √ s = 5.02 and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of √s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within 0.8pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|2GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at √s=13TeV.

Constraining the K‾N{\overline{\textrm{K}}}{\textrm{N}} coupled channel dynamics using femtoscopic correlations at the LHC

The interaction of ${\rm{K}^{-}}$ with protons is characterised by the presence of several coupled channels, systems like ${\rm \overline{K}^0}$n and ${\pi\Sigma}$ with a similar mass and the same quantum numbers as the ${\rm{K}^{-}}$ p state. The strengths of these couplings to the ${\rm{K}^{-}}$p system are of crucial importance for the understanding of the nature of the $\Lambda(1405)$ resonance and of the attractive ${\rm{K}^{-}}$ p strong interaction. In this article, we present measurements of the ${\rm{K}^{-}}$p correlation functions in relative momentum space obtained in pp collisions at $\sqrt{s} = 13$~TeV, in p$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$~TeV, and (semi)peripheral Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$~TeV. The emitting source size, composed of a core radius anchored to the ${\rm{K}^{+}}$p correlation and of a resonance halo specific to each particle pair, varies between 1 and 2 fm in these collision systems. The strength and the effects of the ${\rm \overline{K}^0}$n and ${\pi\Sigma}$ inelastic channels on the measured ${\rm{K}^{-}}$p correlation function are investigated in the different colliding systems by comparing the data with state-of-the-art models of chiral potentials. A novel approach to determine the conversion weights $\omega$, necessary to quantify the amount of produced inelastic channels in the correlation function, is presented. In this method, particle yields are estimated from thermal model predictions, and their kinematic distribution from blast-wave fits to measured data. The comparison of chiral potentials to the measured ${\rm{K}^{-}}$p interaction indicates that, while the \mbox{${\pi\Sigma}$$-$${\rm{K}^{-}}$p} dynamics is well reproduced by the model, the coupling to the ${\rm \overline{K}^0}$n channel in the model is currently underestimated.The interaction of $\textrm{K}^{-}$with protons is characterised by the presence of several coupled channels, systems like ${\overline{\textrm{K}}}^0$n and \uppi \Sigma with a similar mass and the same quantum numbers as the $\textrm{K}^{-}$p state. The strengths of these couplings to the $\textrm{K}^{-}$p system are of crucial importance for the understanding of the nature of the $\Lambda (1405)$ resonance and of the attractive $\textrm{K}^{-}$p strong interaction. In this article, we present measurements of the $\textrm{K}^{-}$p correlation functions in relative momentum space obtained in pp collisions at $\sqrt{s}~=~13$ Te, in p–Pb collisions at $\sqrt{s_{\textrm{NN}}}~=~5.02$ Te, and (semi)peripheral Pb–Pb collisions at $\sqrt{s_{\textrm{NN}}}~=~5.02$ Te. The emitting source size, composed of a core radius anchored to the $\textrm{K}^{+}$p correlation and of a resonance halo specific to each particle pair, varies between 1 and 2 fm in these collision systems. The strength and the effects of the ${\overline{\textrm{K}}}^0$n and \uppi \Sigma inelastic channels on the measured $\textrm{K}^{-}$p correlation function are investigated in the different colliding systems by comparing the data with state-of-the-art models of chiral potentials. A novel approach to determine the conversion weights $\omega$, necessary to quantify the amount of produced inelastic channels in the correlation function, is presented. In this method, particle yields are estimated from thermal model predictions, and their kinematic distribution from blast-wave fits to measured data. The comparison of chiral potentials to the measured $\textrm{K}^{-}$p interaction indicates that, while the \uppi \Sigma –$\textrm{K}^{-}$p dynamics is well reproduced by the model, the coupling to the ${\overline{\textrm{K}}}^0$n channel in the model is currently underestimated.The interaction of $\rm{K}^{-}$ with protons is characterised by the presence of several coupled channels, systems like ${\rm \overline{K}^0}$n and $\pi\Sigma$ with a similar mass and the same quantum numbers as the $\rm{K}^{-}$p state. The strengths of these couplings to the $\rm{K}^{-}$p system are of crucial importance for the understanding of the nature of the $\Lambda(1405)$ resonance and of the attractive $\rm{K}^{-}$p strong interaction. In this article, we present measurements of the $\rm{K}^{-}$p correlation functions in relative momentum space obtained in pp collisions at $\sqrt{s}~=~13$ TeV, in p-Pb collisions at $\sqrt{s_{\mathrm{NN}}}~=~5.02$ TeV, and (semi)peripheral Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}~=~5.02$ TeV. The emitting source size, composed of a core radius anchored to the $\rm{K}^{+}$p correlation and of a resonance halo specific to each particle pair, varies between 1 and 2 fm in these collision systems. The strength and the effects of the ${\rm \overline{K}^0}$n and $\pi\Sigma$ inelastic channels on the measured $\rm{K}^{-}$p correlation function are investigated in the different colliding systems by comparing the data with state-of-the-art models of chiral potentials. A novel approach to determine the conversion weights $\omega$, necessary to quantify the amount of produced inelastic channels in the correlation function, is presented. In this method, particle yields are estimated from thermal model predictions, and their kinematic distribution from blast-wave fits to measured data. The comparison of chiral potentials to the measured $\rm{K}^{-}$p interaction indicates that, while the $\pi\Sigma-\rm{K}^{-}$p dynamics is well reproduced by the model, the coupling to the ${\rm \overline{K}^0}$n channel in the model is currently underestimated

Measurement of the production of charm jets tagged with D0^{0} mesons in pp collisions at s \sqrt{s} = 5.02 and 13 TeV

The measurement of the production of charm jets, identified by the presence of a ${\rm D^0}$ meson in the jet constituents, is presented in proton–proton collisions at centre-of-mass energies of $\sqrt{s}$ = 5.02 and 13 TeV with the ALICE detector at the CERN LHC. The D0 mesons were reconstructed from their hadronic decay ${\rm D^0} \rightarrow {\rm K^-}\pi^+$ and the respective charge conjugate. Jets were reconstructed from ${\rm D^0}$-meson candidates and charged particles using the anti-$k_{\rm T}$ algorithm, in the jet transverse momentum range $5<p_{\rm T;chjet}<50$ GeV/$c$, pseudorapidity $|\eta_{\rm jet}| <0.9-R$, and with the jet resolution parameters $R$ = 0.2, 0.4, 0.6. The distribution of the jet momentum fraction carried by a ${\rm D^0}$ meson along the jet axis ($z^{\rm ch}_{||}$) was measured in the range $0.4 < z^{\rm ch}_{||} < 1.0$ in four ranges of the jet transverse momentum. Comparisons of results for different collision energies and jet resolution parameters are also presented. The measurements are compared to predictions from Monte Carlo event generators based on leading-order and next-to-leading-order perturbative quantum chromodynamics calculations. A generally good description of the main features of the data is obtained in spite of a few discrepancies at low $p_{\rm T;chjet}$. Measurements were also done for $R = 0.3$ at $\sqrt{s}$ = 5.02 TeV and are shown along with their comparisons to theoretical predictions in an appendix to this paper.The measurement of the production of charm jets, identified by the presence of a D$^{0}$ meson in the jet constituents, is presented in proton–proton collisions at centre-of-mass energies of $\sqrt{s}$ = 5.02 and 13 TeV with the ALICE detector at the CERN LHC. The D$^{0}$ mesons were reconstructed from their hadronic decay D$^{0}$ → K$^{−}$π$^{+}$ and the respective charge conjugate. Jets were reconstructed from D$^{0}$-meson candidates and charged particles using the anti-k$_{T}$ algorithm, in the jet transverse momentum range 5 < p$_{T,chjet}$< 50 GeV/c, pseudorapidity |η$_{jet}$| < 0.9 − R, and with the jet resolution parameters R = 0.2, 0.4, 0.6. The distribution of the jet momentum fraction carried by a D$^{0}$ meson along the jet axis $\left({z}_{\Big\Vert}^{\textrm{ch}}\right)$ was measured in the range 0.4 <${z}_{\Big\Vert}^{\textrm{ch}}$< 1.0 in four ranges of the jet transverse momentum. Comparisons of results for different collision energies and jet resolution parameters are also presented. The measurements are compared to predictions from Monte Carlo event generators based on leading-order and next-to-leading-order perturbative quantum chromodynamics calculations. A generally good description of the main features of the data is obtained in spite of a few discrepancies at low p$_{T,chjet}$. Measurements were also done for R = 0.3 at $\sqrt{s}$ = 5.02 and are shown along with their comparisons to theoretical predictions in an appendix to this paper.[graphic not available: see fulltext]The measurement of the production of charm jets, identified by the presence of a ${\rm D^0}$ meson in the jet constituents, is presented in proton-proton collisions at centre-of-mass energies of $\sqrt{s}$ = 5.02 and 13 TeV with the ALICE detector at the CERN LHC. The ${\rm D^0}$ mesons were reconstructed from their hadronic decay ${\rm D^0} \rightarrow {\rm K^-}\pi^+$ and the respective charge conjugate. Jets were reconstructed from ${\rm D^0}$-meson candidates and charged particles using the anti-$k_{\rm T}$ algorithm, in the jet transverse momentum range $5<p_{\rm T;chjet}<50$ GeV/$c$, pseudorapidity $|\eta_{\rm jet}| <0.9-R$, and with the jet resolution parameters $R$ = 0.2, 0.4, 0.6. The distribution of the jet momentum fraction carried by a ${\rm D^0}$ meson along the jet axis ($z^{\rm ch}_{||}$) was measured in the range $0.4 < z^{\rm ch}_{||} < 1.0$ in four ranges of the jet transverse momentum. Comparisons of results for different collision energies and jet resolution parameters are also presented. The measurements are compared to predictions from Monte Carlo event generators based on leading-order and next-to-leading-order perturbative quantum chromodynamics calculations. A generally good description of the main features of the data is obtained in spite of a few discrepancies at low $p_{\rm T;chjet}$. Measurements were also done for $R = 0.3$ at $\sqrt{s}$ = 5.02 TeV and are shown along with their comparisons to theoretical predictions in an appendix to this paper