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The production of charged pions, kaons and (anti)protons has been measured at mid-rapidity (−0.5<y<0) in p–Pb collisions at √sNN=5.02 TeV using the ALICE detector at the LHC. Exploiting particle identification capabilities at high transverse momentum (pT), the previously published pT spectra have been extended to include measurements up to 20 GeV/c for seven event multiplicity classes. The pT spectra for pp collisions at s=7 TeV, needed to interpolate a pp reference spectrum, have also been extended up to 20 GeV/c to measure the nuclear modification factor (RpPb) in non-single diffractive p–Pb collisions. At intermediate transverse momentum (2<pT<10 GeV/c) the proton-to-pion ratio increases with multiplicity in p–Pb collisions, a similar effect is not present in the kaon-to-pion ratio. The pT dependent structure of such increase is qualitatively similar to those observed in pp and heavy-ion collisions. At high pT (>10 GeV/c), the particle ratios are consistent with those reported for pp and Pb–Pb collisions at the LHC energies. At intermediate pT the (anti)proton RpPb shows a Cronin-like enhancement, while pions and kaons show little or no nuclear modification. At high pT the charged pion, kaon and (anti)proton RpPb are consistent with unity within statistical and systematic uncertainties.
The production of prompt D0, Ds+, and Λc+ hadrons, and their ratios, Ds+/D0 and Λc+/D0, are measured in proton–proton collisions at √s=13 TeV at midrapidity (|y|<0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (pT) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange Ds+/D0 ratio indicates no significant multiplicity dependence, the baryon-to-meson pT-differential Λc+/D0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3σ for 1<pT<12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Λc+/D0 ratios as a function of pT present a similar shape and magnitude as the Λ/KS0 ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charm-hadron formation, with analogous multiplicity dependence. The pT-integrated ratios, extrapolated down to pT=0, do not show a significant dependence on multiplicity within the uncertainties.
Direct photon production at mid-rapidity in Pb–Pb collisions at √sNN=2.76 TeV was studied in the transverse momentum range 0.9<pT<14 GeV/c. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the ALICE detector material with the e+e− pair reconstructed in the central tracking system. The results of the two methods were combined and direct photon spectra were measured for the 0–20%, 20–40%, and 40–80% centrality classes. For all three classes, agreement was found with perturbative QCD calculations for pT≳5 GeV/c. Direct photon spectra down to pT≈1 GeV/c could be extracted for the 20–40% and 0–20% centrality classes. The significance of the direct photon signal for 0.9<pT<2.1 GeV/c is 2.6σ for the 0–20% class. The spectrum in this pT range and centrality class can be described by an exponential with an inverse slope parameter of (297±12stat±41syst) MeV. State-of-the-art models for photon production in heavy-ion collisions agree with the data within uncertainties.
We present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possible Λn‾ bound state. The search is performed with the ALICE detector in central (0–10%) Pb–Pb collisions at √sNN=2.76 TeV, by invariant mass analysis in the decay modes Λn‾→d‾π+ and H-dibaryon →Λpπ−. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.
The pseudorapidity (η) and transverse-momentum (pT) distributions of charged particles produced in proton–proton collisions are measured at the centre-of-mass energy √s=13 TeV. The pseudorapidity distribution in |η|<1.8 is reported for inelastic events and for events with at least one charged particle in |η|<1. The pseudorapidity density of charged particles produced in the pseudorapidity region |η|<0.5 is 5.31±0.18 and 6.46±0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15<pT<20 GeV/c and |η|<0.8 for events with at least one charged particle in |η|<1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators.
We present the first systematic comparison of the charged-particle pseudorapidity densities for three widely different collision systems, pp, pPb, and PbPb, at the top energy of the Large Hadron Collider (√sNN=5.02TeV) measured over a wide pseudorapidity range (−3.5<η<5), the widest possible among the four experiments at that facility. The systematic uncertainties are minimised since the measurements are recorded by the same experimental apparatus (ALICE). The distributions for pPb and PbPb collisions are determined as a function of the centrality of the collisions, while results from pp collisions are reported for inelastic events with at least one charged particle at midrapidity. The charged-particle pseudorapidity densities are, under simple and robust assumptions, transformed to charged-particle rapidity densities. This allows for the calculation and the presentation of the evolution of the width of the rapidity distributions and of a lower bound on the Bjorken energy density, as a function of the number of participants in all three collision systems. We find a decreasing width of the particle production, and roughly a smooth ten fold increase in the energy density, as the system size grows, which is consistent with a gradually higher dense phase of matter.
Multiplicity (Nch) distributions and transverse momentum (pT) spectra of inclusive primary charged particles in the kinematic range of |η|<0.8 and 0.15 GeV/c<pT<10 GeV/c are reported for pp, p–Pb, Xe–Xe and Pb–Pb collisions at centre-of-mass energies per nucleon pair ranging from √sNN=2.76 TeV up to 13 TeV. A sequential two-dimensional unfolding procedure is used to extract the correlation between the transverse momentum of primary charged particles and the charged-particle multiplicity of the corresponding collision. This correlation sharply characterises important features of the final state of a collision and, therefore, can be used as a stringent test of theoretical models. The multiplicity distributions as well as the mean and standard deviation derived from the pT spectra are compared to state-of-the-art model predictions. Providing these fundamental observables of bulk particle production consistently across a wide range of collision energies and system sizes can serve as an important input for tuning Monte Carlo event generators.
The interaction between Λ baryons and kaons/antikaons is a crucial ingredient for the strangeness S=0 and S=−2 sector of the meson–baryon interaction at low energies. In particular, the ΛK‾ might help in understanding the origin of states such as the Ξ(1620), whose nature and properties are still under debate. Experimental data on Λ–K and Λ–K‾ systems are scarce, leading to large uncertainties and tension between the available theoretical predictions constrained by such data. In this Letter we present the measurements of Λ–K⊕+Λ‾–K− and Λ–K⊕−Λ‾–K+ correlations obtained in the high-multiplicity triggered data sample in pp collisions at s=13 TeV recorded by ALICE at the LHC. The correlation function for both pairs is modeled using the Lednický–Lyuboshits analytical formula and the corresponding scattering parameters are extracted. The Λ–K⊕−Λ‾–K+ correlations show the presence of several structures at relative momenta k⁎ above 200 MeV/c, compatible with the Ω baryon, the Ξ(1690), and Ξ(1820) resonances decaying into Λ–K− pairs. The low k⁎ region in the Λ–K⊕−Λ‾–K+ also exhibits the presence of the Ξ(1620) state, expected to strongly couple to the measured pair. The presented data allow to access the ΛK+ and ΛK− strong interaction with an unprecedented precision and deliver the first experimental observation of the Ξ(1620) decaying into ΛK−.
Fluctuation measurements are important sources of information on the mechanism of particle production at LHC energies. This article reports the first experimental results on third-order cumulants of the net-proton distributions in Pb–Pb collisions at a center-of-mass energy √sNN=5.02 TeV recorded by the ALICE detector. The results on the second-order cumulants of net-proton distributions at √sNN=2.76 and 5.02 TeV are also discussed in view of effects due to the global and local baryon number conservation. The results demonstrate the presence of long-range rapidity correlations between protons and antiprotons. Such correlations originate from the early phase of the collision. The experimental results are compared with HIJING and EPOS model calculations, and the dependence of the fluctuation measurements on the phase-space coverage is examined in the context of lattice quantum chromodynamics (LQCD) and hadron resonance gas (HRG) model estimations. The measured third-order cumulants are consistent with zero within experimental uncertainties of about 4% and are described well by LQCD and HRG predictions.
Effects of a phase transition on HBT correlations in an integrated Boltzmann+hydrodynamics approach
(2009)
A systematic study of HBT radii of pions, produced in heavy ion collisions in the intermediate energy regime (SPS), from an integrated (3+1)d Boltzmann+hydrodynamics approach is presented. The calculations in this hybrid approach, incorporating an hydrodynamic stage into the Ultra-relativistic Quantum Molecular Dynamics transport model, allow for a comparison of different equations of state retaining the same initial conditions and final freeze-out. The results are also compared to the pure cascade transport model calculations in the context of the available data. Furthermore, the effect of different treatments of the hydrodynamic freeze-out procedure on the HBT radii are investigated. It is found that the HBT radii are essentially insensitive to the details of the freeze-out prescription as long as the final hadronic interactions in the cascade are taken into account. The HBT radii RL and RO and the RO/RS ratio are sensitive to the EoS that is employed during the hydrodynamic evolution. We conclude that the increased lifetime in case of a phase transition to a QGP (via a Bag Model equation of state) is not supported by the available data.
The ALICE experiment has measured low-mass dimuon production in pp collisions at √s=7 TeV in the dimuon rapidity region 2.5<y<4. The observed dimuon mass spectrum is described as a superposition of resonance decays (η,ρ,ω,η′,ϕ) into muons and semi-leptonic decays of charmed mesons. The measured production cross sections for ω and ϕ are σω(1<pt<5 GeV/c,2.5<y<4)=5.28±0.54(stat)±0.49(syst) mb and σϕ(1<pt<5 GeV/c,2.5<y<4)=0.940±0.084(stat)±0.076(syst) mb. The differential cross sections d2σ/dydpt are extracted as a function of pt for ω and ϕ. The ratio between the ρ and ω cross section is obtained. Results for the ϕ are compared with other measurements at the same energy and with predictions by models.
he first measurements of the invariant differential cross sections of inclusive π0 and η meson production at mid-rapidity in proton–proton collisions at s=0.9 TeV and s=7 TeV are reported. The π0 measurement covers the ranges 0.4<pT<7 GeV/c and 0.3<pT<25 GeV/c for these two energies, respectively. The production of η mesons was measured at s=√7 TeV in the range 0.4<pT<15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the π0 spectrum at s=0.9 TeV, overestimate those of π0 and η mesons at s=√7 TeV, but agree with the measured η/π0 ratio at s=√7 TeV.
Rapidity and transverse momentum dependence of inclusive J/ψ production in pp collisions at √s=7 TeV
(2011)
The ALICE experiment at the LHC has studied inclusive J/ψ production at central and forward rapidities in pp collisions at √s=7 TeV. In this Letter, we report on the first results obtained detecting the J/ψ through the dilepton decay into e+e− and μ+μ− pairs in the rapidity ranges |y|<0.9 and 2.5<y<4, respectively, and with acceptance down to zero pT. In the dielectron channel the analysis was carried out on a data sample corresponding to an integrated luminosity Lint=5.6 nb−1 and the number of signal events is NJ/ψ=352±32(stat.)±28(syst.); the corresponding figures in the dimuon channel are Lint=15.6 nb−1 and NJ/ψ=1924±77(stat.)±144(syst.). The measured production cross sections are σJ/ψ(|y|<0.9)=10.7±1.0(stat.)±1.6(syst.)−2.3+1.6(syst.pol.)μb and σJ/ψ(2.5<y<4)=6.31±0.25(stat.)±0.76(syst.)−1.96+0.95(syst.pol.)μb. The differential cross sections, in transverse momentum and rapidity, of the J/ψ were also measured.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.
In this paper, we present an overview of some of the existing issues of the research in quantum gravity. We also introduce the basic ideas that led Padmanabhan to consider a duality property in path integrals. Such a duality is consistent with the T-duality in string theory. More importantly, the path integral duality discloses a universal feature of any quantum geometry, namely the existence of a zero point length L0. We also comment about recent developments aiming to expose effects of the zero point length in strong electrodynamics and black holes. There are reasons to believe that the main characters of the phenomenology of quantum gravity may be described by means of a single parameter like L0.
In this Letter we derive the gravity field equations by varying the action for an ultraviolet complete quantum gravity. Then we consider the case of a static source term and we determine an exact black hole solution. As a result we find a regular spacetime geometry: in place of the conventional curvature singularity extreme energy fluctuations of the gravitational field at small length scales provide an effective cosmological constant in a region locally described in terms of a de Sitter space. We show that the new metric coincides with the noncommutative geometry inspired Schwarzschild black hole. Indeed, we show that the ultraviolet complete quantum gravity, generated by ordinary matter is the dual theory of ordinary Einstein gravity coupled to a noncommutative smeared matter. In other words we obtain further insights about that quantum gravity mechanism which improves Einstein gravity in the vicinity of curvature singularities. This corroborates all the existing literature in the physics and phenomenology of noncommutative black holes.
In this Letter we study the radiation measured by an accelerated detector, coupled to a scalar field, in the presence of a fundamental minimal length. The latter is implemented by means of a modified momentum space Green's function. After calibrating the detector, we find that the net flux of field quanta is negligible, and that there is no Planckian spectrum. We discuss possible interpretations of this result, and we comment on experimental implications in heavy ion collisions and atomic systems.
Fuzziness at the horizon
(2010)
We study the stability of the noncommutative Schwarzschild black hole interior by analysing the propagation of a massless scalar field between the two horizons. We show that the spacetime fuzziness triggered by the field higher momenta can cure the classical exponential blue-shift divergence, suppressing the emergence of infinite energy density in a region nearby the Cauchy horizon.
In this Letter, we propose a new scenario emerging from the conjectured presence of a minimal length ℓ in the spacetime fabric, on the one side, and the existence of a new scale invariant, continuous mass spectrum, of un-particles on the other side. We introduce the concept of un-spectral dimension DU of a d-dimensional, euclidean (quantum) spacetime, as the spectral dimension measured by an “un-particle” probe. We find a general expression for the un-spectral dimension DU labelling different spacetime phases: a semi-classical phase, where ordinary spectral dimension gets contribution from the scaling dimension dU of the un-particle probe; a critical “Planckian phase”, where four-dimensional spacetime can be effectively considered two-dimensional when dU=1; a “Trans-Planckian phase”, which is accessible to un-particle probes only, where spacetime as we currently understand it looses its physical meaning.
Quarkyonic or baryquark matter? On the dynamical generation of momentum space shell structure
(2023)
We study the equation of state of a mixture of (quasi-)free constituent quarks and nucleons with hard-core repulsion at zero temperature. Two opposite scenarios for the realization of the Pauli exclusion principle are considered: (i) a Fermi sea of quarks surrounded by a shell of baryons – the quarkyonic matter, and (ii) a Fermi sea of nucleons surrounded by a shell of quarks which we call baryquark matter. In both scenarios, the sizes of the Fermi sea and shell are fixed through energy minimization at fixed baryon number density. While both cases yield a qualitatively similar transition from hadronic to quark matter, we find that baryquark matter is energetically favored in this setup and yields a physically acceptable behavior of the speed of sound without the need to introduce an infrared regulator. In order to retain the theoretically more appealing quarkyonic matter as the preferred form of dense QCD matter will thus require modifications to the existing dynamical generation mechanisms, such as, for example, the introduction of momentum-dependent nuclear interactions.
The production of the hypertriton nuclei HΛ3 and H‾Λ¯3 has been measured for the first time in Pb–Pb collisions at sNN=2.76 TeV with the ALICE experiment at LHC. The pT-integrated HΛ3 yield in one unity of rapidity, dN/dy×B.R.(HΛ3→He3,π−)=(3.86±0.77(stat.)±0.68(syst.))×10−5 in the 0–10% most central collisions, is consistent with the predictions from a statistical thermal model using the same temperature as for the light hadrons. The coalescence parameter B3 shows a dependence on the transverse momentum, similar to the B2 of deuterons and the B3 of 3He nuclei. The ratio of yields S3=HΛ3/(He3×Λ/p) was measured to be S3=0.60±0.13(stat.)±0.21(syst.) in 0–10% centrality events; this value is compared to different theoretical models. The measured S3 is compatible with thermal model predictions. The measured HΛ3 lifetime, τ=181−39+54(stat.)±33(syst.)ps is in agreement within 1σ with the world average value.
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.
Convolutional neural networks (CNNs) are one of the most successful computer vision systems to solve object recognition. Furthermore, CNNs have major applications in understanding the nature of visual representations in the human brain. Yet it remains poorly understood how CNNs actually make their decisions, what the nature of their internal representations is, and how their recognition strategies differ from humans. Specifically, there is a major debate about the question of whether CNNs primarily rely on surface regularities of objects, or whether they are capable of exploiting the spatial arrangement of features, similar to humans. Here, we develop a novel feature-scrambling approach to explicitly test whether CNNs use the spatial arrangement of features (i.e. object parts) to classify objects. We combine this approach with a systematic manipulation of effective receptive field sizes of CNNs as well as minimal recognizable configurations (MIRCs) analysis. In contrast to much previous literature, we provide evidence that CNNs are in fact capable of using relatively long-range spatial relationships for object classification. Moreover, the extent to which CNNs use spatial relationships depends heavily on the dataset, e.g. texture vs. sketch. In fact, CNNs even use different strategies for different classes within heterogeneous datasets (ImageNet), suggesting CNNs have a continuous spectrum of classification strategies. Finally, we show that CNNs learn the spatial arrangement of features only up to an intermediate level of granularity, which suggests that intermediate rather than global shape features provide the optimal trade-off between sensitivity and specificity in object classification. These results provide novel insights into the nature of CNN representations and the extent to which they rely on the spatial arrangement of features for object classification.
In this paper, we present a family of regular black hole solutions in the presence of charge and angular momentum. We also discuss the related thermodynamics and we comment about the black hole life cycle during the balding and spin down phases. Interestingly the static solution resembles the Ayón-Beato–García spacetime, provided the T-duality scale is redefined in terms of the electric charge, l0→Q. The key factor at the basis of our derivation is the employment of Padmanabhan's propagator to calculate static potentials. Such a propagator encodes string T-duality effects. This means that the regularity of the spacetimes here presented can open a new window on string theory phenomenology.
In gastric cancer (GC), there are four molecular subclasses that indicate whether patients respond to chemotherapy or immunotherapy, according to the TCGA. In clinical practice, however, not every patient undergoes molecular testing. Many laboratories have used well-implemented in situ techniques (IHC and EBER-ISH) to determine the subclasses in their cohorts. Although multiple stains are used, we show that a staining approach is unable to correctly discriminate all subclasses. As an alternative, we trained an ensemble convolutional neuronal network using bagging that can predict the molecular subclass directly from hematoxylin–eosin histology. We also identified patients with predicted intra-tumoral heterogeneity or with features from multiple subclasses, which challenges the postulated TCGA-based decision tree for GC subtyping. In the future, deep learning may enable targeted testing for molecular subtypes and targeted therapy for a broader group of GC patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) can show variable histological growth patterns and present remarkable overlap with T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Previous studies suggest that NLPHL histological variants represent progression forms of NLPHL and THRLBCL transformation in aggressive disease. Since molecular studies of both lymphomas are limited due to the low number of tumor cells, the present study aimed to learn if a better understanding of these lymphomas is possible via detailed measurements of nuclear and cell size features in 2D and 3D sections. Whereas no significant differences were visible in 2D analyses, a slightly increased nuclear volume and a significantly enlarged cell size were noted in 3D measurements of the tumor cells of THRLBCL in comparison to typical NLPHL cases. Interestingly, not only was the size of the tumor cells increased in THRLBCL but also the nuclear volume of concomitant T cells in the reactive infiltrate when compared with typical NLPHL. Particularly CD8+ T cells had frequent contacts to tumor cells of THRLBCL. However, the nuclear volume of B cells was comparable in all cases. These results clearly demonstrate that 3D tissue analyses are superior to conventional 2D analyses of histological sections. Furthermore, the results point to a strong activation of T cells in THRLBCL, representing a cytotoxic response against the tumor cells with unclear effectiveness, resulting in enhanced swelling of the tumor cell bodies and limiting proliferative potential. Further molecular studies combining 3D tissue analyses and molecular data will help to gain profound insight into these ill-defined cellular processes.
The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval. In agreement with experimental data, simulations in a reconstructed CA3 pyramidal neuron with physiological patterns of correlated activity revealed that coincident glutamatergic synaptic inputs contribute significantly to the activity-dependent [Cl-]i changes. Whereas the influence of spatial correlation between distributed glutamatergic and GABAergic inputs was negligible, their temporal correlation played a significant role. In summary, our results demonstrate that glutamatergic co-stimulation had a substantial impact on ionic plasticity of GABAergic responses, enhancing the attenuation of GABAergic inhibition in the mature nervous systems, but suppressing GABAergic [Cl-]i changes in the immature brain. Therefore, glutamatergic shift in GABAergic Cl--fluxes should be considered as a relevant factor of short-term plasticity.
Natural scene responses in the primary visual cortex are modulated simultaneously by attention and by contextual signals about scene statistics stored across the connectivity of the visual processing hierarchy. Here, we hypothesized that attentional and contextual top-down signals interact in V1, in a manner that primarily benefits the representation of natural visual stimuli, rich in high-order statistical structure. Recording from two macaques engaged in a spatial attention task, we found that attention enhanced the decodability of stimulus identity from population responses evoked by natural scenes but, critically, not by synthetic stimuli in which higher-order statistical regularities were eliminated. Population analysis revealed that neuronal responses converged to a low dimensional subspace for natural but not for synthetic images. Critically, we determined that the attentional enhancement in stimulus decodability was captured by the dominant low dimensional subspace, suggesting an alignment between the attentional and natural stimulus variance. The alignment was pronounced for late evoked responses but not for early transient responses of V1 neurons, supporting the notion that top-down feedback was required. We argue that attention and perception share top-down pathways, which mediate hierarchical interactions optimized for natural vision.
Sharp wave-ripples (SPW-Rs) are a hippocampal network phenomenon critical for memory consolidation and planning. SPW-Rs have been extensively studied in the adult brain, yet their developmental trajectory is poorly understood. While SPWs have been recorded in rodents shortly after birth, the time point and mechanisms of ripple emergence are still unclear. Here, we combine in vivo electrophysiology with optogenetics and chemogenetics in 4 to 12 days-old mice to address this knowledge gap. We show that ripples are robustly detected and induced by light stimulation of ChR2-transfected CA1 pyramidal neurons only from postnatal day (P) 10 onwards. Leveraging a spiking neural network model, we mechanistically link the maturation of inhibition and ripple emergence. We corroborate these findings by reducing ripple rate upon chemogenetic silencing of CA1 interneurons. Finally, we show that early SPW-Rs elicit a more robust prefrontal cortex response then SPWs lacking ripples. Thus, development of inhibition promotes ripples emergence.
We present a model for the autonomous learning of active binocular vision using a recently developed biome-chanical model of the human oculomotor system. The model is formulated in the Active Efficient Coding (AEC) framework, a recent generalization of classic efficient coding theories to active perception. The model simultaneously learns how to efficiently encode binocular images and how to generate accurate vergence eye movements that facilitate efficient encoding of the visual input. In order to resolve the redundancy problem arising from the actuation of the eyes through antagonistic muscle pairs, we consider the metabolic costs associated with eye movements. We show that the model successfully learns to trade off vergence accuracy against the associated metabolic costs, producing high fidelity vergence eye movements obeying Sherrington’s law of reciprocal innervation.
Motivation: Partial differential equations (PDEs) is a well-established and powerful tool to simulate multi-cellular biological systems. However, available free tools for validation against data are not established. The PDEparams module provides flexible functionality in Python for parameter estimation in PDE models.
Results: The PDEparams module provides a flexible interface and readily accommodates different parameter analysis tools in PDE models such as computation of likelihood profiles, and parametric boot-strapping, along with direct visualisation of the results. To our knowledge, it is the first open, freely available tool for parameter fitting of PDE models.
Availability and implementation: The PDEparams module is distributed under the MIT license. The source code, usage instructions and step-by-step examples are freely available on GitHub at github.com/systemsmedicine/PDE_params.
When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here we show in awake macaque area V1 that both, repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects showed some persistence on the timescale of minutes. Further, gamma increases were specific to the presented stimulus location. Importantly, repetition effects on gamma and on firing rates generalized to natural images. These findings suggest that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters, both for generating efficient stimulus responses and possibly for memory formation.
When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here, we show in awake macaque area V1 that both repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects show some persistence on the timescale of minutes. Gamma increases are specific to the presented stimulus location. Further, repetition effects on gamma and on firing rates generalize to images of natural objects. These findings support the notion that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters.
We estimate the temperature dependence of the bulk viscosity in a relativistic hadron gas. Employing the Green–Kubo formalism in the SMASH (Simulating Many Accelerated Strongly-interacting Hadrons) transport approach, we study different hadronic systems in increasing order of complexity. We analyze the (in)validity of the single exponential relaxation ansatz for the bulk-channel correlation function and the strong influence of the resonances and their lifetimes. We discuss the difference between the inclusive bulk viscosity of an equilibrated, long-lived system, and the effective bulk viscosity of a short-lived mixture like the hadronic phase of relativistic heavy-ion collisions, where the processes whose inverse relaxation rate are larger than the fireball duration are excluded from the analysis. This clarifies the differences between previous approaches which computed the bulk viscosity including/excluding the very slow processes in the hadron gas. We compare our final results with previous hadron gas calculations and confirm a decreasing trend of the inclusive bulk viscosity over entropy density as temperature increases, whereas the effective bulk viscosity to entropy ratio, while being lower than the inclusive one, shows no strong dependence to temperature.
Individual differences in perception are widespread. Considering inter-individual variability, synesthetes experience stable additional sensations; schizophrenia patients suffer perceptual deficits in e.g. perceptual organization (alongside hallucinations and delusions). Is there a unifying principle explaining inter-individual variability in perception? There is good reason to believe perceptual experience results from inferential processes whereby sensory evidence is weighted by prior knowledge about the world. Different perceptual phenotypes may result from different precision weighting of sensory evidence and prior knowledge. We tested this hypothesis by comparing visibility thresholds in a perceptual hysteresis task across medicated schizophrenia patients, synesthetes, and controls. Participants rated the subjective visibility of stimuli embedded in noise while we parametrically manipulated the availability of sensory evidence. Additionally, precise long-term priors in synesthetes were leveraged by presenting either synesthesia-inducing or neutral stimuli. Schizophrenia patients showed increased visibility thresholds, consistent with overreliance on sensory evidence. In contrast, synesthetes exhibited lowered thresholds exclusively for synesthesia-inducing stimuli suggesting high-precision long-term priors. Additionally, in both synesthetes and schizophrenia patients explicit, short-term priors – introduced during the hysteresis experiment – lowered thresholds but did not normalize perception. Our results imply that distinct perceptual phenotypes might result from differences in the precision afforded to prior beliefs and sensory evidence, respectively.
Cyclophilins, or immunophilins, are proteins found in many organisms including bacteria, plants and humans. Most of them display peptidyl-prolyl cis-trans isomerase activity, and play roles as chaperones or in signal transduction. Here, we show that cyclophilin anaCyp40 from the cyanobacterium Anabaena sp. PCC 7120 is enzymatically active, and seems to be involved in general stress responses and in assembly of photosynthetic complexes. The protein is associated with the thylakoid membrane and interacts with phycobilisome and photosystem components. Knockdown of anacyp40 leads to growth defects under high-salt and high-light conditions, and reduced energy transfer from phycobilisomes to photosystems. Elucidation of the anaCyp40 crystal structure at 1.2-Å resolution reveals an N-terminal helical domain with similarity to PsbQ components of plant photosystem II, and a C-terminal cyclophilin domain with a substrate-binding site. The anaCyp40 structure is distinct from that of other multi-domain cyclophilins (such as Arabidopsis thaliana Cyp38), and presents features that are absent in single-domain cyclophilins.
Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signaling pathways. Achieving a detailed understanding of intracellular GSH trafficking and regulation depends on the development of tools to map GSH compartmentalization and intra-organelle fluctuations. Herein, we present a new GSH sensing platform, TRaQ-G, for live-cell imaging. This small-molecule/protein hybrid sensor possesses a unique reactivity turn-on mechanism that ensures that the small molecule is only sensitive to GSH in the desired location. Furthermore, TRaQ-G can be fused to a fluorescent protein of choice to give a ratiometric response. Using TRaQ-G-mGold, we demonstrated that the nuclear and cytosolic GSH pools are independently regulated during cell proliferation. We also used this sensor, in combination with roGFP, to quantify redox potential and GSH concentration simultaneously in the endoplasmic reticulum. Finally, by exchanging the fluorescent protein, we created a near-infrared, targetable and quantitative GSH sensor.
The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe, with about 571,700 confirmed cases and about 26,500 deaths as of March 28th, 2020. We present here the preliminary results of a mathematical study directed at informing on the possible application or lifting of control measures in Germany. The developed mathematical models allow to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions.
The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe with about 2.2 million confirmed cases and more than 150,000 deaths as of April 17, 2020 [37]. In view of most recent information on testing activity [32], we present here an update of our initial work [4]. In this work, mathematical models have been developed to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions. Systems of differential equations of SEIR type are extended here to account for undetected infections, as well as for stages of infections and age groups. The models are calibrated on data until April 5, data from April 6 to 14 are used for model validation. We simulate different possible strategies for the mitigation of the current outbreak, slowing down the spread of the virus and thus reducing the peak in daily diagnosed cases, the demand for hospitalization or intensive care units admissions, and eventually the number of fatalities. Our results suggest that a partial (and gradual) lifting of introduced control measures could soon be possible if accompanied by further increased testing activity, strict isolation of detected cases and reduced contact to risk groups.
To understand the neural mechanisms underlying brain function, neuroscientists aim to quantify causal interactions between neurons, for instance by perturbing the activity of neuron A and measuring the effect on neuron B. Recently, manipulating neuron activity using light-sensitive opsins, optogenetics, has increased the specificity of neural perturbation. However, using widefield optogenetic interventions, multiple neurons are usually perturbed, producing a confound -- any of the stimulated neurons can have affected the postsynaptic neuron making it challenging to discern which neurons produced the causal effect. Here, we show how such confounds produce large biases in interpretations. We explain how confounding can be reduced by combining instrumental variables (IV) and difference in differences (DiD) techniques from econometrics. Combined, these methods can estimate (causal) effective connectivity by exploiting the weak, approximately random signal resulting from the interaction between stimulation and the absolute refractory period of the neuron. In simulated neural networks, we find that estimates using ideas from IV and DiD outperform naive techniques suggesting that methods from causal inference can be useful to disentangle neural interactions in the brain.
A key competence for open-ended learning is the formation of increasingly abstract representations useful for driving complex behavior. Abstract representations ignore specific details and facilitate generalization. Here we consider the learning of abstract representations in a multi-modal setting with two or more input modalities. We treat the problem as a lossy compression problem and show that generic lossy compression of multimodal sensory input naturally extracts abstract representations that tend to strip away modalitiy specific details and preferentially retain information that is shared across the different modalities. Furthermore, we propose an architecture to learn abstract representations by identifying and retaining only the information that is shared across multiple modalities while discarding any modality specific information.
Recent advances in artificial neural networks enabled the quick development of new learning algorithms, which, among other things, pave the way to novel robotic applications. Traditionally, robots are programmed by human experts so as to accomplish pre-defined tasks. Such robots must operate in a controlled environment to guarantee repeatability, are designed to solve one unique task and require costly hours of development. In developmental robotics, researchers try to artificially imitate the way living beings acquire their behavior by learning. Learning algorithms are key to conceive versatile and robust robots that can adapt to their environment and solve multiple tasks efficiently. In particular, Reinforcement Learning (RL) studies the acquisition of skills through teaching via rewards. In this thesis, we will introduce RL and present recent advances in RL applied to robotics. We will review Intrinsically Motivated (IM) learning, a special form of RL, and we will apply in particular the Active Efficient Coding (AEC) principle to the learning of active vision. We also propose an overview of Hierarchical Reinforcement Learning (HRL), an other special form of RL, and apply its principle to a robotic manipulation task.
Human functional brain connectivity can be temporally decomposed into states of high and low cofluctuation, defined as coactivation of brain regions over time. Rare states of particularly high cofluctuation have been shown to reflect fundamentals of intrinsic functional network architecture and to be highly subject-specific. However, it is unclear whether such network-defining states also contribute to individual variations in cognitive abilities – which strongly rely on the interactions among distributed brain regions. By introducing CMEP, a new eigenvector-based prediction framework, we show that as few as 16 temporally separated time frames (< 1.5% of 10min resting-state fMRI) can significantly predict individual differences in intelligence (N = 263, p < .001). Against previous expectations, individual’s network-defining time frames of particularly high cofluctuation do not predict intelligence. Multiple functional brain networks contribute to the prediction, and all results replicate in an independent sample (N = 831). Our results suggest that although fundamentals of person-specific functional connectomes can be derived from few time frames of highest connectivity, temporally distributed information is necessary to extract information about cognitive abilities. This information is not restricted to specific connectivity states, like network-defining high-cofluctuation states, but rather reflected across the entire length of the brain connectivity time series.
Very-long-baseline interferometry (VLBI) observations of active galactic nuclei at millimetre wavelengths have the power to reveal the launching and initial collimation region of extragalactic radio jets, down to 10–100 gravitational radii (rg ≡ GM/c2) scales in nearby sources. Centaurus A is the closest radio-loud source to Earth. It bridges the gap in mass and accretion rate between the supermassive black holes (SMBHs) in Messier 87 and our Galactic Centre. A large southern declination of −43° has, however, prevented VLBI imaging of Centaurus A below a wavelength of 1 cm thus far. Here we show the millimetre VLBI image of the source, which we obtained with the Event Horizon Telescope at 228 GHz. Compared with previous observations, we image the jet of Centaurus A at a tenfold higher frequency and sixteen times sharper resolution and thereby probe sub-lightday structures. We reveal a highly collimated, asymmetrically edge-brightened jet as well as the fainter counterjet. We find that the source structure of Centaurus A resembles the jet in Messier 87 on ~500 rg scales remarkably well. Furthermore, we identify the location of Centaurus A’s SMBH with respect to its resolved jet core at a wavelength of 1.3 mm and conclude that the source’s event horizon shadow should be visible at terahertz frequencies. This location further supports the universal scale invariance of black holes over a wide range of masses.
The cortical networks that underlie behavior exhibit an orderly functional organization at local and global scales, which is readily evident in the visual cortex of carnivores and primates1-6. Here, neighboring columns of neurons represent the full range of stimulus orientations and contribute to distributed networks spanning several millimeters2,7-11. However, the principles governing functional interactions that bridge this fine-scale functional architecture and distant network elements are unclear, and the emergence of these network interactions during development remains unexplored. Here, by using in vivo wide-field and 2-photon calcium imaging of spontaneous activity patterns in mature ferret visual cortex, we find widespread and specific modular correlation patterns that accurately predict the local structure of visually-evoked orientation columns from the spontaneous activity of neurons that lie several millimeters away. The large-scale networks revealed by correlated spontaneous activity show abrupt ‘fractures’ in continuity that are in tight register with evoked orientation pinwheels. Chronic in vivo imaging demonstrates that these large-scale modular correlation patterns and fractures are already present at early stages of cortical development and predictive of the mature network structure. Silencing feed-forward drive through either retinal or thalamic blockade does not affect network structure suggesting a cortical origin for this large-scale correlated activity, despite the immaturity of long-range horizontal network connections in the early cortex. Using a circuit model containing only local connections, we demonstrate that such a circuit is sufficient to generate large-scale correlated activity, while also producing correlated networks showing strong fractures, a reduced dimensionality, and an elongated local correlation structure, all in close agreement with our empirical data. These results demonstrate the precise local and global organization of cortical networks revealed through correlated spontaneous activity and suggest that local connections in early cortical circuits may generate structured long-range network correlations that underlie the subsequent formation of visually-evoked distributed functional networks.
The fundamental structure of cortical networks arises early in development prior to the onset of sensory experience. However, how endogenously generated networks respond to the onset of sensory experience, and how they form mature sensory representations with experience remains unclear. Here we examine this ‘nature-nurture transform’ using in vivo calcium imaging in ferret visual cortex. At eye-opening, visual stimulation evokes robust patterns of cortical activity that are highly variable within and across trials, severely limiting stimulus discriminability. Initial evoked responses are distinct from spontaneous activity of the endogenous network. Visual experience drives the development of low-dimensional, reliable representations aligned with spontaneous activity. A computational model shows that alignment of novel visual inputs and recurrent cortical networks can account for the emergence of reliable visual representations.
The fundamental structure of cortical networks arises early in development prior to the onset of sensory experience. However, how endogenously generated networks respond to the onset of sensory experience, and how they form mature sensory representations with experience remains unclear. Here we examine this "nature-nurture transform" using in vivo calcium imaging in ferret visual cortex. At eye-opening, visual stimulation evokes robust patterns of cortical activity that are highly variable within and across trials, severely limiting stimulus discriminability. Initial evoked responses are distinct from spontaneous activity of the endogenous network. Visual experience drives the development of low-dimensional, reliable representations aligned with spontaneous activity. A computational model shows that alignment of novel visual inputs and recurrent cortical networks can account for the emergence of reliable visual representations.