Numerical methods for the detection of phase defect structures in excitable media

Electrical waves that rotate in the heart organize dangerous cardiac arrhythmias. Finding the region around which such rotation occurs is one of the most important practical questions for arrhythmia management. For many years, the main method for finding such regions was so-called phase mapping, in which a continuous phase was assigned to points in the heart based on their excitation status and defining the rotation region as a point of phase singularity. Recent analysis, however, showed that in many rotation regimes there exist phase discontinuities and the region of rotation must be defined not as a point of phase singularity, but as a phase defect line. In this paper, we use this novel methodology and perform a comparative study of three different phase definitions applied to in silico data and to experimental data obtained from optical voltage mapping experiments on monolayers of human atrial myocytes. We introduce new phase defect detection algorithms and compare them with those that appeared in literature already. We find that the phase definition is more important than the algorithm to identify sudden spatial phase variations. Sharp phase defect lines can be obtained from a phase derived from local activation times observed during one cycle of arrhythmia. Alternatively, similar quality can be obtained from a reparameterization of the classical phase obtained from observation of a single timeframe of transmembrane potential. We found that the phase defect line length was (35.9 ± 6.2)mm in the Fenton-Karma model and (4.01 ± 0.55)mm in cardiac human atrial myocyte monolayers. As local activation times are obtained during standard clinical cardiac mapping, the methods are also suitable to be applied to clinical datasets. All studied methods are publicly available and can be downloaded from an institutional web-server. © 2022 Kabus et al. access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Fonds Wetenschappelijk Onderzoek, FWO: 1177022N, G025820N; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-926; KU Leuven: GPUL/20/012DK is supported by KU Leuven grant GPUL/20/012. LA was funded by a KU Leuven FLOF grant and a FWO-Flanders fellowship, grant 1177022N; LL was funded by KU Leuven and FWO-Flanders, grant G025820N. Research at Sechenov University was financed by The Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers "Digital biodesign and personalized healthcare" 075-15-2020-926. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Sven O. Dekker, Niels Harlaar, Daniël A. Pijnappels and Antoine A.F. de Vries for providing optical voltage mapping data of cardiomyogenically differentiated hiAM monolayers. Moreover, we thank Tim De Coster for helpful comments on the analogy between a PDL and the spiral wave tip trajectory

Scroll Waves and Filaments in Excitable Media of Higher Spatial Dimension

Excitable media are ubiquitous in nature, and in such systems the local excitation tends to self-organize in traveling waves, or in rotating spiral-shaped patterns in two or three spatial dimensions. Examples include waves during a pandemic or electrical scroll waves in the heart. Here we show that such phenomena can be extended to a space of four or more dimensions and propose that connections of excitable elements in a network setting can be regarded as additional spatial dimensions. Numerical simulations are performed in four dimensions using the FitzHugh-Nagumo model, showing that the vortices rotate around a two-dimensional surface which we define as the superfilament. Evolution equations are derived for general superfilaments of codimension two in an N-dimensional space, and their equilibrium configurations are proven to be minimal surfaces. We suggest that biological excitable systems, such as the heart or brain which have nonlocal connections can be regarded, at least partially, as multidimensional excitable media and discuss further possible studies in this direction. © 2023 American Physical Society

Secure referee selection for fair and responsive peer-to-peer gaming

Peer-to-Peer (P2P) architectures for Massively Multiplayer Online Games (MMOG) provide better scalability than Client/Server (C/S); however, they increase the possibility of cheating. Recently proposed P2P protocols use trusted referees that simulate/validate the game to provide security equivalent to C/S. When selecting referees from untrusted peers, selecting non-colluding referees becomes critical. Further, referees should be selected such that the range and length of delays to players is minimised (maximising game fairness and responsiveness). In this paper we formally define the referee selection problem and propose two secure referee selection algorithms, SRS-1 and SRS-2, to solve it. Both algorithms ensure the probability of corrupt referees controlling a zone/region is below a predefined limit, while attempting to maximise responsiveness and fairness. The trade-off between responsiveness and fairness is adjustable for both algorithms. Simulations of three different scenarios show the effectiveness of our algorithms

Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of glucose and ethanol

The in vivo flux through the oxidative branch of the pentose phosphate pathway (oxPPP) in Penicillium chrysogenum was determined during growth in glucose/ethanol carbon-limited chemostat cultures, at the same growth rate. Non-stationary 13C flux analysis was used to measure the oxPPP flux. A nearly constant oxPPP flux was found for all glucose/ethanol ratios studied. This indicates that the cytosolic NADPH supply is independent of the amount of assimilated ethanol. The cofactor assignment in the model of van Gulik et al. (Biotechnol Bioeng 68(6):602–618, 2000) was supported using the published genome annotation of P. chrysogenum. Metabolic flux analysis showed that NADPH requirements in the cytosol remain nearly the same in these experiments due to constant biomass growth. Based on the cytosolic NADPH balance, it is known that the cytosolic aldehyde dehydrogenase in P. chrysogenum is NAD +  dependent. Metabolic modeling shows that changing the NAD + -aldehyde dehydrogenase to NADP + -aldehyde dehydrogenase can increase the penicillin yield on substrate

Skewness and kurtosis of mean transverse momentum fluctuations at the LHC energies

The first measurements of skewness and kurtosis of mean transverse momentum (〈pT〉) fluctuations are reported in Pb–Pb collisions at sNN = 5.02 TeV, Xe–Xe collisions at sNN = 5.44 TeV and pp collisions at s=5.02 TeV using the ALICE detector. The measurements are carried out as a function of system size 〈dNch/dη〉|η|<0.51/3, using charged particles with transverse momentum (pT) and pseudorapidity (η), in the range 0.2<3.0 GeV/c and |η|<0.8, respectively. In Pb–Pb and Xe–Xe collisions, positive skewness is observed in the fluctuations of 〈pT〉 for all centralities, which is significantly larger than what would be expected in the scenario of independent particle emission. This positive skewness is considered a crucial consequence of the hydrodynamic evolution of the hot and dense nuclear matter created in heavy-ion collisions. Furthermore, similar observations of positive skewness for minimum bias pp collisions are also reported here. Kurtosis of 〈pT〉 fluctuations is found to be in good agreement with the kurtosis of Gaussian distribution, for most central Pb–Pb collisions. Hydrodynamic model calculations with MUSIC using Monte Carlo Glauber initial conditions are able to explain the measurements of both skewness and kurtosis qualitatively from semicentral to central collisions in Pb–Pb system. Color reconnection mechanism in PYTHIA8 model seems to play a pivotal role in capturing the qualitative behavior of the same measurements in pp collisions

K *(892)± resonance production in Pb-Pb collisions at √sNN=5.02 TeV

The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN=5.02 TeV using the ALICE detector at the CERN Large Hadron Collider. The resonance is reconstructed via its hadronic decay channel K∗(892)±→KS0π±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. Measurements of integrated yields, mean transverse momenta, and particle yield ratios are reported and found to be consistent with previous ALICE measurements for K∗(892)0 within uncertainties. The pT-integrated yield ratio 2K∗(892)±/(K++K-) in central Pb-Pb collisions shows a significant suppression at a level of 9.3σ relative to pp collisions. Thermal model calculations result in an overprediction of the particle yield ratio. Although both hadron resonance gas in partial chemical equilibrium (HRG-PCE) and music + smash simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas music + smash simulations tend to overpredict the particle yield ratio. These observations, along with the kinetic freeze-out temperatures extracted from the yields measured for light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which decreases with increasing collision centrality percentile. The pT-differential yield ratios 2K∗(892)±/(K++K-) and 2K∗(892)±/(π++π-) are presented and compared with measurements in pp collisions at s=5.02 TeV. Both particle ratios are found to be suppressed by up to a factor of five at pT<2.0 GeV/c in central Pb-Pb collisions and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor (RAA) shows a smooth evolution with centrality and is found to be below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium

Emergence of Long-Range Angular Correlations in Low-Multiplicity Proton-Proton Collisions

This Letter presents the measurement of near-side associated per-trigger yields, denoted ridge yields, from the analysis of angular correlations of charged hadrons in proton-proton collisions at s=13 TeV. Long-range ridge yields are extracted for pairs of charged particles with a pseudorapidity difference of 1.4<|Δη|<1.8 and a transverse momentum of 1<2 GeV/c, as a function of the charged-particle multiplicity measured at midrapidity. This Letter extends the measurements of the ridge yield to the low multiplicity region, where in hadronic collisions it is typically conjectured that a strongly interacting medium is unlikely to be formed. The precision of the new low multiplicity results allows for the first direct quantitative comparison with the results obtained in e+e- collisions at s=91 GeV and s=183-209 GeV, where initial-state effects such as preequilibrium dynamics and collision geometry are not expected to play a role. In the multiplicity range

Observation of flow angle and flow magnitude fluctuations in Pb-Pb collisions at sNN=5.02TeV at the CERN Large Hadron Collider

This Letter reports on the first measurements of transverse momentum dependent flow angle n and flow magnitude vn fluctuations determined using new four-particle correlators. The measurements are performed for various centralities in Pb–Pb collisions at a center-of-mass energy per nucleon pair of √s NN = 5.02 TeV with ALICE at the CERN Large Hadron Collider. Both flow angle and flow magnitude fluctuations are observed in the presented centrality ranges and are strongest in the most central collisions and for a transverse momentum pT > 2 GeV/c. Comparison with theoretical models, including iEBE-VISHNU, MUSIC, and AMPT, show that the measurements exhibit unique sensitivities to the initial state of heavy-ion collisions

First measurement of Ωc 0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon Omega_c^0 is measured for the first time via its hadronic decay into Omega-pi+ at midrapidity (|y|<0.5) in proton–proton (pp) collisions at the centre-of-mass energy sqrt(s) = 13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c . The pT dependence of the Omega_C^0-baryon production relative to the prompt D^0-meson and to the prompt Csi_C^0-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of Omega_c^0 and prompt Lambda_c^+ baryons multiplied by the Omega- pi+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e- collisions

f0(980) production in inelastic pp collisions at s = 5.02 TeV

The measurement of the production of f0(980) in inelastic pp collisions at sqrt(s) = 5.02 TeV is presented. This is the first reported measurement of inclusive f0(980) yield at LHC energies. The production is measured at midrapidity, |y| pi+pi- hadronic decay channel using the ALICE detector. The pT-differential yields are compared to those of pions, protons and ϕ mesons as well as to predictions from the HERWIG 7.2 QCD-inspired Monte Carlo event generator and calculations from a coalescence model that uses the AMPT model as an input. The ratio of the pT-integrated yield of f0(980) relative to pions is compared to measurements in e+e- and pp collisions at lower energies and predictions from statistical hadronisation models and HERWIG 7.2. A mild collision energy dependence of the f0(980) to pion production is observed in pp collisions from SPS to LHC energies. All considered models underpredict the pT-integrated 2f0(980)/(pi+ + pi-) ratio. The prediction from the canonical statistical hadronisation model assuming a zero total strangeness content of f0(980) is consistent with the data within 1.9σ and is the closest to the data. The results provide an essential reference for future measurements of the particle yield and nuclear modification in p–Pb and Pb–Pb collisions, which have been proposed to be instrumental to probe the elusive nature and quark composition of the f0(980) scalar meson