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Background: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness.
Methods and Results: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ~506 ms with notched T waves). Parents were I° cousins – both heterozygous for the mutation and clinically unremarkable (QTc ~447 ms, father and ~396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q.
Conclusion: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.
The knowledge of the material budget with a high precision is fundamental for measurements of direct photon production using the photon conversion method due to its direct impact on the total systematic uncertainty. Moreover, it influences many aspects of the charged-particle reconstruction performance. In this article, two procedures to determine data-driven corrections to the material-budget description in ALICE simulation software are developed. One is based on the precise knowledge of the gas composition in the Time Projection Chamber. The other is based on the robustness of the ratio between the produced number of photons and charged particles, to a large extent due to the approximate isospin symmetry in the number of produced neutral and charged pions. Both methods are applied to ALICE data allowing for a reduction of the overall material budget systematic uncertainty from 4.5% down to 2.5%. Using these methods, a locally correct material budget is also achieved. The two proposed methods are generic and can be applied to any experiment in a similar fashion.
Results on the transverse spherocity dependence of light-flavor particle production (π, K, p, ϕ, K∗0, K0S, Λ, Ξ) at midrapidity in high-multiplicity pp collisions at s√=13 TeV were obtained with the ALICE apparatus. The transverse spherocity estimator (SpT=1O) categorizes events by their azimuthal topology. Utilizing narrow selections on SpT=1O, it is possible to contrast particle production in collisions dominated by many soft initial interactions with that observed in collisions dominated by one or more hard scatterings. Results are reported for two multiplicity estimators covering different pseudorapidity regions. The SpT=1O estimator is found to effectively constrain the hardness of the events when the midrapidity (|η|<0.8) estimator is used. The production rates of strange particles are found to be slightly higher for soft isotropic topologies, and severely suppressed in hard jet-like topologies. These effects are more pronounced for hadrons with larger mass and strangeness content, and observed when the topological selection is done within a narrow multiplicity interval. This demonstrates that an important aspect of the universal scaling of strangeness enhancement with final-state multiplicity is that high-multiplicity collisions are dominated by soft, isotropic processes. On the contrary, strangeness production in events with jet-like processes is significantly reduced. The results presented in this article are compared with several QCD-inspired Monte Carlo event generators. Models that incorporate a two-component phenomenology, either through mechanisms accounting for string density, or thermal production, are able to describe the observed strangeness enhancement as a function of SpT=1O.
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at s√=13 TeV and p−Pb collisions at sNN−−−√=5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle Δφ and pseudorapidity separation Δη for pairs of primary charged particles within the pseudorapidity interval |η|<0.9 and the transverse-momentum interval 1<pT<4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6<|Δη|<1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.
Modification of charged-particle jets in event-shape engineered Pb–Pb collisions at √sNN = 5.02 TeV
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Charged-particle jet yields have been measured in semicentral Pb−Pb collisions at center-of-mass energy per nucleon-nucleon collision sNN−−−√=5 TeV with the ALICE detector at the LHC. These yields are reported as a function of the jet transverse momentum, and further classified by their angle with respect to the event plane and the event shape, characterized by ellipticity, in an effort to study the path-length dependence of jet quenching. Jets were reconstructed at midrapidity from charged-particle tracks using the anti-kT algorithm with resolution parameters R= 0.2 and 0.4, with event-plane angle and event-shape values determined using information from forward scintillating detectors. The results presented in this letter show that, in semicentral Pb−Pb collisions, there is no significant difference between jet yields in predominantly isotropic and elliptical events. However, out-of-plane jets are observed to be more suppressed than in-plane jets. Further, this relative suppression is greater for low transverse momentum (< 50 GeV/c) R= 0.2 jets produced in elliptical events, with out-of-plane to in-plane jet-yield ratios varying up to 5.2σ between different event-shape classes. These results agree with previous studies indicating that jets experience azimuthally anisotropic suppression when traversing the QGP medium, and can provide additional constraints on the path-length dependence of jet energy loss.
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 Lednicky−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−.
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 Lednicky−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−.
The first measurement of the cross section for incoherent photonuclear production of J/ψ vector meson as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultra-peripheral collisions of Pb nuclei at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. This rapidity interval corresponds to a Bjorken-x range (0.3−1.4)×10−3. Cross sections are reported in five |t| intervals in the range 0.04<|t|<1~GeV2 and compared to the predictions of different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t|-dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data.
The measurements of the inclusive J/ψ yield at midrapidity (|y|<0.9) and forward rapidity (2.5 <y< 4) in Pb−Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC are reported. The inclusive J/ψ production yields and nuclear modification factors, RAA, are measured as a function of the collision centrality, J/ψ transverse momentum (pT), and rapidity. The J/ψ average transverse momentum and squared transverse momentum (⟨pT⟩ and ⟨p2T⟩) are evaluated as a function of the centrality at midrapidity. Compared to the previous ALICE publications, here the entire Pb−Pb collisions dataset collected during the LHC Run 2 is used, which improves the precision of the measurements and extends the pT coverage. The pT-integrated RAA shows a hint of an increasing trend towards unity from semicentral to central collisions at midrapidity, while it is flat at forward rapidity. The pT-differential RAA shows a strong suppression at high pT with less suppression at low pT where it reaches a larger value at midrapidity compared to forward rapidity. The ratio of the pT-integrated yields of J/ψ to those of D0 mesons is reported for the first time for the central and semicentral event classes at midrapidity. Model calculations implementing charmonium production via the coalescence of charm quarks and antiquarks during the fireball evolution (transport models) or in a statistical approach with thermal weights are in good agreement with the data at low pT. At higher pT, the data are well described by transport models and a model based on energy loss in the strongly-interacting medium produced in nuclear collisions at the LHC.
The production cross section of inclusive J/ψ pairs in pp collisions at a centre-of-mass energy s√=13 TeV is measured with ALICE. The measurement is performed for J/ψ in the rapidity interval 2.5<y<4.0 and for transverse momentum pT>0. The production cross section of inclusive J/ψ pairs is reported to be 10.3±2.3(stat.)±1.3(syst.) nb in this kinematic interval. The contribution from non-prompt J/ψ (i.e. originated from beauty-hadron decays) to the inclusive sample is evaluated. The effective double-parton scattering cross section is computed, neglecting the single-parton scattering contribution.
The production cross section of inclusive J/ψ pairs in pp collisions at a centre-of-mass energy s√=13 TeV is measured with ALICE. The measurement is performed for J/ψ in the rapidity interval 2.5<y<4.0 and for transverse momentum pT>0. The production cross section of inclusive J/ψ pairs is reported to be 10.3±2.3(stat.)±1.3(syst.) nb in this kinematic interval. The contribution from non-prompt J/ψ (i.e. originated from beauty-hadron decays) to the inclusive sample is evaluated. The effective double-parton scattering cross section is computed, neglecting the single-parton scattering contribution.
Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at s√=13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (pT) of 0.2 GeV/c and up to pT=35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p−Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the pT range 0.5<pT<26 GeV/c at sNN−−−√=8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p−Pb collisions grow faster than linear with the self-normalised multiplicity. A strong pT dependence is observed in pp collisions, where the yield of high-pT electrons increases faster as a function of multiplicity than the one of low-pT electrons. The measurement in p−Pb collisions shows no pT dependence within uncertainties. The self-normalised yields in pp and p−Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations.
The correlations between different moments of two flow amplitudes, extracted with the recently developed asymmetric cumulants, are measured in Pb-Pb collisions at √sNN = 5.02 TeV recorded by the ALICE detector at the CERN Large Hadron Collider. The magnitudes of the measured observables show a dependence on the different moments as well as on the collision centrality, indicating the presence of nonlinear response in all even moments up to the eighth. Furthermore, the higher-order asymmetric cumulants show different signatures than the symmetric and lower-order asymmetric cumulants. Comparisons with state-of-the-art event generators using two different parametrizations obtained from Bayesian optimization show differences between data and simulations in many of the studied observables, indicating a need for further tuning of the models behind those event generators. These results provide new and independent constraints on the initial conditions and transport properties of the system created in heavy-ion collisions.
The pseudorapidity density of charged particles (dNch/dη) at mid-rapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sNN−−−√ = 5.02 TeV. It increases with centrality and reaches a value of 1943±54 in |η|<0.5 for the 5% most central collisions. A rise in dNch/dη as a function of sNN−−−√ for the most central collisions is observed, steeper than that observed in proton-proton collisions and following the trend established by measurements at lower energy. The centrality dependence of dNch/dη as a function of the average number of participant nucleons, ⟨Npart⟩, calculated in a Glauber model, is compared with the previous measurement at lower energy. A constant factor of about 1.2 describes the increase in 2⟨Npart⟩⟨dNch/dη⟩ from sNN−−−√ = 2.76 TeV to sNN−−−√ = 5.02 TeV for all centrality intervals, within the measured range of 0-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions.
The pseudorapidity density of charged particles (dNch/dη) at mid-rapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sNN−−−√ = 5.02 TeV. It increases with centrality and reaches a value of 1943±54 in |η|<0.5 for the 5% most central collisions. A rise in dNch/dη as a function of sNN−−−√ for the most central collisions is observed, steeper than that observed in proton-proton collisions and following the trend established by measurements at lower energy. The centrality dependence of dNch/dη as a function of the average number of participant nucleons, ⟨Npart⟩, calculated in a Glauber model, is compared with the previous measurement at lower energy. A constant factor of about 1.2 describes the increase in 2⟨Npart⟩⟨dNch/dη⟩ from sNN−−−√ = 2.76 TeV to sNN−−−√ = 5.02 TeV for all centrality intervals, within the measured range of 0-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions.
This Letter presents the first measurement of event-by-event fluctuations of the net number (difference between the particle and antiparticle multiplicities) of multistrange hadrons Ξ− and Ξ¯¯¯¯+ and its correlation with the net-kaon number using the data collected by the ALICE Collaboration in pp, p−Pb, and Pb−Pb collisions at a center-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. The statistical hadronization model with a correlation over three units of rapidity between hadrons having the same and opposite strangeness content successfully describes the results. On the other hand, string-fragmentation models that mainly correlate strange hadrons with opposite strange quark content over a small rapidity range fail to describe the data.
he first measurement of 3ΛH and 3Λ¯¯¯¯H¯¯¯¯ differential production with respect to transverse momentum and centrality in Pb−Pb collisions at sNN−−−√=5.02~TeV is presented. The 3ΛH has been reconstructed via its two-charged-body decay channel, i.e., 3ΛH→3He+π−. A Blast-Wave model fit of the pT-differential spectra of all nuclear species measured by the ALICE collaboration suggests that the 3ΛH kinetic freeze-out surface is consistent with that of other nuclei. The ratio between the integrated yields of 3ΛH and 3He is compared to predictions from the statistical hadronisation model and the coalescence model, with the latter being favoured by the presented measurements.
First measurements of hadron(h)−Λ azimuthal angular correlations in p−Pb collisions at sNN−−−√ = 5.02 TeV using the ALICE detector at the LHC are presented. These correlations are used to separate the production of associated Λ baryons into three different kinematic regions, namely those produced in the direction of the trigger particle (near-side), those produced in the opposite direction (away-side), and those whose production is uncorrelated with the jet-axis (underlying event). The per-trigger associated Λ yields in these regions are extracted, along with the near- and away-side azimuthal peak widths, and the results are studied as a function of associated particle pT and event multiplicity. Comparisons with the DPMJET event generator and previous measurements of the ϕ(1020) meson are also made. The final results indicate that strangeness production in the highest multiplicity p−Pb collisions is enhanced relative to low multiplicity collisions in the jet-like regions, as well as the underlying event. The production of Λ relative to charged hadrons is also enhanced in the underlying event when compared to the jet-like regions. Additionally, the results hint that strange quark production in the away-side of the jet is modified by soft interactions with the underlying event.
Measurements of (anti)deuteron and (anti)3He production in the rapidity range |y|< 0.5 as a function of the transverse momentum and event multiplicity in Xe−Xe collisions at a center-of-mass energy per nucleon−nucleon pair of sNN−−−√ = 5.44 TeV are presented. The coalescence parameters B2 and B3 are measured as a function of the transverse momentum per nucleon. The ratios between (anti)deuteron and (anti)3He yields and those of (anti)protons and pions are reported as a function of the mean charged-particle multiplicity density, and compared with two implementations of the statistical hadronization model (SHM) and with coalescence predictions. The elliptic flow of (anti)deuterons is measured for the first time in Xe−Xe collisions and shows features similar to those already observed in Pb−Pb collisions, i.e., the mass ordering at low transverse momentum and the meson−baryon grouping at intermediate transverse momentum. The production of nuclei is particularly sensitive to the chemical freeze-out temperature of the system created in the collision, which is extracted from a grand-canonical-ensemble-based thermal fit, performed for the first time including light nuclei along with light-flavor hadrons in Xe−Xe collisions. The extracted chemical freeze-out temperature Tchem = (154.2 ± 1.1) MeV in Xe−Xe collisions is similar to that observed in Pb−Pb collisions and close to the crossover temperature predicted by lattice QCD calculations.