560 research outputs found

    Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

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    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

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

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    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

    Pseudorapidity dependence of anisotropic flow and its decorrelations using long-range multiparticle correlations in Pb-Pb and Xe-Xe collisions

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    The pseudorapidity dependence of elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of charged particles measured in Pb–Pb collisions at a centre-of-mass energy per nucleon pair of sNN=5.02TeV and in Xe–Xe collisions at sNN=5.44TeV with ALICE at the LHC are presented. The measurements are performed in the pseudorapidity range −3.5<η<5 for various centrality intervals using two- and multi-particle cumulants with the subevent method. The flow probability density function (p.d.f.) is studied with the ratio of flow coefficient v2 calculated with four- and two-particle cumulant, and suggests that the variance of flow p.d.f. is independent of pseudorapidity. The decorrelation of the flow vector in the longitudinal direction is probed using two-particle correlations. The results measured with respect to different reference regions in pseudorapidity exhibit differences, argued to be a result of saturating decorrelation effect above a certain pseudorapidity separation, in contrast to previous publications which assign this observation to non-flow effects. The results are compared to 3+1 dimensional hydrodynamic and the AMPT transport model calculations. Neither of the models is able to simultaneously describe the pseudorapidity dependence of measurements of anisotropic flow and its fluctuations. The results presented in this work highlight shortcomings in our current understanding of initial conditions and subsequent system expansion in the longitudinal direction. Therefore, they provide input for its improvement

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

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    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

    Measurements of inclusive J/ψ production at midrapidity and forward rapidity in Pb-Pb collisions at √sNN=5.02 TeV

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    The measurements of the inclusive J/ψ yield at midrapidity (|y|<0.9) and forward rapidity (2.5 < 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 〈pT2〉) 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

    Multiplicity and event-scale dependent flow and jet fragmentation in pp collisions at √s=13 TeV and in p-Pb collisions at √sNN=5.02 TeV

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    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 ∆φ and pseudorapidity separation ∆η 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 < |∆η| < 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

    Search for jet quenching effects in high-multiplicity pp collisions at √s=13 TeV via di-jet acoplanarity

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    The ALICE Collaboration reports a search for jet quenching effects in high-multiplicity (HM) proton-proton collisions at s = 13 TeV, using the semi-inclusive azimuthal-difference distribution ∆φ of charged-particle jets recoiling from a high transverse momentum (high-pT,trig) trigger hadron. Jet quenching may broaden the ∆φ distribution measured in HM events compared to that in minimum bias (MB) events. The measurement employs a pT,trig-differential observable for data-driven suppression of the contribution of multiple partonic interactions, which is the dominant background. While azimuthal broadening is indeed observed in HM compared to MB events, similar broadening for HM events is observed for simulations based on the PYTHIA 8 Monte Carlo generator, which does not incorporate jet quenching. Detailed analysis of these data and simulations show that the azimuthal broadening is due to bias of the HM selection towards events with multiple jets in the final state. The identification of this bias has implications for all jet quenching searches where selection is made on the event activity

    Prompt and non-prompt J/ψ production at midrapidity in Pb-Pb collisions at √sNN=5.02 TeV

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    The transverse momentum (pT) and centrality dependence of the nuclear modification factor RAA of prompt and non-prompt J/ψ, the latter originating from the weak decays of beauty hadrons, have been measured by the ALICE collaboration in Pb–Pb collisions at sNN = 5.02 TeV. The measurements are carried out through the e+e− decay channel at midrapidity (|y| < 0.9) in the transverse momentum region 1.5 < pT < 10 GeV/c. Both prompt and non-prompt J/ψ measurements indicate a significant suppression for pT > 5 GeV/c, which becomes stronger with increasing collision centrality. The results are consistent with similar LHC measurements in the overlapping pT intervals, and cover the kinematic region down to pT = 1.5 GeV/c at midrapidity, not accessible by other LHC experiments. The suppression of prompt J/ψ in central and semicentral collisions exhibits a decreasing trend towards lower transverse momentum, described within uncertainties by models implementing J/ψ production from recombination of c and c ̄ quarks produced independently in different partonic scatterings. At high transverse momentum, transport models including quarkonium dissociation are able to describe the suppression for prompt J/ψ. For non-prompt J/ψ, the suppression predicted by models including both collisional and radiative processes for the computation of the beauty-quark energy loss inside the quark-gluon plasma is consistent with measurements within uncertainties

    Photoproduction of K+ K- Pairs in Ultraperipheral Collisions

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    K+K- pairs may be produced in photonuclear collisions, either from the decays of photoproduced φ(1020) mesons or directly as nonresonant K+K- pairs. Measurements of K+K- photoproduction probe the couplings between the φ(1020) and charged kaons with photons and nuclear targets. The kaon-proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K+K- pairs on lead ions in ultraperipheral collisions using the ALICE detector, including the first investigation of direct K+K- production. There is significant K+K- production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1<1.4 GeV/c2 above the φ(1020) resonance, for rapidity |yKK|<0.8 and pT,KK<0.1 GeV/c, the measured coherent photoproduction cross section is dσ/dy=3.37±0.61(stat)±0.15(syst) mb. The center-of-mass energy per nucleon of the photon-nucleus (Pb) system WγPb,n ranges from 33 to 188 GeV, far higher than previous measurements on heavy-nucleus targets. The cross section is larger than expected for φ(1020) photoproduction alone. The mass spectrum is fit to a cocktail consisting of φ(1020) decays, direct K+K- photoproduction, and interference between the two. The confidence regions for the amplitude and relative phase angle for direct K+K- photoproduction are presented
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