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Inclusive J/ψ production at forward and backward rapidity in p–Pb collisions at √sNN = 8.16 TeV
(2018)
Inclusive J/ψ production is studied in p-Pb interactions at a centre-of-mass energy per nucleon-nucleon collision sNN−−−√=8.16 TeV, using the ALICE detector at the CERN LHC. The J/ψ meson is reconstructed, via its decay to a muon pair, in the centre-of-mass rapidity intervals 2.03<ycms<3.53 and −4.46<ycms<−2.96, where positive and negative ycms refer to the p-going and Pb-going direction, respectively. The transverse momentum coverage is pT<20 GeV/c. In this paper, ycms- and pT-differential cross sections for inclusive J/ψ production are presented, and the corresponding nuclear modification factors RpPb are shown. Forward results show a suppression of the J/ψ yield with respect to pp collisions, concentrated in the region pT≲5 GeV/c. At backward rapidity no significant suppression is observed. The results are compared to previous measurements by ALICE in p-Pb collisions at sNN−−−√=5.02 TeV and to theoretical calculations. Finally, the ratios RFB between forward- and backward-ycms RpPb values are shown and discussed.
The azimuthal anisotropy coefficient v2 of prompt D0, D+, D∗+ and D+s mesons was measured in mid-central (30-50% centrality class) Pb-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, with the ALICE detector at the LHC. The D mesons were reconstructed via their hadronic decays at mid-rapidity, |y|<0.8, in the transverse momentum interval 1<pT<24 GeV/c. The measured D-meson v2 has similar values as that of charged pions. The D+s v2, measured for the first time, is found to be compatible with that of non-strange D mesons. The measurements are compared with theoretical calculations of charm-quark transport in a hydrodynamically expanding medium and have the potential to constrain medium parameters.
The azimuthal anisotropy coefficient v2 of prompt D0, D+, D∗+ and D+s mesons was measured in mid-central (30-50% centrality class) Pb-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, with the ALICE detector at the LHC. The D mesons were reconstructed via their hadronic decays at mid-rapidity, |y|<0.8, in the transverse momentum interval 1<pT<24 GeV/c. The measured D-meson v2 has similar values as that of charged pions. The D+s v2, measured for the first time, is found to be compatible with that of non-strange D mesons. The measurements are compared with theoretical calculations of charm-quark transport in a hydrodynamically expanding medium and have the potential to constrain medium parameters.
Karl Dedecius, 1921–2016
(2018)
Karl Dedecius gilt als einer der produktivsten deutschen Übersetzer polnischer Literatur und als herausragende Persönlichkeit des deutsch-polnischen Dialogs in der zweiten Hälfte des 20. Jahrhunderts. Er starb am 26. Februar 2016 hochbetagt in Frankfurt am Main und hinterließ ein umfangreiches Œuvre, das ca. 200 übersetzte Bücher polnischer und russischer Literatur (darunter zahlreiche Anthologien) sowie mehrere essayistische Werke umfasst. Das Kernstück bilden die 50 Titel der von ihm initiierten und herausgegebenen "Polnischen Bibliothek" (1982–2000) sowie die sieben jeweils ca. 900 Seiten starken Bände des "Panoramas der polnischen Literatur des 20. Jahrhunderts" (1996–2000). Die Liste der von ihm übersetzten Autoren umfasst gut 300 Namen.
Invariant differential yields of deuterons and anti-deuterons in pp collisions at s√ = 0.9, 2.76 and 7 TeV and the yields of tritons, 3He nuclei and their anti-nuclei at s√ = 7 TeV have been measured with the ALICE detector at the CERN Large Hadron Collider. The measurements cover a wide transverse momentum (pT) range in the rapidity interval |y|<0.5, extending both the energy and the pT reach of previous measurements up to 3 GeV/c for A=2 and 6 GeV/c for A=3. The coalescence parameters of (anti-)deuterons and 3He¯¯¯¯¯¯ nuclei exhibit an increasing trend with pT and are found to be compatible with measurements in pA collisions at low pT and lower energies. The integrated yields decrease by a factor of about 1000 for each increase of the mass number with one (anti-)nucleon. Furthermore, the deuteron-to-proton ratio is reported as a function of the average charged particle multiplicity at different center-of-mass energies.
The pT-differential production cross section of prompt Λ+c charmed baryons was measured with the ALICE detector at the Large Hadron Collider (LHC) in pp collisions at s√=7 TeV and in p-Pb collisions at sNN−−−√=5.02 TeV at midrapidity. The Λ+c and Λ¯¯¯¯−c were reconstructed in the hadronic decay modes Λ+c→pK−π+, Λ+c→pK0S and in the semileptonic channel Λ+c→e+νeΛ (and charge conjugates). The measured values of the Λ+c/D0 ratio, which is sensitive to the c-quark hadronisation mechanism, and in particular to the production of baryons, are presented and are larger than those measured previously in different colliding systems, centre-of-mass energies, rapidity and pT intervals, where the Λ+c production process may differ. The results are compared with the expectations obtained from perturbative Quantum Chromodynamics calculations and Monte Carlo event generators. Neither perturbative QCD calculations nor Monte Carlo models reproduce the data, indicating that the fragmentation of heavy-flavour baryons is not well understood. The first measurement at the LHC of the Λ+c nuclear modification factor, RpPb, is also presented. The RpPb is found to be consistent with unity and with that of D mesons within the uncertainties, and consistent with a theoretical calculation that includes cold nuclear matter effects and a calculation that includes charm quark interactions with a deconfined medium.
The correlations between event-by-event fluctuations of anisotropic flow harmonic amplitudes have been measured in Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the LHC. The results are reported in terms of multiparticle correlation observables dubbed Symmetric Cumulants. These observables are robust against biases originating from nonflow effects. The centrality dependence of correlations between the higher order harmonics (the quadrangular v4 and pentagonal v5 flow) and the lower order harmonics (the elliptic v2 and triangular v3 flow) is presented. The transverse momentum dependence of correlations between v3 and v2 and between v4 and v2 is also reported. The results are compared to calculations from viscous hydrodynamics and A Multi-Phase Transport ({AMPT}) model calculations. The comparisons to viscous hydrodynamic models demonstrate that the different order harmonic correlations respond differently to the initial conditions and the temperature dependence of the ratio of shear viscosity to entropy density (η/s). A small average value of η/s is favored independent of the specific choice of initial conditions in the models. The calculations with the AMPT initial conditions yield results closest to the measurements. Correlations between the magnitudes of v2, v3 and v4 show moderate pT dependence in mid-central collisions. Together with existing measurements of individual flow harmonics, the presented results provide further constraints on the initial conditions and the transport properties of the system produced in heavy-ion collisions.
An invariant differential cross section measurement of inclusive π0 and η meson production at mid-rapidity in pp collisions at s√=8 TeV was carried out by the ALICE experiment at the LHC. The spectra of π0 and η mesons were measured in transverse momentum ranges of 0.3<pT<35 GeV/c and 0.5<pT<35 GeV/c, respectively. Next-to-leading order perturbative QCD calculations using fragmentation functions DSS14 for the π0 and AESSS for the η overestimate the cross sections of both neutral mesons, although such calculations agree with the measured η/π0 ratio within uncertainties. The results were also compared with PYTHIA~8.2 predictions for which the Monash~2013 tune yields the best agreement with the measured neutral meson spectra. The measurements confirm a universal behavior of the η/π0 ratio seen for NA27, PHENIX and ALICE data for pp collisions from s√=27.5 GeV to s√=8 TeV within experimental uncertainties. A relation between the π0 and η production cross sections for pp collisions at s√=8 TeV is given by mT scaling for pT>3.5 GeV/c. However, a deviation from this empirical scaling rule is observed for transverse momenta below pT<3.5 GeV/c in the η/π0 ratio with a significance of 6.2σ.
Delayed-onset muscle soreness (DOMS) is a common symptom in people participating in exercise, sport, or recreational physical activities. Several remedies have been proposed to prevent and alleviate DOMS. In 2008 and 2015, two studies have been conducted to investigate the effects of acupuncture on symptoms and muscle function in eccentric exercise-induced DOMS of the biceps brachii muscle. In 2008 a prospective, randomized, controlled, observer and subject-blinded trial was undertaken with 22 healthy subjects (22–30 years; 12 females) being randomly assigned to three treatment groups: real acupuncture (deep needling at classic acupuncture points and tender points; n = 7), sham-acupuncture (superficial needling at non-acupuncture points; n = 8), and control (n = 7). In 2015, a five-arm randomized controlled study was conducted with 60 subjects (22 females, 23.6 ± 2.8 years). Participants were randomly allocated to needle, laser, sham needle, sham laser acupuncture, and no intervention.
In both cases treatment was applied immediately, 24 and 48 hours after DOMS induction.
The outcome measures included pain perception (visual analogue scale; VAS), mechanical pain threshold (MPT), maximum isometric voluntary force (MIVF) and pressure pain threshold (PPT).
Results: In 2008, following nonparametric testing, there were no significant differences between groups in outcome measures at baseline. After 72 hours, pain perception (VAS) was significantly lower in the acupuncture group compared to the sham acupuncture and control subjects. However, the mean MPT and MIVF scores were not significantly different between groups. This lead to the conclusion, that acupuncture seemed to have no effects on MPT and muscle function, but reduced perceived pain arising from exercise-induced DOMS.
The more recent results from 2015 indicated that neither verum nor sham interventions significantly improved outcomes within 72 hours when compared with the no treatment control (P > 0.05).
Neutral pion and η meson invariant differential yields were measured in non-single diffractive p-Pb collisions at sNN−−−√=5.02 TeV with the ALICE experiment at the CERN LHC. The analysis combines results from three complementary photon measurements, utilizing the PHOS and EMCal calorimeters and the Photon Conversion Method. The invariant differential yields of π0 and η meson inclusive production are measured near mid-rapidity in a broad transverse momentum range of 0.3<pT<20 GeV/c and 0.7<pT<20 GeV/c, respectively. The measured η/π0 ratio increases with pT and saturates for pT>4 GeV/c at 0.483±0.015stat±0.015sys. A deviation from mT scaling is observed for pT<2 GeV/c. The measured η/π0 ratio is consistent with previous measurements from proton-nucleus and pp collisions over the full pT range. The measured η/π0 ratio at high pT also agrees within uncertainties with measurements from nucleus-nucleus collisions. The π0 and η yields in p-Pb relative to the scaled pp interpolated reference, RpPb, are presented for 0.3<pT<20 GeV/c and 0.7<pT<20 GeV/c, respectively. The results are compared with theoretical model calculations. The values of RpPb are consistent with unity for transverse momenta above 2 GeV/c. These results support the interpretation that the suppressed yield of neutral mesons measured in Pb-Pb collisions at LHC energies is due to parton energy loss in the hot QCD medium.
The second (v2) and third (v3) flow harmonic coefficients of J/ψ mesons are measured at forward rapidity (2.5 < y < 4.0) in Pb-Pb collisions at sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. Results are obtained with the scalar product method and reported as a function of transverse momentum, pT, for various collision centralities. A positive value of J/ψ v3 is observed with 3.7σ significance. The measurements, compared to those of prompt D0 mesons and charged particles at mid-rapidity, indicate an ordering with vn(J/ψ) <vn(D0) <vn(h±) (n = 2, 3) at low and intermediate pT up to 6 GeV/c and a convergence with v2(J/ψ) ≈v2(D0) ≈v2(h±) at high pT above 6-8 GeV/c. In semi-central collisions (5-40% and 10-50% centrality intervals) at intermediate pT between 2 and 6 GeV/c, the ratio v3/v2 of J/ψ mesons is found to be significantly lower (4.6σ) with respect to that of charged particles. In addition, the comparison to the prompt D0-meson ratio in the same pT interval suggests an ordering similar to that of the v2 and v3 coefficients. The J/ψ v2 coefficient is further studied using the Event Shape Engineering technique. The obtained results are found to be compatible with the expected variations of the eccentricity of the initial-state geometry.
The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of J/ψ vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. The e+e− and μ+μ− decay channels are used to measure the cross section as a function of the rapidity of the J/ψ in the range −2.5<y<2.7, corresponding to an energy in the γp centre-of-mass in the interval 40<Wγp<550 GeV. The measurements, which are consistent with a power law dependence of the exclusive J/ψ photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.
In this Letter, the ALICE Collaboration presents the first measurements of the charged-particle multiplicity density, dNch/dη, and total charged-particle multiplicity, Ntotch, in Xe-Xe collisions at a centre-of-mass energy per nucleon--nucleon pair of sNN−−−√ = 5.44 TeV. The measurements are performed as a function of collision centrality over a wide pseudorapidity range of −3.5<η<5. The values of dNch/dη at mid-rapidity and Ntotch for central collisions, normalised to the number of nucleons participating in the collision (Npart) as a function of sNN−−−√, follow the trends established in previous heavy-ion measurements. The same quantities are also found to increase as a function of Npart, and up to the 10% most central collisions the trends are the same as the ones observed in Pb-Pb at a similar energy. For more central collisions, the Xe-Xe scaled multiplicities exceed those in Pb-Pb for a similar Npart. The results are compared to phenomenological models and theoretical calculations based on different mechanisms for particle production in nuclear collisions. All considered models describe the data reasonably well within 20%.
We present measurements of two-particle differential number correlation functions R2 and transverse momentum correlation functions P2, obtained from p-Pb collisions at 5.02 TeV and Pb-Pb collisions at 2.76 TeV. The results are obtained using charged particles in the pseudorapidity range |η|< 1.0, and transverse momentum range 0.2<pT<2.0 GeV/c as a function of pair separation in pseudorapidity, |Δη|, azimuthal angle, Δφ, and for several charged-particle multiplicity classes. Measurements are carried out for like-sign and unlike-sign charged-particle pairs separately and combined to obtain charge-independent and charge-dependent correlation functions. We study the evolution of the width of the near-side peak of these correlation functions with collision centrality. Additionally, we study Fourier decompositions of the correlators in Δφ as a function of the pair separation |Δη|. Significant differences in the dependence of their harmonic coefficients on multiplicity classes are found. These differences can be exploited, in theoretical models, to obtain further insight into charged-particle production and transport in heavy-ion collisions. Moreover, an upper limit of non-flow contributions to flow coefficients vn measured in Pb-Pb collisions based on the relative strength of Fourier coefficients measured in p-Pb interactions is estimated.
Angular correlations between heavy-flavour decay electrons and charged particles at mid-rapidity (|η|<0.8) are measured in p-Pb collisions at sNN−−−√ = 5.02 TeV. The analysis is carried out for the 0-20% (high) and 60-100% (low) multiplicity ranges. The jet contribution in the correlation distribution from high-multiplicity events is removed by subtracting the distribution from low-multiplicity events. An azimuthal modulation remains after removing the jet contribution, similar to previous observations in two-particle angular correlation measurements for light-flavour hadrons. A Fourier decomposition of the modulation results in a positive second-order coefficient (v2) for heavy-flavour decay electrons in the transverse momentum interval 1.5<pT<4 GeV/c in high-multiplicity events, with a significance larger than 5σ. The results are compared with those of charged particles at mid-rapidity and of inclusive muons at forward rapidity. The v2 measurement of open heavy-flavour particles at mid-rapidity in small collision systems could provide crucial information to help interpret the anisotropies observed in such systems.
The measurement of dielectron production is presented as a function of invariant mass and transverse momentum (pT) at midrapidity (|ye|<0.8) in proton-proton (pp) collisions at a centre-of-mass energy of s√=13 TeV. The contributions from light-hadron decays are calculated from their measured cross sections in pp collisions at s√=7 TeV or 13 TeV. The remaining continuum stems from correlated semileptonic decays of heavy-flavour hadrons. Fitting the data with templates from two different MC event generators, PYTHIA and POWHEG, the charm and beauty cross sections at midrapidity are extracted for the first time at this collision energy: dσcc¯/dy|y=0=974±138(stat.)±140(syst.) μb and dσbb¯/dy|y=0=79±14(stat.)±11(syst.) μb using PYTHIA simulations and dσcc¯/dy|y=0=1417±184(stat.)±204(syst.) μb and dσbb¯/dy|y=0=48±14(stat.)±7(syst.) μb for POWHEG. These values, whose uncertainties are fully correlated between the two generators, are consistent with extrapolations from lower energies. The different results obtained with POWHEG and PYTHIA imply different kinematic correlations of the heavy-quark pairs in these two generators. Furthermore, comparisons of dielectron spectra in inelastic events and in events collected with a trigger on high charged-particle multiplicities are presented in various pT intervals. The differences are consistent with the already measured scaling of light-hadron and open-charm production at high charged-particle multiplicity as a function of pT. Upper limits for the contribution of virtual direct photons are extracted at 90% confidence level and found to be in agreement with pQCD calculations.
Measurements of inclusive and direct photon production at mid-rapidity in pp collisions at s√=2.76 and 8 TeV are presented by the ALICE experiment at the LHC. The results are reported in transverse momentum ranges of 0.4<pT<10 GeV/c and 0.3<pT<16 GeV/c, respectively. Photons are detected with the electromagnetic calorimeter~(EMCal) and via reconstruction of e+e− pairs from conversions in the ALICE detector material using the central tracking system. For the final measurement of the inclusive photon spectra the results are combined in the overlapping pT interval of both methods. Direct photon spectra, or their upper limits at 90% C.L. are extracted using the direct photon excess ratio Rγ, which quantifies the ratio of inclusive photons over decay photons generated with a decay-photon simulation. An additional hybrid method, combining photons reconstructed from conversions with those identified in the EMCal, is used for the combination of the direct photon excess ratio Rγ, as well as the extraction of direct photon spectra or their upper limits. While no significant signal of direct photons is seen over the full pT range, Rγ for pT>7 GeV/c is at least one σ above unity and consistent with expectations from next-to-leading order pQCD calculations.
Inclusive Υ(1S) and Υ(2S) production have been measured in Pb-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair sNN−−−√=5.02 TeV, using the ALICE detector at the CERN LHC. The Υ mesons are reconstructed in the centre-of-mass rapidity interval 2.5<y<4 and in the transverse-momentum range pT<15 GeV/c, via their decays to muon pairs. In this Letter, we present results on the inclusive Υ(1S) nuclear modification factor RAA as a function of collision centrality, transverse momentum and rapidity. The Υ(1S) and Υ(2S) RAA, integrated over the centrality range 0-90%, are 0.37±0.02(stat)±0.03(syst) and 0.10±0.04(stat)±0.02(syst), respectively, leading to a ratio RΥ(2S)AA/RΥ(1S)AA of 0.28±0.12(stat)±0.06(syst). The observed Υ(1S) suppression increases with the centrality of the collision and no significant variation is observed as a function of transverse momentum and rapidity.
The elliptic flow of inclusive and direct photons was measured at mid-rapidity in two centrality classes 0-20% and 20-40% in Pb-Pb collisions at sNN−−−√ =2.76 TeV by ALICE. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the detector material with the e+e− pairs reconstructed in the central tracking system. The results of the two methods were combined and the direct photon elliptic flow was extracted in the transverse momentum range 0.9<pT<6.2 GeV/c. We test the hypothesis vγ,dir2≡0 for 0.9<pT<2.1 GeV/c and obtain a significance of 1.4σ for the 0-20% class and 1.0σ for the 20-40% class. A comparison to RHIC data shows a similar magnitude of the measured elliptic flow, while hydrodynamic and transport model calculations predict a smaller flow than observed.
The first measurement of e+e− pair production at mid-rapidity (|ηe| < 0.8) in pp collisions at s√=7 TeV with ALICE at the LHC is presented. The dielectron production is studied as a function of the invariant mass (mee < 3.3 GeV/c2), the pair transverse momentum (pT,ee < 8 GeV/c), and the pair transverse impact parameter (DCAee), i.e., the average distance of closest approach of the reconstructed electron and positron tracks to the collision vertex, normalised to its resolution. The results are compared with the expectations from a cocktail of known hadronic sources and are well described when PYTHIA is used to generate the heavy-flavour contributions. In the low-mass region (0.14 < mee < 1.1 GeV/c2), prompt and non-prompt e+e− sources can be separated via the DCAee. In the intermediate-mass region (1.1 < mee < 2.7 GeV/c2), a double-differential fit to the data in mee and pT,ee and a fit of the DCAee distribution allow the total cc¯¯ and bb¯¯¯ cross sections to be extracted. Two different event generators, PYTHIA and POWHEG, can reproduce the shape of the two-dimensional mee and pT,ee spectra, as well as the shape of the DCAee distribution, reasonably well. However, differences in the cc¯¯ and bb¯¯¯ cross sections are observed when using the generators to extrapolate to full phase space. Finally, the ratio of inclusive to decay photons is studied via the measurement of virtual direct photons in the transverse-momentum range 1 < pT < 8 GeV/c. This is found to be unity within the statistical and systematic uncertainties and consistent with expectations from next-to-leading order perturbative quantum chromodynamic calculations.
Inclusive J/ψ production is studied in Xe-Xe interactions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.44 TeV, using the ALICE detector at the CERN LHC. The J/ψ meson is reconstructed via its decay into a muon pair, in the centre-of-mass rapidity interval 2.5<y<4 and down to zero transverse momentum. In this Letter, the nuclear modification factors RAA for inclusive J/ψ, measured in the centrality range 0-90% as well as in the centrality intervals 0-20% and 20-90% are presented. The RAA values are compared to previously published results for Pb-Pb collisions at sNN−−−√=5.02 TeV and to the calculation of a transport model. A good agreement is found between Xe-Xe and Pb-Pb results as well as between data and the model.
We report on the first femtoscopic measurement of baryon pairs, such as p-p, p-Λ and Λ-Λ, measured by ALICE at the Large Hadron Collider (LHC) in proton-proton collisions at s√ = 7 TeV. This study demonstrates the feasibility of such measurements in pp collisions at ultrarelativistic energies. The femtoscopy method is employed to constrain the hyperon-nucleon and hyperon-hyperon interactions, which are still rather poorly understood. A new method to evaluate the influence of residual correlations induced by the decays of resonances and experimental impurities is hereby presented. The p-p, p-Λ and Λ-Λ correlation functions were fitted simultaneously with the help of a new tool developed specifically for the femtoscopy analysis in small colliding systems 'Correlation Analysis Tool using the Schrödinger Equation' (CATS). Within the assumption that in pp collisions the three particle pairs originate from a common source, its radius is found to be equal to r0=1.144±0.019 (stat) +0.069−0.012 (syst) fm. The sensitivity of the measured p-Λ correlation is tested against different scattering parameters which are defined by the interaction among the two particles, but the statistics is not sufficient yet to discriminate among different models. The measurement of the Λ-Λ correlation function constrains the phase space spanned by the effective range and scattering length of the strong interaction. Discrepancies between the measured scattering parameters and the resulting correlation functions at LHC and RHIC energies are discussed in the context of various models.
We report on the first femtoscopic measurement of baryon pairs, such as p-p, p-Λ and Λ-Λ, measured by ALICE at the Large Hadron Collider (LHC) in proton-proton collisions at s√ = 7 TeV. This study demonstrates the feasibility of such measurements in pp collisions at ultrarelativistic energies. The femtoscopy method is employed to constrain the hyperon-nucleon and hyperon-hyperon interactions, which are still rather poorly understood. A new method to evaluate the influence of residual correlations induced by the decays of resonances and experimental impurities is hereby presented. The p-p, p-Λ and Λ-Λ correlation functions were fitted simultaneously with the help of a new tool developed specifically for the femtoscopy analysis in small colliding systems 'Correlation Analysis Tool using the Schrödinger Equation' (CATS). Within the assumption that in pp collisions the three particle pairs originate from a common source, its radius is found to be equal to r0=1.144±0.019 (stat) +0.069−0.012 (syst) fm. The sensitivity of the measured p-Λ correlation is tested against different scattering parameters which are defined by the interaction among the two particles, but the statistics is not sufficient yet to discriminate among different models. The measurement of the Λ-Λ correlation function constrains the phase space spanned by the effective range and scattering length of the strong interaction. Discrepancies between the measured scattering parameters and the resulting correlation functions at LHC and RHIC energies are discussed in the context of various models.
Transverse-momentum (pT) differential yields of electrons from semileptonic heavy-flavour hadron decays have been measured in the most central (0-10%) and in semi-central (20-40%) Pb-Pb collisions at sNN−−−√=2.76 TeV. The corresponding production cross section in pp collisions has been measured at the same energy with substantially reduced systematic uncertainties with respect to previously published results. The modification of the yield in Pb-Pb collisions with respect to the expectation from an incoherent superposition of nucleon-nucleon collisions is quantified at mid-rapidity (|y| < 0.8) in the pT interval 0.5-3 GeV/c via the nuclear modification factor, RAA. This paper extends the pT reach of the RAA measurement towards significantly lower values with respect to a previous publication. In Pb-Pb collisions the pT-differential measurements of yields at low pT are essential to investigate the scaling of heavy-flavour production with the number of binary nucleon-nucleon collisions. Heavy-quark hadronization, a collective expansion and even initial-state effects, such as the nuclear modification of the Parton Distribution Functions, are also expected to have a significant effect on the measured distribution.
Transverse momentum (pT) spectra of charged particles at mid-pseudorapidity in Xe-Xe collisions at sNN−−−√ = 5.44 TeV measured with the ALICE apparatus at the Large Hadron Collider are reported. The kinematic range 0.15<pT<50 GeV/c and |η|<0.8 is covered. Results are presented in nine classes of collision centrality in the 0-80% range. For comparison, a pp reference at the collision energy of s√ = 5.44 TeV is obtained by interpolating between existing \pp measurements at s√ = 5.02 and 7 TeV. The nuclear modification factors in central Xe-Xe collisions and Pb-Pb collisions at a similar center-of-mass energy of sNN−−−√ = 5.02 TeV, and in addition at 2.76 TeV, at analogous ranges of charged particle multiplicity density ⟨dNch/dη⟩ show a remarkable similarity at pT>10 GeV/c. The comparison of the measured RAA values in the two colliding systems could provide insight on the path length dependence of medium-induced parton energy loss. The centrality dependence of the ratio of the average transverse momentum ⟨pT⟩ in Xe-Xe collisions over Pb-Pb collision at s√ = 5.02 TeV is compared to hydrodynamical model calculations.
Charged-particle spectra at midrapidity are measured in Pb-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair sNN−−−√ = 5.02 TeV and presented in centrality classes ranging from most central (0-5%) to most peripheral (95-100%) collisions. Possible medium effects are quantified using the nuclear modification factor (RAA) by comparing the measured spectra with those from proton-proton collisions, scaled by the number of independent nucleon-nucleon collisions obtained from a Glauber model. At large transverse momenta (8<pT<20 GeV/c), the average RAA is found to increase from about 0.15 in 0-5% central to a maximum value of about 0.8 in 75-85% peripheral collisions, beyond which it falls off strongly to below 0.2 for the most peripheral collisions. Furthermore, RAA initially exhibits a positive slope as a function of pT in the 8-20 GeV/c interval, while for collisions beyond the 80% class the slope is negative. To reduce uncertainties related to event selection and normalization, we also provide the ratio of RAA in adjacent centrality intervals. Our results in peripheral collisions are consistent with a PYTHIA-based model without nuclear modification, demonstrating that biases caused by the event selection and collision geometry can lead to the apparent suppression in peripheral collisions. This explains the unintuitive observation that RAA is below unity in peripheral Pb-Pb, but equal to unity in minimum-bias p-Pb collisions despite similar charged-particle multiplicities.
The production of the ρ(770)0 meson has been measured at mid-rapidity (|y|<0.5) in pp and centrality differential Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The particles have been reconstructed in the ρ(770)→π+π− decay channel in the transverse momentum (pT) range 0.5−11 GeV/c. A centrality dependent suppression of the ratio of the integrated yields 2ρ(770)0/(π++π−) is observed. The ratio decreases by ∼40% from pp to central Pb-Pb collisions. A study of the pT-differential 2ρ(770)0/(π++π−) ratio reveals that the suppression occurs at low transverse momenta, pT<2 GeV/c. At higher momentum, particle ratios measured in heavy-ion and pp collisions are consistent. The observed suppression is very similar to that previously measured for the K∗(892)0/K ratio and is consistent with EPOS3 predictions that may imply that rescattering in the hadronic phase is a dominant mechanism for the observed suppression.
Neutral pion and η meson production in the transverse momentum range 1 < pT < 20 GeV/c have been measured at mid-rapidity by the ALICE experiment at the Large Hadron Collider (LHC) in central and semi-central Pb-Pb collisions at sNN−−−−√ = 2.76 TeV. These results were obtained using the photon conversion method as well as the PHOS and EMCal detectors. The results extend the upper pT reach of the previous ALICE π0 measurements from 12 GeV/c to 20 GeV/c and present the first measurement of η meson production in heavy-ion collisions at the LHC. The η/π0 ratio is similar for the two centralities and reaches at high pT a plateau value of 0.457 ± 0.013stat ± 0.018syst. A suppression of similar magnitude for π0 and η meson production is observed in Pb-Pb collisions with respect to their production in pp collisions scaled by the number of binary nucleon-nucleon collisions. We discuss the results in terms of NLO pQCD predictions and hydrodynamic models. The measurements show a stronger suppression with respect to what was observed at lower center-of-mass energies in the pT range 6 < pT < 10 GeV/c. At pT < 3 GeV/c, hadronization models describe the π0 results while for the η some tension is observed.
Neutral pion and η meson production in the transverse momentum range 1 < pT < 20 GeV/c have been measured at mid-rapidity by the ALICE experiment at the Large Hadron Collider (LHC) in central and semi-central Pb-Pb collisions at sNN−−−−√ = 2.76 TeV. These results were obtained using the photon conversion method as well as the PHOS and EMCal detectors. The results extend the upper pT reach of the previous ALICE π0 measurements from 12 GeV/c to 20 GeV/c and present the first measurement of η meson production in heavy-ion collisions at the LHC. The η/π0 ratio is similar for the two centralities and reaches at high pT a plateau value of 0.457 ± 0.013stat ± 0.018syst. A suppression of similar magnitude for π0 and η meson production is observed in Pb-Pb collisions with respect to their production in pp collisions scaled by the number of binary nucleon-nucleon collisions. We discuss the results in terms of NLO pQCD predictions and hydrodynamic models. The measurements show a stronger suppression with respect to what was observed at lower center-of-mass energies in the pT range 6 < pT < 10 GeV/c. At pT < 3 GeV/c, hadronization models describe the π0 results while for the η some tension is observed.
A measurement of beauty hadron production at mid-rapidity in proton-lead collisions at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02 TeV is presented. The semi-inclusive decay channel of beauty hadrons into J/ψ is considered, where the J/ψ mesons are reconstructed in the dielectron decay channel at mid-rapidity down to transverse momenta of 1.3 GeV/c. The bb¯¯¯ production cross section at mid-rapidity, dσbb¯¯¯/dy, and the total cross section extrapolated over full phase space, σbb¯¯¯, are obtained. This measurement is combined with results on inclusive J/ψ production to determine the prompt J/ψ cross sections. The results in p-Pb collisions are then scaled to expectations from pp collisions at the same centre-of-mass energy to derive the nuclear modification factor RpPb, and compared to models to study possible nuclear modifications of the production induced by cold nuclear matter effects. RpPb is found to be smaller than unity at low pT for both J/ψ coming from beauty hadron decays and prompt J/ψ.
A measurement of beauty hadron production at mid-rapidity in proton-lead collisions at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02 TeV is presented. The semi-inclusive decay channel of beauty hadrons into J/ψ is considered, where the J/ψ mesons are reconstructed in the dielectron decay channel at mid-rapidity down to transverse momenta of 1.3 GeV/c. The bb¯¯¯ production cross section at mid-rapidity, dσbb¯¯¯/dy, and the total cross section extrapolated over full phase space, σbb¯¯¯, are obtained. This measurement is combined with results on inclusive J/ψ production to determine the prompt J/ψ cross sections. The results in p-Pb collisions are then scaled to expectations from pp collisions at the same centre-of-mass energy to derive the nuclear modification factor RpPb, and compared to models to study possible nuclear modifications of the production induced by cold nuclear matter effects. RpPb is found to be smaller than unity at low pT for both J/ψ coming from beauty hadron decays and prompt J/ψ.
August Brücher, 1888–1967
(2018)
August Brücher ist in den Jahren des Ersten Weltkriegs und der Weimarer Republik als Übersetzer aus dem Französischen hervorgetreten. Da seine Texte überwiegend in Zeitungen und Zeitschriften veröffentlicht wurden, erlangte er nicht die Bekanntheit anderer zeitgenössischer Übersetzer. Gerade diese Nebenrolle im Literaturbetrieb macht die Beschäftigung mit seinem Leben und Werk zu einer interessanten Aufgabe.
This study will consider the various aspects of the portrayal of Sultan ʿAbd al-Ḥamīd II that were emphasized in the Arab-Islamist revisionist writings about Islamic history. The focus will be especially on the writings of Anwar al-Ǧundī (1917–2002), an Egyptian Islamist writer as it was he who first adopted the process of an “Islamic revision of Islamic history”. His main academic output consisted in responding to the “Orientalist attack on Islam”, and he wrote a number of books towards this aim as as-Sulṭān ʿAbd al-Ḥamīd wa l-ḫilāfa al-islāmiyya, al-Islām fī maʿrakat at-taġrīb and al-Istiʿmār wa l-Islām.
This will be followed by an analysis of the ideological exploitation of the historical personality, and the consequences of the contemporary historical Islamist vision for the development of religious thought.
Im Folgenden soll ein kurzer Überblick gegeben werden über die schiitische Sicht der frühislamischen Geschichte sowie über einige Phänomene, die sich daraus ergeben haben. Sie sind Hindernisse einer islamischen Einheit und müssten, sollte ein ernsthafter Versuch einer solchen verfolgt werden, mit deutlich mehr Mut angegangen werden. Dabei geht es hier weniger darum, alle Unterschiede zwischen Schia und Sunna aufzuzeigen, als sich auf die wirklich problematischen Felder zu konzentrieren, die nicht Folgen späterer, oft zufälliger Entwicklungen sind, sondern Weichenstellungen, die in der Frühgeschichte zu verorten sind. Bisher werden diese neuralgischen Punkte bei den Versuchen einer islamischen Ökumene, um diesen sehr christlich belegten Begriff an dieser Stelle doch einmal zu verwenden, meist umgangen, weil man um ihre Brisanz und Sprengkraft weiß. Doch müsste die Auseinandersetzung mit den unterschiedlichen Geschichtsbildern erfolgen, da sie ein wichtiges innerislamisches Differenzkriterium bilden; zumindest sollte man sich klar darüber sein, dass es unterschiedliche Geschichtsbilder gibt und sie ein Differenzkriterium bilden.
Entstanden in einem Milieu aus exklusivistischen islamischen Bewegungen, baut die Gewalttheologie der dschihadistischen Organisationen wie der al-Qa‘ida oder des IS auf eine Geschichtstheologie, welche Verfalls- und Dekadenzdiagnosen über die Situation der islamischen Welt und der Muslime mit eschatologischen Elementen verknüpft. In der Konsequenz müsse diese Dekadenz zum Zerfall der Welt und zum Anbruch der Endzeit führen, als deren kämpfende Avantgarde und notwendige Vorbedingung sich die dschihadistischen Akteure stilisieren. Videos mit identifizierbaren erzählerischen Elementen gehören dabei zu zentralen Mitteln der dschihadistischen Kommunikation. Anhand eines Fallbeispiels untersucht der Artikel die geschichts- und gewalttheologisch geprägten Strukturen der IS-Videopropaganda. Zugleich wird auf im muslimischen Spektrum generierte Alternativen zu dieser exklusivistischen Geschichtstheologie verwiesen, die nicht von einem sich in der Geschichte enthüllenden ‘Heilsplan’ Gottes ausgehen, sondern auf der Prämisse der Unabgeschlossenheit und der offenen Bewegung menschlichen Denkens beruhen und damit eine Epistemologie anbieten, die nicht Spielarten des Identitären befördert.
Der Artikel wirft einige Schlaglichter auf die Geschichtsbilder und -vorstellungen, die im modernen muslimischen religiösen Denken seit dem späten 19. Jahrhundert zum Tragen gekommen sind. Insbesondere im Blick steht dabei die Frage nach dem Umgang mit eigener Geschichtlichkeit und mit den Konsequenzen, die sich daraus für die Ausgestaltung von Islamität ergeben. Die unterschiedlichen Gewichtungen und Verknüpfungen von Vergangenheit und Gegenwart und die Frage, ob die Bedeutung des historischen Wandels für die eigenen Erkenntnisprozesse mitreflektiert wird, entscheidet, so die These, über den Umgang des religiösen Denkens mit neuen Wissensbeständen, Epistemen und methodischen Verfahren ebenso wie darüber, ob diese als legitim angesehen werden, um als authentisch islamisch akzeptiert zu werden.
Metacognition plays a pivotal role in human development. The ability to realize that we do not know something, or meta-ignorance, emerges after approximately five years of age. We aimed at identifying the brain systems that underlie the developmental emergence of this ability in a preschool sample.
Twenty-four children aged between five and six years answered questions under three conditions of a meta-ignorance task twice. In the critical partial knowledge condition, an experimenter first showed two toys to a child, then announced that she would place one of them in a box behind a screen, out of sight from the child. The experimenter then asked the child whether or not she knew which toy was in the box.
Children who answered correctly both times to the metacognitive question in the partial knowledge condition (n=9) showed greater cortical thickness in a cluster within left medial orbitofrontal cortex than children who did not (n=15). Further, seed-based functional connectivity analyses of the brain during resting state revealed that this region is functionally connected to the medial orbitofrontal gyrus, posterior cingulate gyrus and precuneus, and mid- and inferior temporal gyri.
This finding suggests that the default mode network, critically through its prefrontal regions, supports introspective processing. It leads to the emergence of metacognitive monitoring allowing children to explicitly report their own ignorance.
Osteocalcin, Azan and Toluidine blue staining in fibrous dysplasia and ossifying fibroma of the jaws
(2018)
Background: Fibrous dysplasia (FD) and ossifying fibroma (OF) are fibro-osseous lesions (FOLs) having several overlaps that may make final diagnosis difficult by hematoxylin and eosin (H/E) alone.
Aim: This study seeks to detect any association between Azan and Toluidine blue staining as compared with osteocalcin in FD and OF diagnosis.
Methods:Forty formalin fixed paraffin embedded (FFPE) blocks of FD and OF were prepared for Azan, Toluidine blue and osteocalcin staining. Brown staining of calcified structures was considered as positive for osteocalcin. Scoring for Azan and Toluidine blue was evaluated based on intensity and localization. Level of agreement of original and revised diagnosis was determined.
Results: Six (40%) of 15 FD were corroborated by osteocalcin. Eight cases initially diagnosed as OF were revised to FD. There were 25 OF according to H/E, and 17 (68%) were validated by osteocalcin. Measure of agreement between histology and immunohistochemistry was 0.081; p = .608. Eleven (42.3%) OF expressed strong toluidine blue staining of the intervening fibrous connective tissue stroma while only 2 (14.2%) FD showed similar staining, this difference was statistically significant [p = .001].
Conclusions: Histomorphometric analysis with Toluidine blue may reduce diagnostic errors of OF and FD.
Exposure to locusts, which belong to the arthropod phylum, is an underestimated health problem, especially among workers in research facilities exposed to laboratory animals. We describe a rare case of an occupational immediate-type reaction to locusts with a possible cross-reactivity between desert locust (Schistocerca gregaria) and migratory locust (Locusta migratoria).
Purpose: To report a case of autoimmune keratitis in a patient with mycobacterium tuberculosis (MBT).
Methods: An 84-year-old male with pulmonary tuberculosis (TB) was admitted with chronic, non-healing bilateral ulcerations of the inferior peripheral cornea associated with stromal and subconjunctival nodules.
Results: Clinical examination revealed circumscribed peripheral corneal ulceration with whitish nodules in adjacent stromal and subconjunctival tissue. Microbiological cultures of the corneal tissue were negative for MBT and other microbial pathogens; however, enzyme-linked immunosorbent assay (ELISA) of blood and corneal samples showed significantly elevated levels of IgM and IgA against MBT. In addition to systemic anti-tuberculosis therapy, the patient was treated topically with Polyspectran® eye drops, Dexamethasone eye drops, and Bepanthen® ointment, for 2 weeks. Both eyes showed dramatic improvement after 2 weeks.
Conclusion: The present report demonstrates that MBT is able to initiate delayed autoimmune response within the corneal tissue during an intensive phase of anti-tuberculosis treatment.
Introduction: Ferroptosis has recently been identified as a form of programmed cell death caused by an accumulation of lipid reactive oxygen species (ROS). However, little is yet known about the role in hepatocellular carcinoma (HCC) and its signalling mechanism as well the modulation of ROS.
Material and methods: Human HCC cell lines were treated with different concentrations of ROS modulators (Auranofin, Erastin, BSO). Cell death was determined by analysis of PI-stained nuclei using flow cytometry. ROS production and lipid peroxidation were analysed at early time points before cell death starts. For mechanistic studies we performed Western Blot and a Proteome array. Different inhibitors of cell death target proteins, ROS-scavengers as well as lipoxygenase inhibitors were used. To investigate the functional relevance of NAPDH oxidases (NOX) 1 and 4 for ROS modulation and ferroptosis we genetically silenced its genes using three distinct siRNAs and we used the NOX1/4-inhibitor GKT137831.
Results and discussions: Compared to the single treatment, Auranofin/BSO-cotreatment as well as Erastin/BSO-cotreatment acted in concert to trigger cell death and to reduce cell viability of HCC cells in a dose- and time-dependent manner. Furthermore, both cotreatments induce ROS production, lipid peroxidation and ferroptotic cell death, which could be inhibited by the use of Ferrostatin-1 (inhibitor of lipid peroxidation) and Liproxstatin-1 (specific inhibitor of ferroptosis). The broad-range caspase inhibitor zVAD.fmk failed to rescue cells from Auranofin/BSO- or Erastin/BSO-cotreatment induced cell death. No activation of caspases-3 could be seen in the proteome profiler apoptosis assay. Importantly, the selective lipoxygenase (LOX) inhibitor Baicalain and the pan-LOX inhibitor NDGA protect HCC cells from Auranofin/BSO- and Erastin/BSO-cotreatment stimulated lipid peroxidation, ROS generation and cell death, indication that the induction of ferroptosis may bypass apoptosis resistance of HCC cells. Mechanistic studies showed that Auranofin/BSO-cotreatment decreased TrxR-activity, led to Nrf2 accumulation and promoted the activation of HO-1. In contrast, NOX 1 and 4 were involved in Erastin/BSO-mediated cell death and the use of the NOX1/4-inhibitor GKT137831 rescued HCC cells from the Erastin/BSO-induced cell death.
Conclusion: By providing new insights into the molecular regulation of ROS and ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in HCC cells.
Transverse momentum (pT ) spectra of charged particles at mid-pseudorapidity in Xe–Xe collisions at √sNN=5.44TeV measured with the ALICE apparatus at the Large Hadron Collider are reported. The kinematic range 0.15<pT<50GeV/c and |η|<0.8 is covered. Results are presented in nine classes of collision centrality in the 0–80% range. For comparison, a pp reference at the collision energy of √s=5.44 TeV is obtained by interpolating between existing pp measurements at √s=5.02 and 7 TeV. The nuclear modification factors in central Xe–Xe collisions and Pb–Pb collisions at a similar center-of-mass energy of √sNN=5.02 TeV, and in addition at 2.76 TeV, at analogous ranges of charged particle multiplicity density 〈dNch/dη〉 show a remarkable similarity at pT>10 GeV/c. The centrality dependence of the ratio of the average transverse momentum 〈pT〉 in Xe–Xe collisions over Pb–Pb collision at √s=5.02 TeV is compared to hydrodynamical model calculations.
The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high-transverse momentum trigger hadron in p–Pb collisions at √sNN=5.02 TeV. Jets are reconstructed from charged-particle tracks using the anti-kT algorithm with resolution parameter R=0.2 and 0.4. A data-driven statistical approach is used to correct the uncorrelated background jet yield. Recoil jet distributions are reported for jet transverse momentum 15<pT,jetch<50GeV/c and are compared in various intervals of p–Pb event activity, based on charged-particle multiplicity and zero-degree neutral energy in the forward (Pb-going) direction. The semi-inclusive observable is self-normalized and such comparisons do not require the interpretation of p–Pb event activity in terms of collision geometry, in contrast to inclusive jet observables. These measurements provide new constraints on the magnitude of jet quenching in small systems at the LHC. In p–Pb collisions with high event activity, the average medium-induced out-of-cone energy transport for jets with R=0.4 and 15<pT,jetch<50GeV/c is measured to be less than 0.4 GeV/c at 90% confidence, which is over an order of magnitude smaller than a similar measurement for central Pb–Pb collisions at √sNN=2.76TeV. Comparison is made to theoretical calculations of jet quenching in small systems, and to inclusive jet measurements in p–Pb collisions selected by event activity at the LHC and in d–Au collisions at RHIC.
Ludwig von Alvensleben war einer der produktivsten Übersetzer des 19. Jahrhunderts. Er gilt daher heute manchen als Prototyp des nur auf Quantität bedachten "Fabrikübersetzers". Dass die Zeitgenossen seine Übersetzungstätigkeit nicht ganz so negativ einschätzten, lässt sich an seinerzeit veröffentlichten Rezensionen erkennen. Der Blick in die Bibliographie macht allerdings auch deutlich, dass sich seine Übersetzungen im Literaturbetrieb bzw. am Buchmarkt nicht lange halten konnten.
The Δ-isobar degrees of freedom are included in the covariant density functional (CDF) theory to study the equation of state (EoS) and composition of dense matter in compact stars. In addition to Δ's we include the full octet of baryons, which allows us to study the interplay between the onset of delta isobars and hyperonic degrees of freedom. Using both the Hartree and Hartree–Fock approximation we find that Δ's appear already at densities slightly above the saturation density of nuclear matter for a wide range of the meson–Δ coupling constants. This delays the appearance of hyperons and significantly affects the gross properties of compact stars. Specifically, Δ's soften the EoS at low densities but stiffen it at high densities. This softening reduces the radius of a canonical 1.4M⊙ star by up to 2 km for a reasonably attractive Δ potential in matter, while the stiffening results in larger maximum masses of compact stars. We conclude that the hypernuclear CDF parametrizations that satisfy the 2M⊙ maximum mass constraint remain valid when Δ isobars are included, with the important consequence that the resulting stellar radii are shifted toward lower values, which is in agreement with the analysis of neutron star radii.
Cancer is the leading cause of death worldwide after cardiovascular diseases. This has been the case for the last few decades despite there being an increase in the number of cancer treatments. One reason for the apparent lack of drug effectiveness might be, at least in part, due to unspecificity for tumors; which often leads to substantial side effects. One way to improve the treatment of cancer is to increase the specificity of the treatment in accordance with the concept of individualized medicine. This will help to prevent further progression of an existing cancer or even to reduce the tumor burden. Alternatively it would be much more attractive and efficient to prevent the development of cancer in the first place. Therefore, it is important to understand the risk factors and the mechanisms of carcinogenesis in detail. One such risk factor, often associated with tumorigenesis and tumor progression, is an increased abundance of reactive oxygen species (ROS) arising from an imbalance of ROS-producing and -eliminating components. A surplus of ROS can induce oxidative damage of macromolecules including proteins, lipids and DNA. In contrast, ROS are essential for an adequate signal transduction and are known to regulate crucial cellular processes like cellular quiescence, differentiation and even apoptosis. Therefore, regulated ROS-formation at physiological levels can inhibit tumor formation and progression. With this review we provide an overview on the current knowledge of redox control in cancer development and progression.
MAPK6/ERK3 is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary disfunction and by defects in function, activation and positive selection of T cells. To study the role of ERK3 in vivo, we generated mice carrying a conditional Erk3 allele with exon3 flanked by LoxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-cre and a clear reduction of the protein kinase MK5 is detected, providing first evidence for the existence of the ERK3/MK5 signaling complex in vivo. In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile, do not display pulmonary hypoplasia, acute respiratory failure, abnormal T cell development, reduction of thymocyte numbers or altered T cells selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality, lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin-resistance-cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal suggesting redundant functions of both protein kinases.
isiKnock is a new software that automatically conducts in silico knockouts for mathematical models of biochemical pathways. The software allows for the prediction of the behavior of biological systems after single or multiple knockout. The implemented algorithm applies transition invariants and the novel concept of Manatee invariants. A knockout matrix visualizes the results. The tool enables the analysis of dependencies, for example, in signal flows from the receptor activation to the cell response at steady state.
Bleaching-independent, whole-cell, 3D and multi-color STED imaging with exchangeable fluorophores
(2018)
We demonstrate bleaching-independent STED microscopy using fluorogenic labels that reversibly bind to their target structure. A constant exchange of labels guarantees the removal of photobleached fluorophores and their replacement by intact fluorophores, thereby circumventing bleaching-related limitations of STED super-resolution imaging in fixed and living cells. Foremost, we achieve a constant labeling density and demonstrate a fluorescence signal for long and theoretically unlimited acquisition times. Using this concept, we demonstrate whole-cell, 3D, multi-color and live cell STED microscopy with up to 100 min acquisition time.
Background: MDM2 inhibitors are under investigation for the treatment of acute myeloid leukaemia (AML) patients in phase III clinical trials. To study resistance formation to MDM2 inhibitors in AML cells, we here established 45 sub-lines of the AML TP53 wild-type cell lines MV4-11 (15 sub-lines), OCI-AML-2 (10 sub-lines), OCI-AML-3 (12 sub-lines), and SIG-M5 (8 sub-lines) with resistance to the MDM2 inhibitor nutlin-3.
Methods: Nutlin-3-resistant sub-lines were established by continuous exposure to stepwise increasing drug concentrations. The TP53 status was determined by next generation sequencing, cell viability was measured by MTT assay, and p53 was depleted using lentiviral vectors encoding shRNA.
Results: All MV4-11 sub-lines harboured the same R248W mutation and all OCI-AML-2 sub-lines the same Y220C mutation, indicating the selection of pre-existing TP53-mutant subpopulations. In concordance, rare alleles harbouring the respective mutations could be detected in the parental MV4-11 and OCI-AML-2 cell lines. The OCI-AML-3 and SIG-M5 sub-lines were characterised by varying TP53 mutations or wild type TP53, indicating the induction of de novo TP53 mutations. Doxorubicin, etoposide, gemcitabine, cytarabine, and fludarabine resistance profiles revealed a noticeable heterogeneity among the sub-lines even of the same parental cell lines. Loss-of-p53 function was not generally associated with decreased sensitivity to cytotoxic drugs.
Conclusion: We introduce a substantial set of models of acquired MDM2 inhibitor resistance in AML. MDM2 inhibitors select, in dependence on the nature of a given AML cell population, pre-existing TP53-mutant subpopulations or induce de novo TP53 mutations. Although loss-of-p53 function has been associated with chemoresistance in AML, nutlin-3-adapted sub-lines displayed in the majority of experiments similar or increased drug sensitivity compared to the respective parental cells. Hence, chemotherapy may remain an option for AML patients after MDM2 inhibitor therapy failure. Even sub-lines of the same parental cancer cell line displayed considerable heterogeneity in their response to other anti-cancer drugs, indicating the need for the detailed understanding and monitoring of the evolutionary processes in cancer cell populations in response to therapy as part of future individualised treatment protocols.
Precise slow oscillation-spindle coupling promotes memory consolidation in younger and older adults
(2018)
Memory consolidation during sleep relies on the precisely timed interaction of rhythmic neural events. Here, we investigate differences in slow oscillations (SO) and sleep spindles (SP) and their coupling across the adult human lifespan and ask whether observed alterations relate to the ability to retain associative memories across sleep. We demonstrate that the fine-tuned SO–SP coupling that is present in younger adults diffuses with advanced age and shifts both in time and frequency. Crucially, we show that the tight precision of SO–SP coupling promotes memory consolidation in younger and older adults, and that brain integrity in source regions for the generation of SOs and SPs reinforces this beneficial SO–SP coupling in old age. Our results reveal age-related differences in SO–SP coupling in healthy elderly individuals. Furthermore, they broaden our understanding of the conditions and the functional significance of SO–SP coupling across the entire adult lifespan.
The entire chemical modification repertoire of yeast ribosomal RNAs and the enzymes responsible for it have recently been identified. Nonetheless, in most cases the precise roles played by these chemical modifications in ribosome structure, function and regulation remain totally unclear. Previously, we demonstrated that yeast Rrp8 methylates m1A645 of 25S rRNA in yeast. Here, using mung bean nuclease protection assays in combination with quantitative RP-HPLC and primer extension, we report that 25S/28S rRNA of S. pombe, C. albicans and humans also contain a single m1A methylation in the helix 25.1. We characterized nucleomethylin (NML) as a human homolog of yeast Rrp8 and demonstrate that NML catalyzes the m1A1322 methylation of 28S rRNA in humans. Our in vivo structural probing of 25S rRNA, using both DMS and SHAPE, revealed that the loss of the Rrp8-catalyzed m1A modification alters the conformation of domain I of yeast 25S rRNA causing translation initiation defects detectable as halfmers formation, likely because of incompetent loading of 60S on the 43S-preinitiation complex. Quantitative proteomic analysis of the yeast Δrrp8 mutant strain using 2D-DIGE, revealed that loss of m1A645 impacts production of specific set of proteins involved in carbohydrate metabolism, translation and ribosome synthesis. In mouse, NML has been characterized as a metabolic disease-associated gene linked to obesity. Our findings in yeast also point to a role of Rrp8 in primary metabolism. In conclusion, the m1A modification is crucial for maintaining an optimal 60S conformation, which in turn is important for regulating the production of key metabolic enzymes.
The entire chemical modification repertoire of yeast ribosomal RNAs and the enzymes responsible for it have recently been identified. Nonetheless, in most cases the precise roles played by these chemical modifications in ribosome structure, function and regulation remain totally unclear. Previously, we demonstrated that yeast Rrp8 methylates m1A645 of 25S rRNA in yeast. Here, using mung bean nuclease protection assays in combination with quantitative RP-HPLC and primer extension, we report that 25S/28S rRNA of S. pombe, C. albicans and humans also contain a single m1A methylation in the helix 25.1. We characterized nucleomethylin (NML) as a human homolog of yeast Rrp8 and demonstrate that NML catalyzes the m1A1322 methylation of 28S rRNA in humans. Our in vivo structural probing of 25S rRNA, using both DMS and SHAPE, revealed that the loss of the Rrp8-catalyzed m1A modification alters the conformation of domain I of yeast 25S rRNA causing translation initiation defects detectable as halfmers formation, likely because of incompetent loading of 60S on the 43S-preinitiation complex. Quantitative proteomic analysis of the yeast Δrrp8 mutant strain using 2D-DIGE, revealed that loss of m1A645 impacts production of specific set of proteins involved in carbohydrate metabolism, translation and ribosome synthesis. In mouse, NML has been characterized as a metabolic disease-associated gene linked to obesity. Our findings in yeast also point to a role of Rrp8 in primary metabolism. In conclusion, the m1A modification is crucial for maintaining an optimal 60S conformation, which in turn is important for regulating the production of key metabolic enzymes.
Modularity is an aspect of a decomposable system with a coordinating authority that acts as a glue which holds the loosely held components. These multi-component entities (“modules”) facilitate rewiring into different designs allowing for change. Such modular character is a fundamental property of many biological entities, especially the family of megasynthases such as polyketide synthases (PKSs). The ability of these PKSs to produce diverse product spectra is strongly coupled to their broad architectural modularity. Decoding the molecular basis of modularity, i.e. identifying the folds and domains that comprise the modules as well as understanding constrains of the assembly of modules, is of utmost importance for harnessing megasynthases for the synthesis of designer compounds. In this study, we exploit the close semblance between PKSs and animal FAS to re-engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by structural and sequence information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS-like modules as well as bimodular constructs. The novel engineered modules resemble all four common module types of PKSs and demonstrate that this approach can be a powerful tool to create higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS-based biosynthetic pathways for custom compound design.
Single-particle electron cryo-microscopy (cryoEM) has undergone a “resolution revolution” that makes it possible to characterize megadalton (MDa) complexes at atomic resolution without crystals. To fully exploit the new opportunities in molecular microscopy, new procedures for the cloning, expression and purification of macromolecular complexes need to be explored. Macromolecular assemblies are often unstable, and invasive construct design or inadequate purification conditions or sample preparation methods can result in disassembly or denaturation. The structure of the 2.6 MDa yeast fatty acid synthase (FAS) has been studied by electron microscopy since the 1960s. We report a new, streamlined protocol for the rapid production of purified yeast FAS for structure determination by high-resolution cryoEM. Together with a companion protocol for preparing cryoEM specimens on a hydrophilized graphene layer, our new protocol has yielded a 3.1 Å map of yeast FAS from 15,000 automatically picked particles within a day. The high map quality enabled us to build a complete atomic model of an intact fungal FAS.
Engineering of assembly line polyketide synthases (PKSs) to produce novel bioactive compounds has been a goal for over twenty years. The apparent modularity of PKSs has inspired many engineering attempts in which entire modules or single domains were exchanged. In recent years, it has become evident that certain domain-domain interactions are evolutionarily optimized, and if disrupted, cause a decrease of the overall turnover rate of the chimeric PKS. In this study, we compared different types of chimeric PKSs in order to define the least invasive interface and to expand the toolbox for PKS engineering. We generated bimodular chimeric PKSs in which entire modules were exchanged, while either retaining a covalent linker between heterologous modules or introducing a non-covalent docking domain- or SYNZIP domain-mediated interface. These chimeric systems exhibited non-native domain-domain interactions during intermodular polyketide chain translocation. They were compared to otherwise equivalent bimodular PKSs in which a non-covalent interface was introduced between the condensing and processing parts of a module, resulting in non-native domain interactions during the extender unit acylation and polyketide chain elongation steps of their catalytic cycles. We show that the natural PKS docking domains can be efficiently substituted with SYNZIP domains and that the newly introduced non-covalent interface between the condensing and processing parts of a module can be harnessed for PKS engineering. Additionally, we established SYNZIP domains as a new tool for engineering PKSs by efficiently bridging non-native interfaces without perturbing PKS activity.
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.
Frankfurter Zeitschrift für islamisch-theologische Studien. 4/2018. Geschichte und Geschichtlichkeit
(2018)
Autosomal recessive Ataxia Telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the Ataxia-Telangiectasia-Mutated (ATM) gene, a serine-threonine protein kinase involved in DNA-damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
The basidiomycete smut fungi are predominantly plant parasitic, causing severe losses in some crops. Most species feature a saprotrophic haploid yeast stage, and several smut fungi are only known from this stage, with some isolated from habitats without suitable hosts, e.g. from Antarctica. Thus, these species are generally believed to be apathogenic, but recent findings that some of these might have a plant pathogenic sexual counterpart, casts doubts on the validity of this hypothesis. Here, four Pseudozyma genomes were re-annotated and compared to published smut pathogens and the well-characterised effector gene Pep1 from these species was checked for its ability to complement a Pep1 deletion strain of Ustilago maydis. It was found that 113 high-confidence putative effector proteins were conserved among smut and Pseudozyma genomes. Among these were several validated effector proteins, including Pep1. By genetic complementation we show that Pep1 homologs from the supposedly apathogenic yeasts restore virulence in Pep1-deficient mutants Ustilago maydis. Thus, it is concluded that Pseudozyma species have retained a suite of effectors. This hints at the possibility that Pseudozyma species have kept an unknown plant pathogenic stage for sexual recombination or that these effectors have positive effects when colonising plant surfaces.
The gradual heterogeneity of climatic factors pose varying selection pressures across geographic distances that leave signatures of clinal variation in the genome. Separating signatures of clinal adaptation from signatures of other evolutionary forces, such as demographic processes, genetic drift, and adaptation to non-clinal conditions of the immediate local environment is a major challenge. Here, we examine climate adaptation in five natural populations of the harlequin fly Chironomus riparius sampled along a climatic gradient across Europe. Our study integrates experimental data, individual genome resequencing, Pool-Seq data, and population genetic modelling. Common-garden experiments revealed a positive correlation of population growth rates corresponding to the population origin along the climate gradient, suggesting thermal adaptation on the phenotypic level. Based on a population genomic analysis, we derived empirical estimates of historical demography and migration. We used an FST outlier approach to infer positive selection across the climate gradient, in combination with an environmental association analysis. In total we identified 162 candidate genes as genomic basis of climate adaptation. Enriched functions among these candidate genes involved the apoptotic process and molecular response to heat, as well as functions identified in other studies of climate adaptation in other insects. Our results show that local climate conditions impose strong selection pressures and lead to genomic adaptation despite strong gene flow. Moreover, these results imply that selection to different climatic conditions seems to converge on a functional level, at least between different insect species.
One of the major problems in evolutionary biology is to elucidate the relationships between historical events and the tempo and mode of lineage divergence. The development of relaxed molecular clock models and the increasing availability of DNA sequences resulted in more accurate estimations of taxa divergence times. However, finding the link between competing historical events and divergence is still challenging. Here we investigate assigning constrained-age priors to nodes of interest in a time-calibrated phylogeny as a means of hypothesis comparison. These priors are equivalent to historic scenarios for lineage origin. The hypothesis that best explains the data can be selected by comparing the likelihood values of the competing hypotheses, modelled with different priors. A simulation approach was taken to evaluate the performance of the prior-based method and to compare it with an unconstrained approach. We explored the effect of DNA sequence length and the temporal placement and span of competing hypotheses (i.e. historic scenarios) on selection of the correct hypothesis and the strength of the inference. Competing hypotheses were compared applying a posterior simulation analogue of the Akaike Information Criterion and Bayes factors (obtained after calculation of the marginal likelihood with three estimators: Harmonic Mean, Stepping Stone and Path Sampling). We illustrate the potential application of the prior-based method on an empirical data set to compare competing geological hypotheses explaining the biogeographic patterns in Pleurodeles newts. The correct hypothesis was selected on average 89% times. The best performance was observed with DNA sequence length of 3500-10000 bp. The prior-based method is most reliable when the hypotheses compared are not temporally too close. The strongest inferences were obtained when using the Stepping Stone and Path Sampling estimators. The prior-based approach proved effective in discriminating between competing hypotheses when used on empirical data. The unconstrained analyses performed well but it probably requires additional computational effort. Researchers applying this approach should rely only on inferences with moderate to strong support. The prior-based approach could be applied on biogeographical and phylogeographical studies where robust methods for historical inferences are still lacking.
All giraffe (Giraffa) were previously assigned to a single species (G. Camelopardalis) and nine subspecies. However, multi-locus analyses of all subspecies have shown that there are four genetically distinct clades and suggest four giraffe species. This conclusion might not be fully accepted due to limited data and lack of explicit gene flow analyses. Here we present an extended study based on 21 independent nuclear loci from 137 individuals. Explicit gene flow analyses identify less than one migrant per generation, including between the closely related northern and reticulated giraffe. Thus, gene flow analyses and population genetics of the extended dataset confirm four genetically distinct giraffe clades and support four independent giraffe species. The new findings call for a revision of the IUCN classification of giraffe taxonomy. Three of the four species are threatened with extinction, mostly occurring in politically unstable regions, and as such, require the highest conservation support possible.
The debate on effects of globalization on welfare states is extensive. Often couched in terms of a battle between the compensation and the efficiency thesis, the scholarly literature has provided contradictory arguments and findings. This article contributes to the scholarly debate by exploring in greater detail the micro-level foundations of compensation theory. More specifically, we distinguish between individual policy preferences for compensatory social policies (unemployment insurance) and human capital-focused social investment policies (education) and expect globalization to mainly affect demand for educational investment. A multi-level analysis of ISSP survey data provides empirical support for this hypothesis. This finding provides an important revision and extension of the classical analytical perspective of compensation theory, because it shows that citizens value the social investment function of the welfare state above and beyond simple compensation via social transfers. This might be particularly relevant in today's skill-centered knowledge economies.
Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 seconds, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.
Summary statement When echolocating under demanding conditions e.g. noisy, narrow space, or cluttered environments, frugivorous bats adapt their call pattern by increasing the call rate within biosonar groups.
Abstract For orientation, echolocating bats emit biosonar calls and use echoes arising from call reflections. They often pattern their calls into groups which increases the rate of sensory feedback over time. Insectivorous bats emit call groups at a higher rate when orienting in cluttered compared to uncluttered environments. Frugivorous bats increase the rate of call group emission when they echolocate in noisy environments. Here, calls emitted by conspecifics potentially interfere with the bat’s biosonar signals and complicate the echolocation behavior. To minimize the information loss followed by signal interference, bats may profit from a temporally increased sensory acquisition rate, as it is the case for the call groups. In frugivorous bats, it remains unclear if call group emission represents an exclusive adaptation to avoid interference by signals from other bats or if it represents an adaptation that allows to orient under demanding environmental conditions. Here, we compared the emission pattern of the frugivorous bat Carollia perspicillata when the bats were flying in noisy versus silent, narrow versus wide or cluttered versus non-cluttered corridors. According to our results, the bats emitted larger call groups and they increased the call rate within the call groups when navigating in narrow, cluttered, or noisy environments. Thus, call group emission represents an adaptive behavior when the bats orient in complex environments.
The outstanding speed of language comprehension necessitates a highly efficient implementation of cognitive-linguistic processes. The domain-general theory of Predictive Coding suggests that our brain solves this problem by continuously forming linguistic predictions about expected upcoming input. The neurophysiological implementation of these predictive linguistic processes, however, is not yet understood. Here, we use EEG (human participants, both sexes) to investigate the existence and nature of online-generated, category-level semantic representations during sentence processing. We conducted two experiments in which some nouns – embedded in a predictive spoken sentence context – were unexpectedly delayed by 1 second. Target nouns were either abstract/concrete (Experiment 1) or animate/inanimate (Experiment 2). We hypothesized that if neural prediction error signals following (temporary) omissions carry specific information about the stimulus, the semantic category of the upcoming target word is encoded in brain activity prior to its presentation. Using time-generalized multivariate pattern analysis, we demonstrate significant decoding of word category from silent periods directly preceding the target word, in both experiments. This provides direct evidence for predictive coding during sentence processing, i.e., that information about a word can be encoded in brain activity before it is perceived. While the same semantic contrast could also be decoded from EEG activity elicited by isolated words (Experiment 1), the identified neural patterns did not generalize to pre-stimulus delay period activity in sentences. Our results not only indicate that the brain processes language predictively, but also demonstrate the nature and sentence-specificity of category-level semantic predictions preactivated during sentence comprehension.
Changes in the efficacies of synapses are thought to be the neurobiological basis of learning and memory. The efficacy of a synapse depends on its current number of neurotransmitter receptors. Recent experiments have shown that these receptors are highly dynamic, moving back and forth between synapses on time scales of seconds and minutes. This suggests spontaneous fluctuations in synaptic efficacies and a competition of nearby synapses for available receptors. Here we propose a mathematical model of this competition of synapses for neurotransmitter receptors from a local dendritic pool. Using minimal assumptions, the model produces a fast multiplicative scaling behavior of synapses. Furthermore, the model explains a transient form of heterosynaptic plasticity and predicts that its amount is inversely related to the size of the local receptor pool. Overall, our model reveals logistical tradeoffs during the induction of synaptic plasticity due to the rapid exchange of neurotransmitter receptors between synapses.
Changes in the efficacies of synapses are thought to be the neurobiological basis of learning and memory. The efficacy of a synapse depends on its current number of neurotransmitter receptors. Recent experiments have shown that these receptors are highly dynamic, moving back and forth between synapses on time scales of seconds and minutes. This suggests spontaneous fluctuations in synaptic efficacies and a competition of nearby synapses for available receptors. Here we propose a mathematical model of this competition of synapses for neurotransmitter receptors from a local dendritic pool. Using minimal assumptions, the model produces a fast multiplicative scaling behavior of synapses. Furthermore, the model explains a transient form of heterosynaptic plasticity and predicts that its amount is inversely related to the size of the local receptor pool. Overall, our model reveals logistical tradeoffs during the induction of synaptic plasticity due to the rapid exchange of neurotransmitter receptors between synapses.
Orthologs document the evolution of genes and metabolic capacities encoded in extant and ancient genomes. Orthologous genes that are detected across the full diversity of contemporary life allow reconstructing the gene set of LUCA, the last universal common ancestor. These genes presumably represent the functional repertoire common to – and necessary for – all living organisms. Design of artificial life has the potential to test this. Recently, a minimal gene (MG) set for a self-replicating cell was determined experimentally, and a surprisingly high number of genes have unknown functions and are not represented in LUCA. However, as similarity between orthologs decays with time, it becomes insufficient to infer common ancestry, leaving ancient gene set reconstructions incomplete and distorted to an unknown extent. Here we introduce the evolutionary traceability, together with the software protTrace, that quantifies, for each protein, the evolutionary distance beyond which the sensitivity of the ortholog search becomes limiting. We show that the LUCA set comprises only high-traceable proteins most of which have catalytic functions. We further show that proteins in the MG set lacking orthologs outside bacteria mostly have low traceability, leaving open whether their eukaryotic orthologs have just been overlooked. On the example of REC8, a protein essential for chromosome cohesion, we demonstrate how a traceability-informed adjustment of the search sensitivity identifies hitherto missed orthologs in the fast-evolving microsporidia. Taken together, the evolutionary traceability helps to differentiate between true absence and non-detection of orthologs, and thus improves our understanding about the evolutionary conservation of functional protein networks.
Stockpiling neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir is part of a global effort to be prepared for an influenza pandemic. However, the contribution of NAIs for treatment and prevention of influenza and its complications is largely debatable. Here, we developed a transparent mathematical modelling setting to analyse the impact of NAIs on influenza disease at within-host and population level. Analytical and simulation results indicate that even assuming unrealistically high efficacies for NAIs, drug intake starting on the onset of symptoms has a negligible effect on an individual's viral load and symptoms score. Increasing NAIs doses does not provide a better outcome as is generally believed. Considering Tamiflu's pandemic regimen for prophylaxis, different multiscale simulation scenarios reveal modest reductions in epidemic size despite high investments in stockpiling. Our results question the use of NAIs in general to treat influenza as well as the respective stockpiling by regulatory authorities.
The successful elimination of bacteria such as Streptococcus pneumoniae from a host involves the coordination between different parts of the immune system. Previous studies have explored the effects of the initial pneumococcal load (bacterial dose) on different representations of innate immunity, finding that pathogenic outcomes can vary with the size of the bacterial dose. However, others yield support to the notion of dose-independent factors contributing to bacterial clearance. In this paper, we seek to provide a deeper understanding of the immune responses associated to the pneumococcus. To this end, we formulate a model that realizes an abstraction of the innate-regulatory immune host response. Stability and bifurcation analyses of the model reveal the following trichotomy of pneumococcal outcomes determined by the bifurcation parameters: (i) dose-independent clearance; (ii) dose-independent persistence; and (iii) dose-limited clearance. Bistability, where the bacteria-free equilibrium co-stabilizes with the most substantial steady-state bacterial load is the specific result behind dose-limited clearance. The trichotomy of pneumococcal outcomes here described integrates all previously observed bacterial fates into a unified framework.
Background Corticospinal excitability depends on the current brain state. The recent development of real-time EEG-triggered transcranial magnetic stimulation (EEG-TMS) allows studying this relationship in a causal fashion. Specifically, it has been shown that corticospinal excitability is higher during the scalp surface negative EEG peak compared to the positive peak of µ-oscillations in sensorimotor cortex, as indexed by larger motor evoked potentials (MEPs) for fixed stimulation intensity.
Objective We further characterize the effect of µ-rhythm phase on the MEP input-output (IO) curve by measuring the degree of excitability modulation across a range of stimulation intensities. We furthermore seek to optimize stimulation parameters to enable discrimination of functionally relevant EEG-defined brain states.
Methods A real-time EEG-TMS system was used to trigger MEPs during instantaneous brain-states corresponding to µ-rhythm surface positive and negative peaks with five different stimulation intensities covering an individually calibrated MEP IO curve in 15 healthy participants.
Results MEP amplitude is modulated by µ-phase across a wide range of stimulation intensities, with larger MEPs at the surface negative peak. The largest relative MEP-modulation was observed for weak intensities, the largest absolute MEP-modulation for intermediate intensities. These results indicate a leftward shift of the MEP IO curve during the µ-rhythm negative peak.
Conclusion The choice of stimulation intensity influences the observed degree of corticospinal excitability modulation by µ-phase. Lower stimulation intensities enable more efficient differentiation of EEG µ-phase-defined brain states.
Objectives Omeprazole was shown to improve the anti-cancer effect of the nucleoside-analogue 5-fluorouracil. Here, we investigated the effects of omeprazole on the activities of the antiviral nucleoside analogues ribavirin and acyclovir.
Methods West Nile virus-infected Vero cells and influenza A H1N1-infected MDCK cells were treated with omeprazole and/ or ribavirin. Herpes simplex virus 1 (HSV-1)- or HSV-2-infected Vero or HaCat cells were treated with omeprazole and/ or acyclovir. Antiviral effects were determined by examination of cytopathogenic effects (CPE), immune staining, and virus yield assay. Cell viability was investigated by MTT assay.
Results Omeprazole concentrations up to 80μg/mL did not affect the antiviral effects of ribavirin. In contrast, omeprazole increased the acyclovir-mediated effects on HSV-1- and HSV-2-induced CPE formation in a dose-dependent manner in Vero and HaCat cells. Addition of omeprazole 80μg/mL resulted in a 10.8-fold reduction of the acyclovir concentration that reduces CPE formation by 50% (IC50) in HSV-1-infected Vero cells and in a 47.7-fold acyclovir IC50 reduction in HSV-1-infected HaCat cells. In HSV-2-infected cells, omeprazole reduced the acyclovir IC50 by 7.3-fold (Vero cells) or by 12.9-fold (HaCat cells). Omeprazole also enhanced the acyclovir-mediated effects on viral antigen expression and virus replication in HSV-1- and HSV-2-infected cells. In HSV-1-infected HaCat cells, omeprazole 80μg/mL reduced the virus titre in the presence of acyclovir 1μg/mL by 1.6×105-fold. In HSV-2-infected HaCat cells omeprazole 80μg/mL reduced the virus titre in the presence of acyclovir 2μg/mL by 9.2×103-fold. The investigated drug concentrations did not affect cell viability, neither alone nor in combination.
Conclusions Omeprazole increases the anti-HSV activity of acyclovir. As clinically well-established and tolerated drug, it is a candidate drug for antiviral therapies in combination with acyclovir.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
By means of available ice nucleating particle (INP) parameterization schemes we compute profiles of dust INP number concentration utilizing Polly-XT and CALIPSO lidar observations during the INUIT-BACCHUS-ACTRIS 2016 campaign. The polarization-lidar photometer networking (POLIPHON) method is used to separate dust and non-dust aerosol backscatter, extinction, mass concentration, particle number concentration (for particles with radius > 250 nm) and surface area concentration. The INP final products are compared with aerosol samples collected from unmanned aircraft systems (UAS) and analyzed using the ice nucleus counter FRIDGE.
Testing a non-perturbative mechanism for elementary fermion mass generation: numerical results
(2018)
Based on a recent proposal according to which elementary particle masses could be generated by a non-perturbative dynamical phenomenon, alternative to the Higgs mechanism, we carry out lattice simulations of a model where a non-abelian strongly interacting fermion doublet is also coupled to a doublet of complex scalar fields via a Yukawa and an “irrelevant" Wilson-like term. In this pioneering study we use naive fermions and work in the quenched approximation. We present preliminary numerical results both in the Wigner and in the Nambu-Goldstone phase, focusing on the observables relevant to check the occurrence of the conjectured dynamical fermion mass generation effect in the continuum limit of the critical theory in its spontaneously broken phase.
We study the impact of the Gradient Flow on the topology in various models of lattice field theory. The topological susceptibility Xt is measured directly, and by the slab method, which is based on the topological content of sub-volumes (“slabs”) and estimates Xt even when the system remains trapped in a fixed topological sector. The results obtained by both methods are essentially consistent, but the impact of the Gradient Flow on the characteristic quantity of the slab method seems to be different in 2-flavour QCD and in the 2d O(3) model. In the latter model, we further address the question whether or not the Gradient Flow leads to a finite continuum limit of the topological susceptibility (rescaled by the correlation length squared, ξ2). This ongoing study is based on direct measurements of Xt in L × L lattices, at L/ξ ≃6.
The aim of this paper is to understand resonance production (and more generally particle production) for different collision systems, namely proton-proton (pp), proton-nucleus (pA), and nucleus-nucleus (AA) scattering at the LHC. We will investigate in particular particle yields and ratios versus multiplicity, using the same multiplicity definition for the three different systems, in order to analyse in a compact way the evolution of particle production with the system size and the origin of a very different system size dependence of the different particles.
Frankfurt ist Knotenpunkt globaler Güter-, Finanz-, Wissens- und Migrationsbewegungen. Die Arbeitsmärkte und -verhältnisse in der Stadt sind Ausdruck einer globalen Verwobenheit, die diskursiv oft mit dem Label der ›Global City‹ markiert wird. In einer Zeit, in der Arbeit als Feld der Produktion und Reproduktion weitreichenden Transformationsprozessen ausgesetzt ist, in der das sogenannte Normalarbeitsverhältnis zunehmend erodiert, in der Arbeitsverhältnisse oft räumlich, sozial und zeitlich entgrenzt und flexibilisiert sind und in der gut bezahlte Jobs und schlecht- bezahlte, teils prekarisierte Formen der Beschäftigung koexistieren – zum Teil im gleichen Betrieb –, muss es Aufgabe wirtschaftsgeographischer Forschung sein, die Lebenswelten von Arbeitenden in einer räumlichen Perspektive zu beleuchten. Genau dies will der vorliegende Band tun. Er versammelt engagierte, theoretisch gesättigte und empirisch geerdete Beiträge von Studierenden des Instituts für Humangeographie, die einen kritischen Blick auf die Formen, Praktiken, Beziehungen und gesellschaftliche Einbettung von Arbeit in unterschiedlichen Branchen in der ›Global City‹ Frankfurt werfen.
Charmonium production in heavy ion collisions is considered as an important diagnostic probe for studying the phase diagram of strongly interacting matter for potential phase transitions. The interpretation of existing data from the CERN SPS is hampered by a lack of knowledge on the properties of open charm particle production in the fireball. Moreover, open charm production in heavy ion collisions by itself is poorly understood. To overcome this obstacle, the NA61/SHINE was equipped with a Small Acceptance Vertex Detector (SAVD), which is predicted to make the experiment sensitive to open charm mesons produced in A-A collisions at the SPS top energy. This paper will introduce the concept and the hardware of the SAVD. Moreover, first running experience as obtained in a commissioning run with a 150 AGeV/c Pb+Pb collision system will be reported.
The quantum van der Waals (QvdW) extension of the ideal hadron resonance gas (HRG) model which includes the attractive and repulsive interactions between baryons – the QvdW-HRG model – is applied to study the behavior of the baryon number related susceptibilities in the crossover temperature region. Inclusion of the QvdW interactions leads to a qualitatively different behavior of susceptibilities, in many cases resembling lattice QCD simulations. It is shown that for some observables, in particular for χBQ11/χB2, effects of the QvdW interactions essentially cancel out. It is found that the inclusion of the finite resonance widths leads to an improved description of χB2, but it also leads to a worse description of χBQ11/χB2, as compared to the lattice data. On the other hand, inclusion of the extra, unconfirmed baryons into the hadron list leads to a simultaneous improvement in the description of both observables.
We have extended the Langevin equations to 4 dimensions (4D) by allowing the independent deformation for the left (δ1) and right fragments (δ2) of the fissioning nucleus. At the moment we are only able to use them in conjunction with the macroscopic transport coefficients. Nevertheless, we can see a considerable improvement in the preliminary results for the fission observables, especially those related to the total kinetic energy (TKE) of fission fragments. By plotting the TKE distributions we have revealed the super-long fission modes in 236U and super-short fission modes in 257Fm. By plotting the distribution of δ against the fragment’s TKE we have noted a correlation between the values of δ and Brosa’s fission modes. We have found that the standard fission modes correspond to prolate tips of the light fragments while the complementary heavy fragments have oblate fission tips. On the other hand, if both fragments were prolate at the tips, we get super-long fission modes. If both fragments were oblate at the tips, we get super-short fission modes.
The slow neutron capture process (s-process) is responsible for producing about half of the elemental abundances heavier than iron in the universe. Neutron capture cross sections on stable isotopes are a key nuclear physics input for s-process studies. The 72Ge(n, γ) cross section has an important influence on production of isotopes between Ge and Zr during s-process in massive stars and therefore experimental data are urgently required. 72Ge(n, γ) was measured at the neutron time-of-flight facility n_TOF (CERN) for the first time at stellar energies. The measurement was performed using an enriched 72GeO2 sample at a flight path of 185m with a set of liquid scintillation detectors (C6D6). The motivation, experiment and current status of the data analysis are reported.
The neutron capture cross section of some unstable nuclei is especially relevant for s-process nucleosynthesis studies. This magnitude is crucial to determine the local abundance pattern, which can yield valuable information of the s-process stellar environment. In this work we describe the neutron capture (n,γ) measurement on two of these nuclei of interest, 204Tl and 171Tm, from target production to the final measurement, performed successfully at the n_TOF facility at CERN in 2014 and 2015. Preliminary results on the ongoing experimental data analysis will also be shown. These results include the first ever experimental observation of capture resonances for these two nuclei.