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The First World War brought devastating consequences for German linguistics. Formerly one of the most prestigious foreign languages taught at schools and universities outside Germany, after the war German disappeared from almost all curricula abroad. Furthermore, it proved impossible to establish a structuralist school (such as the Prague school) in Germany. The article suggests that this was neither due to the long tradition of the Jungian grammarians nor due to the Nazis' official condemnation of structuralism as being incompatible with the ideology of the state. It is shown that such a development should instead be attributed to the so-called "Krieg der Geister" ("war of the intellect"), which remained present even after the military peace (1918) amid a feeling of national insecurity. The article concludes that such a nationalistic social and political environment proved to be fertile ground for Whorfianism, and the influence of the so-called 'Sprachinhaltsforschung' prevailed towards structuralism.
Das Modische : Zu Entstehungsbedingungen und Funktionen einer bestimmten Art von Konformismus
(2016)
Das als "modisch" im engeren Sinn Bezeichnete, die Kleidung, ist durch kurzfristige Wandlungsprozesse charakterisiert und steht dem allgemeinen Verständnis nach im Gegensatz zu den Prinzipien der Dauer und der Beständigkeit, durch welche man die traditionellen Trachten bestimmt sieht. Aber wie ist es dann beispielsweise um die Sinnhaftigkeit der Rede von "Trachtenmode" bestellt? Und wie sehr sind die mit der Kleidermode verbundenen Begleitvorstellungen des Modischen für andere Bereiche des Lebens charakteristisch?
Transverse momentum (pT) spectra of pions, kaons, and protons up to pT=20 GeV/c have been measured in Pb-Pb collisions at sNN−−−√=2.76 TeV using the ALICE detector for six different centrality classes covering 0-80%. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT≈3 GeV/c in central Pb-Pb collisions that decreases towards more peripheral collisions. For pT>10 GeV/c, the nuclear modification factor is found to be the same for all three particle species in each centrality interval within systematic uncertainties of 10-20%. This suggests there is no direct interplay between the energy loss in the medium and the particle species composition in the hard core of the quenched jet. For pT<10 GeV/c, the data provide important constraints for models aimed at describing the transition from soft to hard physics.
The production of J/ψ and ψ(2S) was measured with the ALICE detector in Pb-Pb collisions at the LHC. The measurement was performed at forward rapidity (2.5<y<4) down to zero transverse momentum (pT) in the dimuon decay channel. Inclusive J/ψ yields were extracted in different centrality classes and the centrality dependence of the average pT is presented. The J/ψ suppression, quantified with the nuclear modification factor (RAA), was studied as a function of centrality, transverse momentum and rapidity. Comparisons with similar measurements at lower collision energy and theoretical models indicate that the J/ψ production is the result of an interplay between color screening and recombination mechanisms in a deconfined partonic medium, or at its hadronization. Results on the ψ(2S) suppression are provided via the ratio of ψ(2S) over J/ψ measured in pp and Pb-Pb collisions.
We present measurements of the elliptic (v2), triangular (v3) and quadrangular (v4) anisotropic azimuthal flow over a wide range of pseudorapidities (−3.5<η<5). The measurements are performed with Pb–Pb collisions at √sNN=2.76 TeV using the ALICE detector at the Large Hadron Collider (LHC). The flow harmonics are obtained using two- and four-particle correlations from nine different centrality intervals covering central to peripheral collisions. We find that the shape of vn(η) is largely independent of centrality for the flow harmonics n=2–4, however the higher harmonics fall off more steeply with increasing |η|. We assess the validity of extended longitudinal scaling of v2 by comparing to lower energy measurements, and find that the higher harmonic flow coefficients are proportional to the charged particle densities at larger pseudorapidities. Finally, we compare our measurements to both hydrodynamical and transport models, and find they both have challenges when it comes to describing our data.
Jet-like correlations with neutral pion triggers in pp and central Pb–Pb collisions at 2.76 TeV
(2016)
We present measurements of two-particle correlations with neutral pion trigger particles of transverse momenta 8<pTtrig<16 GeV/c and associated charged particles of 0.5<pTassoc<10 GeV/c versus the azimuthal angle difference Δφ at midrapidity in pp and central Pb–Pb collisions at √sNN=2.76 TeV with ALICE. The new measurements exploit associated charged hadrons down to 0.5 GeV/c, which significantly extends our previous measurement that only used charged hadrons above 3 GeV/c. After subtracting the contributions of the flow background, v2 to v5, the per-trigger yields are extracted for |Δφ|<0.7 on the near and for |Δφ−π|<1.1 on the away side. The ratio of per-trigger yields in Pb–Pb to those in pp collisions, IAA, is measured on the near and away side for the 0–10% most central Pb–Pb collisions. On the away side, the per-trigger yields in Pb–Pb are strongly suppressed to the level of IAA≈0.6 for pTassoc>3 GeV/c, while with decreasing momenta an enhancement develops reaching about 5 at low pTassoc. On the near side, an enhancement of IAA between 1.2 at the highest to 1.8 at the lowest pTassoc is observed. The data are compared to parton-energy-loss predictions of the JEWEL and AMPT event generators, as well as to a perturbative QCD calculation with medium-modified fragmentation functions. All calculations qualitatively describe the away-side suppression at high pTassoc. Only AMPT captures the enhancement at low pTassoc, both on the near and away side. However, it also underpredicts IAA above 5 GeV/c, in particular on the near-side.
Higher harmonic flow coefficients of identified hadrons in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
The elliptic, triangular, quadrangular and pentagonal anisotropic flow coefficients for π±, K± and p+p¯¯¯ in Pb-Pb collisions at sNN−−−√=2.76 TeV were measured with the ALICE detector at the Large Hadron Collider. The results were obtained with the Scalar Product method, correlating the identified hadrons with reference particles from a different pseudorapidity region. Effects not related to the common event symmetry planes (non-flow) were estimated using correlations in pp collisions and were subtracted from the measurement. The obtained flow coefficients exhibit a clear mass ordering for transverse momentum (pT) values below ≈ 3 GeV/c. In the intermediate pT region (3<pT<6 GeV/c), particles group at an approximate level according to the number of constituent quarks, suggesting that coalescence might be the relevant particle production mechanism in this region. The results for pT<3 GeV/c are described fairly well by a hydrodynamical model (iEBE-VISHNU) that uses initial conditions generated by A Multi-Phase Transport model (AMPT) and describes the expansion of the fireball using a value of 0.08 for the ratio of shear viscosity to entropy density (η/s), coupled to a hadronic cascade model (UrQMD). Finally, expectations from AMPT alone fail to quantitatively describe the measurements for all harmonics throughout the measured transverse momentum region. However, the comparison to the AMPT model highlights the importance of the late hadronic rescattering stage to the development of the observed mass ordering at low values of pT and of coalescence as a particle production mechanism for the particle type grouping at intermediate values of pT for all harmonics.
Background: In the context of the investigation of the quark gluon plasma produced in heavy-ion collisions, hadrons containing heavy (charm or beauty) quarks play a special role for the characterization of the hot and dense medium created in the interaction. The measurement of the production of charm and beauty hadrons in proton–proton collisions, besides providing the necessary reference for the studies in heavy-ion reactions, constitutes an important test of perturbative quantum chromodynamics (pQCD) calculations. Heavy-flavor production in proton–nucleus collisions is sensitive to the various effects related to the presence of nuclei in the colliding system, commonly denoted cold-nuclear-matter effects. Most of these effects are expected to modify open-charm production at low transverse momenta (pT) and, so far, no measurement of D-meson production down to zero transverse momentum was available at mid-rapidity at the energies attained at the CERN Large Hadron Collider (LHC).
Purpose: The measurements of the production cross sections of promptly produced charmed mesons in p-Pb collisions at the LHC down to pT=0 and the comparison to the results from pp interactions are aimed at the assessment of cold-nuclear-matter effects on open-charm production, which is crucial for the interpretation of the results from Pb-Pb collisions.
Methods: The prompt charmed mesons D0,D+,D*+, and D+s were measured at mid-rapidity in p-Pb collisions at a center-of-mass energy per nucleon pair √sNN=5.02 TeV with the ALICE detector at the LHC. D mesons were reconstructed from their decays D0→K−π+,D+→K−π+π+, D*+→D0π+,D+s→ϕπ+→K−K+π+, and their charge conjugates, using an analysis method based on the selection of decay topologies displaced from the interaction vertex. In addition, the prompt D0 production cross section was measured in pp collisions at √s=7 TeV and p-Pb collisions at √sNN=5.02 TeV down to pT=0 using an analysis technique that is based on the estimation and subtraction of the combinatorial background, without reconstruction of the D0 decay vertex.
Results: The production cross section in pp collisions is described within uncertainties by different implementations of pQCD calculations down to pT=0. This allowed also a determination of the total c¯c production cross section in pp collisions, which is more precise than previous ALICE measurements because it is not affected by uncertainties owing to the extrapolation to pT=0. The nuclear modification factor RpPb(pT), defined as the ratio of the pT-differential D meson cross section in p-Pb collisions and that in pp collisions scaled by the mass number of the Pb nucleus, was calculated for the four D-meson species and found to be compatible with unity within uncertainties. The results are compared to theoretical calculations that include cold-nuclear-matter effects and to transport model calculations incorporating the interactions of charm quarks with an expanding deconfined medium.
Conclusions: These measurements add experimental evidence that the modification of the D-meson transverse momentum distributions observed in Pb–Pb collisions with respect to pp interactions is due to strong final-state effects induced by the interactions of the charm quarks with the hot and dense partonic medium created in ultrarelativistic heavy-ion collisions. The current precision of the measurement does not allow us to draw conclusions on the role of the different cold-nuclear-matter effects and on the possible presence of additional hot-medium effects in p-Pb collisions. However, the analysis technique without decay-vertex reconstruction, applied on future larger data samples, should provide access to the physics-rich range down to pT=0.
The elliptic flow of electrons from heavy-flavour hadron decays at mid-rapidity (|y| < 0.7) is measured in Pb-Pb collisions at sNN−−−√=2.76 TeV with ALICE at the LHC. The particle azimuthal distribution with respect to the reaction plane can be parametrized with a Fourier expansion, where the second coefficient (v2) represents the elliptic flow. The v2 coefficient of inclusive electrons is measured in three centrality classes (0-10%, 10-20% and 20-40%) with the event plane and the scalar product methods in the transverse momentum (pT) intervals 0.5-13 GeV/c and 0.5-8 GeV/c, respectively. After subtracting the background, mainly from photon conversions and Dalitz decays of neutral mesons, a positive v2 of electrons from heavy-flavour hadron decays is observed in all centrality classes, with a maximum significance of 5.9σ in the interval 2< pT < 2.5 GeV/c in semi-central collisions (20-40%). The value of v2 decreases towards more central collisions at low and intermediate pT (0.5 < pT < 3 GeV/c). The v2 of electrons from heavy-flavour hadron decays at mid-rapidity is found to be similar to the one of muons from heavy-flavour hadron decays at forward rapidity (2.5 < y < 4). The results are described within uncertainties by model calculations including substantial elastic interactions of heavy quarks with an expanding strongly-interacting medium.
We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian PID approach for charged pions, kaons and protons in the central barrel of ALICE is studied. PID is performed via measurements of specific energy loss (dE/dx) and time-of-flight. PID efficiencies and misidentification probabilities are extracted and compared with Monte Carlo simulations using high-purity samples of identified particles in the decay channels K0S→π−π+, ϕ→K−K+, and Λ→pπ− in p-Pb collisions at sNN−−−√=5.02 TeV. In order to thoroughly assess the validity of the Bayesian approach, this methodology was used to obtain corrected pT spectra of pions, kaons, protons, and D0 mesons in pp collisions at s√=7 TeV. In all cases, the results using Bayesian PID were found to be consistent with previous measurements performed by ALICE using a standard PID approach. For the measurement of D0→K−π+, it was found that a Bayesian PID approach gave a higher signal-to-background ratio and a similar or larger statistical significance when compared with standard PID selections, despite a reduced identification efficiency. Finally, we present an exploratory study of the measurement of Λ+c→pK−π+ in pp collisions at s√=7 TeV, using the Bayesian approach for the identification of its decay products.
We report the first results of elliptic (v2), triangular (v3) and quadrangular flow (v4) of charged particles in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurements are performed in the central pseudorapidity region |η|<0.8 and for the transverse momentum range 0.2<pT<5 GeV/c. The anisotropic flow is measured using two-particle correlations with a pseudorapidity gap greater than one unit and with the multi-particle cumulant method. Compared to results from Pb-Pb collisions at sNN−−−√=2.76 TeV, the anisotropic flow coefficients v2, v3 and v4 are found to increase by (3.0±0.6)%, (4.3±1.4)% and (10.2±3.8)%, respectively, in the centrality range 0-50%. This increase can be attributed mostly to an increase of the average transverse momentum between the two energies. The measurements are found to be compatible with hydrodynamic model calculations. This comparison provides a unique opportunity to test the validity of the hydrodynamic picture and the power to further discriminate between various possibilities for the temperature dependence of shear viscosity to entropy density ratio of the produced matter in heavy-ion collisions at the highest energies.
The inclusive production of the ψ(2S) charmonium state was studied as a function of centrality in p-Pb collisions at the nucleon-nucleon center of mass energy sNN−−−√ = 5.02 TeV at the CERN LHC. The measurement was performed with the ALICE detector in the center of mass rapidity ranges −4.46<ycms<−2.96 and 2.03<ycms<3.53, down to zero transverse momentum, by reconstructing the ψ(2S) decay to a muon pair. The ψ(2S) production cross section σψ(2S) is presented as a function of the collision centrality, which is estimated through the energy deposited in forward rapidity calorimeters. The relative strength of nuclear effects on the ψ(2S) and on the corresponding 1S charmonium state J/ψ is then studied by means of the double ratio of cross sections [σψ(2S)/σJ/ψ]pPb/[σψ(2S)/σJ/ψ]pp between p-Pb and pp collisions, and by the values of the nuclear modification factors for the two charmonium states. The results show a large suppression of ψ(2S) production relative to the J/ψ at backward (negative) rapidity, corresponding to the flight direction of the Pb-nucleus, while at forward (positive) rapidity the suppressions of the two states are comparable. Finally, comparisons to results from lower energy experiments and to available theoretical models are presented.
We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (η), ⟨dET/dη⟩, in 0-5% central collisions is 1737 ± 6(stat.) ± 97(sys.) GeV. We find a similar centrality dependence of the shape of ⟨dET/dη⟩ as a function of the number of participating nucleons to that seen at lower energies. The growth in ⟨dET/dη⟩ at the LHC sNN−−−√ exceeds extrapolations of low energy data. We observe a nearly linear scaling of ⟨dET/dη⟩ with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0-5% central Pb-Pb collisions at sNN−−−√ = 2.76 TeV is 12.3 ± 1.0 GeV/fm3\xspace and that the energy density at the most central 80 fm2 of the collision is at least 21.5 ± 1.7 GeV/fm3. This is roughly 2.3 times that observed in 0-5% central Au-Au collisions at sNN−−−√ = 200 GeV.
Correlated event-by-event fluctuations of flow harmonics in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from non-flow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the centre-of-mass energy per nucleon pair of sNN−−−√=2.76 TeV by the ALICE experiment at the Large Hadron Collider (LHC). The centrality dependence of correlation between event-by-event fluctuations of the elliptic, v2, and quadrangular, v4, flow harmonics, as well as of anti-correlation between v2 and triangular, v3, flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry-dominated (in mid-central collisions) and fluctuation-dominated (in the most central collisions). Comparisons are made to predictions from MC-Glauber, viscous hydrodynamics, AMPT and HIJING models. Together with the existing measurements of individual flow harmonics the presented results provide further constraints on initial conditions and the transport properties of the system produced in heavy-ion collisions.
Measurements of charged jet production as a function of centrality are presented for p-Pb collisions recorded at sNN−−−√=5.02 TeV with the ALICE detector. Centrality classes are determined via the energy deposit in neutron calorimeters at zero degree, close to the beam direction, to minimise dynamical biases of the selection. The corresponding number of participants or binary nucleon-nucleon collisions is determined based on the particle production in the Pb-going rapidity region. Jets have been reconstructed in the central rapidity region from charged particles with the anti-kT algorithm for resolution parameters R=0.2 and R=0.4 in the transverse momentum range 20 to 120 GeV/c. The reconstructed jet momentum and yields have been corrected for detector effects and underlying-event background. In the five centrality bins considered, the charged jet production in p-Pb collisions is consistent with the production expected from binary scaling from pp collisions. The ratio of jet yields reconstructed with the two different resolution parameters is also independent of the centrality selection, demonstrating the absence of major modifications of the radial jet structure in the reported centrality classes.
The production of charged pions, kaons and (anti)protons has been measured at mid-rapidity (−0.5<y<0) in p–Pb collisions at √sNN=5.02 TeV using the ALICE detector at the LHC. Exploiting particle identification capabilities at high transverse momentum (pT), the previously published pT spectra have been extended to include measurements up to 20 GeV/c for seven event multiplicity classes. The pT spectra for pp collisions at s=7 TeV, needed to interpolate a pp reference spectrum, have also been extended up to 20 GeV/c to measure the nuclear modification factor (RpPb) in non-single diffractive p–Pb collisions. At intermediate transverse momentum (2<pT<10 GeV/c) the proton-to-pion ratio increases with multiplicity in p–Pb collisions, a similar effect is not present in the kaon-to-pion ratio. The pT dependent structure of such increase is qualitatively similar to those observed in pp and heavy-ion collisions. At high pT (>10 GeV/c), the particle ratios are consistent with those reported for pp and Pb–Pb collisions at the LHC energies. At intermediate pT the (anti)proton RpPb shows a Cronin-like enhancement, while pions and kaons show little or no nuclear modification. At high pT the charged pion, kaon and (anti)proton RpPb are consistent with unity within statistical and systematic uncertainties.
The multi-strange baryon yields in PbPb collisions have been shown to exhibit an enhancement relative to pp reactions. In this work, Ξ and Ω production rates have been measured with the ALICE experiment as a function of transverse momentum, pT, in pPb collisions at a centre-of-mass energy of sNN=5.02 TeV. The results cover the kinematic ranges 0.6 GeV/c<pT<7.2 GeV/c and 0.8 GeV/c<pT<5 GeV/c, for Ξ and Ω respectively, in the common rapidity interval −0.5<yCMS<0. Multi-strange baryons have been identified by reconstructing their weak decays into charged particles. The pT spectra are analysed as a function of event charged-particle multiplicity, which in pPb collisions ranges over one order of magnitude and lies between those observed in pp and PbPb collisions. The measured pT distributions are compared to the expectations from a Blast-Wave model. The parameters which describe the production of lighter hadron species also describe the hyperon spectra in high multiplicity pPb collisions. The yield of hyperons relative to charged pions is studied and compared with results from pp and PbPb collisions. A continuous increase in the yield ratios as a function of multiplicity is observed in pPb data, the values of which range from those measured in minimum bias pp to the ones in PbPb collisions. A statistical model qualitatively describes this multiplicity dependence using a canonical suppression mechanism, in which the small volume causes a relative reduction of hadron production dependent on the strangeness content of the hyperon.
The production of K∗(892)0 and ϕ(1020) mesons has been measured in p–Pb collisions at √sNN = 5.02 TeV. K∗0 and ϕ are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range - 0.5 < y < 0. The transverse momentum spectra, measured as a function of the multiplicity, have a pT range from 0 to 15 GeV/c for K∗0 and from 0.3 to 21 GeV/c for ϕ. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at √s = 7 TeV and Pb–Pb collisions at √sNN = 2.76 TeV. In Pb–Pb and p–Pb collisions, K∗0 and ϕ probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-ϕ ratio are discussed as a function of the multiplicity of the event. The short-lived K∗0 is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.
Three- and four-pion Bose-Einstein correlations are presented in pp, p-Pb, and Pb-Pb collisions at the LHC. We compare our measured four-pion correlations to the expectation derived from two- and three-pion measurements. Such a comparison provides a method to search for coherent pion emission. We also present mixed-charge correlations in order to demonstrate the effectiveness of several analysis procedures such as Coulomb corrections. Same-charge four-pion correlations in pp and p-Pb appear consistent with the expectations from three-pion measurements. However, the presence of non-negligible background correlations in both systems prevent a conclusive statement. In Pb-Pb collisions, we observe a significant suppression of three- and four-pion Bose-Einstein correlations compared to expectations from two-pion measurements. There appears to be no centrality dependence of the suppression within the 0%–50% centrality interval. The origin of the suppression is not clear. However, by postulating either coherent pion emission or large multibody Coulomb effects, the suppression may be explained.
The pseudorapidity density of charged particles (dNch/dη) at mid-rapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sNN−−−√ = 5.02 TeV. It increases with centrality and reaches a value of 1943±54 in |η|<0.5 for the 5% most central collisions. A rise in dNch/dη as a function of sNN−−−√ for the most central collisions is observed, steeper than that observed in proton-proton collisions and following the trend established by measurements at lower energy. The centrality dependence of dNch/dη as a function of the average number of participant nucleons, ⟨Npart⟩, calculated in a Glauber model, is compared with the previous measurement at lower energy. A constant factor of about 1.2 describes the increase in 2⟨Npart⟩⟨dNch/dη⟩ from sNN−−−√ = 2.76 TeV to sNN−−−√ = 5.02 TeV for all centrality intervals, within the measured range of 0-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions.
The production of (anti-)deuteron and (anti-)3He nuclei in Pb-Pb collisions at sNN−−−√ = 2.76 TeV has been studied using the ALICE detector at the LHC. The spectra exhibit a significant hardening with increasing centrality. Combined blast-wave fits of several particles support the interpretation that this behavior is caused by an increase of radial flow. The integrated particle yields are discussed in the context of coalescence and thermal-statistical model expectations. The particle ratios, 3He/d and 3He/p, in Pb-Pb collisions are found to be in agreement with a common chemical freeze-out temperature of Tchem≈156 MeV. These ratios do not vary with centrality which is in agreement with the thermal-statistical model. In a coalescence approach, it excludes models in which nucleus production is proportional to the particle multiplicity and favors those in which it is proportional to the particle density instead. In addition, the observation of 31 anti-tritons in Pb-Pb collisions is reported. For comparison, the deuteron spectrum in pp collisions at s√=7 TeV is also presented. While the p/π ratio is similar in pp and Pb-Pb collisions, the d/p ratio in pp collisions is found to be lower by a factor of 2.2 than in Pb-Pb collisions.
The production of the hypertriton nuclei HΛ3 and H‾Λ¯3 has been measured for the first time in Pb–Pb collisions at sNN=2.76 TeV with the ALICE experiment at LHC. The pT-integrated HΛ3 yield in one unity of rapidity, dN/dy×B.R.(HΛ3→He3,π−)=(3.86±0.77(stat.)±0.68(syst.))×10−5 in the 0–10% most central collisions, is consistent with the predictions from a statistical thermal model using the same temperature as for the light hadrons. The coalescence parameter B3 shows a dependence on the transverse momentum, similar to the B2 of deuterons and the B3 of 3He nuclei. The ratio of yields S3=HΛ3/(He3×Λ/p) was measured to be S3=0.60±0.13(stat.)±0.21(syst.) in 0–10% centrality events; this value is compared to different theoretical models. The measured S3 is compatible with thermal model predictions. The measured HΛ3 lifetime, τ=181−39+54(stat.)±33(syst.)ps is in agreement within 1σ with the world average value.
We report on results obtained with the Event Shape Engineering technique applied to Pb-Pb collisions at sNN−−−√=2.76 TeV. By selecting events in the same centrality interval, but with very different average flow, different initial state conditions can be studied. We find the effect of the event-shape selection on the elliptic flow coefficient v2 to be almost independent of transverse momentum pT, as expected if this effect is due to fluctuations in the initial geometry of the system. Charged hadron, pion, kaon, and proton transverse momentum distributions are found to be harder in events with higher-than-average elliptic flow, indicating an interplay between radial and elliptic flow.
We report on the measurement of freeze-out radii for pairs of identical-charge pions measured in Pb--Pb collisions at sNN−−−√=2.76 TeV as a function of collision centrality and the average transverse momentum of the pair kT. Three-dimensional sizes of the system (femtoscopic radii), as well as direction-averaged one-dimensional radii are extracted. The radii decrease with kT, following a power-law behavior. This is qualitatively consistent with expectations from a collectively expanding system, produced in hydrodynamic calculations. The radii also scale linearly with ⟨dNch/dη⟩1/3. This behaviour is compared to world data on femtoscopic radii in heavy-ion collisions. While the dependence is qualitatively similar to results at smaller sNN−−−√, a decrease in the Rout/Rside ratio is seen, which is in qualitative agreement with specific predictions from hydrodynamic models. The results provide further evidence for the production of a collective, strongly coupled system in heavy-ion collisions at the LHC.
Direct photon production at mid-rapidity in Pb–Pb collisions at √sNN=2.76 TeV was studied in the transverse momentum range 0.9<pT<14 GeV/c. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the ALICE detector material with the e+e− pair reconstructed in the central tracking system. The results of the two methods were combined and direct photon spectra were measured for the 0–20%, 20–40%, and 40–80% centrality classes. For all three classes, agreement was found with perturbative QCD calculations for pT≳5 GeV/c. Direct photon spectra down to pT≈1 GeV/c could be extracted for the 20–40% and 0–20% centrality classes. The significance of the direct photon signal for 0.9<pT<2.1 GeV/c is 2.6σ for the 0–20% class. The spectrum in this pT range and centrality class can be described by an exponential with an inverse slope parameter of (297±12stat±41syst) MeV. State-of-the-art models for photon production in heavy-ion collisions agree with the data within uncertainties.
We report on measurements of a charge-dependent flow using a novel three-particle correlator with ALICE in Pb-Pb collisions at the LHC, and discuss the implications for observation of local parity violation and the Chiral Magnetic Wave (CMW) in heavy-ion collisions. Charge-dependent flow is reported for different collision centralities as a function of the event charge asymmetry. While our results are in qualitative agreement with expectations based on the CMW, the nonzero signal observed in higher harmonics correlations indicates a possible significant background contribution. We also present results on a differential correlator, where the flow of positive and negative charges is reported as a function of the mean charge of the particles and their pseudorapidity separation. We argue that this differential correlator is better suited to distinguish the differences in positive and negative charges expected due to the CMW and the background effects, such as local charge conservation coupled with strong radial and anisotropic flow.
The measurement of prompt D-meson production as a function of multiplicity in p-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC is reported. D0, D+ and D∗+ mesons are reconstructed via their hadronic decay channels in the centre-of-mass rapidity range −0.96<ycms<0.04 and transverse momentum interval 1<pT<24 GeV/c. The multiplicity dependence of D-meson production is examined by either comparing yields in p-Pb collisions in different event classes, selected based on the multiplicity of produced particles or zero-degree energy, with those in pp collisions, scaled by the number of binary nucleon-nucleon collisions (nuclear modification factor); as well as by evaluating the per-event yields in p-Pb collisions in different multiplicity intervals normalised to the multiplicity-integrated ones (relative yields). The nuclear modification factors for D0, D+ and D∗+ are consistent with one another. The D-meson nuclear modification factors as a function of the zero-degree energy are consistent with unity within uncertainties in the measured pT regions and event classes. The relative D-meson yields, calculated in various pT intervals, increase as a function of the charged-particle multiplicity. The results are compared with the equivalent pp measurements at s√=7 TeV as well as with EPOS~3 calculations.
Measurement of D+s production and nuclear modification factor in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
The production of prompt D+s mesons was measured for the first time in collisions of heavy nuclei with the ALICE detector at the LHC. The analysis was performed on a data sample of Pb-Pb collisions at a centre-of-mass energy per nucleon pair, sNN−−−√, of 2.76 TeV in two different centrality classes, namely 0-10% and 20-50%. D+s mesons and their antiparticles were reconstructed at mid-rapidity from their hadronic decay channel D+s→ϕπ+, with ϕ→K−K+, in the transverse momentum intervals 4<pT<12 GeV/c and 6<pT<12 GeV/c for the 0-10% and 20-50% centrality classes, respectively. The nuclear modification factor RAA was computed by comparing the pT-differential production yields in Pb-Pb collisions to those in proton-proton (pp) collisions at the same energy. This pp reference was obtained using the cross section measured at s√=7 TeV and scaled to s√=2.76 TeV. The RAA of D+s mesons was compared to that of non-strange D mesons in the 10% most central Pb-Pb collisions. At high pT (8<pT<12 GeV/c) a suppression of the D+s-meson yield by a factor of about three, compatible within uncertainties with that of non-strange D mesons, is observed. At lower pT (4<pT<8 GeV/c) the values of the D+s-meson RAA are larger than those of non-strange D mesons, although compatible within uncertainties. The production ratios D+s/D0 and D+s\D+ were also measured in Pb-Pb collisions and compared to their values in proton-proton collisions.
The production of prompt charmed mesons D0, D+ and D∗+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at the centre-of-mass energy per nucleon pair, sNN−−−√, of 2.76 TeV. The production yields for rapidity |y|<0.5 are presented as a function of transverse momentum, pT, in the interval 1-36 GeV/c for the centrality class 0-10% and in the interval 1-16 GeV/c for the centrality class 30-50%. The nuclear modification factor RAA was computed using a proton-proton reference at s√=2.76 TeV, based on measurements at s√=7 TeV and on theoretical calculations. A maximum suppression by a factor of 5-6 with respect to binary-scaled pp yields is observed for the most central collisions at pT of about 10 GeV/c. A suppression by a factor of about 2-3 persists at the highest pT covered by the measurements. At low pT (1-3 GeV/c), the RAA has large uncertainties that span the range 0.35 (factor of about 3 suppression) to 1 (no suppression). In all pT intervals, the RAA is larger in the 30-50% centrality class compared to central collisions. The D-meson RAA is also compared with that of charged pions and, at large pT, charged hadrons, and with model calculations.
Measurement of an excess in the yield of J/ψ at very low pT in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (pT<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sNN−−−√ = 2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor of J/ψ in the rapidity range 2.5<y<4 reaches about 7 (2) in the pT range 0-0.3 GeV/c in the 70-90% (50-70%) centrality class. The J/ψ production cross section associated with the observed excess is obtained under the hypothesis that coherent photoproduction of J/ψ is the underlying physics mechanism. If confirmed, the observation of J/ψ coherent photoproduction in Pb-Pb collisions at impact parameters smaller than twice the nuclear radius opens new theoretical and experimental challenges and opportunities. In particular, coherent photoproduction accompanying hadronic collisions may provide insight into the dynamics of photoproduction and nuclear reactions, as well as become a novel probe of the Quark-Gluon Plasma.
We report on the inclusive production cross sections of J/ψ, ψ(2S), Υ(1S), Υ(2S) and Υ(3S), measured at forward rapidity with the ALICE detector in pp collisions at a center-of-mass energy s√=8 TeV. The analysis is based on data collected at the LHC and corresponds to an integrated luminosity of 1.28 pb−1. Quarkonia are reconstructed in the dimuon-decay channel. The differential production cross sections are measured as a function of the transverse momentum pT and rapidity y, over the pT ranges 0<pT<20 GeV/c for J/ψ, 0<pT<12 GeV/c for all other resonances, and for 2.5<y<4. The cross sections, integrated over pT and y, and assuming unpolarized quarkonia, are σJ/ψ=8.98±0.04±0.82 μb, σψ(2S)=1.23±0.08±0.22 μb, σΥ(1S)=71±6±7 nb, σΥ(2S)=26±5±4 nb and σΥ(3S)=9±4±1 nb, where the first uncertainty is statistical and the second one is systematic. These values agree, within at most 1.4σ, with measurements performed by the LHCb collaboration in the same rapidity range.
We report on two-particle charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions as a function of the pseudorapidity and azimuthal angle difference, Δη and Δφ respectively. These correlations are studied using the balance function that probes the charge creation time and the development of collectivity in the produced system. The dependence of the balance function on the event multiplicity as well as on the trigger and associated particle transverse momentum (pT) in pp, p-Pb, and Pb-Pb collisions at sNN−−−√=7, 5.02, and 2.76 TeV, respectively, are presented. In the low transverse momentum region, for 0.2<pT<2.0 GeV/c, the balance function becomes narrower in both Δη and Δφ directions in all three systems for events with higher multiplicity. The experimental findings favor models that either incorporate some collective behavior (e.g. AMPT) or different mechanisms that lead to effects that resemble collective behavior (e.g. PYTHIA8 with color reconnection). For higher values of transverse momenta the balance function becomes even narrower but exhibits no multiplicity dependence, indicating that the observed narrowing with increasing multiplicity at low pT is a feature of bulk particle production.
The centrality dependence of the charged-particle pseudorapidity density measured with ALICE in Pb–Pb collisions at √sNN=2.76 TeV over a broad pseudorapidity range is presented. This Letter extends the previous results reported by ALICE to more peripheral collisions. No strong change of the overall shape of charged-particle pseudorapidity density distributions with centrality is observed, and when normalised to the number of participating nucleons in the collisions, the evolution over pseudorapidity with centrality is likewise small. The broad pseudorapidity range (−3.5<η<5) allows precise estimates of the total number of produced charged particles which we find to range from 162±22(syst.) to 17170±770(syst.) in 80–90% and 0–5% central collisions, respectively. The total charged-particle multiplicity is seen to approximately scale with the number of participating nucleons in the collision. This suggests that hard contributions to the charged-particle multiplicity are limited. The results are compared to models which describe dNch/dη at mid-rapidity in the most central Pb–Pb collisions and it is found that these models do not capture all features of the distributions.
In ∼30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we performed exome sequencing of leukocyte DNA from 102 unrelated individuals with unexplained adenomatous polyposis. We identified two unrelated individuals with differing compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3. The impact of the MSH3 mutations (c.1148delA, c.2319−1G>A, c.2760delC, and c.3001−2A>C) was indicated at the RNA and protein levels. Analysis of the diseased individuals’ tumor tissue demonstrated high microsatellite instability of di- and tetranucleotides (EMAST), and immunohistochemical staining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effect and causal relevance of the mutations. The pedigrees, genotypes, and frequency of MSH3 mutations in the general population are consistent with an autosomal-recessive mode of inheritance. Both index persons have an affected sibling carrying the same mutations. The tumor spectrum in these four persons comprised colorectal and duodenal adenomas, colorectal cancer, gastric cancer, and an early-onset astrocytoma. Additionally, we detected one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch-repair deficiency. Potentially causative variants in 14 more candidate genes identified in 26 other individuals require further workup. In the present study, we identified biallelic germline MSH3 mutations in individuals with a suspected hereditary tumor syndrome. Our data suggest that MSH3 mutations represent an additional recessive subtype of colorectal adenomatous polyposis.
Prosodie ist nach neuesten Untersuchungen das wichtigste Merkmal der deutschen Sprache und umfasst auditiv wahrnehmbare Merkmale wie Akzent, Rhythmus, Stimmfarbe, Melodie, Lautheit, Sprechgeschwindigkeit, Pausen usw. Die Funktionen, die durch die Prosodie im Deutschen erfüllt werden, sind sehr vielschichtig und tragen eindeutig zur besseren Verständlichkeit und zum reibungsloseren Verlauf der Kommunikation bei. In den letzten Jahren hat man zahlreiche Untersuchungen auf dem Gebiet phonetischer Fehlleistungen ausländischer Deutschlerner durchgeführt. Es zeigte sich rasch, dass die Fehler, die den kommunikativen Erfolg von Sprechakten am stärksten beeinträchtigen, in den Bereich der prosodischen Realisierung fallen.
Background: It is occasionally difficult to distinguish the stellate reticulum-like region of ameloblastoma from the fibrous connective tissue stroma. This difficulty is further pronounced in the plexiform variant of ameloblastoma that has very sparse fibrous connective tissue.
Aim: To test the utility of Azan trichrome stain in marking tumour regions and the peri-tumour environment of ameloblastoma.
Materials and Methods: Sections were prepared for 18 formalin fixed paraffin-embedded blocks of ameloblastoma cases and stained with Azan trichrome stain according to the manufacturer's specification.
Results and Conclusions: The tumour areas were stained mostly brown, with the ameloblasts mainly marked as deep brown while the stellate reticulum-like region was light brown. The structures in the peri-tumour region were marked with different shades of blue. Azan trichrome staining was able to distinguish between the fibrous connective tissue and the stellate reticulum-like areas in 100% of the cases.
In ihrem Gespräch beschäftigen sich Prof. Dr. Bekim Agai, geschäftsführender Direktor des Instituts für Studien der Kultur und Religion des Islam, und Ulrike Jaspers, Redakteurin von "Forschung Frankfurt", mit dem Wahrheitsanspruch der Religionen, der Debattenkultur in Deutschland, der jungen islamischen Theologie, den fundamentalistischen Strömungen und anderem mehr.
Este texto tem como propósito analisar a construção crítica teórica de Axel Honneth das instituições sociais como efetivação da liberdade social que oferece condições para a autorrealização e a justiça. O método do trabalho consiste em se realizar a leitura interna do desenvolvimento na obra do autor à luz de sua consonância com a teoria crítica. Como conclusão discute-se em que medida o progresso moral dessas instituições se relaciona com a efetivação de seu princípio interno, de forma imanente, ou de uma pressão externa normativa da igualdade a partir do direito e da democracia.
Die steigende Nachfrage nach großmaßstäblichen Standorts-und Bodeninformationen im Bereich der forstlichen Planungs- und Entscheidungsunterstützung umfasst auch die Grundwasserflurabstände. Diese gehen entweder direkt in statistische und prozessorientierte Modelle ein oder sind eine wichtige Grundlage für die digitale Standortsprognose. In dieser Untersuchung wurde für das niedersächsische Tiefland ein Disaggregierungsansatz entwickelt, mit dem der mittlere Grundwassertiefstand (MNGW) der flächendeckenden BÜK50 von Niedersachsen (1 : 50000) in die Grundwasserflurabstandseinstufung der Standortskartierung (1 : 25000) übersetzt werden kann, die nicht flächendeckend vorliegt. Die Ergebnisse zeigen, dass durch die Disaggregierung eine Verbesserung der Ableitung von Grundwasserinformation für Waldstandorte aus der BÜK50 erreicht werden kann. Die Genauigkeit (AC) erhöhte sich von 0,64 auf 0,69 und der Kappa-Koeffizient von 0,34 auf 0,48. Trotzdem ist die Übereinstimmung zwischen modellierten und kartierten Einstufungen mit einem Kappa-Koeffizienten von 0,48 des Validierungsdatensatzes nur als „moderat“ zu bezeichnen.
In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion. Among these associations (peaks) we focused our attention on those proximal to the regulatory region of HOTAIR and MALAT1. These transcripts appeared regulated by estrogens and able to control ERs function by interacting with ERα/ERβ as indicated by RNA-ChIP. Further studies performed by ChIRP revealed that in unstimulated condition, HOTAIR and MALAT1 were present on pS2, hTERT and HOTAIR promoters at the ERE/eNOS peaks. Interestingly, upon treatment with17β-estradiol HOTAIR recruitment to chromatin increased significantly while that of MALAT1 was reduced, suggesting an opposite regulation and function for these lncRNAs. Similar results were obtained in cells and in an ex vivo prostate organotypic slice cultures. Overall, our data provide evidence of a crosstalk between lncRNAs, estrogens and estrogen receptors in prostate cancer with important consequences on gene expression regulation.
Çeviri eyleminin yüzyıllarla ifade edilen ve Milattan önceki devirlere kadar uzanan tarihine karşın çeviri etkinliğinin öğretilebilir bir olgu olarak ele alınması, bilindiği üzere yeni bir konudur. Bu öğretme işinin eğitme biçimiyle ele alınıp üniversiter eğitim modelleri ile ele alınması ise, görece çok daha yeni bir görüngüdür. Türkiye'de de son birkaç on yıldır çeviri eğitimi veren akademik birimlerin varlığı ile konu tamamı ile akademik mecraya taşınmış ve tartışılmaya başlanmıştır. Bu tartışmalar ise, akademik çeviri eğitimi yoluyla oluşturulması ve/veya geliştirilmesi amaçlanan 'çeviri edinci' kavramı üzerinden yürütülmektedir. Çeviri edinci, akademik çeviri eğitimi açısından merkezi bir konu olarak değerlendirilebilir. Çünkü 'çeviri edinci'nin nasıl tanımlandığı, verilen eğitimin içeriğini ve usulünü belirleyebilecek denli temel bir sorgulamadır. Bu çalışmada 'çeviri edinci' kavramı tanımlanmaya çalışılacak, buradan hareketle akademik çeviri eğitiminin koşulları ve çevirmenin öznitelikleri içeriklendirilmeye çalışılacaktır.
The neuronal transcriptome changes dynamically to adapt to stimuli from the extracellular and intracellular environment. In this study, we adapted for the first time a click chemistry technique to label the newly synthesized RNA in cultured hippocampal neurons and intact larval zebrafish brain. Ethynyl uridine (EU) was incorporated into neuronal RNA in a time- and concentration-dependent manner. Newly synthesized RNA granules observed throughout the dendrites were colocalized with mRNA and rRNA markers. In zebrafish larvae, the application of EU to the swim water resulted in uptake and labeling throughout the brain. Using a GABA receptor antagonist, PTZ (pentylenetetrazol), to elevate neuronal activity, we demonstrate that newly transcribed RNA signal increased in specific regions involved in neurogenesis.
The CBM experiment (FAIR/GSI, Darmstadt, Germany) will focus on the measurement of rare probes at interaction rates up to 10MHz with data flow of up to 1 TB/s. It requires a novel read-out and data-acquisition concept with self-triggered electronics and free-streaming data. In this case resolving different collisions is a non-trivial task and event building must be performed in software online. That requires full online event reconstruction and selection not only in space, but also in time, so-called 4D event building and selection. This is a task of the First-Level Event Selection (FLES).
The FLES reconstruction and selection package consists of several modules: track finding, track fitting, short-lived particles finding, event building and event selection. The Cellular Automaton (CA) track finder algorithm was adapted towards time-based reconstruction. In this article, we describe in detail the modification done to the algorithm, as well as the performance of the developed time-based CA approach.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection.
Study of hard core repulsive interactions in an hadronic gas from a comparison with lattice QCD
(2016)
We study the influence of hard-core repulsive interactions within the Hadron-Resonace Gas model in comparison to first principle calculation performed on a lattice. We check the effect of a bag-like parametrization for particle eigenvolume on flavor correlators, looking for an extension of the agreement with lattice simulations up to higher temperatures, as was yet pointed out in an analysis of hadron yields measured by the ALICE experiment. Hints for a flavor depending eigenvolume are present.
The sequenced genome of the poly-extremophile Exiguobacterium sp. S17, isolated from modern stromatolites at Laguna Socompa (3,570 m), a High-Altitude Andean Lake (HAAL) in Argentinean Puna revealed a putative proteorhodopsin-encoding gene. The HAAL area is exposed to the highest UV irradiation on Earth, making the microbial community living in the stromatolites test cases for survival strategies under extreme conditions. The heterologous expressed protein E17R from Exiguobacterium (248 amino acids, 85% sequence identity to its ortholog ESR from E. sibiricum) was assembled with retinal displaying an absorbance maximum at 524 nm, which makes it a member of the green-absorbing PR-subfamily. Titration down to low pH values (eventually causing partial protein denaturation) indicated a pK value between two and three. Global fitting of data from laser flash-induced absorption changes gave evidence for an early red-shifted intermediate (its formation being below the experimental resolution) that decayed (τ1 = 3.5 μs) into another red-shifted intermediate. This species decayed in a two-step process (τ2 = 84 μs, τ3 = 11 ms), to which the initial state of E17-PR was reformed with a kinetics of 2 ms. Proton transport capability of the HAAL protein was determined by BLM measurements. Additional blue light irradiation reduced the proton current, clearly identifying a blue light absorbing, M-like intermediate. The apparent absence of this intermediate is explained by closely matching formation and decay kinetics.
Background and aims: Despite the clinical importance of atherosclerosis, the origin of cells within atherosclerotic plaques is not fully understood. Due to the lack of a definitive lineage-tracing strategy, previous studies have provided controversial results about the origin of cells expressing smooth muscle and macrophage markers in atherosclerosis. We here aim to identify the origin of vascular smooth muscle (SM) cells and macrophages within atherosclerosis lesions.
Methods: We combined a genetic fate mapping approach with single cell expression analysis in a murine model of atherosclerosis.
Results: We found that 16% of CD68-positive plaque macrophage-like cells were derived from mature SM cells and not from myeloid sources, whereas 31% of αSMA-positive smooth muscle-like cells in plaques were not SM-derived. Further analysis at the single cell level showed that SM-derived CD68+ cells expressed higher levels of inflammatory markers such as cyclooxygenase 2 (Ptgs2, p = 0.02), and vascular cell adhesion molecule (Vcam1, p = 0.05), as well as increased mRNA levels of genes related to matrix synthesis such as Col1a2 (p = 0.01) and Fn1 (p = 0.04), than non SM-derived CD68+ cells.
Conclusions: These results demonstrate that smooth muscle cells within atherosclerotic lesions can switch to a macrophage-like phenotype characterized by higher expression of inflammatory and synthetic markers genes that may further contribute to plaque progression.
Stroke is a major public health issue worldwide. The prevalence of stroke in 2010 was 33 million, with 16.9 million people having a first stroke.1 Stroke was the second‐leading cause of death behind heart disease globally, accounting for over 10% of total deaths worldwide.
Stroke is a heterogeneous condition that can be due to rupture of a blood vessel (hemorrhagic) or to blockage of a vessel (ischemic). About 85% of strokes are ischemic in origin and these are often classified by mechanism. This should be distinguished from risk factors such as hypertension, diabetes, smoking, etc. Risk factors increase the risk of stroke but do not necessarily explain the mechanism of a particular stroke. About 25% of ischemic strokes have a radiographic appearance similar to that seen in patients with cardioembolic sources (such as atrial fibrillation [AF], prosthetic valves, valvular prolapse, or mitral valve regurgitation), but no embolic source is found. These "cryptogenic strokes" (CS; also called embolic strokes of undetermined source) pose a particular clinical challenge in that the optimal antithrombotic therapy to reduce recurrence is uncertain. Since there are currently no data to support long‐term oral anticoagulation (OAC) in CS, but also no specific trials that have addressed this question, guidelines recommend antiplatelet therapy. Identification of AF in these patients changes the most likely mechanism to cardioembolism, and thus changes the recommended antithrombotic therapy to OAC, which is extremely effective in preventing stroke in patients with AF.
This report is based on discussions held at The Diagnostics and Monitoring Stroke Focus Group, a meeting held on January 15 to 17, 2015. The meeting focused on CS as a healthcare issue, and the utility of extended cardiac monitoring for AF in patients with strokes of unknown origin. The objectives of the meeting were to review existing information on the subject, define areas where knowledge was lacking or limited, and discuss study designs by which information gaps might be filled.
Il saggio si propone di approfondire due tendenze tipiche della musica contemporanea: la prima è il Minimalismo, movimento rappresentato da musicisti come La Monte Young, Philip Glass and Steve Reich, la seconda è la rave music (come la techno), caratteristica della popular culture nell’era postmoderna. Attraverso il pensiero di Adorno, e a partire dalla sua analisi dialettica del dualismo Schönberg-Stravinskij, il saggio propone una comprensione filosofica di concetti come “ripetizione” e “trascendenza”; l’assenza dello “sviluppo” in gran parte della produzione musicale degli ultimi decenni, nella popular music quanto nella musica colta, dimostra una dispersione del soggetto e dell’individuo, smarrito all’interno di un “eterno ritorno” della struttura ritmica che può essere ricompreso nei termini di un “eterno ritorno dell’identico” e non nei termini di un “eterno ritorno della possibilità”; in quest’ottica, a venire sacrificata è anche la dimensione della trascendenza, che non a caso viene ricercata spesso nell’esotismo dei culti orientali o nel consumo di sostanze stupefacenti. L’insistenza nel Minimalismo della ripetizione come unica ed estrema categoria di riferimento e norma estetica, produrrà infatti nel corso degli ultimi anni una dicotomia apparentemente contraddittoria, ma che invece esprime la medesima matrice logica: da un lato l’invasamento edonistico del beat elettronico della musica dance elettronica, dall’altro la proposta commerciale della produzione industriale della musica pop. Non è un caso che proprio il Minimalismo sia sfociato in entrambe queste due tendenze, mostrandosi come la cifra comune originaria, traducendosi nella musica rave o nella musica rock.
The genus Thlaspi has been variously subdivided since its description by Linnaeus in 1753, but due to similarities in fruit shape several segregates have still not gained broad recognition, despite the fact that they are not directly related to Thlaspi. This applies especially to segregates now considered to belong to the tribe Coluteocarpeae, which includes several well-studied taxa, e.g., Noccaea caerulescens (syn. Thlaspi caerulescens), and the widespread Microthlaspi perfoliatum (syn. Thlaspi perfoliatum). The taxonomy of this tribe is still debated, as a series of detailed monographs on Coluteocarpeae was not published in English and a lack of phylogenetic resolution within this tribe was found in previous studies. The current study presents detailed phylogenetic investigations and a critical review of morphological features, with focus on taxa previously placed in Microthlaspi. Based on one nuclear (ITS) and two chloroplast (matK, trnL-F) loci, four strongly supported major groups were recovered among the Coluteocarpeae genera included, corresponding to Ihsanalshehbazia gen. nov., Friedrichkarlmeyeria gen. nov., Microthlaspi s.str., and Noccaea s.l. In addition, two new species of Microthlaspi, M. sylvarum-cedri sp. nov. and M. mediterraneo-orientale sp. nov., were discovered, which are well supported by both morphological and molecular data. Furthermore, M. erraticum comb. nov. (diploid) and M. perfoliatum s.str. (polyploid) were shown to be distinct species, phylogenetically widely separate, but with some overlap in several morphological characters. Detailed descriptions, notes on taxonomy, geographical distribution, and line drawings for the new species and each species previously included in Microthlaspi are provided. In addition, the current taxonomic state of the tribe Coluteocarpeae is briefly discussed and it is concluded that while several annual taxa are clearly distinct from Noccaea, many perennial taxa, after thorough phylogenetic and morphological investigations, may have to be merged with this genus.
IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in childhood B-cell precursor acute lymphoblastic leukemia. Because of its clinical importance, we previously mapped breakpoints of intragenic deletions and developed a multiplex PCR assay to detect recurrent intragenic ΔIKZF1. Since the multiplex PCR was not able to detect complete deletions (IKZF1 Δ1-8), which account for ~30% of all ΔIKZF1, we aimed at investigating the genomic scenery of IKZF1 Δ1-8. Six samples of cases with IKZF1 Δ1-8 were analyzed by microarray assay, which identified monosomy 7, isochromosome 7q, and large interstitial deletions presenting breakpoints within COBL gene. Then, we established a multiplex ligation-probe amplification (MLPA) assay and screened copy number alterations within chromosome 7 in 43 diagnostic samples with IKZF1 Δ1-8. Our results revealed that monosomy and large interstitial deletions within chromosome 7 are the main causes of IKZF1 Δ1-8. Detailed analysis using long distance inverse PCR showed that six patients (16%) had large interstitial deletions starting within intronic regions of COBL at diagnosis, which is ~611 Kb downstream of IKZF1, suggesting that COBL is a hotspot for ΔIKZF1. We also investigated a series of 25 intragenic deletions (Δ2–8, Δ3–8 or Δ4–8) and 24 relapsed samples, and found one IKZF1-COBL tail-to-tail fusion, thus supporting that COBL is a novel hotspot for ΔIKZF1. Finally, using RIC score methodology, we show that breakpoint sequences of IKZF1 Δ1-8 are not analog to RAG-recognition sites, suggesting a different mechanism of error promotion than that suggested for intragenic ΔIKZF1.
Biallelic mutations in TMEM126B cause severe complex i deficiency with a variable clinical phenotype
(2016)
Complex I deficiency is the most common biochemical phenotype observed in individuals with mitochondrial disease. With 44 structural subunits and over 10 assembly factors, it is unsurprising that complex I deficiency is associated with clinical and genetic heterogeneity. Massively parallel sequencing (MPS) technologies including custom, targeted gene panels or unbiased whole-exome sequencing (WES) are hugely powerful in identifying the underlying genetic defect in a clinical diagnostic setting, yet many individuals remain without a genetic diagnosis. These individuals might harbor mutations in poorly understood or uncharacterized genes, and their diagnosis relies upon characterization of these orphan genes. Complexome profiling recently identified TMEM126B as a component of the mitochondrial complex I assembly complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1. Here, we describe the clinical, biochemical, and molecular findings in six cases of mitochondrial disease from four unrelated families affected by biallelic (c.635G>T [p.Gly212Val] and/or c.401delA [p.Asn134Ilefs∗2]) TMEM126B variants. We provide functional evidence to support the pathogenicity of these TMEM126B variants, including evidence of founder effects for both variants, and establish defects within this gene as a cause of complex I deficiency in association with either pure myopathy in adulthood or, in one individual, a severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy. Functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined.
Este texto é uma resposta ao texto de Fernando de Moraes Barros, intitulado “Ontologia coercitiva da obra de arte: Adorno contra Heidegger”. Em linhas gerais, trata-se de um exame do funcionamento interno do texto “A origem da obra de arte”, de Heidegger. Assume-se a coexistência de dois eixos no texto de Heidegger, um crítico, compatível com o pensamento de Adorno, e outro ontológico, incompatível com a reflexão de Adorno sobre a arte.
O estudo aqui desenvolvido trata da formação da consciência social tensionada pela alienação e emancipação intersubjetiva. O problema da pesquisa é saber como o agir comunicativo de Habermas pode contribuir para a formação da consciência social/ética, contraposta aos processos de alienação. Para tanto, será feito uma releitura histórico-conceitual de alguns pontos da filosofia habermasiana. Objetiva-se, assim, discutir quais os principais elementos da Teoria do Agir Comunicativo contribuem para a formação de uma consciência social que concilie comunidade e pluralidade. Os sujeitos inevitavelmente fazem parte de certos contextos. Participar de um contexto/comunidade, exige uma consciência social atravessando as relações, o que implica co-responsabilidade e cooperação. Por fim, a formação de uma consciência sócio-ética só é possível através de uma comunicação aberta e argumentativa, cuja normatividade traz uma pretensão de validade pública.
Capoeta damascina was earlier considered by many authors as one of the most common freshwater fish species found throughout the Levant, Mesopotamia, Turkey, and Iran. However, owing to a high variation in morphological characters among and within its various populations, 17 nominal species were described, several of which were regarded as valid by subsequent revising authors. Capoeta damascina proved to be a complex of closely related species, which had been poorly studied. The current study aims at defining C. damascina and the C. damascina species complex. It investigates phylogenetic relationships among the various members of the C. damascina complex, based on mitochondrial and nuclear DNA sequences. Phylogenetic relationships were projected against paleogeographical events to interpret the geographic distribution of the taxa under consideration in relation to the area’s geological history. Samples were obtained from throughout the geographic range and were subjected to genetic analyses, using two molecular markers targeting the mitochondrial cytochrome oxidase I (n = 103) and the two adjacent divergence regions (D1-D2) of the nuclear 28S rRNA genes (n = 65). Six closely related species were recognized within the C. damascina complex, constituting two main lineages: A western lineage represented by C. caelestis, C. damascina, and C. umbla and an eastern lineage represented by C. buhsei, C. coadi, and C. saadii. The results indicate that speciation of these taxa is rather a recent event. Dispersal occurred during the Pleistocene, resulting in present-day distribution patterns. A coherent picture of the phylogenetic relationships and evolutionary history of the C. damascina species complex is drawn, explaining the current patterns of distribution as a result of paleogeographic events and ecological adaptations.
Através da ideia de quimera, esse ensaio tentará compreender a constituição aberta do personagem Odradek, da narrativa curta "A preocupação do pai de família" de Franz Kafka. O interestante nessa construção literária seria o deslocamento (inclusive das possibilidades de expressão de gênero nas línguas) que Odradek impõe ao esforço constante do narrador (representante de grupos sociais específicos) em categorizá-lo e, por consequência, do leitor, que tentaria encerrá-lo num tipo fechado de interpretação. Odradek parece um tipo de ser incapturável pelas principais categorias, sejam elas literárias, biológicas ou sociais, que ajudaram a fundar a ideia de Modernidade.
Mitochondrial cristae are connected to the inner boundary membrane via crista junctions which are implicated in the regulation of oxidative phosphorylation, apoptosis, and import of lipids and proteins. The MICOS complex determines formation of crista junctions. We performed complexome profiling and identified Mic13, also termed Qil1, as a subunit of the MICOS complex. We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex. Using the CRISPR/Cas method we generated the first cell line deleted for MIC13. These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions. MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex suggesting that the latter is not sufficient for crista junction formation. MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration. In summary, we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.
BACKGROUND: We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean-dose-optimized and real-time motion-compensated robotic stereotactic body radiation therapy (SBRT) in the treatment of liver metastases.
METHODS: Between March 2011 and July 2015, 52 patients were treated with SBRT for a total of 91 liver metastases (one to four metastases per patient) with a median GTV volume of 12 cc (min 1 cc, max 372 cc). The optimization of mean GTV dose was prioritized during treatment planning at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The delivered median GTV biological effective dose (BED10) was 142.1 Gy10 (range, 60.2 Gy10 -165.3 Gy10) and the prescribed PTV BED10 ranged from 40.6 Gy10 to 112.5 Gy10 (median, 86.1 Gy10). We analyzed local control (LC), progression-free interval (PFI), overall survival (OS), and toxicity.
RESULTS: Median follow-up was 17 months (range, 2-49 months). The 2-year actuarial LC, PFI, and OS rates were 82.1, 17.7, and 45.0 %, and the median PFI and OS were 9 and 23 months, respectively. In univariate analysis histology (p < 0.001), PTV prescription BED10 (HR 0.95, CI 0.91-0.98, p = 0.002) and GTV mean BED10 (HR 0.975, CI 0.954-0.996, p = 0.011) were predictive for LC. Multivariate analysis showed that only extrahepatic disease status at time of treatment was a significant factor (p = 0.033 and p = 0.009, respectively) for PFI and OS. Acute nausea or fatigue grade 1 was observed in 24.1 % of the patients and only 1 patient (1.9 %) had a side effect of grade ≥ 2.
CONCLUSIONS: Robotic real-time motion-compensated SBRT is a safe and effective treatment for one to four liver metastases. Reducing the PTV prescription dose and keeping a high mean GTV dose allowed the reduction of toxicity while maintaining a high local control probability for the treated lesions.
Introduction: The Helicopter Emergency Medical Service (HEMS) was established for the prehospital trauma care of patients. Improved rescue times and increased coverage areas are discussed as specific advantages of HEMS. We recently found evidence that HEMS exerts beneficial effects on outcomes for severely injured patients. However, it still remains unknown which group of trauma patients might benefit most from HEMS rescue. Consequently, the unique aim of this study was to reveal which patients might benefit most from HEMS rescue.
Methods: Trauma patients (ISS ≥9) primarily treated by HEMS or ground emergency medical services (GEMS) between 2002 and 2012 were analysed using the TraumaRegister DGU. A multivariate regression analysis was used to reveal the survival benefit between different trauma populations.
Results: The study included 52 281 trauma patients. Of these, 68.8% (35 974) were rescued by GEMS and 31.2% (16 307) by HEMS. HEMS patients were more severely injured compared to GEMS patients (ISS: HEMS 24.8±13.5 vs. GEMS 21.7±18.0) and more frequently suffered traumatic shock (SBP sys <90mmHg: HEMS 18.3% vs. GEMS 14.8%). However, logistic regression analysis revealed that HEMS rescues resulted in an overall survival benefit compared to GEMS (OR 0.81, 95% CI [0.75–0.87], p<0.001, Nagelkerke's R squared 0.526, area under the ROC curve 0.922, 95% CI [0.919–0.925]). Analysis of specific subgroups demonstrated that patients aged older than 55 years (OR 0.62, 95% CI [0.50–0.77]) had the highest survival benefit after HEMS treatment. Furthermore, HEMS rescue had the most significant impact after ‘low falls’ (OR 0.68, 95% CI [0.55–0.84]) and in the case of minor severity injuries (ISS 9–15) (OR 0.66, 95% CI [0.49–0.88]).
Conclusions: In general, trauma patients benefit from HEMS rescue with in-hospital survival as the main outcome parameter. Focusing on special subgroups, middle aged and older patients, low-energy trauma, and minor severity injuries had the highest survival benefit when rescued by HEMS. Further studies are required to determine the potential reasons of this benefit.
Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of “high risk” patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.
Axel Honneth propone, inspirándose en el joven Hegel, una concepción de la justicia basada en la idea de reconocimiento. Dicha concepción parte del previo acercamiento a una serie de fenómenos negativos, los cuales define como fallas en el reconocimiento. Desde la óptica de Honneth los fenómenos negativos constituyen patologías sociales y formas de injusticia, debido a la falta de calidad moral de las relaciones intersubjetivas. Las consecuencias socio-psicológicas en las personas que los sufren son la construcción de una identidad dañada y dificultades en el logro de la autorrealización. El presente artículo pretende realizar, recogiendo el planteamiento de Honneth, un análisis ético-político de los fenómenos de estigmatización, invisibilización y cosificación sufridos por las personas con diversidad funcional, llegando a la conclusión de que tales fenómenos suponen la negación de la dignidad personal, en la que reside el fundamento de la justicia que nos debemos unos a otros.
Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal) under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3) and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells) showed strong β-gal labeling. In the inner nuclear layer (INL), a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic ‘starburst’ amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.
Background: NH exchangers (NHEs) play a crucial role in regulating intra/extracellular pH, which is altered in cancer cells, and are therefore suitable targets to alter cancer cell metabolism in order to inhibit cell survival and proliferation. Among NHE inhibitors, amiloride family members are commonly used in clinical practice as diuretics; we focused on the amiloride HMA, reporting a net cytotoxic effect on a panel of human cancer cell lines; now we aim to provide new insights into the molecular events leading to cell death by HMA.
Methods: Colon cancer cell lines were treated with HMA and analysed with: morphological and cellular assays for cell viability and death, and autophagy; biochemical approaches to evaluate mitochondrial function and ROS production; in situ detection of DNA damage; molecular tools to silence crucial autophagy/necroptosis factors.
Results: HMA affects cellular morphology, alters mitochondrial structure and function, causes an increase in ROS, which is detrimental to DNA integrity, stimulates poly(ADP-ribose) synthesis, activates RIPK3-dependent death and triggers autophagy, which is unable to rescue cell survival. These features are hot points of an intricate network of processes, including necroptosis and autophagy, regulating the homeostasis between survival and death.
Conclusion: Our results allow the identification of multiple events leading to cell death in cancer cells treated with HMA. The here-defined intricate network activated by HMA could be instrumental to selectively target the key players of each pathway in the attempt to improve the global response to HMA. Our data could be the starting point for developing a newly designed targeted therapy.
Hundreds of genes have been associated with respiratory chain disease (RCD), the most common inborn error of metabolism so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, ρ0 cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. In this study, proteomic data sets including the post-translational modifications (PTMs) phosphorylation and ubiquitination were integrated with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK−. A shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach was applied to elucidate the consequences of the ρ0 state. Pathway and protein–protein interaction (PPI) network analyses revealed a nonuniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle, and the pyruvate metabolism in ρ0 cells. Metabolites of the TCA cycle were dysregulated, such as a reduction of citric acid and cis-aconitic acid (six and 2.5-fold), and an increase of lactic acid, oxalacetic acid (both twofold), and succinic acid (fivefold) in ρ0 cells. Signaling pathways such as GPCR, EGFR, G12/13 alpha, and Rho GTPases were up-regulated in ρ0 cells, which could be indicative for the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus. This was supported by our phosphoproteome data, which revealed two main processes, GTPase-related signal transduction and cytoskeleton organization. Furthermore, a general de-ubiquitination in ρ0 cells was observed, for example, 80S ribosomal proteins were in average threefold and SLC amino acid transporters fivefold de-ubiquitinated. The latter might cause the observed significant increase of amino acid levels in ρ0 cells. We conclude that an elimination of the respiratory electron chain, e.g. mtDNA depletion, not only leads to an uneven down-regulation of mitochondrial energy pathways, but also triggers the retrograde response.
Die aus Südafrika stammende Zweireihige Wasserähre (Aponogeton distachyos; Alismatales, Aponogetonaceae) ist in mehreren Ländern Westeuropas eingebürgert. 2014 bis 2016 wurden insgesamt bis etwa einhundert Pflanzen an drei Fundorten im Saalekreis und im Kreis Nordsachsen im Grenzgebiet zwischen Sachsen-Anhalt und Sachsen nachgewiesen. Auch in Mitteldeutschland erwies sich die Pflanze als winterhart und wird zur Bepflanzung von Gartenteichen genutzt. Noch ist unsicher, ob sie sich hier dauerhaft etablieren kann, weil das Hauptvorkommen durch Verschilfung des Gewässers zu erlöschen droht.
Background: Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.
Methods: In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0–F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression.
Results: Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0–F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen.
Conclusions: Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.
Trial Registration: ClinicalTrials.gov NCT01846832
The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing-thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2.PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.
We report on new results on the infrared behavior of the three-gluon vertex in quenched Quantum Chromodynamics, obtained from large-volume lattice simulations. The main focus of our study is the appearance of the characteristic infrared feature known as ‘zero crossing’, the origin of which is intimately connected with the nonperturbative masslessness of the Faddeev–Popov ghost. The appearance of this effect is clearly visible in one of the two kinematic configurations analyzed, and its theoretical origin is discussed in the framework of Schwinger–Dyson equations. The effective coupling in the momentum subtraction scheme that corresponds to the three-gluon vertex is constructed, revealing the vanishing of the effective interaction at the exact location of the zero crossing.
This letter reports on how the Wilson flow technique can efficaciously kill the short-distance quantum fluctuations of 2- and 3-gluon Green functions, remove the ΛQCD scale and destroy the transition from the confining non-perturbative to the asymptotically-free perturbative sector. After the Wilson flow, the behavior of the Green functions with momenta can be described in terms of the quasi-classical instanton background. The same behavior also occurs, before the Wilson flow, at low-momenta. This last result permits applications as, for instance, the detection of instanton phenomenological properties or a determination of the lattice spacing only from the gauge sector of the theory.
Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3' splice sites is coupled with longer repressive uridine tracts. Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons.
Background The endogenous amino acid homoarginine predicts mortality in cerebro‐ and cardiovascular disease. The objective was to explore whether homoarginine is associated with atrial fibrillation (AF) and outcome in patients with acute chest pain.
Methods and Results One thousand six hundred forty‐nine patients with acute chest pain were consecutively enrolled in this study, of whom 589 were diagnosed acute coronary syndrome (ACS). On admission, plasma concentrations of homoarginine as well as brain natriuretic peptide (BNP), and high‐sensitivity assayed troponin I (hsTnI) were determined along with electrocardiography (ECG) variables. During a median follow‐up of 183 days, 60 major adverse cardiovascular events (MACEs; 3.8%), including all‐cause death, myocardial infarction, or stroke, were registered in the overall study population and 43 MACEs (7.5%) in the ACS subgroup. Adjusted multivariable Cox regression analyses revealed that an increase of 1 SD of plasma log‐transformed homoarginine (0.37) was associated with a hazard reduction of 26% (hazard ratio [HR], 0.74; 95% CI, 0.57–0.96) for incident MACE and likewise of 35% (HR, 0.65; 95% CI, 0.49–0.88) in ACS patients. In Kaplan–Meier survival curves, homoarginine was predictive for patients with high‐sensitivity assayed troponin I (hsTnI) above 27 ng/L (P<0.05). Last, homoarginine was inversely associated with QTc duration (P<0.001) and prevalent AF (OR, 0.83; 95% CI, 0.71–0.95).
Conclusion Low plasma homoarginine was identified as a risk marker for incident MACEs in patients with acute chest pain, in particular, in those with elevated hsTnI. Impaired homoarginine was associated with prevalent AF. Further studies are needed to investigate the link to AF and evaluate homoarginine as a therapeutic option for these patients.
Hereditary Parkinson’s disease can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) or the autosomal recessive deficiency of PINK1. We recently showed that the combination of PINK1-knockout with overexpression of A53T-SNCA in double mutant (DM) mice potentiates phenotypes and reduces survival. Now we studied brain hemispheres of DM mice at age of 18 months in a hypothesis-free approach, employing a quantitative label-free global proteomic mass spectrometry scan of posttranslational modifications focusing on methyl-arginine. The strongest effects were documented for the adhesion modulator CMAS, the mRNA decapping/deadenylation factor PATL1, and the synaptic plasticity mediator CRTC1/TORC1. In addition, an intriguing effect was observed for the splicing factor PSF/SFPQ, known to interact with the dopaminergic differentiation factor NURR1 as well as with DJ-1, the protein responsible for the autosomal recessive PARK7 variant of PD. CRTC1, PSF, and DJ-1 are modulators of PGC1alpha and of mitochondrial biogenesis. This pathway was further stressed by dysregulations of oxygen sensor EGLN3 and of nuclear TMPO. PSF and TMPO cooperate with dopaminergic differentiation factors LMX1B and NURR1. Further dysregulations concerned PRR18, TRIO, HNRNPA1, DMWD, WAVE1, ILDR2, DBNDD1, and NFM. Thus, we report selective novel endogenous stress responses in brain, which highlight early dysregulations of mitochondrial homeostasis and midbrain vulnerability.
Chemical reduction-oxidation mechanisms within mantle rocks link to the terrestrial carbon cycle by influencing the depth at which magmas can form, their composition, and ultimately the chemistry of gases released into the atmosphere. The oxidation state of the uppermost mantle has been widely accepted to be unchanged over the past 3800 m.y., based on the abundance of redox-sensitive elements in greenstone belt–associated samples of different ages. However, the redox signal in those rocks may have been obscured by their complex origins and emplacement on continental margins. In contrast, the source and processes occurring during decompression melting at spreading ridges are relatively well constrained. We retrieve primary redox conditions from metamorphosed mid-oceanic ridge basalts (MORBs) and picrites of various ages (ca. 3000–550 Ma), using V/Sc as a broad redox proxy. Average V/Sc values for Proterozoic suites (7.0 ± 1.4, 2σ, n = 6) are similar to those of modern MORB (6.8 ± 1.6), whereas Archean suites have lower V/Sc (5.2 ± 0.4, n = 5). The lower Archean V/Sc is interpreted to reflect both deeper melt extraction from the uppermost mantle, which becomes more reduced with depth, and an intrinsically lower redox state. The pressure-corrected oxygen fugacity (expressed relative to the fayalite-magnetite-quartz buffer, ΔFMQ, at 1 GPa) of Archean sample suites (ΔFMQ –1.19 ± 0.33, 2σ) is significantly lower than that of post-Archean sample suites, including MORB (ΔFMQ –0.26 ± 0.44). Our results imply that the reducing Archean atmosphere was in equilibrium with Earth’s mantle, and further suggest that magmatic gases crossed the threshold that allowed a build-up in atmospheric O2 levels ca. 3000 Ma, accompanied by the first “whiffs” of oxygen in sediments of that age.
Objective: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.
Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.
Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks.
Conclusion: The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts.
Neural responses to heartbeats in the default network encode the self in spontaneous thoughts
(2016)
The default network (DN) has been consistently associated with self-related cognition, but alsoto bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the firstperson perspective subject or agent inthethought (“I”), and on another scaleto what degreethey werethinking aboutthemselves (“Me”). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the “I” and the “Me” dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN.
Background: Differential RNA-Seq (dRNA-Seq) is a recently developed method of performing primary transcriptome analyses that allows for the genome-wide mapping of transcriptional start sites (TSSs) and the identification of novel transcripts. Although the transcriptomes of diverse bacterial species have been characterized by dRNA-Seq, the transcriptome analysis of archaeal species is still rather limited. Therefore, we used dRNA-Seq to characterize the primary transcriptome of the model archaeon Haloferax volcanii.
Results: Three independent cultures of Hfx. volcanii grown under optimal conditions to the mid-exponential growth phase were used to determine the primary transcriptome and map the 5′-ends of the transcripts. In total, 4749 potential TSSs were detected. A position weight matrix (PWM) was derived for the promoter predictions, and the results showed that 64 % of the TSSs were preceded by stringent or relaxed basal promoters. Of the identified TSSs, 1851 belonged to protein-coding genes. Thus, fewer than half (46 %) of the 4040 protein-coding genes were expressed under optimal growth conditions. Seventy-two percent of all protein-coding transcripts were leaderless, which emphasized that this pathway is the major pathway for translation initiation in haloarchaea. A total of 2898 of the TSSs belonged to potential non-coding RNAs, which accounted for an unexpectedly high fraction (61 %) of all transcripts. Most of the non-coding TSSs had not been previously described (2792) and represented novel sequences (59 % of all TSSs). A large fraction of the potential novel non-coding transcripts were cis-antisense RNAs (1244 aTSSs). A strong negative correlation between the levels of antisense transcripts and cognate sense mRNAs was found, which suggested that the negative regulation of gene expression via antisense RNAs may play an important role in haloarchaea. The other types of novel non-coding transcripts corresponded to internal transcripts overlapping with mRNAs (1153 iTSSs) and intergenic small RNA (sRNA) candidates (395 TSSs).
Conclusion: This study provides a comprehensive map of the primary transcriptome of Hfx. volcanii grown under optimal conditions. Fewer than half of all protein-coding genes have been transcribed under these conditions. Unexpectedly, more than half of the detected TSSs belonged to several classes of non-coding RNAs. Thus, RNA-based regulation appears to play a more important role in haloarchaea than previously anticipated.
In her article, Karin Littau proposes a material or medial turn in the humanities and social sciences to end the neglect of the material basis to every act of communication, including translation. This proposal is warmly welcomed. As a comparatist who has for some time been trying to build bridges between literary studies and book history, I strongly support Littau's point of view – all the more since I am less optimistic regarding the general acceptance of such ideas in the humanities, and especially in literary and translation studies. I am not so sure that McLuhan and the other authorities for the importance of mediality and technicity whom Littau quotes (e.g. Kittler, Ong, and Gumbrecht) have really provoked a "crisis in the self-understanding of the human sciences". For brevity's sake, in my response below, I leave aside literary studies to focus on translation studies.
Background: Use of blood oxygenation level-dependent cardiovascular magnetic resonance (BOLD-CMR) to assess perfusion in the lower limb has been hampered by poor reproducibility and a failure to reliably detect post-revascularization improvements in patients with critical limb ischemia (CLI).
Objectives: This study sought to develop BOLD-CMR as an objective, reliable clinical tool for measuring calf muscle perfusion in patients with CLI.
Methods: The calf was imaged at 3-T in young healthy control subjects (n = 12), age-matched control subjects (n = 10), and patients with CLI (n = 34). Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperemia (Grad). BOLD-CMR was used to assess changes in perfusion following revascularization in 12 CLI patients. Muscle biopsies (n = 28), obtained at the level of BOLD-CMR measurement and from healthy proximal muscle of patients undergoing lower limb amputation (n = 3), were analyzed for capillary-fiber ratio.
Results: There was good interuser and interscan reproducibility for Grad and SRi (all p < 0.0001). The ischemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched control subjects, and young control subjects (p < 0.001 for all comparisons). Successful revascularization resulted in improvement in Grad (p < 0.0001) and SRi (p < 0.0005). There was a significant correlation between capillary-fiber ratio (p < 0.01) in muscle biopsies from amputated limbs and Grad measured pre-operatively at the corresponding level.
Conclusions: BOLD-CMR showed promise as a reliable tool for assessing perfusion in the lower limb musculature and merits further investigation in a clinical trial.
Causative, which is analyzed in the context of voice, differs widely in Turkish and German languages. A causative can be obtained nearly from each verb in Turkish language while this category is not productive in German Language. Like prefixes, which are of great importance in German language, the causative has the same significance in Turkish language. Causatives can be divided into three: a) lexical causative, causative existing in words' own meaning; for instance, there exists such a relationship between the words "slide" and "fall"; b) morphological causative consists of morphemes (öl-dür-t-mek); c) whereas, the context is important for the operant causative. When we say “It smells gas in here’ it may have been intended to open a window and we can make it done. There is a direct connection between the causative and causality. Because, in causative instead of doing something directly, it may be caused to be done or occurred. The notion of causative in German has been reviewed in the semantic context at a low degree. This is because of the fact that, morphological causative verbs are fewer and new causative voices can't be formed. However, this issue has been handled in a very detailed manner especially at morphological level in Turkish language. There is even fine detail under the title causative itself. The most important characteristic of causative is to change the combination value of the verbs. However, the relation between causative and passive is just the opposite of this and asymmetric. Structures having semantic similarities with causatives and named as Funktionsverbgefüge (put into practice = apply) in German exist. Reciprocal voices and reflexive voices, the most important voices of Turkish language, generally allow the formation of causative verb.
In this article the author highlights some issues about Adorno’s thought that are fundamental to be acquired in the present age. It focuses on the questions most criticized in the postwar period: cultural industry, managed world, presumed snobbery about mass society, decline of aura, end of individuality, post-individual or pseudo-individuality, ticket mentality. Therefore, the author suggests to explain contemporary age starting from the Adornian model, an important interpretive antecedent to understand new media and the world that they produce. So this article underscores the similarity about many causes for reflection in Theodor W. Adorno and also H. Marcuse: in spite of oustanding differences, both theorists persist on the “power of negative thinking” and on the “feeling of the contrary”. This persistence lays the foundations of critical thought in Adorno, who shows parodying art such as the critical model par excellence. Finally, last pages are directed to remark the importance of Adorno’s thought such as metacritical philosophy, surely more fruitful than the paradigm of the “second generation” in the following decades.
This article focusses on the question of howfar thenew figure of the continuum can capture the categories gender, migration and spaceand how intra- and intercategorial shifts, variabilities, polypolarities can be specified. Also the article will be discussed to what extend the figure of the continuum can meet the challenges of pluralities existing in realities of the lived lifes of human beings as well as in literary texts dealing with gender, migration and/or space.
Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.
The oceans at the time of the Cenomanian–Turonian transition were abruptly perturbed by a period of bottom-water anoxia. This led to the brief but widespread deposition of black organic-rich shales, such as the Livello Bonarelli in the Umbria–Marche Basin (Italy). Despite intensive studies, the origin and exact timing of this event are still debated. In this study, we assess leading hypotheses about the inception of oceanic anoxia in the Late Cretaceous greenhouse world by providing a 6 Myr long astronomically tuned timescale across the Cenomanian–Turonian boundary. We procure insights into the relationship between orbital forcing and the Late Cretaceous carbon cycle by deciphering the imprint of astronomical cycles on lithologic, physical properties, and stable isotope records, obtained from the Bottaccione, Contessa and Furlo sections in the Umbria–Marche Basin. The deposition of black shales and cherts, as well as the onset of oceanic anoxia, is related to maxima in the 405 kyr cycle of eccentricity-modulated precession. Correlation to radioisotopic ages from the Western Interior (USA) provides unprecedented age control for the studied Italian successions. The most likely tuned age for the base of the Livello Bonarelli is 94.17 ± 0.15 Ma (tuning 1); however, a 405 kyr older age cannot be excluded (tuning 2) due to uncertainties in stratigraphic correlation, radioisotopic dating, and orbital configuration. Our cyclostratigraphic framework suggests that the exact timing of major carbon cycle perturbations during the Cretaceous may be linked to increased variability in seasonality (i.e. a 405 kyr eccentricity maximum) after the prolonged avoidance of seasonal extremes (i.e. a 2.4 Myr eccentricity minimum). Volcanism is probably the ultimate driver of oceanic anoxia, but orbital periodicities determine the exact timing of carbon cycle perturbations in the Late Cretaceous. This unites two leading hypotheses about the inception of oceanic anoxia in the Late Cretaceous greenhouse world.
The organic rich Livello Bonarelli formed as a result of oxygen deficiency and carbonate dissolution in the oceans during the Cenomanian/Turonian (C/T) transition. During this Ocean Anoxic Event 2 (OAE2), a combination of factors caused increased productivity, incomplete decomposition of organic matter and widespread deposition of black shales. Although these sediments are extensively studied, the exact extent, cause, timing and duration of oceanic anoxia are debated (Sinton and Duncan, 1997; Mitchell et al., 2008). Contrasting causal mechanisms have been suggested, including stratification of the water column (Lanci et al., 2010) versus intensification of the hydrological cycle driving a dynamic ocean circulation (Trabucho-Alexandre et al., 2010). Studies on trace-elemental and (radiogenic) isotope compositions of Cenomanian marine successions have suggested a volcanic origin of OAE2, by delivering nutrients to the semi-enclosed proto-North Atlantic (Zheng et al., 2013, and references therein; Du Vivier et al., 2014). Deciphering the importance of volcanic and oceanographic processes requires tight constraints on their relative timing. Regularly occurring black cherts and shales below the Livello Bonarelli demonstrate that oceanic conditions in the Umbria-Marche Basin were punctuated by episodes of regional anoxia from the mid-Cenomanian onwards. Their hierarchical stacking pattern suggests an orbital control on the deposition of organic rich horizons (Mitchell et al., 2008; Lanci et al., 2010). Stable carbon isotope data reveal that long-term 15 variations in eccentricity paced the carbon cycle (Sprovieri et al., 2013) and sea level changes (Voigt et al., 2006) of the Late Cretaceous. Here we investigate the role of orbital forcing on climate and the carbon cycle, and, specifically, on organic-rich sedimentation prior, during, and after OAE2.
We also explore the potential for establishing an anchored astrochronology for the C/T interval in Europe. Recent improvements in the astronomical solution (La2011; Laskar et al., 2011b) and in the intercalibration of radiometric and astronomical dating techniques (Kuiper et al., 2008; Renne et al., 2013) allow the extension of the astronomical time scale into the Cretaceous. The C/T boundary in the Western Interior (USA) has been dated at 93.90 ± 0.15 Ma by intercalibration of radio-isotopic and astrochronologic time scales (Meyers et al., 2012b). Also, reinterpretation of proxy records spanning the C/T interval seems to resolve discrepancies in reported durations of the OAE2 (Sageman et al., 2006; Meyers et al., 2012a). The well-documented Italian rhythmic successions, reference sections for climatic processes in the Tethyan realm, need to be tied in with the absolute time scale. Biostratigraphic correlation to radioisotopically-dated ash beds in the Western Interior is complicated by the provinciality of faunas and floras. However, δ13C stratigraphy provides a reliable correlation tool (Gale et al., 2005) and we present a new 40Ar/39Ar age for the Thatcher bentonite from the Western Interior occurring within the mid-Cenomanian δ13C event (MCE). This study integrates the well-developed cyclostratigraphy from the Umbria-Marche Basin with radioisotopic ages from the Western Interior and derives a numerical timescale for this critical interval in Earth’s history.
Thomas Mann und Otto Dix hätten die Kriegsjahre von 1914 bis 1918 nicht unterschiedlicher erleben können: Der Schriftsteller Mann, der mit 25 schon nach kurzer Zeit wegen eines Plattfußes und einer Sehnenscheidenentzündung aus dem Pflichtwehrdienst entlassen wurde, meldete sich 1914 zum Landsturm, wurde aber 1916 endgültig wegen Magenproblemen und Nervosität für untauglich erklärt und war so nie an der Front. Der Künstler Dix hingegen wurde als Ersatz-Reservist schon drei Wochen nach Kriegsausbruch zur Ausbildung eingezogen und kämpfte von September 1915 bis zum Kriegsende an der West- und Ostfront. Als Schütze und Führer eines Maschinengewehrzuges stand er dabei immer an vorderster Front.
Während der Kriegsjahre und der Weimarer Republik spielten der Konflikt und seine Auswirkungen auf die deutsche Gesellschaft eine zentrale Rolle in den Werken von Dix und Mann. Ein Vergleich von Dix' Triptychon 'Der Krieg' (1928-1932, Staatliche Kunstsammlungen Dresden) und der Kriegsszene am Ende von Manns Roman 'Der Zauberberg', die der Autor erst kurz vor dessen Veröffentlichung 1924 schrieb, zeigt, dass die beiden Werke sowohl in der Motivik als auch in dem die Darstellungen bestimmenden Verständnis von Krieg als einem Phänomen der menschlichen Existenz übereinstimmen. Beide Werke werden gewöhnlich als realistische Schilderungen der grausamen, entindividualisierenden und entmenschlichenden Kräfte des Krieges verstanden.
BACKGROUND: Geographical variation of the general practitioner (GP) workforce is known between rural and urban areas. However, data about the variation between and within urban areas are lacking.
METHOD: We analyzed distribution patterns of GP full time equivalents (FTE) in German cities with a population size of more than 500,000. We correlated their distribution with area measures of social deprivation in order to analyze preferences within neighborhood characteristics. For this purpose, we developed two area measures of deprivation: Geodemographic Index (GDI) and Cultureeconomic Index (CEI).
RESULTS: In total n = 9034.75 FTE were included in n = 14 cities with n = 171 districts. FTE were distributed equally on inter-city level (mean: 6.49; range: 5.12-7.20; SD: 0.51). However, on intra-city level, GP distribution was skewed (mean: 6.54; range: 1.80-43.98; SD: 3.62). Distribution patterns of FTE per 10^4 residents were significantly correlated with GDI (r = -0.49; p < 0.001) and CEI (r = -0.22; p = 0.005). Therefore, location choices of GPs were mainly positively correlated with 1) central location (r = -0.50; p < 0.001), 2) small household size of population (r = -0.50; p < 0.001) and 3) population density (r = 0.35; p < 0.001).
CONCLUSION: Intra-city distribution of GPs was skewed, which could affect the equality of access for the urban population. Furthermore, health services planners should be aware of GP location preferences. This could be helpful to better understand and plan delivery of health services. Within this process the presented Geodemographic Index (GDI) could be of use.
We integrated recent improvements within the floating catchment area (FCA) method family into an integrated ‘iFCA`method. Within this method we focused on the distance decay function and its parameter. So far only distance decay functions with constant parameters have been applied. Therefore, we developed a variable distance decay function to be used within the FCA method. We were able to replace the impedance coefficient β by readily available distribution parameter (i.e. median and standard deviation (SD)) within a logistic based distance decay function. Hence, the function is shaped individually for every single population location by the median and SD of all population-to-provider distances within a global catchment size. Theoretical application of the variable distance decay function showed conceptually sound results. Furthermore, the existence of effective variable catchment sizes defined by the asymptotic approach to zero of the distance decay function was revealed, satisfying the need for variable catchment sizes. The application of the iFCA method within an urban case study in Berlin (Germany) confirmed the theoretical fit of the suggested method. In summary, we introduced for the first time, a variable distance decay function within an integrated FCA method. This function accounts for individual travel behaviors determined by the distribution of providers. Additionally, the function inherits effective variable catchment sizes and therefore obviates the need for determining variable catchment sizes separately.
Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-induced surface crevice with a KD = 150 μM, thereby increasing the melting temperature of the protein and slowing its rate of aggregation. Incorporation of fluorine atoms into small molecule ligands can substantially improve binding affinity to their protein targets. We have, therefore, harnessed fluorine–protein interactions to improve the affinity of this ligand. Step-wise introduction of fluorines at the carbazole ethyl anchor, which is deeply buried within the binding site in the Y220C–PhiKan083 complex, led to a 5-fold increase in affinity for a 2,2,2-trifluoroethyl anchor (ligand efficiency of 0.3 kcal mol–1 atom–1). High-resolution crystal structures of the Y220C–ligand complexes combined with quantum chemical calculations revealed favorable interactions of the fluorines with protein backbone carbonyl groups (Leu145 and Trp146) and the sulfur of Cys220 at the mutation site. Affinity gains were, however, only achieved upon trifluorination, despite favorable interactions of the mono- and difluorinated anchors with the binding pocket, indicating a trade-off between energetically favorable protein–fluorine interactions and increased desolvation penalties. Taken together, the optimized carbazole scaffold provides a promising starting point for the development of high-affinity ligands to reactivate the tumor suppressor function of the p53 mutant Y220C in cancer cells.
Webportal Polyphonie. Mehrsprachigkeit_Kreativität_Schreiben http://www.polyphonie.at
Das Webportal Polyphonie. Mehrsprachigkeit_Kreativität_Schreiben ist 2012 aus dem gleichnamigen Forschungsprojekt entstanden, das 2009 von einer Gruppe von ForscherInnen aus Italien und Österreich ins Leben gerufen wurde. Das Projekt untersucht die vielfältigen Zusammenhänge zwischen Mehrsprachigkeit und Kreativität im Schreiben systematisch und aus interdisziplinärer Perspektive. Es setzt sich zum Ziel, den mehr oder weniger stringenten Zusammenhang von individueller oder gesellschaftlicher Mehrsprachigkeit und Kreativität im Allgemeinen bzw. literarischer Kreativität im Besonderen zu erforschen.
Elevational gradients in high mountain ranges are particularly suitable to study and understand patterns and drivers of plant community diversity and composition, yet there are only few studies that explicitly addressed this topic for the European Alps. Here we analysed an elevational gradient in grasslands of the Gran Paradiso National Park (NW Italy) from c. 1,700 to 3,100 m a.s.l. We recorded vascular plant species composition in 13 100-m² plots, each with two series of nested subplots from 0.0001 to 10 m², as well as a set of environmental parameters (topography, soil). Beta-diversity was assessed via the z-values of power-law species-area relationships, both across all plot sizes and from one plot size to the next bigger one. Diversity-environment relationships were assessed with multi-model inference based on Akaike information criterion (AIC), while scale dependence in z-values across plot sizes was analysed with an ANOVA. Life forms and three major functional traits (specific leaf area = SLA, canopy height, seed mass) were derived from trait databases to calculate fractions of life forms and community-weighted means for the metric traits. Species richness on 100 m² ranged from 17 to 65, with a mean of 43.5. The z-values were within a typical range known for European grasslands (mean: 0.227), with non-significant scale dependence. The importance of environmental factors for richness changed across grain sizes, with inclination (positive effect), mean soil depth and soil skeleton content (both: negative effect) being most influential at grain sizes of 0.0001–1 m². By contrast, soil pH was most important (with a unimodal relationship) for 10 and 100 m². After account-ing for the other environmental factors, elevation showed a moderate unimodal relationship only for the two largest grain sizes. By contrast, functional composition showed strong and mostly significant rela-tionships with elevation: hemicryptophytes and geophytes became rarer and chamaephytes more fre-quent, while community-weighted means of SLA, canopy height and seed mass decreased. Our findings highlight the scale dependence of biodiversity patterns, thus pointing to the need of multi-scale sampling to reach comprehensive understanding. Further, we could provide one of the first documentations of biodiversity and functional composition along an elevational gradient in the Alps, some in agreement with expectations, others not. This suggests that more extensive studies with a similar design in this and other regions of the Alps could be a valuable contribution to the understanding of how environmental factors drive components of biodiversity as well a functional community assembly.
Zu den Funktionen der Mode
(2016)
In der Literatur über die Mode herrscht Einvernehmen darüber, dass die Moden früher die oberen Schichten oder Stände von den nächstfolgenden abgrenzten; ging eine Mode erst einmal auf andere Schichten über, so musste eine neue Mode entwickelt, ein neues Abzeichen gefunden werden. Diese Bewegung gibt es, auch wenn die treffliche Charakterisierung durch den Rechtshistoriker Jhering von der "Hetzjagd der Standeseitelkeit" inzwischen überholt ist, noch immer. Auch in unserer Gesellschaft bietet die Mode - und zwar nicht nur die Kleidermode, sondern jede Form des modischen Konsums - die Möglichkeit, die Zugehörigkeit zu einem bestimmten Kreis, einer bestimmten Gruppe anzudeuten. Dies gilt im Hinblick auf die sozialen Schichten, so wenig diese im einzelnen definierbar sein mögen; es gilt aber auch im Blick auf andere Gruppierungen wie die Jugend, die heute ein ganz wesentlicher Ausgangspunkt für Moden ist, die sich von hier aus über die ganze Gesellschaft verbreiten. Die Jugendlichen bleiben so lange bei einer Mode, bis die anfängliche Barriere von den anderen übersprungen wird [...].
Bacterial sugar symporters in the Major Facilitator Superfamily (MFS) use the H+ (and in a few cases Na+) electrochemical gradients to achieve active transport of sugar into the cell. Because a number of structures of MFS sugar symporters have been solved recently, molecular insight into the transport mechanism is possible from detailed functional analysis. We present here a comparative electrophysiological study of the lactose permease (LacY), the fucose permease (FucP) and the xylose permease (XylE), which reveals common mechanistic principles and differences. In all three symporters energetically downhill electrogenic sugar/H+ symport is observed. Comparison of the pH dependence of symport at symmetrical pH exhibits broad bell-shaped pH profiles extending over 3 to 6 pH units and a decrease at extremely alkaline pH ≥ 9.4 and at acidic to neutral pH = 4.6–7.5. The pH dependence can be described by an acidic to neutral apparent pK (pKapp) and an alkaline pKapp. Experimental evidence suggests that the alkaline pKapp is due to H+ depletion at the protonation site, while the acidic pKapp is due to inhibition of deprotonation. Since previous studies suggest that a single carboxyl group in LacY (Glu325) may be the only side chain directly involved in H+ translocation and a carboxyl side chain with similar properties has been identified in FucP (Asp46) and XylE (Asp27), the present results imply that the pK of this residue is switched during H+/sugar symport in all three symporters.
Este artigo é baseado em duas publicações anteriores (BAßLER 2013a; 2013b) e analisa o realismo como procedimento narrativo do nosso presente; para esse fim, são tratadas obras da literatura de expressão alemã e da televisão. O autor constata, tanto na chamada alta literatura quanto em gêneros como fantasia e séries televisivas um realismo que invoca e confirma, mediante frames convencionalizados, a imagem corrente da realidade e os códigos de significado vigentes do presente, indiferente da apresentação do conteúdo como realista ou fantástico. Este tipo de literatura é bem-sucedida porque possibilita uma leitura fácil e, ao mesmo tempo, reclama legitimidade através de uma autenticidade de alta literatura. Como alternativa a este estilo internacional de realismo trivial se oferecem, por um lado, obras pós-modernas e da cultura pop que expõem abertamente ser construídas por citações e, por outro, procedimentos como short cuts que dissecam a narrativa linear metonímica e a reconfiguram numa nova totalidade complexa e significativa.
We compare the reconstructed hadronization conditions in relativistic nuclear collisions in the nucleon–nucleon centre-of-mass energy range 4.7–2760 GeV in terms of temperature and baryon-chemical potential with lattice QCD calculations, by using hadronic multiplicities. We obtain hadronization temperatures and baryon chemical potentials with a fit to measured multiplicities by correcting for the effect of post-hadronization rescattering. The post-hadronization modification factors are calculated by means of a coupled hydrodynamical-transport model simulation under the same conditions of approximate isothermal and isochemical decoupling as assumed in the statistical hadronization model fits to the data. The fit quality is considerably better than without rescattering corrections, as already found in previous work. The curvature of the obtained “true” hadronization pseudo-critical line κ is found to be 0.0048 ± 0.0026, in agreement with lattice QCD estimates; the pseudo-critical temperature at vanishing is found to be 164.3 ± 1.8 MeV.
Seit 11 Jahren werden von Mitgliedern der Eurasian Dry Gassland Group (EDDG) und deren Vorgängerorganisationen Grasland-Sonderteile in Tuexenia herausgegeben. Der diesjährige Sonderteil präsentiert sechs Artikel mit unterschiedlichen Fragestellungen zu Trockenrasen und verwandten Graslandtypen aus sechs europäischen Ländern: Belgien, Bosnien-Herzegowina, Deutschland, Italien, Serbien und Ungarn. Ein Artikel behandelt syntaxonomische Aspekte der Serpentin-Steppenrasen des Balkans (s. auch Umschlagfoto). Zwei Beiträge untersuchen funktionelle Eigenschaften von Pflanzenarten im Grasland, der eine (in belgischen Trockenrasen) die Variationen funktioneller Merkmale in Abhängigkeit von den Umweltbedingungen und der andere die Mengenverhältnisse von funktionellen Merkmalen entlang eines Höhengradienten in den italienischen Alpen. Ein Artikel zeigt mithilfe eines experimentellen Ansatzes, dass artenarmes ungarisches Grasland durch Diasporenzufuhr in artenreiche Wiesen überführt werden kann, während ein anderer Beitrag ökologische Theorien am Grasland in einer ungarischen Stadt überprüft. Der sechste Artikel behandelt schließlich Vegetationsveränderungen von Steppenrasen in Nordostdeutschland nach 20 Jahren.
Effect of M3 muscarinic acetylcholine receptor deficiency on collagen antibody-induced arthritis
(2016)
Background: There is increasing evidence that the non-neuronal cholinergic system might be of importance for the pathology of rheumatoid arthritis. The role of M3 muscarinic acetylcholine receptor (M3R) in this regard has, however, not been investigated to date. Thus, in the present study we analyzed if M3R deficiency might have a protective effect on experimentally induced arthritis.
Methods: Collagen antibody-induced arthritis (CAIA) was evoked in M3R-deficient (M3R −/− ) mice and wild-type (WT) littermates. Severity of arthritis was assessed by scoring of paw swelling. The joints of arthritic and nonarthritic animals were analyzed for histopathological changes regarding synovial tissue, cartilage degradation and bone destruction. Further, gene expression analysis of respective markers was performed. Systemic and local inflammatory response was determined by flow cytometry and immunohistochemistry for leukocytes as well as mRNA and protein measurements for pro-inflammatory cytokines and chemokines.
Results: In arthritic M3R −/− mice the number of leukocytes, specifically neutrophils, was enhanced even though clinical arthritis score was not significantly different between WT and M3R −/− mice with CAIA. In M3R −/− mice, levels of neutrophil chemoattractant chemokine C-X-C-motif ligand 2 (CXCL2) as well as the pro-inflammatory cytokine interleukin-6 were already strongly increased in mice with low arthritis score, whereas WT mice only showed prominent expression of these markers when reaching high arthritis scores. Furthermore, arthritic M3R −/− mice displayed a stronger degradation of collagen II in the articular cartilage and, most strikingly, histopathological evaluation revealed more severe bone destruction in arthritic mice with M3R deficiency compared to WT littermates. Moreover, in M3R −/− mice, gene expression of markers for bone degradation (matrix metalloproteinase 13, cathepsin K and receptor activator of nuclear factor-κB ligand) was already increased in mice with low arthritis score.
Conclusions: Taken together, the present study shows that while M3R −/− mice were not protected from CAIA, they had a tendency toward a higher inflammatory response after arthritis induction than WT mice. Further, arthritis-induced joint destruction was significantly stronger in mice with M3R deficiency, indicating that stimulation of M3R might have protective effects on arthritis.
Purpose: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC).
Methods: A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing.
Results: Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with non-clear cell RCC (non-ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR-targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited.
Conclusions: Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI–TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.