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Background and Aims: Fecal biomarkers are important non-invasive markers monitoring disease activity in inflammatory bowel disease (IBD). We compared the significance of fecal eosinophil cationic protein (fECP) and fecal calprotectin (fCal).
Methods: fECP and fCal were measured in patients with Crohn's disease (CD, n = 97), ulcerative colitis (UC, n = 53), Clostridioides difficile infection (CDI, n = 9), primary food allergy (PFA, n = 11), pollen-associated food allergy (n = 25) and non-inflammatory controls (n = 78). Results were correlated with clinical and endoscopic IBD activity scores.
Results: fECP was significantly elevated in CD, UC, CDI and PFA compared to controls. fCal was significantly increased in CD, UC and CDI. fECP had lower diagnostic accuracy than fCal (area under the curve (AUC) = 0.88) in differentiating between endoscopically active and inactive patients with IBD (AUC = 0.77, ROC analysis). In contrast to fCal, fECP correlated negatively with age and levels were also elevated in clinically and endoscopically inactive patients with IBD <45 years (endoscopically inactive IBD vs controls; AUC for fECP = 0.86; AUC for fCal = 0.62). However, in those patients with low inflammatory activity (fCal <250 mg/kg), high fECP indicated the need for treatment modification or surgery (fECP <200 µg/kg = 22%; 200–600 µg/kg = 44%; >600 µg/kg = 82%) at month 48 of follow-up.
Conclusions: fECP is a diagnostic and prognostic marker in young patients with IBD in remission.
Measurements of the π±, K±, and proton double differential yields emitted from the surface of the 90-cm-long carbon target (T2K replica) were performed for the incoming 31 GeV/c protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential π± yields were measured with increased precision compared to the previously published NA61/SHINE results, while the K± and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.
Ein Zell-Atlas des kranken Herzens : Einzelzelltechniken ermöglichen neue Einsichten auf Zellebene
(2019)
Herz und Gefäße bilden ein hochkomplexes Organsystem, in dem unterschiedlichste Zellen korrekt zusammenarbeiten müssen, um alle Organe mit Blut zu versorgen. In den vergangenen Jahrzehnten hat die Herzbiologie ganze Gewebe oder Zellisolate in den Blick genommen. Doch jetzt erlauben neue Technologien, die Vielfalt der Zelltypen und ihre individuelle Antwort auf Signale bis auf die Ebene von Proteinen und Genen zu verfolgen. Forscher hoffen, kranken Herzen dadurch besser bei der Regeneration helfen zu können.
The following article attempts to clarify the ambivalent relationship that Max Horkheimer and Herbert Marcuse developed with the vitalist and phenomenological tendencies that permeated philosophy and the social sciences during the Weimar Republic. More precisely, it traces how both thinkers, in spite of acknowledging the “truth moment” contained in the criticism that the philosophical exponents of both movements (Husserl, Bergson, Dilthey) developed of 19th century positivism, also recognized in its shallow popularization the advancement of a dangerous philosophical irrationalism, suspicious of science and Enlightenment values, that would soon become an accomplice to the rise of fascism.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at √s=13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT > 1.7 GeV/c are σmπ0 = 4.56 ± 0.03 MeV/c2 and σmη = 15.3 ± 1.0 MeV/c2, respectively.
The jet radial structure and particle transverse momentum (pT) composition within jets are presented in centrality-selected Pb–Pb collisions at √sNN = 2.76 TeV. Track-based jets, which are also called charged jets, were reconstructed with a resolution parameter of R = 0.3 at midrapidity |ηch jet| < 0.6 for transverse momenta pT, ch jet = 30–120 GeV/c. Jet–hadron correlations in relative azimuth and pseudorapidity space (Δϕ, Δη) are measured to study the distribution of the associated particles around the jet axis for different pT,assoc-ranges between 1 and 20 GeV/c. The data in Pb–Pb collisions are compared to reference distributions for pp collisions, obtained using embedded PYTHIA simulations. The number of high-pT associate particles (4 < pT,assoc < 20 GeV/c) in Pb–Pb collisions is found to be suppressed compared to the reference by 30 to 10% depending on centrality. The radial particle distribution relative to the jet axis shows a moderate modification in Pb–Pb collisions with respect to PYTHIA. High-pT associate particles are slightly more collimated in Pb–Pb collisions compared to the reference, while low-pT associate particles tend to be broadened. The results, which are presented for the first time down to pT, ch jet = 30 GeV/c in Pb–Pb collisions, are compatible with both previous jet–hadron-related measurements from the CMS Collaboration and jet shape measurements from the ALICE Collaboration at higher pT, and add further support for the established picture of in-medium parton energy loss.
Study of the Λ–Λ interaction with femtoscopy correlations in pp and p–Pb collisions at the LHC
(2019)
This work presents new constraints on the existence and the binding energy of a possible – bound state, the H-dibaryon, derived from – femtoscopic measurements by the ALICE collaboration. The results are obtained from a new measurement using the femtoscopy technique in pp collisions at √s = 13 TeV and p–Pb collisions at √sNN = 5.02 TeV, combined with previously published results from pp collisions at √s = 7 TeV. The – scattering parameter space, spanned by the inverse scattering length f −1 0 and the effective range d0, is constrained by comparing the measured – correlation function with calculations obtained within the Lednický model. The data are compatible with hypernuclei results and lattice computations, both predicting a shallow attractive interaction, and permit to test different theoretical approaches describing the – interaction. The region in the (f −1 0 ,d0) plane which would accommodate a – bound state is substantially restricted compared to previous studies. The binding energy of the possible – bound state is estimated within an effective-range expansion approach and is found to be B = 3.2+1.6 −2.4(stat)+1.8 −1.0(syst) MeV.
The ALICE collaboration performed the first rapidity-differential measurement of coherent J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at a center-of-mass energy √sNN = 5.02 TeV. The J/ψ is detected via its dimuon decay in the forward rapidity region (−4.0 < y < −2.5) for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 750 μb−1. The cross section for coherent J/ψ production is presented in six rapidity bins. The results are compared with theoretical models for coherent J/ψ photoproduction. These comparisons indicate that gluon shadowing effects play a role in the photoproduction process. The ratio of ψ to J/ψ coherent photoproduction cross sections was measured and found to be consistent with that measured for photoproduction off protons.
Measurement of the production of charm jets tagged with D0 mesons in pp collisions at √s = 7 TeV
(2019)
The production of charm jets in proton-proton collisions at a center-of-mass energy of s√=7 TeV was measured with the ALICE detector at the CERN Large Hadron Collider. The measurement is based on a data sample corresponding to a total integrated luminosity of 6.23 nb−1, collected using a minimum-bias trigger. Charm jets are identified by the presence of a D0 meson among their constituents. The D0 mesons are reconstructed from their hadronic decay D0 →K−π+. The D0-meson tagged jets are reconstructed using tracks of charged particles (track-based jets) with the anti-kT algorithm in the jet transverse momentum range 5<pchT,jet< 30 GeV/c and pseudorapidity |ηjet| < 0.5. The fraction of charged jets containing a D0-meson increases with pchT,jet from 0.042 ± 0.004 (stat) ± 0.006 (syst) to 0.080 ± 0.009 (stat) ± 0.008 (syst). The distribution of D0-meson tagged jets as a function of the jet momentum fraction carried by the D0 meson in the direction of the jet axis (zch∥) is reported for two ranges of jet transverse momenta, 5<pchT,jet< 15 GeV/c and 15<pchT,jet< 30 GeV/c in the intervals 0.2<zch∥∥<1.0 and 0.4<zch∥∥<1.0, respectively. The data are compared with results from Monte Carlo event generators (PYTHIA 6, PYTHIA 8 and Herwig 7) and with a Next-to-Leading-Order perturbative Quantum Chromodynamics calculation, obtained with the POWHEG method and interfaced with PYTHIA 6 for the generation of the parton shower, fragmentation, hadronisation and underlying event.