Triterpene-Based Carboxamides Act as Good Inhibitors of Butyrylcholinesterase

A set of overall 40 carboxamides was prepared from five different natural occurring triterpenoids including oleanolic, ursolic, maslinic, betulinic, and platanic acid. All of which were derived from ethylene diamine holding an additional substituent connected to the ethylene diamine group. These derivatives were evaluated regarding their inhibitory activity of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) employing Ellman’s assay. We further determined the type of inhibition and inhibition constants. Carboxamides derived from platanic acid have been shown to be potent and selective BChE inhibitors. Especially the mixed-type inhibitor (3β)-N-(2-pyrrolidin-1-ylethyl)-3-acetyloxy-20-oxo-30-norlupan-28-amide (35) showed a remarkably low Ki of 0.07 ± 0.01 µM (Ki′ = 2.38 ± 0.48 µM) for the inhibition of BChE

Kurt Schumacher und der 'Neubau' der deutschen Sozialdemokratie nach 1945 Referate und Podiumsdiskussion eines Kolloquiums des Gespraechskreises Geschichte der Friedrich-Ebert-Stiftung in Bonn am 12./13. Oktober 1995

UuStB Koeln(38)-970106033 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation

INTRODUCTION Circulating histones have been identified as mediators of damage in animal models of sepsis and in patients with trauma-associated lung injury. Despite existing controversies on actual histone concentrations, clinical implications and mechanism of action in various disease conditions, histone levels in human sepsis, association with disease progression and mediated effects on endothelial and immune cells remain unreported. This study aimed to determine histone levels and its clinical implication in septic patients and to elucidate histone-mediated effects ex-vivo. METHODS Histone levels, endogenous activated protein C (APC) levels and clinical data from two independent cohorts of septic patients were obtained. Histone levels were compared with various control groups including healthy individuals, intensive care unit (ICU) patients without sepsis, ICU patients with multiple organ failure and patients with minor or multiple trauma, all without infection. Endothelial and monocytic cells were stimulated with histones. Cellular integrity and sepsis prototypical cytokines were evaluated. The mechanism of action of histones via Toll-like receptor 4 (TLR4) was evaluated using a function blocking antibody. Histone degradation in plasma was studied by immunoblotting. RESULTS Histone H4 levels were significantly elevated in patients with sepsis (cohort I; n = 15 and cohort II; n = 19) versus ICU controls (n = 12), patients with multiple organ failure (n = 12) or minor trauma (n = 7), associated with need for renal replacement therapy and decrease in platelet count during disease progression, and remarkably were significantly associated with increased mortality rates in septic patients (ICU-, 28 day- and 90 day mortality rates). There was an inverse correlation between plasma histones and endogenous APC levels. Histone stimulation induced the release of sepsis prototypic cytokines and decreased cell integrity indicated by a significant increase of lactate dehydrogenase (LDH) and propidium iodide (PI) staining. Blocking of TLR4 decreased cellular cytotoxicity on endothelial cells. The calculated half-life of histones in spiked plasma was 4.6 minutes. CONCLUSIONS Histone levels in septic patients are significantly increased and might mediate disease aggravation by cellular injury and inflammation via TLR4 signaling, which potentially results in multiple organ failure and fatal outcome

Measurement of the cross section of top quark-antiquark pair production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

The production of a top quark-antiquark pair in association with a W boson ($\textrm{t}\overline{\textrm{t}}\textrm{W}$) is measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analyzed data was recorded by the CMS experiment at the CERN LHC and corresponds to an integrated luminosity of 138 fb$^{−1}$. Events with two or three leptons (electrons and muons) and additional jets are selected. In events with two leptons, a multiclass neural network is used to distinguish between the signal and background processes. Events with three leptons are categorized based on the number of jets and of jets originating from b quark hadronization, and the lepton charges. The inclusive $\textrm{t}\overline{\textrm{t}}\textrm{W}$ production cross section in the full phase space is measured to be 868 ± 40(stat) ± 51(syst) fb. The $\textrm{t}\overline{\textrm{t}}\textrm{W} ^{+}$ and $\textrm{t}\overline{\textrm{t}}\textrm{W} ^{−}$ cross sections are also measured as 553 ± 30(stat) ± 30(syst) and 343 ± 26(stat) ± 25(syst) fb, respectively, and the corresponding ratio of the two cross sections is found to be $1.61\pm 0.15{\left(\textrm{stat}\right)}_{-0.05}^{+0.07}\left(\textrm{syst}\right)$. The measured cross sections are larger than but consistent with the standard model predictions within two standard deviations, and represent the most precise measurement of these cross sections to date.[graphic not available: see fulltext

Measurement of the cross section of top quark-antiquark pair production in association with a W boson in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe production of a top quark-antiquark pair in association with a W boson ($\mathrm{t\bar{t}}$W) is measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analyzed data was recorded by the CMS experiment at the CERN LHC and corresponds to an integrated luminosity of 138 fb$^{-1}$. Events with two or three leptons (electrons and muons) and additional jets are selected. In events with two leptons, a multiclass neural network is used to distinguish between the signal and background processes. Events with three leptons are categorized based on the number of jets and of jets originating from b quark hadronization, and the lepton charges. The inclusive $\mathrm{t\bar{t}}$W production cross section in the full phase space is measured to be 868 $\pm$ 40 (stat) $\pm$ 51 (syst) fb. The $\mathrm{t\bar{t}}$W$^+$ and $\mathrm{t\bar{t}}$W$^-$ cross sections are also measured as 553 $\pm$ 30 (stat) $\pm$ 30 (syst) and 343 $\pm$ 26 (stat) $\pm$ 25 (syst) fb, respectively, and the corresponding ratio of the two cross sections is found to be 1.61 $\pm$ 0.15 (stat) $^{+0.07}_{-0.05}$ (syst). The measured cross sections are larger than but consistent with the standard model predictions within two standard deviations, and represent the most precise measurement of these cross sections to date