Biogenic and Synthetic Polyamines Bind Cationic Dendrimers

Biogenic polyamines are essential for cell growth and differentiation, while polyamine analogues exert antitumor activity in multiple experimental model systems, including breast and lung cancer. Dendrimers are widely used for drug delivery in vitro and in vivo. We report the bindings of biogenic polyamines, spermine (spm), and spermidine (spmd), and their synthetic analogues, 3,7,11,15-tetrazaheptadecane.4HCl (BE-333) and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333) to dendrimers of different compositions, mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4). FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyze polyamine binding mode, the binding constant and the effects of polyamine complexation on dendrimer stability and conformation. Structural analysis showed that polyamines bound dendrimers through both hydrophobic and hydrophilic contacts with overall binding constants of Kspm-mPEG-G3 = 7.6×104 M−1, Kspm-mPEG-PAMAM-G4 = 4.6×104 M−1, Kspm-PAMAM-G4 = 6.6×104 M−1, Kspmd-mPEG-G3 = 1.0×105 M−1, Kspmd-mPEG-PAMAM-G4 = 5.5×104 M−1, Kspmd-PAMAM-G4 = 9.2×104 M−1, KBE-333-mPEG-G3 = 4.2×104 M−1, KBe-333-mPEG-PAMAM-G4 = 3.2×104 M−1, KBE-333-PAMAM-G4 = 3.6×104 M−1, KBE-3333-mPEG-G3 = 2.2×104 M−1, KBe-3333-mPEG-PAMAM-G4 = 2.4×104 M−1, KBE-3333-PAMAM-G4 = 2.3×104 M−1. Biogenic polyamines showed stronger affinity toward dendrimers than those of synthetic polyamines, while weaker interaction was observed as polyamine cationic charges increased. The free binding energies calculated from docking studies were: −3.2 (spermine), −3.5 (spermidine) and −3.03 (BE-3333) kcal/mol, with the following order of binding affinity: spermidine-PAMAM-G-4>spermine-PAMMAM-G4>BE-3333-PAMAM-G4 consistent with spectroscopic data. Our results suggest that dendrimers can act as carrier vehicles for delivering antitumor polyamine analogues to target tissues

Approaching effects of the economic crisis on university efficiency: a comparative study of Germany and Italy

In this paper, we compare the efficiency of the Italian and German universities in the process of transforming public funding into the multiple outputs of a university, i.e. graduating students, publishing research, and patenting activity. We do this with a particular focus on the policies implemented following the financial crisis in 2008. Using a sample of 133 public universities, of which 73 public universities in Germany and 60 public universities in Italy observed over the period 2006–2011 we find that Italian universities perform significantly better in terms of output maximization than German universities. The crisis does not show a general impact, while the treatment effect indicates that Italian universities coped better during the crisis than their German counterparts at a highly significant level

Search for the production of W^{\pm} W^{\pm} W^{\mp} events at \sqrt{s} = 13 TeV

A search for the production of events containing three W bosons predicted by the standard model is reported. The search is based on a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment at the CERN LHC and corresponding to a total integrated luminosity of 35.9 fb^{-1}. The search is performed in final states with three leptons (electrons or muons), or with two same-charge leptons plus two jets. The observed (expected) significance of the signal for W^{\pm} W^{\pm} W^{\mp} production is 0.60 (1.78) standard deviations, and the ratio of the measured signal yield to that expected from the standard model is 0.34_{-0.34}^{+0.62}. Limits are placed on three anomalous quartic gauge couplings and on the production of massive axionlike particles

Evidence for light-by-light scattering and searches for axion-like particles in ultraperipheral PbPb collisions at root s(NN)=5.02 TeV

Evidence for the light-by-light scattering process, gamma gamma -> gamma gamma, in ultraperipheral PbPb collisions at a centre-of-mass energy per nucleon pair of 5.02 TeV is reported. The analysis is conducted using a data sample corresponding to an integrated luminosity of 390 mu b(-1) recorded by the CMS experiment at the LHC. Light-by-light scattering processes are selected in events with two photons exclusively produced, each with transverse energy E-T(gamma) > 2 GeV, pseudorapidity vertical bar eta(gamma)vertical bar 5 GeV, diphoton transverse momentum p(T)(gamma gamma) gamma gamma) = 120 +/- 46(stat) +/- 28(syst) +/- 12(theo) nb, is consistent with the standard model prediction. The m(gamma gamma) distribution is used to set new exclusion limits on the production of pseudoscalar axion-like particles, via the gamma gamma -> a -> gamma gamma process, in the mass range m(a) = 5-90 GeV. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

Pileup mitigation at CMS in 13 TeV data

With increasing instantaneous luminosity at the LHC come additional reconstruction challenges. At high luminosity, many collisions occur simultaneously within one proton-proton bunch crossing. The isolation of an interesting collision from the additional "pileup" collisions is needed for effective physics performance. In the CMS Collaboration, several techniques capable of mitigating the impact of these pileup collisions have been developed. Such methods include charged-hadron subtraction, pileup jet identification, isospin-based neutral particle "delta beta" correction, and, most recently, pileup per particle identification. This paper surveys the performance of these techniques for jet and missing transverse momentum reconstruction, as well as muon isolation. The analysis makes use of data corresponding to 35.9 fb(-1) collected with the CMS experiment in 2016 at a center-of-mass energy of 13 TeV. The performance of each algorithm is discussed for up to 70 simultaneous collisions per bunch crossing. Significant improvements are found in the identification of pileup jets, the jet energy, mass, and angular resolution, missing transverse momentum resolution, and muon isolation when using pileup per particle identification.Peer reviewe

Measurements of (tt)over-barH Production and the CP Structure of the Yukawa Interaction between the Higgs Boson and Top Quark in the Diphoton Decay Channel

The first observation of the (tt) over barH process in a single Higgs boson decay channel with the full reconstruction of the final state (H -> gamma gamma) is presented, with a significance of 6.6 standard deviations (sigma). The CP structure of Higgs boson couplings to fermions is measured, resulting in an exclusion of the pure CP-odd structure of the top Yukawa coupling at 3.2 sigma. The measurements are based on a sample of protonproton collisions at a center-of-mass energy root s = 13 TeV collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross section times branching fraction of the (tt) over barH process is measured to be sigma B-(tt) over barH(gamma gamma) = 1.56(-0.32)(+0.34) th, which is compatible with the standard model prediction of 1.13(-0.11)(+0.08) fb. The fractional contribution of the CP-odd component is measured to be f(CP)(Hu) = 0.00 +/- 0.33.Peer reviewe

Nuclear modification of Y states in pPb collisions at √SNN_{NN} = 5.02 TeV

Production cross sections of Υ(1S), Υ(2S), and Υ(3S) states decaying into μ+μ− in proton-lead (pPb) collisions are reported using data collected by the CMS experiment at √sNN = 5.02 TeV. A comparison is made with corresponding cross sections obtained with pp data measured at the same collision energy and scaled by the Pb nucleus mass number. The nuclear modification factor for Υ(1S) is found to be RpPb(Υ(1S)) = 0.806±0.024 (stat)±0.059 (syst). Similar results for the excited states indicate a sequential suppression pattern, such that RpPb(Υ(1S)) > RpPb(Υ(2S)) > RpPb(Υ(3S)). The suppression of all states is much less pronounced in pPb than in PbPb collisions, and independent of transverse momentum pΥT and center-of-mass rapidity yΥCM of the individual Υ state in the studied range p ΥT < 30 GeV/c and |yΥCM| <1.93. Models that incorporate final-state effects of bottomonia in pPb collisions are in better agreement with the data than those which only assume initial-state modifications

Observation of Two Excited B-c(+) States and Measurement of the B-c(+) (2S) Mass in pp Collisions at root s=13 TeV

Signals consistent with the B-c(+)(2S) and B-c*(+)(2S) states are observed in proton-proton collisions at root s = 13 TeV, in an event sample corresponding to an integrated luminosity of 143 fb(-1), collected by the CMS experiment during the 2015-2018 LHC running periods. These excited (b) over barc states are observed in the B-c(+)pi(+)pi(-) invariant mass spectrum, with the ground state B-c(+) reconstructed through its decay to J/psi pi(+). The two states are reconstructed as two well-resolved peaks, separated in mass by 29.1 +/- 1.5(stat) +/- 0.7(syst) MeV. The observation of two peaks, rather than one, is established with a significance exceeding five standard deviations. The mass of the B-c(+)(2S) meson is measured to be 6871.0 +/- 1.2(stat) +/- 0.8(syst) +/- 0.8(B-c(+)) MeV, where the last term corresponds to the uncertainty in the world-average B-c(+) mass.Peer reviewe