Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

risk factors associated with road traffic injuries in Mozambique: results of the 2016 INCOMAS study

publishersversionpublishe

The imprints of superstatistics in multiparticle production processes

We provide an update of the overview of imprints of Tsallis nonextensive statistics seen in a multiparticle production processes. They reveal an ubiquitous presence of power law distributions of different variables characterized by the nonextensivity parameter q > 1. In nuclear collisions one additionally observes a q-dependence of the multiplicity fluctuations reflecting the finiteness of the hadronizing source. We present sum rules connecting parameters q obtained from an analysis of different observables, which allows us to combine different kinds of fluctuations seen in the data and analyze an ensemble in which the energy (E), temperature (T) and multiplicity (N) can all fluctuate. This results in a generalization of the so called Lindhard's thermodynamic uncertainty relation. Finally, based on the example of nucleus-nucleus collisions (treated as a quasi-superposition of nucleon-nucleon collisions) we demonstrate that, for the standard Tsallis entropy with degree of nonextensivity q < 1, the corresponding standard Tsallis distribution is described by q' = 2 - q > 1.Comment: 12 pages, 3 figures. Based on invited talk given by Z.Wlodarczyk at SigmaPhi2011 conference, Larnaka, Cyprus, 11-15 July 2011. To be published in Cent. Eur. J. Phys. (2011

Planar Graph Coloring with Forbidden Subgraphs: Why Trees and Paths Are Dangerous

We consider the problem of coloring a planar graph with the minimum number of colors such that each color class avoids one or more forbidden graphs as subgraphs. We perform a detailed study of the computational complexity of this problem. We present a complete picture for the case with a single forbidden connected (induced or non-induced) subgraph. The 2-coloring problem is NP-hard if the forbidden subgraph is a tree with at least two edges, and it is polynomially solvable in all other cases. The 3-coloring problem is NP-hard if the forbidden subgraph is a path, and it is polynomially solvable in all other cases. We also derive results for several forbidden sets of cycles

Bose-Einstein Correlations in e+e- to W+W- at 172 and 183 GeV

Bose-Einstein correlations between like-charge pions are studied in hadronic final states produced by e+e- annihilations at center-of-mass energies of 172 and 183 GeV. Three event samples are studied, each dominated by one of the processes W+W- to qqlnu, W+W- to qqqq, or (Z/g)* to qq. After demonstrating the existence of Bose-Einstein correlations in W decays, an attempt is made to determine Bose-Einstein correlations for pions originating from the same W boson and from different W bosons, as well as for pions from (Z/g)* to qq events. The following results are obtained for the individual chaoticity parameters lambda assuming a common source radius R: lambda_same = 0.63 +- 0.19 +- 0.14, lambda_diff = 0.22 +- 0.53 +- 0.14, lambda_Z = 0.47 +- 0.11 +- 0.08, R = 0.92 +- 0.09 +- 0.09. In each case, the first error is statistical and the second is systematic. At the current level of statistical precision it is not established whether Bose-Einstein correlations, between pions from different W bosons exist or not.Comment: 24 pages, LaTeX, including 6 eps figures, submitted to European Physical Journal

Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.

Determination of alpha_s using Jet Rates at LEP with the OPAL detector

Hadronic events produced in e+e- collisions by the LEP collider and recorded by the OPAL detector were used to form distributions based on the number of reconstructed jets. The data were collected between 1995 and 2000 and correspond to energies of 91 GeV, 130-136 GeV and 161-209 GeV. The jet rates were determined using four different jet-finding algorithms (Cone, JADE, Durham and Cambridge). The differential two-jet rate and the average jet rate with the Durham and Cambridge algorithms were used to measure alpha(s) in the LEP energy range by fitting an expression in which order alpah_2s calculations were matched to a NLLA prediction and fitted to the data. Combining the measurements at different centre-of-mass energies, the value of alpha_s (Mz) was determined to be alpha(s)(Mz)=0.1177+-0.0006(stat.)+-0.0012$(expt.)+-0.0010(had.)+-0.0032(theo.) \.Comment: 40 pages, 17 figures, Submitted to Euro. Phys. J.

Measurement of triple gauge boson couplings from WW production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb^-1. After combining with our previous measurements at centre-of-mass energies of 161-183 GeV we obtain k_g=0.97 +0.20 -0.16, g_1^z=0.991 +0.060 -0.057 and lambda_g=-0.110 +0.058 -0.055, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their SM values. These results are consistent with the Standard Model expectations.Comment: 28 pages, 8 figures, submitted to Eur. Phys. J.

Tests of model of color reconnection and a search for glueballs using gluon jets with a rapidity gap

Gluon jets with a mean energy of 22 GeV and purity of 95% are selected from hadronic Z0 decay events produced in e+e- annihilations. A subsample of these jets is identified which exhibits a large gap in the rapidity distribution of particles within the jet. After imposing the requirement of a rapidity gap, the gluon jet purity is 86%. These jets are observed to demonstrate a high degree of sensitivity to the presence of color reconnection, i.e. higher order QCD processes affecting the underlying color structure. We use our data to test three QCD models which include a simulation of color reconnection: one in the Ariadne Monte Carlo, one in the Herwig Monte Carlo, and the other by Rathsman in the Pythia Monte Carlo. We find the Rathsman and Ariadne color reconnection models can describe our gluon jet measurements only if very large values are used for the cutoff parameters which serve to terminate the parton showers, and that the description of inclusive Z0 data is significantly degraded in this case. We conclude that color reconnection as implemented by these two models is disfavored. The signal from the Herwig color reconnection model is less clear and we do not obtain a definite conclusion concerning this model. In a separate study, we follow recent theoretical suggestions and search for glueball-like objects in the leading part of the gluon jets. No clear evidence is observed for these objects.Comment: 42 pages, 18 figure