CD20-targeting immunotherapy promotes cellular senescence in B-cell lymphoma

The CD20-targeting monoclonal antibody Rituximab is an established component of immunochemotherapeutic regimens against B-cell lymphomas, where its co-administration with conventional anti-cancer agents has significantly improved long-term outcome. However, the cellular mechanisms by which Rituximab exerts its anti-lymphoma activity are only partially understood. We show here that Rituximab induces typical features of cellular senescence, a long-term growth arrest of viable cells with distinct biological properties, in established B-cell lymphoma cell lines as well as primary transformed B-cells. In addition, Rituximab-based immunotherapy sensitized lymphoma cells to senescence induction by the chemotherapeutic compound Adriamycin (a.k.a. Doxorubicin), and, to a lesser extent, by the antimicrotubule agent Vincristine. Anti-CD20 treatment further enhanced secretion of senescence-associated cytokines, and augmented the DNA damage response (DDR) signaling cascade triggered by Adriamycin. As the underlying pro-senescence mechanism, we found intracellular reactive oxygen species (ROS) levels to be elevated in response to Rituximab, and, in turn, the ROS scavenger N-acetylcysteine (NAC) to largely abrogate Rituximab-mediated senescence. Our results, further supported by gene set enrichment analyses in a clinical data set of chronic lymphocytic leukemia patient samples exposed to a Rituximab-containing treatment regimen, provide important mechanistic insights into the biological complexity of anti-CD20-evoked tumor responses, and unveil cellular senescence as a hitherto unrecognized effector principle of the antibody component in lymphoma immunochemotherapy

Search for a Standard Model Higgs Boson in CMS via Vector Boson Fusion in the H->WW->l\nu l\nu Channel

We present the potential for discovering the Standard Model Higgs boson produced by the vector-boson fusion mechanism. We considered the decay of Higgs bosons into the W+W- final state, with both W-bosons subsequently decaying leptonically. The main background is ttbar with one or more jets produced. This study is based on a full simulation of the CMS detector, and up-to-date reconstruction codes. The result is that a signal of 5 sigma significance can be obtained with an integrated luminosity of 12-72 1/fb for Higgs boson masses between 130-200 GeV. In addition, the major background can be measured directly to 7% from the data with an integrated luminosity of 30 1/fb. In this study, we also suggested a method to obtain information in Higgs mass using the transverse mass distributions.Comment: 26 pages, 22 figure

Annual cambial rhythm in Pinus halepensis and Pinus sylvestris as indicator for climate adaptation

To understand better the adaptation strategies of intra-annual radial growth in Pinus halepensis and Pinus sylvestris to local environmental conditions, we examined the seasonal rhythm of cambial activity and cell differentiation at tissue and cellular levels. Two contrasting sites differing in temperature and amount of precipitation were selected for each species, one typical for their growth and the other represented border climatic conditions, where the two species coexisted. Mature P. halepensis trees from Mediterranean (Spain) and sub-Mediterranean (Slovenia) sites, and P. sylvestris from sub-Mediterranean (Slovenia) and temperate (Slovenia) sites were selected. Repeated sampling was performed throughout the year and samples were prepared for examination with light and transmission electron microscopes. We hypothesized that cambial rhythm in trees growing at the sub-Mediterranean site where the two species co-exist will be similar as at typical sites for their growth. Cambium in P. halepensis at the Mediterranean site was active throughout the year and was never truly dormant, whereas at the sub-Mediterranean site it appeared to be dormant during the winter months. In contrast, cambium in P. sylvestris was clearly dormant at both sub-Mediterranean and temperate sites, although the dormant period seemed to be significantly longer at the temperate site. Thus, the hypothesis was only partly confirmed. Different cambial and cell differentiation rhythms of the two species at the site where both species co-exist and typical sites for their growth indicate their high but different adaptation strategies in terms of adjustment of radial growth to environmental heterogeneity, crucial for long-term tree performance and survival

Unfolding of differential energy spectra in the MAGIC experiment

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.Comment: Submitted to NIM

Implementation of the Random Forest Method for the Imaging Atmospheric Cherenkov Telescope MAGIC

The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.Comment: 16 pages, 8 figure

Probing quantum gravity using photons from a flare of the active galactic nucleus Markarian 501 observed by the MAGIC telescope

We analyze the timing of photons observed by the MAGIC telescope during a flare of the active galactic nucleus Mkn 501 for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index \simeq 1 + (E/M_{QGn})^n, n = 1,2. Parametrizing the delay between gamma-rays of different energies as \Delta t =\pm\tau_l E or \Delta t =\pm\tau_q E^2, we find \tau_l=(0.030\pm0.012) s/GeV at the 2.5-sigma level, and \tau_q=(3.71\pm2.57)x10^{-6} s/GeV^2, respectively. We use these results to establish lower limits M_{QG1} > 0.21x10^{18} GeV and M_{QG2} > 0.26x10^{11} GeV at the 95% C.L. Monte Carlo studies confirm the MAGIC sensitivity to propagation effects at these levels. Thermal plasma effects in the source are negligible, but we cannot exclude the importance of some other source effect.Comment: 12 pages, 3 figures, Phys. Lett. B, reflects published versio

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio