Nonsteroidal Anti-Inflammatory Drugs and Ectodomain Shedding of the Amyloid Precursor Protein

Background: Epidemiological studies have suggested that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). Several mechanisms have been proposed to explain these findings including increased shedding of the soluble ectodomain of the amyloid precursor protein (sAPP), which functions as a neurotrophic and neuroprotective factor in vitro and in vivo. Objective: To clarify whether NSAIDs consistently stimulate sAPP secretion. Methods: 293-EBNA cells with stable overexpression of an APP-alkaline phosphatase fusion protein (APP-AP), SH-SY5Y and PC12 cells or primary telencephalic chicken neurons were treated with ibuprofen or indomethacin. APP shedding was then determined by measuring AP activity in conditioned media, Western blot analysis with antibodies against total sAPP or specific for sAPP-alpha, or in a pulse-chase paradigm. Results: AP activity in conditioned media was not increased after NSAID treatment of 293-EBNA cells whereas it was elevated by phorbol ester. Surprisingly, ibuprofen or indomethacin treatment of SH-SY5Y and PC12 cells expressing endogenous APP did not cause changes in sAPP or sAPP-alpha secretion or downregulation of cellular APP. These findings were further corroborated in primary chicken neuronal cultures. Conclusions: Using various experimental settings, we were unable to confirm sAPP or sAPP-alpha stimulation with the NSAIDs ibuprofen and indomethacin in transfected and nontransfected cells of neuronal and nonneuronal origin. Importantly, these findings seem to rule out chronic sAPP stimulation as an alternative mechanism of NSAID action in AD. Copyright (C) 2008 S. Karger AG, Base

Improved Fast Neutron Spectroscopy via Detector Segmentation

Organic scintillators are widely used for fast neutron detection and spectroscopy. Several effects complicate the interpretation of results from detectors based upon these materials. First, fast neutrons will often leave a detector before depositing all of their energy within it. Second, fast neutrons will typically scatter several times within a detector, and there is a non-proportional relationship between the energy of, and the scintillation light produced by, each individual scatter; therefore, there is not a deterministic relationship between the scintillation light observed and the neutron energy deposited. Here we demonstrate a hardware technique for reducing both of these effects. Use of a segmented detector allows for the event-by-event correction of the light yield non-proportionality and for the preferential selection of events with near-complete energy deposition, since these will typically have high segment multiplicities.Comment: Accepted for publication in Nuclear Instruments and Methods in Physics Research Section

Characterization of a Li-6 loaded liquid organic scintillator for fast neutron spectrometry and thermal neutron detection

The characterization of a liquid scintillator incorporating an aqueous solution of enriched lithium chloride to produce a scintillator with 0.40% Li-6 is presented, including the performance of the scintillator in terms of its optical properties and neutron response. The scintillator was incorporated into a fast neutron spectrometer, and the light output spectra from 2.5 MeV, 14.1 MeV, and Cf-252 neutrons were measured using capture-gated coincidence techniques. The spectrometer was operated without coincidence to perform thermal neutron measurements. Possible improvements in spectrometer performance are discussed.Comment: Submitted to Applied Radiation and Isotopes. 11 pages, 7 figures, 3 tables. Revision addresses reviewers' comment

Investigation of Large LGB Detectors for Antineutrino Detection

A detector material or configuration that can provide an unambiguous indication of neutron capture can substantially reduce random coincidence backgrounds in antineutrino detection and capture-gated neutron spectrometry applications. Here we investigate the performance of such a material, a composite of plastic scintillator and $^6$Li$_6^{nat}$Gd$(^{10}$BO$_{3})_{3}$:Ce (LGB) crystal shards of ~1 mm dimension and comprising 1% of the detector by mass. While it is found that the optical propagation properties of this material as currently fabricated are only marginally acceptable for antineutrino detection, its neutron capture identification ability is encouraging.Comment: 6 pages, 7 figures, submitted to Nuclear Instruments and Methods

Detection of Supernova Neutrinos by Neutrino-Proton Elastic Scattering

We propose that neutrino-proton elastic scattering, $\nu + p \to \nu + p$, can be used for the detection of supernova neutrinos in scintillator detectors. Though the proton recoil kinetic energy spectrum is soft, with $T_p \simeq 2 E_\nu^2/M_p$, and the scintillation light output from slow, heavily ionizing protons is quenched, the yield above a realistic threshold is nearly as large as that from $\bar{\nu}_e + p \to e^+ + n$. In addition, the measured proton spectrum is related to the incident neutrino spectrum, which solves a long-standing problem of how to separately measure the total energy and temperature of $\nu_\mu$, $\nu_\tau$, $\bar{\nu}_\mu$, and $\bar{\nu}_\tau$. The ability to detect this signal would give detectors like KamLAND and Borexino a crucial and unique role in the quest to detect supernova neutrinos.Comment: 10 pages, 9 figures, revtex

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

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal