2,542 research outputs found
Geant4 Muon Digitization in the ATHENA Framework
The aim of this note is to describe the Muon Digitization software packages, completely re-written to run in the Athena framework and to interface with the Geant4 Muon Spectrometer simulation. The Muon Digitization is the simulation of the Raw Data Objects (RDO), or the electronic output, of the Muon Spectrometer. It consists of two steps: in the first step, the output of the detector simulation, the Muon Hits, is converted to Muon Digits, namely intermediate objects that can be fed into the reconstruction. In the second step, the Muon Digits are converted into RDO, the transient representation of raw data byte stream. We describe the detailed implementation of the first step of the Muon Digitization, where the detector simulation output is âワdigitizedâ into Muon Digits. We describe the fundamentals of the Muon Digitization algorithms, outlining their global structure and the infrastructure for the simulation of piled-up events. We also describe the details of the digitization validation procedures against the Monte Carlo information
Updates of the ATLAS Tracking Event Data Model (Release 13)
In a previous document we have presented the ATLAS tracking Event Data Model (EDM) that has been developed during the recent restructuring of the ATLAS offline track reconstruction. The tracking EDM has become a cornerstone of the new modular track reconstruction algorithms of both tracking devices of the ATLAS detector, the Inner Detector and the Muon System. Recently, some components have undergone yet another design evolution targeted at completing missing modules and at establishing anticipated functionality for the startup of the ATLAS experiment. One particular aspect of the EDM is that is does not only have to fulfill the requirements of today's algorithmic modules, but has to provide the flexibility for future developments. This document is based on ATLAS software release 13.0.0
Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology
BACKGROUND:
Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer's disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.
METHOD:
We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.
RESULTS:
First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 (pS199/pS202) site tau phosphorylation, with the maximum effect peaking at 60-90 min after stimulation. Second, treatment of old (~20 months of age) hTau mice with MW181 (1 mg/kg body weight; 14 days via oral gavage) significantly reduced p38α MAPK activation compared with vehicle-administered hTau mice. This also resulted in a significant reduction in AT180 (pT231) site tau phosphorylation and Sarkosyl-insoluble tau aggregates. Third, MW181 treatment significantly increased synaptophysin protein expression and resulted in improved working memory. Fourth, MW181 administration reduced phosphorylated MAPK-activated protein kinase 2 (pMK2) and phosphorylated activating transcription factor 2 (pATF2), which are known substrates of p38α MAPK. Finally, MW181 reduced the expression of interferon-γ and interleukin-1β.
CONCLUSIONS:
Taken together, these studies support p38α MAPK as a valid therapeutic target for the treatment of tauopathies
MW151 Inhibited IL-1β Levels After Traumatic Brain Injury with No Effect on Microglia Physiological Responses
A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5–5.0 mg/kg) administration of MW151 suppresses interleukin-1 beta (IL-1β) levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1β increases while sparing other glial responses to injury
Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas
Impairment of vascular pathways of cerebral β-amyloid (Aβ) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral Aβ clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with Aβ within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-Aβ co-deposits. LRP1-mediated Aβ transport across the blood-brain barrier and Aβ clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by Aβ deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and Aβ pathology
Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT
Studying the temporal variability of BL Lac objects at the highest energies
provides unique insights into the extreme physical processes occurring in
relativistic jets and in the vicinity of super-massive black holes. To this
end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in
the high (HE, 100 MeV 200 GeV)
gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE
light curve in the quiescent state is consistent with a log-normal behavior.
The VHE variability in this state is well described by flicker noise
(power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales
larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives
consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10
days) compatible with the VHE findings. The HE and VHE power spectral densities
show a scale invariance across the probed time ranges. A direct linear
correlation between the VHE and HE fluxes could neither be excluded nor firmly
established. These long-term-variability properties are discussed and compared
to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during
VHE-flaring states. The difference in power spectral noise behavior at VHE
energies during quiescent and flaring states provides evidence that these
states are influenced by different physical processes, while the compatibility
of the HE and VHE long-term results is suggestive of a common physical link as
it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure
Study of Leading Hadrons in Gluon and Quark Fragmentation
The study of quark jets in e+e- reactions at LEP has demonstrated that the
hadronisation process is reproduced well by the Lund string model. However, our
understanding of gluon fragmentation is less complete. In this study enriched
quark and gluon jet samples of different purities are selected in three-jet
events from hadronic decays of the Z collected by the DELPHI experiment in the
LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are
defined by requiring a rapidity gap and their sum of charges is studied. An
excess of leading systems with total charge zero is found for gluon jets in all
cases, when compared to Monte Carlo Simulations with JETSET (with and without
Bose-Einstein correlations included) and ARIADNE. The corresponding leading
systems of quark jets do not exhibit such an excess. The influence of the gap
size and of the gluon purity on the effect is studied and a concentration of
the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is
observed, indicating that gluon jets might have an additional hitherto
undetected fragmentation mode via a two-gluon system. This could be an
indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.
Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3
Context. Recently, the high-energy (HE, 0.1-100 GeV) -ray emission
from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered
to be modulated with a 10.3-day period, making it the first extra-galactic
-ray binary.
Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV)
-ray emission and the search for modulation of the VHE signal with the
orbital period of the binary system.
Methods. LMC P3 has been observed with the High Energy Stereoscopic System
(H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has
been folded with the known orbital period of the system in order to test for
variability of the emission. Energy spectra are obtained for the orbit-averaged
data set, and for the orbital phase bin around the VHE maximum.
Results. VHE -ray emission is detected with a statistical
significance of 6.4 . The data clearly show variability which is
phase-locked to the orbital period of the system. Periodicity cannot be deduced
from the H.E.S.S. data set alone. The orbit-averaged luminosity in the
TeV energy range is erg/s. A luminosity of erg/s is reached during 20% of the orbit. HE and VHE
-ray emissions are anti-correlated. LMC P3 is the most luminous
-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&
Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector
Inclusive J/psi production in photon-photon collisions has been observed at
LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X
is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an
integrated luminosity of 617 pb^{-1}, yielding a cross-section of
sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the
event shapes of different types of gamma gamma processes in the PYTHIA program,
we conclude that (74 +/- 22)% of the observed J/psi events are due to
`resolved' photons, the dominant contribution of which is most probably due to
the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.
Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance
This paper presents DELPHI measurements and interpretations of
cross-sections, forward-backward asymmetries, and angular distributions, for
the e+e- -> ffbar process for centre-of-mass energies above the Z resonance,
from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are
consistent with the predictions of the Standard Model and are used to study a
variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering
and several models which include physics beyond the Standard Model: the
exchange of Z' bosons, contact interactions between fermions, the exchange of
gravitons in large extra dimensions and the exchange of sneutrino in R-parity
violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.
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