168 research outputs found
Protein kinase B (AKT) upregulation and Thy-1-ι<sub>v</sub>β<sub>3</sub> integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.
In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including ι <sub>v</sub> β <sub>3</sub> integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined.
Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1 <sup>G93A</sup> transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi).
The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1 <sup>G93A</sup> transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation.
Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis
Van der Waals-Casimir-Polder interaction of an atom with a composite surface
We study the dispersion interaction of the van der Waals and Casimir-Polder
(vdW-CP) type between a neutral atom and the surface of a metal by allowing for
nonlocal electrodynamics, i.e. electron diffusion. We consider two models: (i)
bulk diffusion, and (ii) diffusion in a surface charge layer. In both cases the
transition to a semiconductor is continuous as a function of the conductivity,
unlike the case of a local model. The relevant parameter is the electric
screening length and depends on the carrier diffusion constant. We find that
for distances comparable to the screening length, vdW-CP data can distinguish
between bulk and surface diffusion, hence it can be a sensitive probe for
surface states.Comment: v2: expanded references, statements on current status in the field.
10 pages, 6 figure
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV
Results are presented from a search for a W' boson using a dataset
corresponding to 5.0 inverse femtobarns of integrated luminosity collected
during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV.
The W' boson is modeled as a heavy W boson, but different scenarios for the
couplings to fermions are considered, involving both left-handed and
right-handed chiral projections of the fermions, as well as an arbitrary
mixture of the two. The search is performed in the decay channel W' to t b,
leading to a final state signature with a single lepton (e, mu), missing
transverse energy, and jets, at least one of which is tagged as a b-jet. A W'
boson that couples to fermions with the same coupling constant as the W, but to
the right-handed rather than left-handed chiral projections, is excluded for
masses below 1.85 TeV at the 95% confidence level. For the first time using LHC
data, constraints on the W' gauge coupling for a set of left- and right-handed
coupling combinations have been placed. These results represent a significant
improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe
Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV
A search for a Higgs boson decaying into two photons is described. The
analysis is performed using a dataset recorded by the CMS experiment at the LHC
from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an
integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross
section of the standard model Higgs boson decaying to two photons. The expected
exclusion limit at 95% confidence level is between 1.4 and 2.4 times the
standard model cross section in the mass range between 110 and 150 GeV. The
analysis of the data excludes, at 95% confidence level, the standard model
Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The
largest excess of events above the expected standard model background is
observed for a Higgs boson mass hypothesis of 124 GeV with a local significance
of 3.1 sigma. The global significance of observing an excess with a local
significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is
estimated to be 1.8 sigma. More data are required to ascertain the origin of
this excess.Comment: Submitted to Physics Letters
Measurement of charm production at central rapidity in proton-proton collisions at TeV
The -differential production cross sections of the prompt (B
feed-down subtracted) charmed mesons D, D, and D in the rapidity
range , and for transverse momentum GeV/, were
measured in proton-proton collisions at TeV with the ALICE
detector at the Large Hadron Collider. The analysis exploited the hadronic
decays DK, DK, DD, and their charge conjugates, and was performed on a
nb event sample collected in 2011 with a
minimum-bias trigger. The total charm production cross section at TeV and at 7 TeV was evaluated by extrapolating to the full phase space
the -differential production cross sections at TeV
and our previous measurements at TeV. The results were compared
to existing measurements and to perturbative-QCD calculations. The fraction of
cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/307
Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at = 2.76 TeV
The yield of charged particles associated with high- trigger
particles ( GeV/) is measured with the ALICE detector in
Pb-Pb collisions at = 2.76 TeV relative to proton-proton
collisions at the same energy. The conditional per-trigger yields are extracted
from the narrow jet-like correlation peaks in azimuthal di-hadron correlations.
In the 5% most central collisions, we observe that the yield of associated
charged particles with transverse momenta GeV/ on the
away-side drops to about 60% of that observed in pp collisions, while on the
near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/350
Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV
The Lambda(b) differential production cross section and the cross section
ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum
pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7
TeV using data collected by the CMS experiment at the LHC. The measurements are
based on Lambda(b) decays reconstructed in the exclusive final state J/Psi
Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and
Lambda to proton pion, using a data sample corresponding to an integrated
luminosity of 1.9 inverse femtobarns. The product of the cross section times
the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls
faster than that of b mesons. The measured value of the cross section times the
branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06
+/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for
anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are
statistical and systematic, respectively.Comment: Submitted to Physics Letters
Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV
A search is presented for physics beyond the standard model (BSM) in final
states with a pair of opposite-sign isolated leptons accompanied by jets and
missing transverse energy. The search uses LHC data recorded at a
center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to
an integrated luminosity of approximately 5 inverse femtobarns. Two
complementary search strategies are employed. The first probes models with a
specific dilepton production mechanism that leads to a characteristic kinematic
edge in the dilepton mass distribution. The second strategy probes models of
dilepton production with heavy, colored objects that decay to final states
including invisible particles, leading to very large hadronic activity and
missing transverse energy. No evidence for an event yield in excess of the
standard model expectations is found. Upper limits on the BSM contributions to
the signal regions are deduced from the results, which are used to exclude a
region of the parameter space of the constrained minimal supersymmetric
extension of the standard model. Additional information related to detector
efficiencies and response is provided to allow testing specific models of BSM
physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO
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