256 research outputs found
Loss of huntingtin function complemented by small molecules acting as repressor element 1/neuron restrictive silencer element silencer modulators
Increased levels of the repressor element 1/neuron restrictive silencer element (RE1/NRSE) silencing activity promoter, and a consequent reduction in the transcription of many RE1/NRSE-bearing neuronal genes, including brain-derived neurotrophic factor (BDNF), have been demonstrated in Huntington disease (HD) and represent one possible effector of its selective neuronal vulnerability. Restoring the expression levels of neuronal genes in diseased neurons therefore seems to be an attractive therapeutic approach. To this end, we have developed a cell-based reporter assay for monitoring RE1/NRSE silencing activity and validated it by genetically inactivating the RE1/NRSE or pharmacologically stimulating global transcription. In a pilot compound screen, we identified three closely related structural analogues that up-regulate reporter expression at low nanomolar concentrations, and follow-up studies have shown that they efficaciously increase endogenous BDNF levels in HD cells. Moreover, one of the compounds increases the viability of HD cells. Our findings suggest a new avenue for the development of drugs for HD and other neurodegenerative disorders based on the pharmacological up-regulation of the production of the neuronal survival factor BDNF and of other RE1/NRSE-regulated neuronal gene
Magnetic Field Generation in Stars
Enormous progress has been made on observing stellar magnetism in stars from
the main sequence through to compact objects. Recent data have thrown into
sharper relief the vexed question of the origin of stellar magnetic fields,
which remains one of the main unanswered questions in astrophysics. In this
chapter we review recent work in this area of research. In particular, we look
at the fossil field hypothesis which links magnetism in compact stars to
magnetism in main sequence and pre-main sequence stars and we consider why its
feasibility has now been questioned particularly in the context of highly
magnetic white dwarfs. We also review the fossil versus dynamo debate in the
context of neutron stars and the roles played by key physical processes such as
buoyancy, helicity, and superfluid turbulence,in the generation and stability
of neutron star fields.
Independent information on the internal magnetic field of neutron stars will
come from future gravitational wave detections. Thus we maybe at the dawn of a
new era of exciting discoveries in compact star magnetism driven by the opening
of a new, non-electromagnetic observational window.
We also review recent advances in the theory and computation of
magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo
theory. These advances offer insight into the action of stellar dynamos as well
as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field
generation in stars to appear in Space Science Reviews, Springe
Magnetic Field Amplification in Galaxy Clusters and its Simulation
We review the present theoretical and numerical understanding of magnetic
field amplification in cosmic large-scale structure, on length scales of galaxy
clusters and beyond. Structure formation drives compression and turbulence,
which amplify tiny magnetic seed fields to the microGauss values that are
observed in the intracluster medium. This process is intimately connected to
the properties of turbulence and the microphysics of the intra-cluster medium.
Additional roles are played by merger induced shocks that sweep through the
intra-cluster medium and motions induced by sloshing cool cores. The accurate
simulation of magnetic field amplification in clusters still poses a serious
challenge for simulations of cosmological structure formation. We review the
current literature on cosmological simulations that include magnetic fields and
outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure
System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV
We present azimuthal angle correlations of intermediate transverse momentum
(1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) =
62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is
broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and
semi-central collisions in all the systems. The broadening and peak location
are found to depend upon the number of participants in the collision, but not
on the collision energy or beam nuclei. These results are consistent with sound
or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables.
Submitted to Physical Review Letters. Plain text data tables for the points
plotted in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
Improved Measurement of Double Helicity Asymmetry in Inclusive Midrapidity pi^0 Production for Polarized p+p Collisions at sqrt(s)=200 GeV
We present an improved measurement of the double helicity asymmetry for pi^0
production in polarized proton-proton scattering at sqrt(s) = 200 GeV employing
the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The
improvements to our previous measurement come from two main factors: Inclusion
of a new data set from the 2004 RHIC run with higher beam polarizations than
the earlier run and a recalibration of the beam polarization measurements,
which resulted in reduced uncertainties and increased beam polarizations. The
results are compared to a Next to Leading Order (NLO) perturbative Quantum
Chromodynamics (pQCD) calculation with a range of polarized gluon
distributions.Comment: 389 authors, 4 pages, 2 tables, 1 figure. Submitted to Phys. Rev. D,
Rapid Communications. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (or will be) publicly
available at http://www.phenix.bnl.gov/papers.htm
Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration
Extensive experimental data from high-energy nucleus-nucleus collisions were
recorded using the PHENIX detector at the Relativistic Heavy Ion Collider
(RHIC). The comprehensive set of measurements from the first three years of
RHIC operation includes charged particle multiplicities, transverse energy,
yield ratios and spectra of identified hadrons in a wide range of transverse
momenta (p_T), elliptic flow, two-particle correlations, non-statistical
fluctuations, and suppression of particle production at high p_T. The results
are examined with an emphasis on implications for the formation of a new state
of dense matter. We find that the state of matter created at RHIC cannot be
described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted
to Nuclear Physics A as a regular article; v3 has minor changes in response
to referee comments. Plain text data tables for the points plotted in figures
for this and previous PHENIX publications are (or will be) publicly available
at http://www.phenix.bnl.gov/papers.htm
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
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
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