4,074 research outputs found
Gene therapy with mesenchymal stem cells expressing IFN-Ă ameliorates neuroinflammation in experimental models of multiple sclerosis
[Background and Purpose]: Recombinant IFNâĂ is one of the firstâline treatments in multiple sclerosis (MS), despite its lack of efficacy in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, by taking advantage of their pathotropism, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues. Here, we report the therapeutic effect of systemic delivery of adiposeâderived MSCs (AdMSCs), transduced with the IFNâÎČ gene, into mice with experimental autoimmune encephalomyelitis (EAE).[Experimental Approach]: Relapsingâremitting and chronic progressive EAE were induced in mice. Cells were injected i.v. Disease severity, inflammation and tissue damage were assessed clinically, by flow cytometry of spleens and histopathological evaluation of the CNS respectively.[Key Results]: Genetic engineering did not modify the biological characteristics of these AdMSCs (morphology, growth rate, immunophenotype and multipotency). Furthermore, the transduction of IFNâĂ to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuroâinflammation.[Conclusion and Implications]: Gene therapy was found to be more effective than cell therapy in ameliorating several clinical parameters in both EAE models, presumably due to the continuous expression of IFNâÎČ. Furthermore, it has significant advantages over AdMSC therapy, and also over systemic IFNâĂ treatment, by providing longâterm expression of the cytokine at therapeutic concentrations and reducing the frequency of injections, while minimizing doseâlimiting side effects.This work was supported by Fondo de Investigaciones Sanitarias ISCIII (Spain) and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union through the research grants PI12/01097 and PI15/00963 and ISCIII Red de Terapia Celular TerCel RD12/0019/0006 to F.M., by the ConsejerĂa de EconomĂa, InnovaciĂłn, Ciencia y Empleo, Junta de AndalucĂaâFEDER/Fondo de Cohesion Europeo (FSE) de AndalucĂa through the research grants P09âCTSâ04532, PIâ57069 and PAIDIâBioâ326 to F.M. and PIâ0160/2012 to K.B. M.J.P.âM. has been supported by grants from Red TemĂĄtica de InvestigaciĂłn Cooperativa Red Española de Esclerosis MĂșltiple REEM (RD07/0060 and RD12/0032). B.O. is financed by a contract from Excelent Project CTSâ7670/11 from ConsejerĂa de EconomĂa, InnovaciĂłn, Ciencia y Empleo (Junta de AndalucĂa)
Spawning rings of exceptional points out of Dirac cones
The Dirac cone underlies many unique electronic properties of graphene and
topological insulators, and its band structure--two conical bands touching at a
single point--has also been realized for photons in waveguide arrays, atoms in
optical lattices, and through accidental degeneracy. Deformations of the Dirac
cone often reveal intriguing properties; an example is the quantum Hall effect,
where a constant magnetic field breaks the Dirac cone into isolated Landau
levels. A seemingly unrelated phenomenon is the exceptional point, also known
as the parity-time symmetry breaking point, where two resonances coincide in
both their positions and widths. Exceptional points lead to counter-intuitive
phenomena such as loss-induced transparency, unidirectional transmission or
reflection, and lasers with reversed pump dependence or single-mode operation.
These two fields of research are in fact connected: here we discover the
ability of a Dirac cone to evolve into a ring of exceptional points, which we
call an "exceptional ring." We experimentally demonstrate this concept in a
photonic crystal slab. Angle-resolved reflection measurements of the photonic
crystal slab reveal that the peaks of reflectivity follow the conical band
structure of a Dirac cone from accidental degeneracy, whereas the complex
eigenvalues of the system are deformed into a two-dimensional flat band
enclosed by an exceptional ring. This deformation arises from the dissimilar
radiation rates of dipole and quadrupole resonances, which play a role
analogous to the loss and gain in parity-time symmetric systems. Our results
indicate that the radiation that exists in any open system can fundamentally
alter its physical properties in ways previously expected only in the presence
of material loss and gain
Inclusive Dielectron Production in Ar+KCl Collisions at 1.76 AGeV studied with HADES
Results of the HADES measurement of inclusive dielectron production in Ar+KCl
collisions at a kinetic beam energy of 1.76 AGeV are presented. For the first
time, high mass resolution spectroscopy was performed. The invariant mass
spectrum of dielectrons is compared with predictions of UrQMD and HSD transport
codes.Comment: 4 pages, 3 figures - To appear in the conference proceedings for
Quark Matter 2009, March 30 - April 4, Knoxville, Tennesse
Future perspectives at SIS-100 with HADES-at-FAIR
Currently, the HADES spectrometer undergoes un upgrade program to be prepared
for measurements at the upcoming SIS-100 synchrotron at FAIR. We describe the
current status of the HADES di-electron measurements at the SIS-18 and our
future plans for SIS-100.Comment: Invited contribution presented at the XLVII International Winter
Meeting on Nuclear Physics, Bormio (Italy), Jan. 26-30, 200
The structure of mercantile communities in the Roman world : how open were Roman trade networks?
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
The Pierre Auger Observatory III: Other Astrophysical Observations
Astrophysical observations of ultra-high-energy cosmic rays with the Pierre
Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference,
Beijing, China, August 201
Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory
The azimuthal asymmetry in the risetime of signals in Auger surface detector
stations is a source of information on shower development. The azimuthal
asymmetry is due to a combination of the longitudinal evolution of the shower
and geometrical effects related to the angles of incidence of the particles
into the detectors. The magnitude of the effect depends upon the zenith angle
and state of development of the shower and thus provides a novel observable,
, sensitive to the mass composition of cosmic rays
above eV. By comparing measurements with predictions from
shower simulations, we find for both of our adopted models of hadronic physics
(QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass
increases slowly with energy, as has been inferred from other studies. However,
the mass estimates are dependent on the shower model and on the range of
distance from the shower core selected. Thus the method has uncovered further
deficiencies in our understanding of shower modelling that must be resolved
before the mass composition can be inferred from .Comment: Replaced with published version. Added journal reference and DO
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
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