432 research outputs found
Synthetic Cell-Based Immunotherapies for Neurologic Diseases
The therapeutic success and widespread approval of genetically engineered T cells for a variety of hematologic malignancies spurred the development of synthetic cell-based immunotherapies for CNS lymphoma, primary brain tumors, and a growing spectrum of nononcologic disease conditions of the nervous system. Chimeric antigen receptor effector T cells bear the potential to deplete target cells with higher efficacy, better tissue penetration, and greater depth than antibody-based cell depletion therapies. In multiple sclerosis and other autoimmune disorders, engineered T-cell therapies are being designed and currently tested in clinical trials for their safety and efficacy to eliminate pathogenic B-lineage cells. Chimeric autoantibody receptor T cells expressing a disease-relevant autoantigen as cell surface domains are designed to selectively deplete autoreactive B cells. Alternative to cell depletion, synthetic antigen-specific regulatory T cells can be engineered to locally restrain inflammation, support immune tolerance, or efficiently deliver neuroprotective factors in brain diseases in which current therapeutic options are very limited. In this article, we illustrate prospects and bottlenecks for the clinical development and implementation of engineered cellular immunotherapies in neurologic diseases
Search for non-relativistic Magnetic Monopoles with IceCube
The IceCube Neutrino Observatory is a large Cherenkov detector instrumenting
of Antarctic ice. The detector can be used to search for
signatures of particle physics beyond the Standard Model. Here, we describe the
search for non-relativistic, magnetic monopoles as remnants of the GUT (Grand
Unified Theory) era shortly after the Big Bang. These monopoles may catalyze
the decay of nucleons via the Rubakov-Callan effect with a cross section
suggested to be in the range of to
. In IceCube, the Cherenkov light from nucleon decays
along the monopole trajectory would produce a characteristic hit pattern. This
paper presents the results of an analysis of first data taken from May 2011
until May 2012 with a dedicated slow-particle trigger for DeepCore, a
subdetector of IceCube. A second analysis provides better sensitivity for the
brightest non-relativistic monopoles using data taken from May 2009 until May
2010. In both analyses no monopole signal was observed. For catalysis cross
sections of the flux of non-relativistic
GUT monopoles is constrained up to a level of at a 90% confidence level,
which is three orders of magnitude below the Parker bound. The limits assume a
dominant decay of the proton into a positron and a neutral pion. These results
improve the current best experimental limits by one to two orders of magnitude,
for a wide range of assumed speeds and catalysis cross sections.Comment: 20 pages, 20 figure
Determining neutrino oscillation parameters from atmospheric muon neutrino disappearance with three years of IceCube DeepCore data
We present a measurement of neutrino oscillations via atmospheric muon
neutrino disappearance with three years of data of the completed IceCube
neutrino detector. DeepCore, a region of denser instrumentation, enables the
detection and reconstruction of atmospheric muon neutrinos between 10 GeV and
100 GeV, where a strong disappearance signal is expected. The detector volume
surrounding DeepCore is used as a veto region to suppress the atmospheric muon
background. Neutrino events are selected where the detected Cherenkov photons
of the secondary particles minimally scatter, and the neutrino energy and
arrival direction are reconstructed. Both variables are used to obtain the
neutrino oscillation parameters from the data, with the best fit given by
and
(normal mass hierarchy assumed). The
results are compatible and comparable in precision to those of dedicated
oscillation experiments.Comment: 10 pages, 7 figure
A combined maximum-likelihood analysis of the high-energy astrophysical neutrino flux measured with IceCube
Evidence for an extraterrestrial flux of high-energy neutrinos has now been
found in multiple searches with the IceCube detector. The first solid evidence
was provided by a search for neutrino events with deposited energies
TeV and interaction vertices inside the instrumented volume. Recent
analyses suggest that the extraterrestrial flux extends to lower energies and
is also visible with throughgoing, -induced tracks from the Northern
hemisphere. Here, we combine the results from six different IceCube searches
for astrophysical neutrinos in a maximum-likelihood analysis. The combined
event sample features high-statistics samples of shower-like and track-like
events. The data are fit in up to three observables: energy, zenith angle and
event topology. Assuming the astrophysical neutrino flux to be isotropic and to
consist of equal flavors at Earth, the all-flavor spectrum with neutrino
energies between 25 TeV and 2.8 PeV is well described by an unbroken power law
with best-fit spectral index and a flux at 100 TeV of
.
Under the same assumptions, an unbroken power law with index is disfavored
with a significance of 3.8 () with respect to the best
fit. This significance is reduced to 2.1 () if instead we
compare the best fit to a spectrum with index that has an exponential
cut-off at high energies. Allowing the electron neutrino flux to deviate from
the other two flavors, we find a fraction of at Earth.
The sole production of electron neutrinos, which would be characteristic of
neutron-decay dominated sources, is rejected with a significance of 3.6
().Comment: 16 pages, 10 figures; accepted for publication in The Astrophysical
Journal; updated one referenc
Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube
A diffuse flux of astrophysical neutrinos above has been
observed at the IceCube Neutrino Observatory. Here we extend this analysis to
probe the astrophysical flux down to and analyze its flavor
composition by classifying events as showers or tracks. Taking advantage of
lower atmospheric backgrounds for shower-like events, we obtain a shower-biased
sample containing 129 showers and 8 tracks collected in three years from 2010
to 2013. We demonstrate consistency with the
flavor ratio at Earth
commonly expected from the averaged oscillations of neutrinos produced by pion
decay in distant astrophysical sources. Limits are placed on non-standard
flavor compositions that cannot be produced by averaged neutrino oscillations
but could arise in exotic physics scenarios. A maximally track-like composition
of is excluded at , and a purely shower-like
composition of is excluded at .Comment: 8 pages, 3 figures. Submitted to PR
Lateral Distribution of Muons in IceCube Cosmic Ray Events
In cosmic ray air showers, the muon lateral separation from the center of the
shower is a measure of the transverse momentum that the muon parent acquired in
the cosmic ray interaction. IceCube has observed cosmic ray interactions that
produce muons laterally separated by up to 400 m from the shower core, a factor
of 6 larger distance than previous measurements. These muons originate in high
pT (> 2 GeV/c) interactions from the incident cosmic ray, or high-energy
secondary interactions. The separation distribution shows a transition to a
power law at large values, indicating the presence of a hard pT component that
can be described by perturbative quantum chromodynamics. However, the rates and
the zenith angle distributions of these events are not well reproduced with the
cosmic ray models tested here, even those that include charm interactions. This
discrepancy may be explained by a larger fraction of kaons and charmed
particles than is currently incorporated in the simulations
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