294 research outputs found
Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells
The prevalence of atopic asthma, a Th2-dependent disease, is reaching
epidemic proportions partly due to improved hygiene in industrialized
countries. There is an inverse correlation between the level of
environmental endotoxin exposure and the prevalence of atopic
sensitization. As dendritic cells (DC) have been implicated in causing
sensitization to inhaled Ag, we studied the effect of endotoxin on Th2
development induced by bone marrow DC in vitro and by intratracheal
injection in vivo, with particular emphasis on the role played by the
polarizing cytokine IL-12. Bone marrow-derived DC stimulated with
Escherichia coli O26:B6 LPS produced IL-12p70 for a limited period of
time, after which production became refractory to further stimulation with
CD40 ligand, a phenomenon previously called "exhaustion." The level of
IL-12 production of DC did not correlate with Th1 development, as
exhausted OVA-pulsed DC were still capable of shifting the cytokine
pattern of responding OVA-specific Th cells toward Th1 in vitro and in
vivo. When mice were first immunized by intratracheal injection of OVA-DC
and subsequently challenged with OVA aerosol, prior in vitro stimulation
of DC with LPS reduced the development of airway eosinophilia and Th2
cytokine production. Most surprisingly, the capacity of LPS to reduce
Th2-dependent eosinophilic airway inflammation was IL-12-independent
altogether, as IL-12p40 knockout DC had a similar reduced capacity to
prime for Th2 responses. These results suggest that LPS reduces
sensitization to inhaled Ag by reducing DC-driven Th2 development, but
that IL-12 is not necessary for this effect
Nuclear shadowing in polarized DIS on ^6LiD at small x and its effect on the extraction of the deuteron spin structure function g_{1}^{d}(x,Q^2)
We consider the effect of nuclear shadowing in polarized deep inelastic
scattering (DIS) on ^6LiD at small Bjorken x and its relevance to the
extraction of the deuteron spin structure function g_{1}^{d}(x,Q^2). Using
models, which describe nuclear shadowing in unpolarized DIS, we demonstrate
that the nuclear shadowing correction to g_{1}^{d}(x,Q^2) is significant.Comment: 17 pages, 2 figure
A-dependence of nuclear transparency in quasielastic A(e,e'p) at high Q^2
The A-dependence of the quasielastic A(e,e'p) reaction has been studied at
SLAC with H-2, C, Fe, and Au nuclei at momentum transfers Q^2 = 1, 3, 5, and
6.8 (GeV/c)^2. We extract the nuclear transparency T(A,Q^2), a measure of the
average probability that the struck proton escapes from the nucleus A without
interaction. Several calculations predict a significant increase in T with
momentum transfer, a phenomenon known as Color Transparency. No significant
rise within errors is seen for any of the nuclei studied.Comment: 5 pages incl. 2 figures, Caltech preprint OAP-73
Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.
Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes
Noise Characterization and Filtering in the MicroBooNE Liquid Argon TPC
The low-noise operation of readout electronics in a liquid argon time
projection chamber (LArTPC) is critical to properly extract the distribution of
ionization charge deposited on the wire planes of the TPC, especially for the
induction planes. This paper describes the characteristics and mitigation of
the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase
LArTPC comprises two induction planes and one collection sense wire plane with
a total of 8256 wires. Current induced on each TPC wire is amplified and shaped
by custom low-power, low-noise ASICs immersed in the liquid argon. The
digitization of the signal waveform occurs outside the cryostat. Using data
from the first year of MicroBooNE operations, several excess noise sources in
the TPC were identified and mitigated. The residual equivalent noise charge
(ENC) after noise filtering varies with wire length and is found to be below
400 electrons for the longest wires (4.7 m). The response is consistent with
the cold electronics design expectations and is found to be stable with time
and uniform over the functioning channels. This noise level is significantly
lower than previous experiments utilizing warm front-end electronics.Comment: 36 pages, 20 figure
The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector
The development and operation of Liquid-Argon Time-Projection Chambers for
neutrino physics has created a need for new approaches to pattern recognition
in order to fully exploit the imaging capabilities offered by this technology.
Whereas the human brain can excel at identifying features in the recorded
events, it is a significant challenge to develop an automated, algorithmic
solution. The Pandora Software Development Kit provides functionality to aid
the design and implementation of pattern-recognition algorithms. It promotes
the use of a multi-algorithm approach to pattern recognition, in which
individual algorithms each address a specific task in a particular topology.
Many tens of algorithms then carefully build up a picture of the event and,
together, provide a robust automated pattern-recognition solution. This paper
describes details of the chain of over one hundred Pandora algorithms and tools
used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE
detector. Metrics that assess the current pattern-recognition performance are
presented for simulated MicroBooNE events, using a selection of final-state
event topologies.Comment: Preprint to be submitted to The European Physical Journal
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The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.
The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies
Measurement of cosmic-ray reconstruction efficiencies in the MicroBooNE LArTPC using a small external cosmic-ray counter
The MicroBooNE detector is a liquid argon time projection chamber at Fermilab
designed to study short-baseline neutrino oscillations and neutrino-argon
interaction cross-section. Due to its location near the surface, a good
understanding of cosmic muons as a source of backgrounds is of fundamental
importance for the experiment. We present a method of using an external 0.5 m
(L) x 0.5 m (W) muon counter stack, installed above the main detector, to
determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are
acquired with this external muon counter stack placed in three different
positions, corresponding to cosmic rays intersecting different parts of the
detector. The data reconstruction efficiency of tracks in the detector is found
to be , in good agreement with the Monte Carlo reconstruction
efficiency . This analysis represents
a small-scale demonstration of the method that can be used with future data
coming from a recently installed cosmic-ray tagger system, which will be able
to tag of the cosmic rays passing through the MicroBooNE
detector.Comment: 19 pages, 12 figure
Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE
The single-phase liquid argon time projection chamber (LArTPC) provides a
large amount of detailed information in the form of fine-grained drifted
ionization charge from particle traces. To fully utilize this information, the
deposited charge must be accurately extracted from the raw digitized waveforms
via a robust signal processing chain. Enabled by the ultra-low noise levels
associated with cryogenic electronics in the MicroBooNE detector, the precise
extraction of ionization charge from the induction wire planes in a
single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event
display images, and quantitatively demonstrated via waveform-level and
track-level metrics. Improved performance of induction plane calorimetry is
demonstrated through the agreement of extracted ionization charge measurements
across different wire planes for various event topologies. In addition to the
comprehensive waveform-level comparison of data and simulation, a calibration
of the cryogenic electronics response is presented and solutions to various
MicroBooNE-specific TPC issues are discussed. This work presents an important
improvement in LArTPC signal processing, the foundation of reconstruction and
therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at
arXiv:1802.0870
Design and construction of the MicroBooNE Cosmic Ray Tagger system
The MicroBooNE detector utilizes a liquid argon time projection chamber
(LArTPC) with an 85 t active mass to study neutrino interactions along the
Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground
level, the detector records many cosmic muon tracks in each beam-related
detector trigger that can be misidentified as signals of interest. To reduce
these cosmogenic backgrounds, we have designed and constructed a TPC-external
Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for
High Energy Physics (LHEP), Albert Einstein center for fundamental physics,
University of Bern. The system utilizes plastic scintillation modules to
provide precise time and position information for TPC-traversing particles.
Successful matching of TPC tracks and CRT data will allow us to reduce
cosmogenic background and better characterize the light collection system and
LArTPC data using cosmic muons. In this paper we describe the design and
installation of the MicroBooNE CRT system and provide an overview of a series
of tests done to verify the proper operation of the system and its components
during installation, commissioning, and physics data-taking
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