742 research outputs found
Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo
High-affinity IgE receptor (FcɛRI) cross-linking on mast cells (MCs) induces secretion of preformed allergy mediators (degranulation) and synthesis of lipid mediators and cytokines. Degranulation produces many symptoms of immediate-type allergic reactions and is modulated by adhesion to surfaces coated with specific extracellular matrix (ECM) proteins. The signals involved in this modulation are mostly unknown and their contribution to allergic reactions in vivo is unclear. Here we report the generation of monoclonal antibodies that potently suppress FcɛRI-induced degranulation, but not leukotriene synthesis. We identified the antibody target as the tetraspanin CD63. Tetraspanins are membrane molecules that form multimolecular complexes with a broad array of molecules including ECM protein-binding β integrins. We found that anti-CD63 inhibits MC adhesion to fibronectin and vitronectin. Furthermore, anti-CD63 inhibits FcɛRI-mediated degranulation in cells adherent to those ECM proteins but not in nonadherent cells. Thus the inhibition of degranulation by anti-CD63 correlates with its effect on adhesion. In support of a mechanistic linkage between the two types of inhibition, anti-CD63 had no effect on FcɛRI-induced global tyrosine phosphorylation and calcium mobilization but impaired the Gab2–PI3K pathway that is known to be essential for both degranulation and adhesion. Finally, we showed that these antibodies inhibited FcɛRI-mediated allergic reactions in vivo. These properties raise the possibility that anti-CD63 could be used as therapeutic agents in MC-dependent diseases
A Quantum Langevin Formulation of Risk-Sensitive Optimal Control
In this paper we formulate a risk-sensitive optimal control problem for
continuously monitored open quantum systems modelled by quantum Langevin
equations. The optimal controller is expressed in terms of a modified
conditional state, which we call a risk-sensitive state, that represents
measurement knowledge tempered by the control purpose. One of the two
components of the optimal controller is dynamic, a filter that computes the
risk-sensitive state.
The second component is an optimal control feedback function that is found by
solving the dynamic programming equation. The optimal controller can be
implemented using classical electronics.
The ideas are illustrated using an example of feedback control of a two-level
atom
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
A Joint Search for Gravitational Wave Bursts with AURIGA and LIGO
The first simultaneous operation of the AURIGA detector and the LIGO
observatory was an opportunity to explore real data, joint analysis methods
between two very different types of gravitational wave detectors: resonant bars
and interferometers. This paper describes a coincident gravitational wave burst
search, where data from the LIGO interferometers are cross-correlated at the
time of AURIGA candidate events to identify coherent transients. The analysis
pipeline is tuned with two thresholds, on the signal-to-noise ratio of AURIGA
candidate events and on the significance of the cross-correlation test in LIGO.
The false alarm rate is estimated by introducing time shifts between data sets
and the network detection efficiency is measured with simulated signals with
power in the narrower AURIGA band. In the absence of a detection, we discuss
how to set an upper limit on the rate of gravitational waves and to interpret
it according to different source models. Due to the short amount of analyzed
data and to the high rate of non-Gaussian transients in the detectors noise at
the time, the relevance of this study is methodological: this was the first
joint search for gravitational wave bursts among detectors with such different
spectral sensitivity and the first opportunity for the resonant and
interferometric communities to unify languages and techniques in the pursuit of
their common goal.Comment: 18 pages, IOP, 12 EPS figure
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007
We present the results of the first search for gravitational wave bursts
associated with high energy neutrinos. Together, these messengers could reveal
new, hidden sources that are not observed by conventional photon astronomy,
particularly at high energy. Our search uses neutrinos detected by the
underwater neutrino telescope ANTARES in its 5 line configuration during the
period January - September 2007, which coincided with the fifth and first
science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed
for candidate gravitational-wave signals coincident in time and direction with
the neutrino events. No significant coincident events were observed. We place
limits on the density of joint high energy neutrino - gravitational wave
emission events in the local universe, and compare them with densities of
merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at
http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000
Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis
Immunization of volunteers under chloroquine prophylaxis by bites of *Plasmodium falciparum* sporozoite (PfSPZ)–infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ
chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3x monthly immunizations with 7.5 x 10^4
PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60
days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and
underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of
mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2)
became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain
reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR.
Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up
to 3 x 10^5 PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf
CHMI.
INTRODUCTIO
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