Regulatory exosite I of thrombin is present on prothrombin in a precursor state (proexosite I) that specifically binds the Tyr63-sulfated peptide, hirudin54–65(Hir54–65(SO3−)) and the nonsulfated ...analog. The role of proexosite I in the mechanism of factor Va acceleration of prothrombin activation was investigated in kinetic studies of the effects of peptide binding. The initial rate of human prothrombin activation by factor Xa was inhibited by the peptides in the presence of factor Va but not in the absence of the cofactor. Factor Xa and factor Va did not bind the peptide with significant affinity compared with prothrombin. Maximum inhibition reduced the factor Va-accelerated rate to a level indistinguishable from the rate in the absence of the cofactor. The effect of Hir54–65(SO3−) on the kinetics of prothrombin activation obeyed a model in which binding of the peptide to proexosite I prevented productive prothrombin interactions with the factor Xa-factor Va complex. Comparison of human and bovine prothrombin as substrates demonstrated a similar correlation between peptide binding and inhibition of factor Va acceleration. Inhibition of prothrombin activation by hirudin peptides was opposed by assembly on phospholipid vesicles of the membrane-bound factor Xa-factor-Va-prothrombin complex. Factor Va interactions of human and bovine prothrombin activation are concluded to share a common mechanism in which proexosite I participates in productive interactions of prothrombin as the substrate of the factor Xa-factor Va complex, possibly by directly mediating productive prothrombin-factor Va binding.
The influence of wind stress, small‐scale waves, and surface films on air‐sea gas exchange at low to moderate wind speeds (<10 m s−1) is examined. Coincident observations of wind stress, heat ...transfer velocity, surface wave slope, and surface film enrichments were made in coastal and offshore waters south of Cape Cod, New England, in July 1997 as part of the NSF‐CoOP Coastal Air‐Sea Chemical Fluxes study. Gas transfer velocities have been extrapolated from aqueous heat transfer velocities derived from infrared imagery and direct covariance and bulk heat flux estimates. Gas transfer velocity is found to follow a quadratic relationship with wind speed, which accounts for ∼75–77% of the variance but which overpredicts transfer velocity in the presence of surface films. The dependence on wind stress as represented by the friction velocity is also nonlinear, reflecting a wave field‐dependent transition between limiting transport regimes. In contrast, the dependence on mean square slope computed for the wave number range of 40–800 rad m−1 is found to be linear and in agreement with results from previous laboratory wind wave studies. The slope spectrum of the small‐scale waves and the gas transfer velocity are attenuated in the presence of surface films. Observations over large‐scale gradients of biological productivity and dissolved organic matter show that the reduction in slope and transfer velocity are more clearly correlated with surface film enrichments than with bulk organic matter concentrations. The mean square slope parameterization explains ∼89–95% of the observed variance in the data and does not overpredict transfer velocities where films are present. While the specific relationships between gas transfer velocity and wind speed or mean square slope vary slightly with the choice of Schmidt number exponent used to scale the heat transfer velocities to gas transfer velocities, the correlation of heat or gas transfer velocity with mean square slope is consistently better than with wind speed.
There is now enough experience with the use of double-blind, placebo-controlled, food challenge (DBPCFC) to recommend its use as an office procedure for most patients complaining of adverse reactions ...to foods. This manual discusses the practical methods required for the allergist to undertake DBPCFC in the office. Thorough histories supplemented by food allergen skin testing are used to design a DBPCFC that carefully attempts to reproduce the history of food-induced symptoms described by the patient. Precautions that must be taken are delineated before challenge, as is treatment that may be required if a reaction occurs. For those foods to which challenges are positive, longitudinal evaluation with repeated challenge at appropriate intervals help to determine whether or not the problem will resolve over a period of time.
Context. The W51 complex hosts the supernova remnant W51C which is known to interact with the molecular clouds in the star forming region W51B. In addition, a possible pulsar wind nebula CXO ...J192318.5+140305 was found likely associated with the supernova remnant. Gamma-ray emission from this region was discovered by Fermi/LAT (between 0.2 and 50 GeV) and H.E.S.S. (>1 TeV). The spatial distribution of the events could not be used to pinpoint the location of the emission among the pulsar wind nebula, the supernova remnant shell and/or the molecular cloud. However, the modeling of the spectral energy distribution presented by the Fermi/LAT collaboration suggests a hadronic emission mechanism. The possibility that the gamma-ray emission from such an object is of hadronic origin can contribute to solvingthe long-standing problem of the contribution to galactic cosmic rays by supernova remnants. Aims. Our aim is to determine the morphology of the very-high-energy gamma-ray emission of W51 and measure its spectral properties. Methods. We performed observations of the W51 complex with the MAGIC telescopes for more than 50 h. The energy range accessible with MAGIC extends from 50 GeV to several TeV, allowing for the first spectral measurement at these energies. In addition, the good angular resolution in the medium (few hundred GeV) to high (above 1 TeV) energies allow us to perform morphological studies. We look for underlying structures by means of detailed morphological studies. Multi-wavelength data from this source have been sampled to model the emission with both leptonic and hadronic processes. Results. We detect an extended emission of very-high-energy gamma rays, with a significance of 11 standard deviations. We extend the spectrum from the highest Fermi/LAT energies to ~5 TeV and find that it follows a single power law with an index of 2.58 ± 0.07stat ± 0.22syst. The main part of the emission coincides with the shocked cloud region, while we find a feature extending towards the pulsar wind nebula. The possible contribution of the pulsar wind nebula, assuming a point-like source, shows no dependence on energy and it is about 20% of the overall emission. The broad band spectral energy distribution can be explained with a hadronic model that implies proton acceleration above 100 TeV. This result, together with the morphology of the source, tentatively suggests that we observe ongoing acceleration of ions in the interaction zone between supernova remnant and cloud.
We present the results of five years (2005-2009) of MAGIC observations of the BL Lac object PG 1553+113 at very high energies (VHEs; E > 100 GeV). Power-law fits of the individual years are ...compatible with a steady mean photon index Gamma = 4.27 + or - 0.14. In the last three years of data, the flux level above 150 GeV shows a clear variability (probability of constant flux < 0.001%). The flux variations are modest, lying in the range from 4% to 11% of the Crab Nebula flux. Simultaneous optical data also show only modest variability that seems to be correlated with VHE gamma-ray variability. We also performed a temporal analysis of (all available) simultaneous Fermi/Large Area Telescope data of PG 1553+113 above 1 GeV, which reveals hints of variability in the 2008-2009 sample. Finally, we present a combination of the mean spectrum measured at VHEs with archival data available for other wavelengths. The mean spectral energy distribution can be modeled with a one-zone synchrotron self-Compton model, which gives the main physical parameters governing the VHE emission in the blazar jet.
We report new constraints on flavor-changing nonstandard neutrino interactions from the MINOS long-baseline experiment using νe and ν¯e appearance candidate events from predominantly νμ and ν¯μ ...beams. We used a statistical selection algorithm to separate νe candidates from background events, enabling an analysis of the combined MINOS neutrino and antineutrino data. We observe no deviations from standard neutrino mixing, and thus place constraints on the nonstandard interaction matter effect, |ϵeτ|, and phase, (δCP+δeτ), using a 30-bin likelihood fit.
We present very high energy (E > 100 GeV) gamma -ray observations of the gamma -ray binary system LS I +61degrees303 obtained with the MAGIC stereo system between 2009 October and 2010 January. We ...detect a 6.3sigma gamma -ray signal above 400 GeV in the combined data set. The integral flux above an energy of 300 GeV is F(E > 300 GeV) = (1.4 + or - 0.3 sub(stat) + or - 0.4 sub(syst)) x 10 super(-12) cm super(-2) s super(-1), which corresponds to about 1.3% of the Crab Nebula flux in the same energy range. The orbit-averaged flux of LS I +61degrees303 in the orbital phase interval 0.6-0.7, where a maximum of the TeV flux is expected, is lower by almost an order of magnitude compared to our previous measurements between 2005 September and 2008 January. This provides evidence for a new low-flux state in LS I +61degrees303. We find that the change to the low-flux state cannot be solely explained by an increase of photon-photon absorption around the compact star.
Context. The blazar Markarian 421 is one of the brightest TeV gamma-ray sources of the northern sky. From December 2007 until June 2008 it was intensively observed in the very high energy (VHE, ...E > 100 GeV) band by the single-dish Major Atmospheric Gamma-ray Imaging Cherenkov telescope (MAGIC-I). Aims. We aimed to measure the physical parameters of the emitting region of the blazar jet during active states. Methods. We performed a dense monitoring of the source in VHE with MAGIC-I, and also collected complementary data in soft X-rays and optical-UV bands; then, we modeled the spectral energy distributions (SED) derived from simultaneous multi-wavelength data within the synchrotron self-Compton (SSC) framework. Results. The source showed intense and prolonged γ-ray activity during the whole period, with integral fluxes (E > 200 GeV) seldom below the level of the Crab Nebula, and up to 3.6 times this value. Eight datasets of simultaneous optical-UV (KVA, Swift/UVOT), soft X-ray (Swift/XRT) and MAGIC-I VHE data were obtained during different outburst phases. The data constrain the physical parameters of the jet, once the spectral energy distributions obtained are interpreted within the framework of a single-zone SSC leptonic model. Conclusions. The main outcome of the study is that within the homogeneous model high Doppler factors (40 ≤ δ ≤ 80) are needed to reproduce the observed SED; but this model cannot explain the observed short time-scale variability, while it can be argued that inhomogeneous models could allow for less extreme Doppler factors, more intense magnetic fields and shorter electron cooling times compatible with hour or sub-hour scale variability.
Context. We present the discovery of very high energy (VHE, E > 100 GeV) γ-ray emission from the BL Lac object 1ES 1215+303 by the MAGIC telescopes and simultaneous multi-wavelength data in a broad ...energy range from radio to γ-rays. Aims. We study the VHE γ-ray emission from 1ES 1215+303 and its relation to the emissions in other wavelengths. Methods. Triggered by an optical outburst, MAGIC observed the source in 2011 January − February for 20.3 h. The target was monitored in the optical R-band by the KVA telescope that also performed optical polarization measurements. We triggered target of opportunity observations with the Swift satellite and obtained simultaneous and quasi-simultaneous data from the Fermi Large Area Telescope and from the Metsähovi radio telescope. We also present the analysis of older MAGIC data taken in 2010. Results. The MAGIC observations of 1ES 1215+303 carried out in 2011 January − February resulted in the first detection of the source at VHE with a statistical significance of 9.4σ. Simultaneously, the source was observed in a high optical and X-ray state. In 2010 the source was observed in a lower state in optical, X-ray, and VHE, while the GeV γ-ray flux and the radio flux were comparable in 2010 and 2011. The spectral energy distribution obtained with the 2011 data can be modeled with a simple one zone SSC model, but it requires extreme values for the Doppler factor or the electron energy distribution.
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