52 research outputs found

    A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

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    Background: b2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of b2GPI generated by anti-b2GPI antibodies is pathologically important, in contrast to monomeric b2GPI which is abundant in plasma. Principal Findings: We created a dimeric inhibitor, A1-A1, to selectively target b2GPI in b2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of b2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of b2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of b2GPI present in human serum, b2GPI purified from human plasma and the individual domain V of b2GPI. We demonstrated that when b2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of b2GPI to cardiolipin, regardless of the source of b2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of b2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-b2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric b2GPI to cardiolipin. Conclusions: Our results suggest that the approach of using a dimeric inhibitor to block b2GPI in the pathologica

    Progress and Research Needs of Plant Biomass Degradation by Basidiomycete Fungi

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    The Day I Heard the Moon Roar

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    Neptune at summer solstice: Zonal mean temperatures from ground-based observations, 2003-2007

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    Imaging and spectroscopy of Neptune's thermal infrared emission from Keck/LWS (2003), Gemini-N/MICHELLE (2005); VLT/VISIR (2006) and Gemini-S/TReCS (2007) is used to assess seasonal changes in Neptune's zonal mean temperatures between Voyager-2 observations (1989, heliocentric longitude Ls=236°) and southern summer solstice (2005, Ls=270°). Our aim was to analyse imaging and spectroscopy from multiple different sources using a single self-consistent radiative-transfer model to assess the magnitude of seasonal variability. Globally-averaged stratospheric temperatures measured from methane emission tend towards a quasi-isothermal structure (158-164K) above the 0.1-mbar level, and are found to be consistent with spacecraft observations of AKARI. This remarkable consistency, despite very different observing conditions, suggests that stratospheric temporal variability, if present, is <±5K at 1mbar and <±3K at 0.1mbar during this solstice period. Conversely, ethane emission is highly variable, with abundance determinations varying by more than a factor of two (from 500 to 1200ppb at 1mbar). The retrieved C2H6 abundances are extremely sensitive to the details of the T(p) derivation, although the underlying cause of the variable ethane emission remains unidentified. Stratospheric temperatures and ethane are found to be latitudinally uniform away from the south pole (assuming a latitudinally-uniform distribution of stratospheric methane), with no large seasonal hemispheric asymmetries evident at solstice. At low and mid-latitudes, comparisons of synthetic Voyager-era images with solstice-era observations suggest that tropospheric zonal temperatures are unchanged since the Voyager 2 encounter, with cool mid-latitudes and a warm equator and pole. A re-analysis of Voyager/IRIS 25-50μm mapping of tropospheric temperatures and para-hydrogen disequilibrium (a tracer for vertical motions) suggests a symmetric meridional circulation with cold air rising at mid-latitudes (sub-equilibrium para-H2 conditions) and warm air sinking at the equator and poles (super-equilibrium para-H2 conditions). The most significant atmospheric changes have occurred at high southern latitudes, where zonal temperatures retrieved from 2003 images suggest a polar enhancement of 7-8K above the tropopause, and an increase of 5-6K throughout the 70-90°S region between 0.1 and 200mbar. Such a large perturbation, if present in 1989, would have been detectable by Voyager/IRIS in a single scan despite its long-wavelength sensitivity, and we conclude that Neptune's south polar cyclonic vortex increased in strength significantly from Voyager to solstice. © 2013 Elsevier Inc

    Neptune at summer solstice: Zonal mean temperatures from ground-based observations, 2003-2007

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    Imaging and spectroscopy of Neptune's thermal infrared emission from Keck/LWS (2003), Gemini-N/MICHELLE (2005); VLT/VISIR (2006) and Gemini-S/TReCS (2007) is used to assess seasonal changes in Neptune's zonal mean temperatures between Voyager-2 observations (1989, heliocentric longitude Ls=236°) and southern summer solstice (2005, Ls=270°). Our aim was to analyse imaging and spectroscopy from multiple different sources using a single self-consistent radiative-transfer model to assess the magnitude of seasonal variability. Globally-averaged stratospheric temperatures measured from methane emission tend towards a quasi-isothermal structure (158-164K) above the 0.1-mbar level, and are found to be consistent with spacecraft observations of AKARI. This remarkable consistency, despite very different observing conditions, suggests that stratospheric temporal variability, if present, is &lt;±5K at 1mbar and &lt;±3K at 0.1mbar during this solstice period. Conversely, ethane emission is highly variable, with abundance determinations varying by more than a factor of two (from 500 to 1200ppb at 1mbar). The retrieved C2H6 abundances are extremely sensitive to the details of the T(p) derivation, although the underlying cause of the variable ethane emission remains unidentified. Stratospheric temperatures and ethane are found to be latitudinally uniform away from the south pole (assuming a latitudinally-uniform distribution of stratospheric methane), with no large seasonal hemispheric asymmetries evident at solstice. At low and mid-latitudes, comparisons of synthetic Voyager-era images with solstice-era observations suggest that tropospheric zonal temperatures are unchanged since the Voyager 2 encounter, with cool mid-latitudes and a warm equator and pole. A re-analysis of Voyager/IRIS 25-50μm mapping of tropospheric temperatures and para-hydrogen disequilibrium (a tracer for vertical motions) suggests a symmetric meridional circulation with cold air rising at mid-latitudes (sub-equilibrium para-H2 conditions) and warm air sinking at the equator and poles (super-equilibrium para-H2 conditions). The most significant atmospheric changes have occurred at high southern latitudes, where zonal temperatures retrieved from 2003 images suggest a polar enhancement of 7-8K above the tropopause, and an increase of 5-6K throughout the 70-90°S region between 0.1 and 200mbar. Such a large perturbation, if present in 1989, would have been detectable by Voyager/IRIS in a single scan despite its long-wavelength sensitivity, and we conclude that Neptune's south polar cyclonic vortex increased in strength significantly from Voyager to solstice. © 2013 Elsevier Inc

    The aftermath of the July 2009 impact on Jupiter: Ammonia, temperatures and particulates from Gemini thermal infrared spectroscopy

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    We obtained longitudinally resolved thermal infrared spectra (8-13μm and 17-25μm) of Jupiter's impact debris at the Gemini South Telescope on July 24, 2009; five days after the July 19th collision. These were used to study the mechanisms responsible for the redistribution of thermal energy and material (ammonia and stratospheric particulates) following the impact. Upwelling of (8.5±4.1)×10 14g of tropospheric air was sufficient to deposit (6.7±4.1)×10 12g of NH 3 over a 6° longitude range above the impact core. The NH 3 was distributed over the 20-80mbar region with a peak abundance of 1.0±0.6ppm at 45mbar. Only a 10th of this abundance was observed over the western ejecta, and it is unlikely that these observations were sensitive to NH 3 entrained in the ballistic plume itself. The pattern of excess thermal energy was markedly different from that of Shoemaker-Levy 9 (SL9), with a localized tropospheric perturbation of 2.0±1.0K at 200-300 mbar and a broader stratospheric warming of up to 3.5±2.0K at 10-30mbar. We find no evidence of residual warmth at p<1mbar five days after the impact. The excess thermal energy places lower limits on the total energy of the impact (1.8-15.7×10 26 ergs), which limits the impactor diameter to 70-510m (depending on the bulk density chosen for the material).The models of the Gemini spectra required three distinct aerosol features, indicative of the mineralogy of the dark particulate debris, centred at 9.1, 10.0 and 18.5μm. The retrieved opacities for each of these features were distributed over a larger area (9-10° longitude) and at higher altitudes (above the 10-mbar level) than the stratospheric NH 3, and they are more spatially inhomogeneous. This implies the particulates were either entrained with the rising hot plume or created upon plume re-entry and are subsequently redistributed by stratospheric winds. The three particulate features were consistent with a mixture of amorphous iron and magnesium-rich silicates and silicas in the debris field. A broad 10-μm signature was coincident with peaks expected from material rich in amorphous olivines (but poor in pyroxenes), and similar to silicate features observed during SL9. A narrow 9.1-μm signature was interpreted as a combination of amorphous and crystalline silica. Finally, a broad 18.5-μm emitter was not adequately reproduced by a mixture of simple olivines and pyroxenes and remains to be identified. © 2010 Elsevier Inc

    Neptune's global circulation deduced from multi-wavelength observations

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    We observed Neptune between June and October 2003 at near- and mid-infrared wavelengths with the 10-m W.M. Keck II and I telescopes, respectively; and at radio wavelengths with the Very Large Array. Images were obtained at near-infrared wavelengths with NIRC2 coupled to the adaptive optics system in both broad- and narrow-band filters between 1.2 and 2.2 μ. In the mid-infrared we imaged Neptune at wavelengths between 8 and 22 μm, and obtained slit-resolved spectra at 8-13 μm and 18-22 μm. At radio wavelengths we mapped the planet in discrete filters between 0.7 and 6. cm.We analyzed each dataset separately with a radiative-transfer program that is optimized for that particular wavelength regime. At southern midlatitudes the atmosphere appears to be cooler at mid-infrared wavelengths than anywhere else on the planet. We interpret this to be caused by adiabatic cooling due to air rising at midlatitudes at all longitudes from the upper troposphere up to ≲0.1. mbar levels. At near-infrared wavelengths we find two distinct cloud layers at these latitudes: a relatively deep layer of clouds (presumably methane) in the troposphere at pressure levels P ~ 300 - ≳ 600 mbar, which we suggest to be caused by the large-scale upwelling and its accompanying adiabatic cooling and condensation of metha≠ and a higher, spatially intermittent, layer of clouds in the stratosphere at 20-30. mbar. The latitudes of these high clouds encompass an anticyclonic band of zonal flow, which suggests that they may be due to strong, but localized, vertical upwellings associated with local anticyclones, rather than plumes in convective (i.e., cyclonic) storms. Clouds at northern midlatitudes are located at the highest altitudes in the atmosphere, near 10. mbar.Neptune's south pole is considerably enhanced in brightness at both mid-infrared and radio wavelengths, i.e., from ~ 0.1 mbar levels in the stratosphere down to tens of bars in the troposphere. We interpret this to be due to subsiding motions from the stratosphere all the way down to the deep troposphere. The enhanced brightness observed at mid-infrared wavelengths is interpreted to be due to adiabatic heating by compression in the stratosphere, and the enhanced brightness temperature at radio wavelengths reveals that the subsiding air over the pole is very dry; the relative humidity of H2S over the pole is only 5% at altitudes above the NH4SH cloud at ~ 40 bar. The low humidity region extends from the south pole down to latitudes of 66°S. This is near the same latitudes as the south polar prograde jet signifying the boundary of the polar vortex. We suggest that the South Polar Features (SPFs) at latitudes of 60-70° are convective storms, produced by baroclinic instabilities expected to be produced at latitudes near the south polar prograde jet. © 2014 Elsevier Inc

    A multi-wavelength study of the 2009 impact on Jupiter: Comparison of high resolution images from Gemini, Keck and HST

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    Within several days of A. Wesley's announcement that Jupiter was hit by an object on UT 19 July 2009, we observed the impact site with (1) the Hubble Space Telescope (HST) at UV through visible (225-924nm) wavelengths, (2) the 10-m W.M. Keck II telescope in the near-infrared (1-5μm), and (3) the 8-m Gemini-North telescope in the mid-infrared (7.7-18μm). All observations reported here were obtained between 22 and 25 July 2009. Observations at visible and near-infrared wavelengths show that large (∼0.75-μm radius) dark (imaginary index of refraction mi∼0.01-0.1) particulates were deposited at atmospheric pressures between 10 and 200-300mbar; analysis of HST-UV data reveals that in addition smaller-sized (∼0.1μm radius) material must have been deposited at the highest altitudes (∼10mbar). Differences in morphology between the UV and visible/near-IR images suggest three-dimensional variations in particle size and density across the impact site, which probably were induced during the explosion and associated events. At mid-infrared wavelengths the brightness temperature increased due to both an enhancement in the stratospheric NH3 gas abundance and the physical temperature of the atmosphere. This high brightness temperature coincides with the center part of the impact site as seen with HST. This observation, combined with (published) numerical simulations of the Shoemaker-Levy 9 impacts on Jupiter and the Tunguska airburst on Earth, suggests that the downward jet from the terminal explosion probably penetrated down to the ∼700-mbar level. © 2010 Elsevier Inc
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