Abstract The effect of hydration on the mechanical properties of osteonal bone, in directions parallel and perpendicular to the bone axis, was studied on three length scales: (i) the mineralized ...fibril level (~100 nm), (ii) the lamellar level (~6 µm); and (iii) the osteon level (up to ~30 µm).We used a number of techniques, namely atomic force microscopy (AFM), nanoindentation and microindentation. The mechanical properties (stiffness, modulus and/or hardness) have been studied under dry and wet conditions. On all three length scales the mechanical properties under dry conditions were found to be higher by 30–50% compared to wet conditions. Also the mechanical anisotropy, represented by the ratio between the properties in directions parallel and perpendicular to the osteon axis (anisotropy ratio, designated here by AnR), surprisingly decreased somewhat upon hydration. AFM imaging of osteonal lamellae revealed a disappearance of the distinctive lamellar structure under wet conditions. Altogether, these results suggest that a change in mineralized fibril orientation takes place upon hydration.
Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation ...suggested a requirement for IL‐17. We have used this orthotopic mouse model to investigate the source of IL‐17A and the requirement for T cells producing IL‐17A. The major sources of IL‐17A were CD4+ T cells and γδ T cells. Depletion of CD4+ T cells led to a significantly decreased frequency and number of IL‐17A+ lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3‐deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL‐17A+ cells was not decreased in mice with STAT3‐deficient T cells due mainly to the presence of IL‐17A+ γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4+ T cells are required for OB development and expansion of IL‐17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.
This study finds that CD4+ T cell deficiency attenuates the IL‐17 immune response and prevents lung transplant obliterative bronchiolitis in a mouse model, but the absence of either major source of IL‐17, Th17 cells or yδ T cells, is not sufficient to prevent allograft rejection and airway fibrosis.
The vital enzyme O-linked β-N-acetylglucosamine transferase (OGT) catalyzes the O-GlcNAcylation of intracellular proteins coupling the metabolic status to cellular signaling and transcription ...pathways. Aberrant levels of O-GlcNAc and OGT have been linked to metabolic diseases as cancer and diabetes. Here, a new series of peptidomimetic OGT inhibitors was identified highlighting the compound LQMed 330, which presented better IC50 compared to the most potent inhibitors found in the literature. Molecular modeling study of selected inhibitors into the OGT binding site provided insight into the behavior by which these compounds interact with the enzyme. The results obtained in this study provided new perspectives on the design and synthesis of highly specific OGT inhibitors.
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The Earth Observing System (EOS) Microwave Limb Sounder (MLS) aboard the Aura satellite has provided essentially daily global measurements of ozone (O3) profiles from the upper troposphere to the ...upper mesosphere since August of 2004. This paper focuses on validation of the MLS stratospheric standard ozone product and its uncertainties, as obtained from the 240 GHz radiometer measurements, with a few results concerning mesospheric ozone. We compare average differences and scatter from matched MLS version 2.2 profiles and coincident ozone profiles from other satellite instruments, as well as from aircraft lidar measurements taken during Aura Validation Experiment (AVE) campaigns. Ozone comparisons are also made between MLS and balloon‐borne remote and in situ sensors. We provide a detailed characterization of random and systematic uncertainties for MLS ozone. We typically find better agreement in the comparisons using MLS version 2.2 ozone than the version 1.5 data. The agreement and the MLS uncertainty estimates in the stratosphere are often of the order of 5%, with values closer to 10% (and occasionally 20%) at the lowest stratospheric altitudes, where small positive MLS biases can be found. There is very good agreement in the latitudinal distributions obtained from MLS and from coincident profiles from other satellite instruments, as well as from aircraft lidar data along the MLS track.
The coupling of laser energy to electrons is fundamental to almost all topics in intense laser-plasma interactions, including laser-driven particle and radiation generation, relativistic optics, ...inertial confinement fusion and laboratory astrophysics. We report measurements of total energy absorption in foil targets ranging in thickness from 20 μm, for which the target remains opaque and surface interactions dominate, to 40 nm, for which expansion enables relativistic-induced transparency and volumetric interactions. We measure a total peak absorption of ∼80% at an optimum thickness of ∼380 nm. For thinner targets, for which some degree of transparency occurs, although the total absorption decreases, the number of energetic electrons escaping the target increases. 2D particle-in-cell simulations indicate that this results from direct laser acceleration of electrons as the intense laser pulse propagates within the target volume. The results point to a trade-off between total energy coupling to electrons and efficient acceleration to higher energies.
Aims. We report about a 230 GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT ...of the Arizona Radio Observatory (ARO). Methods. We installed VLBI equipment and measured the APEX station position to 1 cm accuracy (1σ). We then observed 3C 279 on 2012 May 7 in a 5 h 230 GHz VLBI track with baseline lengths of 2800 Mλ to 7200 Mλ and a finest fringe spacing of 28.6 μas. Results. Fringes were detected on all baselines with signal-to-noise ratios of 12 to 55 in 420 s. The correlated flux density on the longest baseline was ~0.3 Jy beam-1, out of a total flux density of 19.8 Jy. Visibility data suggest an emission region ≲ 38 μas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 1010 K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ~ 38 μas. Conclusions. With APEX the angular resolution of 230 GHz VLBI improves to 28.6 μas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40 μas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.
The expanding remnant from SN 1987A is an excellent laboratory for investigating the physics of supernovae explosions. There is still a large number of outstanding questions, such as the reason for ...the asymmetric radio morphology, the structure of the pre-supernova environment, and the efficiency of particle acceleration at the supernova shock. We explore these questions using three-dimensional simulations of the expanding remnant between days 820 and 10,000 after the supernova. We combine a hydrodynamical simulation with semi-analytic treatments of diffusive shock acceleration and magnetic field amplification to derive radio emission as part of an inverse problem. Simulations show that an asymmetric explosion, combined with magnetic field amplification at the expanding shock, is able to replicate the persistent one-sided radio morphology of the remnant. We use an asymmetric Truelove & McKee progenitor with an envelope mass of 10 M sub(middot in circle) and an energy of 1.5 x 10 super(44)J. A termination shock in the progenitor's stellar wind at a distance of 0."43-0."51 provides a good fit to the turn on of radio emission around day 1200. For the H II region, a minimum distance of 0."63 + or - 0."01 and maximum particle number density of (7.11 + or - 1.78) x 10 super(7) m super(-3) produces a good fit to the evolving average radius and velocity of the expanding shocks from day 2000 to day 7000 after explosion. The model predicts a noticeable reduction, and possibly a temporary reversal, in the asymmetric radio morphology of the remnant after day 7000, when the forward shock left the eastern lobe of the equatorial ring.