Exostosin-1 (EXT1) and EXT2 are the major genetic etiologies of multiple hereditary exostoses and are essential for heparan sulfate (HS) biosynthesis. Previous studies investigating HS in several ...mouse models of multiple hereditary exostoses have reported that aberrant bone morphogenetic protein (BMP) signaling promotes osteochondroma formation in Ext1-deficient mice. This study examined the mechanism underlying the effects of HS deficiency on BMP/Smad signaling in articular cartilage in a cartilage-specific Ext−/− mouse model.
We generated mice with a conditional Ext1 knockout in cartilage tissue (Ext1-cKO mice) using Prg4-Cre transgenic mice. Structural cartilage alterations were histologically evaluated and phospho-Smad1/5/9 (pSmad1/5/9) expression in mouse chondrocytes was analyzed. The effect of pharmacological intervention of BMP signaling using a specific inhibitor was assessed in the articular cartilage of Ext1-cKO mice.
Hypertrophic chondrocytes were significantly more abundant (P = 0.021) and cartilage thickness was greater in Ext1-cKO mice at 3 months postnatal than in control littermates (P = 0.036 for femur; and P < 0.001 for tibia). However, osteoarthritis did not spontaneously occur before the 1-year follow-up. matrix metalloproteinase (MMP)-13 and adamalysin-like metalloproteinases with thrombospondin motifs(ADAMTS)-5 were upregulated in hypertrophic chondrocytes of transgenic mice. Immunostaining and western blotting revealed that pSmad1/5/9-positive chondrocytes were more abundant in the articular cartilage of Ext1-cKO mice than in control littermates. Furthermore, the BMP inhibitor significantly decreased the number of hypertrophic chondrocytes in Ext1-cKO mice (P = 0.007).
HS deficiency in articular chondrocytes causes chondrocyte hypertrophy, wherein upregulated BMP/Smad signaling partially contributes to this phenotype. HS might play an important role in maintaining the cartilaginous matrix by regulating BMP signaling.
ABSTRACT Photon imaging for MeV gammas has serious difficulties due to huge backgrounds and unclearness in images, which originate from incompleteness in determining the physical parameters of ...Compton scattering in detection, e.g., lack of the directional information of the recoil electrons. The recent major mission/instrument in the MeV band, Compton Gamma Ray Observatory/COMPTEL, which was Compton Camera (CC), detected a mere ∼30 persistent sources. It is in stark contrast with the ∼2000 sources in the GeV band. Here we report the performance of an Electron-Tracking Compton Camera (ETCC), and prove that it has a good potential to break through this stagnation in MeV gamma-ray astronomy. The ETCC provides all the parameters of Compton-scattering by measuring 3D recoil electron tracks; then the Scatter Plane Deviation (SPD) lost in CCs is recovered. The energy loss rate (dE/dx), which CCs cannot measure, is also obtained, and is found to be helpful to reduce the background under conditions similar to those in space. Accordingly, the significance in gamma detection is improved severalfold. On the other hand, SPD is essential to determine the point-spread function (PSF) quantitatively. The SPD resolution is improved close to the theoretical limit for multiple scattering of recoil electrons. With such a well-determined PSF, we demonstrate for the first time that it is possible to provide reliable sensitivity in Compton imaging without utilizing an optimization algorithm. As such, this study highlights the fundamental weak-points of CCs. In contrast we demonstrate the possibility of ETCC reaching the sensitivity below 1 × 10−12 erg cm−2 s−1 at 1 MeV.
X-ray and gamma-ray polarimetry is a promising tool to study the geometry and the magnetic configuration of various celestial objects, such as binary black holes or gamma-ray bursts (GRBs). However, ...statistically significant polarizations have been detected in few of the brightest objects. Even though future polarimeters using X-ray telescopes are expected to observe weak persistent sources, there are no effective approaches to survey transient and serendipitous sources with a wide field of view (FoV). Here we present an electron-tracking Compton camera (ETCC) as a highly sensitive gamma-ray imaging polarimeter. The ETCC provides powerful background rejection and a high modulation factor over an FoV of up to 2π sr thanks to its excellent imaging based on a well-defined point-spread function. Importantly, we demonstrated for the first time the stability of the modulation factor under realistic conditions of off-axis incidence and huge backgrounds using the SPring-8 polarized X-ray beam. The measured modulation factor of the ETCC was 0.65 0.01 at 150 keV for an off-axis incidence with an oblique angle of 30° and was not degraded compared to the 0.58 0.02 at 130 keV for on-axis incidence. These measured results are consistent with the simulation results. Consequently, we found that the satellite-ETCC proposed in Tanimori et al. would provide all-sky surveys of weak persistent sources of 13 mCrab with 10% polarization for a 107 s exposure and over 20 GRBs down to a 6 × 10−6 erg cm−2 fluence and 10% polarization during a one-year observation.
Dynamics of a polymer chain confined in a membrane Ramachandran, S.; Komura, S.; Seki, K. ...
The European physical journal. E, Soft matter and biological physics,
05/2011, Letnik:
34, Številka:
5
Journal Article
Recenzirano
Odprti dostop
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We present a Brownian dynamics theory with full hydrodynamics (Stokesian dynamics) for a Gaussian polymer chain embedded in a liquid membrane which is surrounded by bulk solvent and walls. The ...mobility tensors are derived in Fourier space for the two geometries, namely, a free membrane embedded in a bulk fluid, and a membrane sandwiched by the two walls. Within the preaveraging approximation, a new expression for the diffusion coefficient of the polymer is obtained for the free-membrane geometry. We also carry out a Rouse normal mode analysis to obtain the relaxation time and the dynamical structure factor. For large polymer size, both quantities show Zimm-like behavior in the free-membrane case, whereas they are Rouse-like for the sandwiched membrane geometry. We use the scaling argument to discuss the effect of excluded-volume interactions on the polymer relaxation time.
For MeV gamma-ray astronomy, we have developed an electron-tracking Compton camera (ETCC) as a MeV gamma-ray telescope capable of rejecting the radiation background and attaining the high sensitivity ...of near 1mCrab in space. Our ETCC comprises a gaseous time-projection chamber (TPC) with a micro pattern gas detector for tracking recoil electrons and a position-sensitive scintillation camera for detecting scattered gamma rays. After the success of a first balloon experiment in 2006 with a small ETCC (using a 10×10×15cm3 TPC) for measuring diffuse cosmic and atmospheric sub-MeV gamma rays (Sub-MeV gamma-ray Imaging Loaded-on-balloon Experiment I; SMILE-I), a (30cm)3 medium-sized ETCC was developed to measure MeV gamma-ray spectra from celestial sources, such as the Crab Nebula, with single-day balloon flights (SMILE-II). To achieve this goal, a 100-times-larger detection area compared with that of SMILE-I is required without changing the weight or power consumption of the detector system. In addition, the event rate is also expected to dramatically increase during observation. Here, we describe both the concept and the performance of the new data-acquisition system with this (30cm)3 ETCC to manage 100 times more data while satisfying the severe restrictions regarding the weight and power consumption imposed by a balloon-borne observation. In particular, to improve the detection efficiency of the fine tracks in the TPC from ~10% to ~100%, we introduce a new data-handling algorithm in the TPC. Therefore, for efficient management of such large amounts of data, we developed a data-acquisition system with parallel data flow.
Micro pixel chambers (μ-PICs), which are a type of the micro-pattern gas chambers, are usually manufactured using the printed-circuit-board (PCB) technology. However, recent application projects have ...begun to require higher gas gains and finer position resolution than those obtainable with current μ-PICs. It is difficult to improve the electrode structure to achieve these improvements because PCB technology limits the precision of electrode fabrication and the thickness of the substrate. We have therefore adopted micro-electro-mechanical-systems (MEMS) technology and developed the first prototype of a through-glass-via (TGV) μ-PIC. This prototype TGV μ-PIC worked well, achieving a maximum gain of approximately 20,000 and an energy resolution of 20.6% (FWHM) at 5.9 keV over the whole 5 × 5 cm2 detection area.
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