579 research outputs found

    Raft-derived tau-associated vesicles

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    Aims: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper‐phosphorylated tau protein. Recently, several other molecules, including flotillin‐1, phosphatidylinositol‐4,5‐bisphosphate [PtdIns(4,5)P2] and cyclin‐dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin‐1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. Methods: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2‐immunopositive material in detail, using super‐resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2‐immunopositive material and tau kinases through double immunofluorescence analysis. Results: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2‐immunopositive small vesicles (approximately 1 μm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase‐3β and spleen tyrosine kinase. Conclusions: These observations suggest that clusters of raft‐derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase‐bearing vesicles are likely involved in the modification of tau protein and in NFT formation

    Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity.

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    Interferon γ (IFN-γ), an anticancer agent, is a strong inducer of indoleamine 2, 3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme involved in the induction of tumor immune tolerance. In this study, we investigated the IDO1 expression in organs after IFN-γ gene transfer to mice. IFN-γ gene transfer greatly increased the mRNA expression of IDO1 in many tissues with the highest in the liver. This upregulation was associated with reduced L-tryptophan levels and increased L-kynurenine levels in serum, indicating that IFN-γ gene transfer increased the IDO activity. Then, Lewis lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice were used to investigate the effects of IDO1 on the antitumor activity of IFN-γ. IFN-γ gene transfer significantly retarded the tumor growth in both strains without any significant difference in tumor size between the two groups. By contrast, the IDO1 activity was increased only in the wild-type mice by IFN-γ gene transfer, suggesting that cells other than LLC cells, such as tumor stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken together, these results imply that IFN-γ gene transfer mediated IDO1 upregulation in cells other than LLC cells has hardly any effect on the antitumor activity of IFN-γ

    Study on ^<24>Mg (e, e\u27 α) Reaction(I. Nuclear Physics)

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    The angular correlation of ^Mg(e, e \u27α) reaction was measured for a momentum transfer of 0.51fm^ and energy transfers of 15.5-24.5 MeV. Emitted particles were detected with nine △E-E telescopes located out of plane, rotated around the q axis by 90°. As about a half of approved machine time has been carried, we briefly report a current status of analysis

    Extragalactic MeV gamma-ray emission from cocoons of young radio galaxies

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    Strong γ\gamma-ray emission from cocoons of young radio galaxies is newly predicted. Considering the process of adiabatic injection of the shock dissipation energy and mass of the relativistic jet in active nuclei (AGNs) into the cocoon, while assuming thermalizing electron plasma interactions, we find that the thermal electron temperature of the cocoon is typically predicted in \simMeV, which is determined only by the bulk Lorentz factor of the relativistic jet. Together with the time-dependent dynamics of the cocoon expansion, we find that young cocoons can yield thermal bremsstrahlung emissions at energies \sim MeV.Comment: 5pages, 1figure, MNRAS accepte

    Development and operational experience of magnetic horn system for T2K experiment

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    A magnetic horn system to be operated at a pulsed current of 320 kA and to survive high-power proton beam operation at 750 kW was developed for the T2K experiment. The first set of T2K magnetic horns was operated for over 12 million pulses during the four years of operation from 2010 to 2013, under a maximum beam power of 230 kW, and 6.63×10206.63\times10^{20} protons were exposed to the production target. No significant damage was observed throughout this period. This successful operation of the T2K magnetic horns led to the discovery of the νμνe\nu_{\mu}\rightarrow\nu_e oscillation phenomenon in 2013 by the T2K experiment. In this paper, details of the design, construction, and operation experience of the T2K magnetic horns are described.Comment: 22 pages, 40 figures, also submitted to Nuclear Instrument and Methods in Physics Research,

    Direct Imaging of a Cold Jovian Exoplanet in Orbit around the Sun-like Star GJ 504

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    Several exoplanets have recently been imaged at wide separations of >10 AU from their parent stars. These span a limited range of ages (<50 Myr) and atmospheric properties, with temperatures of 800--1800 K and very red colors (J - H > 0.5 mag), implying thick cloud covers. Furthermore, substantial model uncertainties exist at these young ages due to the unknown initial conditions at formation, which can lead to an order of magnitude of uncertainty in the modeled planet mass. Here, we report the direct imaging discovery of a Jovian exoplanet around the Sun-like star GJ 504, detected as part of the SEEDS survey. The system is older than all other known directly-imaged planets; as a result, its estimated mass remains in the planetary regime independent of uncertainties related to choices of initial conditions in the exoplanet modeling. Using the most common exoplanet cooling model, and given the system age of 160 [+350, -60] Myr, GJ 504 b has an estimated mass of 4 [+4.5, -1.0] Jupiter masses, among the lowest of directly imaged planets. Its projected separation of 43.5 AU exceeds the typical outer boundary of ~30 AU predicted for the core accretion mechanism. GJ 504 b is also significantly cooler (510 [+30, -20] K) and has a bluer color (J-H = -0.23 mag) than previously imaged exoplanets, suggesting a largely cloud-free atmosphere accessible to spectroscopic characterization. Thus, it has the potential of providing novel insights into the origins of giant planets, as well as their atmospheric properties.Comment: 20 pages, 12 figures, Accepted for publication in ApJ. Minor updates from the version

    The K2K SciBar Detector

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    A new near detector, SciBar, for the K2K long-baseline neutrino oscillation expe riment was installed to improve the measurement of neutrino energy spectrum and to study neutrino interactions in the energy region around 1 GeV. SciBar is a 'fully active' tracking detector with fine segmentation consisting of plastic scintillator bars. The detector was constructed in summer 2003 and is taking data since October 2003. The basic design and initial performance is presented.Comment: 7 pages, 4figures, Contributed to Proceedings of the 10th Vienna Conference on Instrumentation, Vienna, February 16-21, 200

    Measurement of radon concentrations at Super-Kamiokande

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    Radioactivity from radon is a major background for observing solar neutrinos at Super-Kamiokande. In this paper, we describe the measurement of radon concentrations at Super-Kamiokande, the method of radon reduction, and the radon monitoring system. The measurement shows that the current low-energy event rate between 5.0 MeV and 6.5 MeV implies a radon concentration in the Super-Kamiokande water of less than 1.4 mBq/m3^3.Comment: 11 pages, 4 figure
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