Febuxostat, an Inhibitor of Xanthine Oxidase, Suppresses Lipopolysaccharide-Induced MCP-1 Production via MAPK Phosphatase-1-Mediated Inactivation of JNK.

Excess reactive oxygen species (ROS) formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO) is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes

Indications of Neutrino Oscillation in a 250 km Long-baseline Experiment

The K2K experiment observes indications of neutrino oscillation: a reduction of $\nu_\mu$ flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of $80.1^{+6.2}_{-5.4}$. Twenty-nine one ring $\mu$-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.Comment: 5 pages, 3 figures embedded, LaTeX with RevTeX style, accepted for publication in PRL on December 13, 200

Measurement of neutrino oscillation by the K2K experiment

We present measurements of nu(mu) disappearance in K2K, the KEK to Kamioka long-baseline neutrino oscillation experiment. One-hundred and twelve beam-originated neutrino events are observed in the fiducial volume of Super-Kamiokande with an expectation of 158.1(-8.6)(+9.2) events without oscillation. A distortion of the energy spectrum is also seen in 58 single-ring muonlike events with reconstructed energies. The probability that the observations are explained by the expectation for no neutrino oscillation is 0.0015% (4.3 sigma). In a two-flavor oscillation scenario, the allowed Delta m(2) region at sin(2)2 theta=1 is between 1.9 and 3.5x10(-3) eV(2) at the 90% C.L. with a best-fit value of 2.8x10(-3) eV(2)

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

A gravitationally unstable gas disk of a starburst galaxy 12 billion years ago

Submillimeter bright galaxies in the early Universe are vigorously forming stars at ~1000 times higher rate than the Milky Way. A large fraction of stars is formed in the central 1 kiloparsec region, that is comparable in size to massive, quiescent galaxies found at the peak of the cosmic star formation history, and eventually the core of giant elliptical galaxies in the present-day Universe. However, the physical and kinematic properties inside a compact starburst core are poorly understood because dissecting it requires angular resolution even higher than the Hubble Space Telescope can offer. Here we report 550 parsec-resolution observations of gas and dust in the brightest unlensed submillimeter galaxy at z=4.3. We map out for the first time the spatial and kinematic structure of molecular gas inside the heavily dust-obscured core. The gas distribution is clumpy while the underlying disk is rotation-supported. Exploiting the high-quality map of molecular gas mass surface density, we find a strong evidence that the starburst disk is gravitationally unstable, implying that the self-gravity of gas overcomes the differential rotation and the internal pressure by stellar radiation feedback. The observed molecular gas would be consumed by star formation in a timescale of 100 million years, that is comparable to those in merging starburst galaxies. Our results suggest that the most extreme starburst in the early Universe originates from efficient star formation due to a gravitational instability in the central 2 kpc region.Comment: Published in Nature on August 30 2018 (submitted version

Space Demonstration of Two-Layer Pop-Up Origami Deployable Membrane Reflectarray Antenna by 3U CubeSat OrigamiSat-2

3U CubeSat OrigamiSat-2 demonstrates a 50-cm × 50-cm two-layer pop-up Origami deployable membrane reflectarray antenna in space. The membrane has small stowage volume and high gain even though it has low flatness because of a large enough antenna area to cover its un-flatness. C-band transmitter is equipped in the CubeSat and offers 20-Mbps amateur satellite communication. In 3U size, a 1-m length deployable gravity gradient mast and magnetic torquer are equipped to stabilize and control its attitude. A camera is attached to the satellite to measure the shape of the membrane antenna. OrigamiSat-2 was selected as the Innovative Satellite Technology Demonstration-4 by Japan Aerospace Exploration Agency (JAXA) and is going to be launched in 2024 by Epsilon Launch Vehicle

Differences in Clinical Features According to Boryoung and Karp Genotypes of Orientia tsutsugamushi

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi. The differences in virulence of O. tsutsugamushi prototypes in humans are still unknown. We investigated whether there are any differences in the clinical features of the Boryoung and Karp genotypes.Patients infected with O. tsutsugamushi, as Boryoung and Karp clusters, who had visited 6 different hospitals in southwestern Korea were prospectively compared for clinical features, complications, laboratory parameters, and treatment responses. Infected patients in the Boryoung cluster had significantly more generalized weakness, eschars, skin rashes, conjunctival injection, high albumin levels, and greater ESR and fibrinogen levels compared to the Karp cluster. The treatment response to current antibiotics was significantly slower in the Karp cluster as compared to the Boryoung cluster.The frequency of occurrence of eschars and rashes may depend on the genotype of O. tsutsugamushi

Partial Depletion of Natural CD4+CD25+ Regulatory T Cells with Anti-CD25 Antibody Does Not Alter the Course of Acute Influenza A Virus Infection

Foxp3+ CD4+ regulatory T cells represent a T cell subset with well-characterized immunosuppressive effects during immune homeostasis and chronic infections, and there is emerging evidence to suggest these cells temper pulmonary inflammation in response to acute viral infection. Recent studies have demonstrated treatment with PC61 CD25-depleting antibody potentiates inflammation in a murine model of RSV infection, while paradoxically delaying recruitment of CD8+ T cells to the site of inflammation. The present study therefore sought to examine the role of these cells in a murine model of acute influenza A virus infection through the administration of PC61 CD25-depleting antibody. PC61 antibody is able to partially deplete CD25+Foxp3+ regulatory T cells to a comparable degree as seen within previous work examining RSV, however this does not alter influenza A-virus induced mortality, weight loss, viral clearance and cellularity within the lung. Collectively, these data demonstrate that partial depletion of CD4+CD25+ regulatory T cells with PC61 antibody does not alter the course of influenza A virus infection