94 research outputs found

    Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice

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    Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP)+ SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP+ SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons. Immunohistochemical examination of LLC-injected bone revealed that the tumor microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H+ secretion from vacuolar proton pump, significantly alleviated bone pain, indicating that the acidic microenvironment contributes to bone pain. We then determined whether the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing nociceptor predominantly expressed on SNs, plays a role in bone pain by intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN excitation in the DRG and spinal dorsal horn were significantly decreased in TRPV1 −/− mice compared with wild-type mice. Our results suggest that TRPV1 activation on SNs innervating bone by the acidic cancer microenvironment in bone contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a potential therapeutic approach to cancer-induced bone pain

    The ASTRO-H X-ray Observatory

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    The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

    The Quiescent Intracluster Medium in the Core of the Perseus Cluster

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    Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

    Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

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    Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Toxicology and Applied Pharmacology 212 (2006): 24-34, doi:10.1016/j.taap.2005.06.016.Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1,000 nM: 0.48-240 µg/L) from 3 hours post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation or mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC50 values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord specific transcripts were altered before and after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, α-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism.This work was supported by grants-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (T.H. and H.T.), and grant-in-aid for JSPS fellows from the Japanese Ministry of Education, Culture, Sports, Science and Technology (W. D.), a grant-in-aid for High Technological Research Center (Rakuno Gakuen University) from the Ministry of Education, Science, Sports and Culture of Japan (H.T.), Technology, cooperative research from active research in Rakuno Gakuen University 2004-7 (H.T.), and NIH/NIEHS grants ES00210 and ES03850 (RT)

    Hitomi (ASTRO-H) X-ray Astronomy Satellite

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    The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

    Hitomi X-Ray Studies of Giant Radio Pulses from the Crab Pulsar

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    To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2300 keV band and the Kashima NICT radio telescope in the 1.41.7 GHz band with a net exposure of about 2 ks on 2016 March 25, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1000 and 100 GRPs were simultaneously observed at the main pulse and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main pulse or inter-pulse phase. All variations are within the 2 fluctuations of the X-ray fluxes at the pulse peaks, and the 3 upper limits of variations of main pulse or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2300 keV band. The values for main pulse or inter-pulse GRPs become 25% or 110%, respectively, when the phase width is restricted to the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.510 keV and 70300 keV bands are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of the main pulse and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) 10(exp 11) erg cm(exp 2), respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magnetosphere. Although the number of photon-emitting particles should temporarily increase to account for the brightening of the radio emission, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a >0.02% brightening of the pulse-peak flux under such conditions

    Facile preparation of self-healing superhydrophobic CeO2 surface by electrochemical processes

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    Herein we report simple electrochemical processes to fabricate a self-healing superhydrophobic CeO2 coating on Type 304 stainless steel. The CeO2 surface anodically deposited on flat stainless steel surface is hydrophilic, although high temperature-sintered and sputter-deposited CeO2 surface was reported to be hydrophobic. The anodically deposited hydrophilic CeO2 surface is transformed to hydrophobic during air exposure. Specific accumulation of contaminant hydrocarbon on the CeO2 surface is responsible for the transformation to hydrophobic state. The deposition of CeO2 on hierarchically rough stainless steel surface produces superhydrophobic CeO2 surface, which also shows self-healing ability; the surface changes to superhydrophilic after oxygen plasma treatment but superhydrophobic state is recovered repeatedly by air exposure. This work provides a facile method for preparing a self-healing superhydrophobic surface using practical electrochemical processes. (C) 2017 Elsevier B.V. All rights reserved

    [MIII(dmit)2]--Coordinated MnIII Salen-Type Dimers (MIII ) NiIII, AuIII; dmit2- ) 1,3-Dithiol-2-thione-4,5-dithiolate): Design of Single-Component Conducting Single-Molecule Magnet-Based Materials

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    12 pagesInternational audienceFour linear-type tetranuclear complexes, [Mn(5-Rsaltmen){M(dmit)2}]2 (R ) MeO, M ) Ni, 1a; M ) Au, 1b; R ) Me, M ) Ni, 2a; M ) Au, 2b), were synthesized and structurally characterized (5-Rsaltmen2- ) N,N ′-(1,1,2,2- tetramethylethylene)-bis(5-Rsalicylideneiminate), dmit2- ) 1,3-dithiol-2-thione-4,5-dithiolate). These compounds crystallize in the same triclinic P¯1 space group (Z ) 1) and have a similar molecular structure with a bridging array of [M-(dmit)-Mn-(OPh)2-Mn-(dmit)-M] and a packing feature where the respective sets of 1a/1b and 2a/2b are isomorphous. Intermolecular π-π/S * * * S contacts are observed between the coordinating [M(dmit)2]- moieties to form zigzag stair-like columns along the a axis direction. Hu¨ckel calculations revealed a strong intermolecular dimerization within the [Ni(dmit)2]- column that makes them magnetically silent even at room temperature. Nevertheless, 1a and 2a with M ) Ni behave as semiconductors with σr.t. ) 7 × 10-4 S * cm-1 and Ea ) 182 meV for 1a and σr.t. ) 1 × 10-4 S * cm-1 and Ea ) 292 meV for 2a, while 1b and 2b with M ) Au are insulators. As a result of the strong dimerization of the [Ni(dmit)2]- anions, the magnetic properties of 1a are essentially identical to those of 1b and 2b, which can be described as isolated Mn(III) dimers, acting as single-molecule magnets (SMM). Meanwhile, the magnetic properties of 2a are dominated by the intermolecular Mn * * * Mn antiferromagnetic interactions via the singlet [Ni(dmit)2]2 2- dimer (JMn * * * Mn/kB ) -2.85 K), inducing a long-range antiferromagnetic order at TN ) 6.4 K. The present systems are unique materials made of neutral single-component complexes that exhibit two major solid-state properties, that is, electrical conductivity and magnetism, varied as semiconductor/SMM for 1a, insulator/SMM for 1b and 2b, and semiconductor/antiferromagnet for 2a by tuning metal center and partial structural modification
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