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Pharmacology & Pharmacy 2016年第5期7卷 193-199页

作者： kazuki ohuchi Kazuhiro Tsuruma Masamitsu Shimazawa Junji Nakamura Hideaki Hara Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan Asahi Kasei Pharma Corporation Tokyo Japan

The expression of cytosolic phospholipase A2 (cPLA2) expression is up-regulated in animal model of ALS and in patients with familial amyotrophic lateral sclerosis (fALS). Inhibition of cyclooxygenase 2 (COX2), which is a downstream enzyme of cPLA2, ameliorates the impairment of motor function in the ALS model mice. Therefore, the arachidonic acid cascade, including the cPLA2-COX2 pathway, is an important therapeutic target of ALS. The current study was designed to investigate the potential of AK106-001616, an inhibitor of cPLA2, in protection of motor neuron cell death induced by mutant superoxide dismutase (SOD1G93A). AK106-001616 (1 - 10 μM) protected NSC34 cells (mouse motor neuron like cells) against SOD1G93A-induced motor neuron cell death. Furthermore, aspirin, an inhibitor of COX1/2, reduced the SOD1G93A-induced motor neuron cell death at a concentration that inhibited COX2. Celecoxib, a selective COX2 inhibitor, also reduced the SOD1G93A-induced motor neuron cell death. These results suggest that the arachidonic acid cascade is important for SOD1G93A-induced motor neuron cell death and AK106-001616 has a potent neuroprotective effect against it. AK106-001616 may be a useful therapeutic agent against SOD1G93A-induced ALS.

关键词： AK106-001616 Amyotrophic Lateral Sclerosis cPLA2 NSC34 SOD1G93A

The Effects of Rufinamide on <i>in Vitro</i>Spinal Muscular Atrophy Model

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Pharmacology & Pharmacy 2019年第4期10卷 159-168页

作者： Shiori Ando Arisu Sato Michinori Funato kazuki ohuchi Satoshi Inagaki Shinsuke Nakamura Masamitsu Shimazawa Hideo Kaneko Hideaki Hideaki Hara Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan Department of Clinical Research National Hospital Organization Nagara Medical Center Gifu Japan

Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein. Our purpose in this study was to evaluate the therapeutic potential of rufinamide, an antiepileptic drug. In this study, SMA patient-derived fibroblasts and differentiated spinal motor neurons (MNs) using SMA patient-derived iPSCs were used as in vitro SMA model. SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts. Furthermore, rufinamide stimulated neurite elongation in type III SMA patient derived-iPSCs-MNs. In contrast of the result using type III SMA patient-derived fibroblasts, the expression level of SMN mRNA was not changed after rufinamide treatment in type I SMA patient-derived fibroblasts, and rufinamide did not affect neurite outgrowth in type I SMA patients derived-iPSCs-MNs. These findings indicate that rufinamide may be one of the potential candidate drugs for mild type of SMA.

关键词： Spinal Muscular Atrophy Rufinamide iPSCs

Identification of the Stress Which Causes Optineurin Aggregation

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Neuroscience & Medicine 2019年第2期10卷 150-161页

作者： Satoshi Inagaki Michinori Funato Junko Seki Chizuru Kawase kazuki ohuchi Shiori Ando Shinsuke Nakamura Masamitsu Shimazawa Hideo Kaneko Hideaki Hara Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan Department of Clinical Research National Hospital Organization Nagara Medical Center Gifu Japan

Glaucoma is a common neurodegenerative disease that can cause blindness and occurs worldwide. Currently, lowering intraocular pressure is the only therapy available to protect retinal ganglion cells (RGCs). However, this therapy does not prevent RGC death in all patients. Therefore, new therapeutic approaches for glaucoma are urgently required, and neuroprotection of RGCs is a focus for many researchers. Optineurin (OPTN) is one of the normal tension glaucoma (NTG) relative genes, while mutant OPTN can form a characteristic aggregation, causing RGC death. Hence, elucidation of the mechanism of OPTN aggregation might provide a clue to help understand RGC death. To examine whether non-mutant OPTN could also aggregate, we pharmacologically induced some glaucoma-related stresses, such as endoplasmic reticulum (ER) stress, glutamate toxicity, activation of TNF-α signaling, mitochondrial dysfunction, and autophagic flux impairment. Our results showed that ER stress, TNF-α signaling, and autophagic flux are involved in OPTN aggregation. Furthermore, our data indicated that increased ER stress, activation of TNF-α signaling, and impaired autophagic flux induce OPTN aggregation, suggesting that OPTN aggregation might be an important therapeutic target not only for familial NTG with mutated OPTN but also for patients with glaucoma more generally.

关键词： Glaucoma Induced Pluripotent Stem Cells Retinal Ganglion Cells Optineurin Protein Aggregation

Electron Temperature Measurement by Floating Probe Method Using AC Voltage

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Plasma Science and Technology 2016年第11期18卷 1089-1094页

作者： Satoshi NODOMI Shuichi SATO Mikio ohuchi Department of Electrical and Electronic Engineering Tokyo Denki University

This study presents a novel floating probe method to measure electron temperatures using a hollow cathode-type discharge tube. The proposed method detects a shift in the floating potential when an AC voltage is applied to a probe through an intermediary blocking capacitor. The shift in the floating potential is described as a function of the electron temperature and the applied AC voltage. The floating probe method is simpler than the Langmuir probe method because it does not require the measurement of volt-ampere characteristics. As the input AC voltage increases, the electron temperature converges. The electron temperature measured using the floating probe method with an applied sinusoidal voltage shows a value close to the first （tail） electron temperature in the range of the floating potential.

关键词： electrostatic probe Langmuir probe floating potential electron temperature sheath

Frequency dependence of electron temperature in hollow cathode-type discharge as measured by several different floating probe methods

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Plasma Science and Technology 2018年第8期20卷 50-57页

作者： Shuichi SATO Hiromu KAWANA Tatsushi FUJIMINE Mikio ohuchi Department of Electronic Engineering Tokyo Denki University

We measured electron temperatures through a hollow cathode-type discharge tube using several different floating probe methods. This method detected a shift in the floating potential when an AC voltage was applied to a probe through an intermediary blocking capacitor. The shift in the floating potential is described as a function of the electron temperature and the applied AC voltage. In this study, the effects of the frequency and waveform on the electron temperatures were systematically investigated. The electron temperature measured when using the floating probe method with applied sinusoidal and triangular voltages was lower than that measured with an applied rectangular *** value in the high frequency range was close to that of the tail electron temperature.

关键词： electrostatic probe Langmuir probe floating potential electron temperature sheath

An effective method for laboratory acoustic emission detection and location using template matching

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Journal of Rock Mechanics and Geotechnical Engineering 2022年第5期14卷 1642-1651页

作者： Xinglin Lei Tomohiro ohuchi Manami Kitamura Xiaying Li Qi Li National Institute of Advanced Industrial Science and Technology(AIST) Tsukuba305-8567Japan Geodynamics Research Center Ehime UniversityMatsuyama790-8577Japan State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

In this paper, a template matching and location method, which has been rapidly adopted in microseismic research in recent years, is applied to laboratory acoustic emission(AE) monitoring. First, we used traditional methods to detect P-wave first motions and locate AE hypocenters in three dimensions. In addition, we selected events located with sufficient accuracy(normally corresponding AE events of relatively larger energy, showing clear P-wave first motion and a higher signal-to-noise ratio in most channels) as template events. Then, the template events were used to scan and match other poorly located events in triggered event records or weak events in continuous records. Through crosscorrelation of the multi-channel waveforms between the template and the event to be detected, the weak signal was detected and located using a grid-searching algorithm(with the grid centered at the template hypocenter). In order to examine the performance of the approach, we calibrated the proposed method using experimental data of different rocks and different types of experiments. The results show that the proposed method can significantly improve the detection capability and location accuracy, and can be applied to various laboratory and in situ experiments, which use multi-channel AE monitoring with waveforms recorded in either triggering or continuous mode.

关键词： Acoustic emission Template matching and location Waveform cross-correlation Grid search

Preliminary Deformation Experiment of Ringwoodite at 20 GPa and 1 700 K Using a D-DIA Apparatus

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Journal of Earth Science 2010年第5期21卷 517-522页

作者： Takaaki Kawazoe Tomohiro ohuchi Norimasa Nishiyama Yu Nishihara Tetsuo Irifune Geodynamics Research Center Ehime University Senior Research Fellow Center Ehime University

A deformation experiment of ringwoodite with a strain of 9% was achieved at 20 GPa and 1 700 K and at a strain rate of 3×10^-5 s^-1 using a deformation-DIA （D-DIA） apparatus and a multi-anvil 6-6 （MA 6-6） assembly. The crystallographic orientations of the deformed sample were successfully analyzed by the electron backscatter diffraction （EBSD） method, although any notable latticepreferred orientation （LPO） was not observed presumably due to the insufficient strain in the present experiment. In this study, the deformation experiment on ringwoodite succeeded at P-T conditions consistent with the lower part of the mantle transition zone and at a controlled strain rate for the first time. The present study extended the pressure range of deformation experiments in the D-DIA apparatus from 16 GPa in our earlier study to 20 GPa at 1 700 K. The successful extension of the pressure range demonstrates potential importance of the D-DIA apparatus in studying rheological properties of minerals under the P-T conditions of the whole mantle transition zone.

关键词： ringwoodite mantle transition zone rheology viscosity mantle dynamics.

Technical Development of Simple Shear Deformation Experiments Using a Deformation-DIA Apparatus

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Journal of Earth Science 2010年第5期21卷 523-531页

作者： Tomohiro ohuchi Takaaki Kawazoe Norimasa Nishiyama Yu Nishihara Tetsuo Irifune Geodynamics Research Center Ehime University Senior Research Fellow Center Ehime University

Technical developments for simple shear deformation experiments at high pressures were made. The newly designed cell assembly can be compressed by deformation-DIA apparatuses with the MA 6-6 system, which consists of six second-stage tungsten carbide anvils （with a truncated edge length of 5 mm） and the anvil guide. Deformation of samples was barely observed during the compression process, showing that the shear strain of the deformed samples can be measured by the rotation of a strain marker. Simple shear deformation experiments on anhydrous and hydrous oli- vine aggregates were conducted under upper mantle conditions （pressures of 5.2-7.6 GPa and temperatures of 1 473-1 573 K）, and sample deformation with a shear strain of 7=0.8-1.2 was successfully achieved at a shear strain rate of 4.0×10^-5-7.5×10^-5 s^-1. The present study extended the pressure range of simple shear deformation experiments in the deformation-DIA apparatus from 3 GPa in an early study to 7.6 GPa at high temperatures.

关键词： simple shear deformation deformation-DIA MA 6-6 upper mantle.

Influence of oxygen exposure on instabilities of perfluoropentacene transistor characteristics with different gate insulators

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Progress in Natural Science:Materials International 2011年第1期21卷 12-16页

作者： Hideharu UEKI Hiroaki YANO Hirokuni ohuchi Yutaro TAKAYANAGI Yasushiro NISHIOKA Department of Precision Machinery College of Science and TechnologyNihon UniversityChiba 274-8501Japan

Pentacene for p-channel organic field effect transistors（OTFTs） and perfluoropentacene for n-channel OTFTs have attracted strong attentions to be used as CMOS type organic semiconductor materials for flexible organic displays.n-channel OTFTs with different gate insulators of polyimide（PI） and SiO2and perfluoropentacene as a semiconductor layer were fabricated,and their instability of the transistor characteristics measured in air,vacuum and oxygen was *** results show that both of the transistors exhibit a significant increase of mobility when measured in ***,the mobility of the transistors is significantly reduced when measured in pure oxygen,and the threshold voltages continuously *** phenomena may be related to water diffusion into the perfluoropentacene/gate insulator interface in air and oxidation of perfluoropentacene in oxygen.

关键词： oxygen exposure OTFT perfluoropentacene gate insulator polyimide SiO2

Thermal simulation and analysis of the STF cryomodule

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Chinese Physics C 2009年第3期33卷 236-239页

作者：徐庆金 ohuchi Norihito Kiyosumi Tsuchiya Tsai Ming-Hsun 宗占国翟纪元高杰 Institute of High Energy Physics Chinese Academy of Sciences High Energy Accelerator Research Organization Synchrotron Radiation Research Center Technical Institute of Physics and Chemistry Chinese Academy of Sciences

STF is a superconducting RF test facility constructed at the high energy accelerator research Organization of Japan （KEK）, as a main part of a R＆D project for the proposed International Linear Collider （ILC） in Asia. Thermal study of the STF 1.3 GHz 9-cell cavity cryomodule was carried out within a collaboration between China and Japan. Static and dynamic thermal behaviors of the STF cryomodule were simulated and analyzed with the FEM method, and some simulation results were compared with the available experimental data. This paper presents the details.

关键词： STF cryomodule thermal simulation ILC