著者

長尾 康次 上田 聡 神田 宗和 大畑 暢敬 山下 道雄 日野 資弘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.11, pp.1471-1478, 2010 (Released:2010-11-01)

参考文献数

10

被引用文献数

2 2

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Natural fermentation products have long been studied as attractive targets for drug discovery due to their amazing diverse, complex chemical structures and biological activities. As such, a number of revolutionary drugs developed from natural fermentation products have contributed to global human health. To commercialize a drug derived from natural fermentation products, an effective chemical entity must be identified and thoroughly researched, and an effective manufacturing process to prepare a commercial supply must be developed. To construct such a manufacturing process for tacrolimus and micafungin, the following studies were conducted: first, we focused on controlling the production of the tacrolimus-related compound FR900525, a fermentation by-product of tacrolimus which was critical for quality assurance of the drug substance. FR900525 production was reduced by using a mutant strain which produced more pipecolic acid, the biosynthesis material of tacrolimus, than the original strain. Then, to optimize the fermentation process of FR901379, an intermediate of micafungin, a fed-batch culture was adopted to increase FR901379 productivity. Additionally, FULLZONETM impeller was installed into the scaled-up fermenter, reducing the agitation-induced damage to the mycelium. As a result, the mycelial form changed from filamentous to pellet-shaped, and the air uptake rate during fermentation was drastically improved. Finally, we conducted screening for FR901379 acylase-producing microorganisms, as FR901379 acylase is necessary to manufacture micafungin. We were able to easily discover FR901379 acylase-producing microorganisms in soil samples using our novel, convenient screening method, which involves comparing the difference in antibiotic activity between FR901379 and its deacylated product.

著者

吉野 純 村上 智一 小林 孝輔 安田 孝志

出版者

公益社団法人 土木学会

雑誌

海岸工学論文集

巻号頁・発行日

vol.54, pp.316-320, 2007

被引用文献数

1

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A new application of modifying initial three-dimensional typhoon meteorologica flields for a mesoscale atmospheric model is developed in this study to evaluate potential storm surge heights that are likely to occur under expected global warming. The initialization technique based on the potential vorticity invertibility principal can arbitrarily control the position and intensity of typhoon in the initial atmospheric conditions, consistent with the balance wind and hydrostatic equilibrium. Preliminary numerical experiments of storm surge scenarios in Ise Bay, using a coupled atmosphere-ocean-wave model, show that the subtle difference of typhoon track causes a large impact on the spatial distribution of storm surge level.

著者

添田,愼介

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi

巻号頁・発行日

vol.76, no.9, 1998-09-25

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Tacrolimus is an immunosuppressant macrolide isolated from Streptomyces tsukubaensis. It is used clinically to prevent the rejection of tissue transplants. To achieve the industrial production of tacrolimus, development research was aimed at breeding strains that efficiently produce tacrolimus, optimizing the cultivation conditions, determining an effective purification method, and establishing a means of rapid quantitative analysis. The wild-type S. tsukubaensis was sequentially treated with ultra violet light to furnish various types of morphologically altered mutants, from which a desired strain was selected and bred. For the fermentation of the new strain, a cultivation medium was formulated with a low viscosity and resistant to thermo-denaturation on sterilization. In a scale-up study, in which the fermentor size was increased from 30l to 25kl, the productivity of tacrolimus was found to be well reproduced by keeping both the dissolved oxygen and the agitation at low levels during the growth phase of the producing strain. As a result of these procedures, the concentration of tacrolimus in the fermentation broth was increased 300-fold over that obtaind in the early stages of the research with the wild strain. S. tsukubaensis produces many kinds of proteins and oligosacchalides as well as various types of tacrolimus related compounds. To remove these impurities effectively, the cultivation broth was directly extracted with acetone. The extract was successively purified with a high porosity absorbance resin, and acidic and natural silica gel column chromatography, followed by recrystalization in aqueous acetonitrile, to obtain tacrolimus monohydrate. Tacrolimus itself is readily converted to optical and steric isomers in an aqueous solution. When tacrolimus was analyzed by HPLC at lower temperatures, the peaks corresponding to the macrolide were complex because of cis-trans isomerization in the column. The problem was overcome by heating the column to 50℃, when the isomerization rate was so high that the peaks were fused into a single, sharp one. The epimerization ratio was found to depend on the concentration of water in the solution, but the ratio remained constant when a Brij-35 solution used as a diluent. By these procedures, a simple, rapid and reliable analytical method was established. The industrial production of tacrolimus was thus achieved by a combination of fermentation, purification, and analytical investigations.

著者

添田 愼介 明石 健志 前田 清 川北 毅

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.76, no.9, pp.389-397, 1998-09-25

参考文献数

11

被引用文献数

2

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Tacrolimus is an immunosuppressant macrolide isolated from Streptomyces tsukubaensis. It is used clinically to prevent the rejection of tissue transplants. To achieve the industrial production of tacrolimus, development research was aimed at breeding strains that efficiently produce tacrolimus, optimizing the cultivation conditions, determining an effective purification method, and establishing a means of rapid quantitative analysis. The wild-type S. tsukubaensis was sequentially treated with ultra violet light to furnish various types of morphologically altered mutants, from which a desired strain was selected and bred. For the fermentation of the new strain, a cultivation medium was formulated with a low viscosity and resistant to thermo-denaturation on sterilization. In a scale-up study, in which the fermentor size was increased from 30l to 25kl, the productivity of tacrolimus was found to be well reproduced by keeping both the dissolved oxygen and the agitation at low levels during the growth phase of the producing strain. As a result of these procedures, the concentration of tacrolimus in the fermentation broth was increased 300-fold over that obtaind in the early stages of the research with the wild strain. S. tsukubaensis produces many kinds of proteins and oligosacchalides as well as various types of tacrolimus related compounds. To remove these impurities effectively, the cultivation broth was directly extracted with acetone. The extract was successively purified with a high porosity absorbance resin, and acidic and natural silica gel column chromatography, followed by recrystalization in aqueous acetonitrile, to obtain tacrolimus monohydrate. Tacrolimus itself is readily converted to optical and steric isomers in an aqueous solution. When tacrolimus was analyzed by HPLC at lower temperatures, the peaks corresponding to the macrolide were complex because of cis-trans isomerization in the column. The problem was overcome by heating the column to 50℃, when the isomerization rate was so high that the peaks were fused into a single, sharp one. The epimerization ratio was found to depend on the concentration of water in the solution, but the ratio remained constant when a Brij-35 solution used as a diluent. By these procedures, a simple, rapid and reliable analytical method was established. The industrial production of tacrolimus was thus achieved by a combination of fermentation, purification, and analytical investigations.

著者

小林 康宏 松井 正宏

出版者

一般社団法人 日本風工学会

雑誌

JWE : 日本風工学研究会誌 : Journal of Wind Engineering (ISSN:09121935)

巻号頁・発行日

no.135, pp.105-106, 2013-04-30

参考文献数

3

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本研究は日本に来襲する台風気圧場パラメータの統計的性質について調べる。  耐風設計の設計風速を決定するために台風モデルを用いたモンテカルロ・シミュレーションが行われることがある。この時に重要なことは、台風気圧場の再現性と、風速場モデルの精度であると言われている。台風気圧場の再現性を向上させるために、過去の台風の気圧場の性質を調べることは重要である。このような研究は、日本の台風に対して、藤井、光田らの一連の研究¹⁾^~³⁾があるが、その研究以降20年以上経過しており本研究では最新のデータもふまえ1951年~2010年のベストトラックおよび1961年~2010年の日本全国の気象台における大気圧の地上観測記録を用いて気圧場を表すパラメータを求め北西太平洋全域にわたる分布について調べた。

著者

柳亭種彦 作

出版者

西村与八[ほか1名]

巻号頁・発行日

vol.二編, 1829

著者

金 洙列 松浦 智典 松見 吉晴 玉井 和久 安田 誠宏 TOM Tracey H. 間瀬 肇

出版者

公益社団法人 土木学会

雑誌

土木学会論文集B2(海岸工学) (ISSN:18842399)

巻号頁・発行日

vol.69, no.2, pp.I_516-I_520, 2013

被引用文献数

3

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This paper describes the performance of the weather research and forecasting (WRF) model applied for Typhoon Maemi in 2003 in the mid-latitude (N35°_55°) using grid point value (GPV) data of NCEP FNL (ds083.2) and NCEP/NCAR Reanalysis (ds090.0), by changing planetary boundary layer scheme and cloud microphysics. It was found that typhoon tracks are closer to the best track when using ds090.0 data, while intensity is well simulated by using ds083.2 in the range of over N30°. In addition, wind is more sensitive to the planetary boundary layer scheme than the cloud microphysics. Sea level pressure is similarly sensitive to both schemes of the planetary boundary layer scheme and the cloud microphysics.

著者

筒井 純一

出版者

公益社団法人 土木学会

雑誌

地球環境シンポジウム講演論文集

巻号頁・発行日

vol.8, pp.181-186, 2000

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To investigate the impacts of anthropogenic global warming on tropical cyclone (TC) activity, climate simulations were conducted under the present and CO<SUB>2</SUB>-warmed conditions using the National Center for Atmospheric Research Community Climate Model version 2. The CO<SUB>2</SUB>-warmed condition includes doubled atmospheric CO<SUB>2</SUB> concentration and about 1&deg;C of tropical sea surface temperature (SST) warming. Simulated TCs were objectively selected from twice daily instantaneous outputs during an eight-year time integration period of each simulation, and the changes associated with global warming were examined in terms of frequency of occurrence and mean intensity.<BR>The frequency of global TC occurrence remains unchanged in response to the CO<SUB>2</SUB>-induced warming. This fairly constant global TC frequency is in agreement with the almost neutral tendency in the zonally-averaged moist instability in the tropics. On the other hand, regional TC frequencies indicate relatively large tendencies depending on TC basins, including increased tendency in the western North Pacific and decreased tendency in the Western Hemisphere. These regional variations are connected with large-scale circulation and similar to the natural variability of observed TCs. Simulated changes in the mean TC intensity highlight increased tendencies over the warm SST regions in the western Pacific, which contribute to the significantly increased mean intensity of global TCs.

著者

中上 英俊

出版者

一般社団法人 照明学会

雑誌

照明学会雑誌

巻号頁・発行日

vol.80, no.6, pp.420-424, 1996

被引用文献数

1

巻号頁・発行日

vol.[200] 奇特之部, 1000

出版者

写

巻号頁・発行日

vol.[77],

著者

実業会中央本部 編

出版者

実業会中央本部

巻号頁・発行日

1899

著者

豊国

出版者

丸甚

雑誌

観音霊験記

巻号頁・発行日

1860

著者

清彭定求等奉敕撰

巻号頁・発行日

vol.[30], 1000

著者

青山 幹雄 山下 利夫 小堀 慎介

出版者

一般社団法人情報処理学会

雑誌

情報処理学会研究報告ソフトウェア工学(SE) (ISSN:09196072)

巻号頁・発行日

vol.1997, no.74, pp.33-40, 1997-07-31

参考文献数

16

被引用文献数

4

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ソフトウェアパッケージやコンポーネント(部品)をネットワーク上で電子取引するソフトウェアコマースのために仕様とカタログ情報を記述するSCL(Software specification and Commerce Language)を提案する.ソフトウェアは電子的に流通が可能であるので,仕様と取引の情報が一体として表現できることが望ましいと考え,SCLはHTMLの拡張として定義した.1つの部品のカタログがWebの1ホームページとして段階的に表現できる.さらに,部品選択を支援するために,コンテキスト表現として部品を取り巻く構造をデザインパターンで記述し,動的挙動をユースケースのシナリオで記述できる表現をとった.さらに,部品をWeb上で試行できるプレイアブルの概念を提案する.This article proposes SCL(Software specification and Commerce Language) which is intended to present the specification and commerce information of software components and packages. Since software can be distributed through the Internet, it is desirable to represent the specification and commerce information in a single language. Thus, SCL is designed as an extension of HTML so that SCL works for a Web-based on-line catalogue of software components. To provide a better understanding on software components, SCL can specify the context and dynamic behavior of software components with design pattern and Use-Case scenario. Furthermore, we proposes playable concept so that users can play with software components on the Web.

著者

關 智子

出版者

日本演劇学会

雑誌

演劇学論集 日本演劇学会紀要 (ISSN:13482815)

巻号頁・発行日

vol.57, pp.39-53, 2013 (Released:2017-01-06)

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Martin CRIMP's Attempts on Her Life (1996) abounds with experimentation that violates the conventional rules of modern dramas. In this paper, I analyse Attempts, focusing on the structure. The play consists of 17 fragmentary scenarios dealing with the concept of character, which is represented by ‘Anne’, who never appears. The purpose in this paper is to shed some light on the peculiarity of this play.All 17 scenarios have the same form, where only the speakers talk about Anne. The content of the scenarios is discontinuous and inconsistent. Moreover, Anne is depicted quite differently by each of the speakers. The consistency of the form emphasises the arbitrariness of the content. This arbitrariness stimulates the imagination of both readers and audiences, and even urges them to imagine another Anne not depicted in the play.This mechanism of stimulation is particularly clear in the first scenario, ‘All Messages Deleted’. In this scenario, the messages on an answering machine are deleted after a pause. Although CRIMP never says how and by whom the messages are deleted, the pause urges readers and audiences to surmise it is Anne who deletes the messages. The mechanism of stimulation in Attempts always encourages readers and audiences to create Anne using their imagination, even though Anne never appears as a physical character in the play.Thus, based on the above, one of the peculiarities of Attempts is this mechanism of stimulation that encourages the creativity and imagination of readers and audiences.

出版者

太平洋学会

著者

鈴木 政登

出版者

The Japanese Society of Physical Fitness and Sports Medicine

雑誌

体力科学 (ISSN:0039906X)

巻号頁・発行日

vol.51, no.5, pp.407-422, 2002-10-01 (Released:2010-12-10)

参考文献数

42

被引用文献数

1 4

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Numerous studies on serum enzymes derived from skeletal muscle, such as CH, AST, LDH, are also being reported in the field of sports medicine. In this article, I would like to summarize the findings on “physical exercise and serum enzymes” studied up to the present. Secondly, I will evaluate the usefulness and limits as indicators of condition and muscle fatigue in athletes. The amount of change and time course of Ch, AST, LDH and myoglobin responses were markedly different in 5-km, marathon and triathalon races, and in trained and untrained subjects. Trained subjects showed peaks of these enzymes one day after endurance running, and untrained subjects had a typical biphasic variation after endurance running. The typical change in untrained subjects might reflect a series of different histopathological changes, including muscle damage, repair and regeneration of muscles. In participants of women's marathon races, higher ranking prize winners showed lower levels before and lower increases in Ch activity after the mice than the other participants. higher serum CIA activity above 300 mU/ml accompanied by increases in serum myosin light chain I (MLC I) concentration (above 2.5 ng/ml) without increases in troponin T and CN-MIA were observed during marathon, triathalon, 100-km and 250 km ultra marathon races. The athletes who showed a higher serum CK activity above 500 mU/ml at the pre-race stage felt subjective fatigue and sonic dropped out from the race. Normal persons who had a lower Ch activity below 40.50 mU/ml indi cated lower levels of serum HDL-C and physical fitness (VO2max) . On the contrary, persons who showed a higher CR level of 100-200 mU/ml or more had higher levels of IIDL-C and VO2max.Measurement of serum CK activity might provide useful information for checking health and physical fitness levels in normal persons, and also the physical and subjective conditions of athletes.

著者

清允祿等奉敕撰

出版者

内府刊朱墨套印

巻号頁・発行日

vol.[1], 1741

著者

高鳥 浩介 近藤 末男

出版者

公益社団法人 日本畜産学会

雑誌

日本畜産学会報 (ISSN:13443941)

巻号頁・発行日

vol.50, no.7, pp.453-459, 1979

被引用文献数

1

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豚の常用飼料についてカビ汚染,分布の実態を調査した.供試飼料として,トウモロコシ,麦類,フスマ,ダイズ粕,魚粉,ルーサンペレット,配合飼料の7種,30点を集め菌学的検索をおこなった.豚飼料の構成は濃厚飼料が主体であり,カビ汚染度をみたところ,103~104/gの範囲にあって,飼料全体の汚染度および分布は比較的似た傾向にあった.またカビの分布をみると,Aspergillus, Penicillumの優先する飼料が多く,なかでもA. flavus, A, versicolor., A. glaucusが各飼料で広範に分布していた.PenicilliumではP. citrinum, P. oxalicum, P. rugulosumが高汚染菌であった.その他のカビでは,ケカビ類のMucorが比較的全般に検出され,他にはCandida, Cladosporium, Fasarium, Scopulariopsis, Wallemiaなどがみられた.カビ毒のうち, A. flavusの産生するアフラトキシン(B1, B2, G1, G2)およびA.versicolorの産生するステリグマトシスチンの産生能を,牛および豚飼料から分離したA.flavus 31株, A, versicolor 19株で行なったところ,アフラトキシン産生8株,ステリグマシスチン産生11株を得た.これらの株のうち,アフラトキシンB1 168.30ppm(トウモロコシ由来株),54.17ppm(ダイズ粕由来株)の高い産生量の2株を認めた.ステリグマトシスチン産生11株は,いずれも1ppm以下であった.しかし, A. versicolorの中でステリグマトシスチン産生株が6割近くに達することを考慮すると,家畜飼料中でのこの種のカビ汚染防除に注意する必要がある.また豚飼料でPenicillium, Fusariumの高い汚染,分布がみられたので,この種のカビ毒産生性を検討する必要がある.