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1. 发明授权

US08053194B2 Labeling substance and chimeric substance and method for preparing the same and method for capturing, structurally analyzing and/or identifying biological substance by means of the labeling substance 失效
标题翻译：标记物质和嵌合物质及其制备方法以及通过标记物质捕获，结构分析和/或识别生物物质的方法
公开(公告)号：US08053194B2
公开(公告)日：2011-11-08
申请号：US10594119
申请日：2005-03-30
申请人： Kazuo Shinya , Tohru Natsume , Takayuki Doi
发明人： Kazuo Shinya , Tohru Natsume , Takayuki Doi
IPC分类号： G01N33/00 , G01N33/53 , G01N33/566 , C07K5/00
CPC分类号： G01N33/532 , Y10T436/13
摘要： Disclosed is a labeling substance capable of reversibly immobilizing (reversible detachment) to a solid surface and to reliably and accurately identify a target biological substance interacting with a probe substance bound to the labeling substance. A chimeric compound is provided, which includes a labeling substance L including (1) an organic compound S with a chemical structure capable of binding to a probe substance P, which can interact with a biological substance B and (2) a peptide bound to the organic compound S and specifically recognized by an antibody A, peptide and a probe substance P at least except a peptide or protein. In addition, a method for preparing the labeling substance L and a method for capturing, structurally analyzing and/or identifying the biological substance using the labeling substance L are provided.
摘要翻译：公开了一种能够可靠地固定（可逆分离）到固体表面并且可靠和准确地识别与结合到标记物质的探针物质相互作用的靶生物物质的标记物质。提供嵌合化合物，其包括标记物质L，其包括（1）具有能够结合探针物质P的化学结构的有机化合物S，其可与生物物质B相互作用;和（2）与有机化合物S，并且至少除了肽或蛋白质之外，被抗体A，肽和探针物质P特别识别。此外，提供了制备标记物质L的方法和使用标记物质L捕获，结构分析和/或识别生物物质的方法。

2. 发明申请

US20070287152A1 Labeling Substance and Chimera Substance, Process for Preparing These Substances, and Method of Biosubstance Trapping, Structural Analysis or/and Identification with Use of the Labeling Substance 失效
标题翻译：标记物质和嵌合物质，制备这些物质的方法以及使用标记物质的生物物质捕获，结构分析或/和鉴定方法
公开(公告)号：US20070287152A1
公开(公告)日：2007-12-13
申请号：US10594119
申请日：2005-03-30
申请人： Kazuo Shinya , Tohru Natsume , Takayuki Doi
发明人： Kazuo Shinya , Tohru Natsume , Takayuki Doi
IPC分类号： G01N33/53 , C07K5/00 , C12Q1/02 , C12Q1/68 , G01N33/00
CPC分类号： G01N33/532 , Y10T436/13
摘要： [Problem] To provide a labeling substance capable of reversibly immobilizing (reversible detachment) to a solid surface and to reliably and accurately identify a target biological substance interacting with a probe substance bound to the labeling substance. [Solving Means] A chimeric compound is provided, which includes a labeling substance L including (1) an organic compounds with a chemical structure capable of binding to a probe substance P, which can interact with a biological substance B and (2) a peptide bound to the organic compound S and specifically recognized by an antibody A, peptide and a probe substance P at least except a peptide or protein. In addition, a method for preparing the labeling substance L and a method for capturing, structurally analyzing and/or identifying the biological substance using the labeling substance L are provided.
摘要翻译： [问题]提供能够可靠地固定（可逆分离）到固体表面并且可靠且准确地识别与结合到标记物质的探针物质相互作用的靶生物物质的标记物质。 [解决方案]提供嵌合化合物，其包括标记物质L，其包括（1）具有能与结合物质P结合的化学结构的有机化合物，其可与生物物质B相互作用;和（2）肽与有机化合物S结合，并且至少除了肽或蛋白质以外由抗体A，肽和探针物质P特异性识别。此外，提供了制备标记物质L的方法和使用标记物质L捕获，结构分析和/或识别生物物质的方法。

3. 发明授权

US08287713B2 Method of producing body having flow path formed therein, and body having flow path formed therein 有权
标题翻译：具有形成在其中的流路的主体的制造方法以及形成有流路的主体
公开(公告)号：US08287713B2
公开(公告)日：2012-10-16
申请号：US12085147
申请日：2006-11-17
申请人： Houkichi Yoshioka , Takahisa Yoshimura , Tohru Natsume
发明人： Houkichi Yoshioka , Takahisa Yoshimura , Tohru Natsume
IPC分类号： C25D1/00
CPC分类号： C25D1/02 , C25D5/02 , C25D5/10 , C25D7/00 , H01L23/473 , H01L2924/0002 , H01L2924/00
摘要： The present invention provides a water-cooled heat sink having an integrated structure, and having inside a precise, freely formed flow path, the water-cooled heat sink being produced without using a technique for pasting a plurality of metal sheets. In a water-cooled heat sink 1, a formed body 2 is provided outwardly, a flow path 3 for passage of a liquid is formed inwardly of the formed body 2, and an inlet 5 and an outlet 4 for the liquid, which communicate with the flow path 3, are formed in the main body of the heat sink 1. The entire formed body 2 of the heat sink 1 is integrally formed by thick coating layers applied by electroplating, and has no joints.
摘要翻译：本发明提供一种水冷式散热器，其具有一体结构，并且具有精确自由形成的流动路径内的水冷散热器，而不使用用于粘贴多个金属片的技术。在水冷散热器1中，成形体2向外侧设置，在成形体2的内侧形成有用于液体通过的流路3，以及用于液体的入口5和出口4，其与流路3形成在散热器1的主体中。散热器1的整体成形体2由通过电镀施加的厚涂层整体形成，并且没有接合部。

4. 发明申请

US20050016263A1 Liquid chromatograph and analysis system 失效
标题翻译：液相色谱和分析系统
公开(公告)号：US20050016263A1
公开(公告)日：2005-01-27
申请号：US10479412
申请日：2001-04-08
申请人： Yoshio Yamauchi , Tohru Natsume , Toshiaki Isobe
发明人： Yoshio Yamauchi , Tohru Natsume , Toshiaki Isobe
IPC分类号： G01N27/62 , G01N30/26 , G01N30/34 , G01N30/72 , G01N30/22 , G01N30/20
CPC分类号： G01N30/34 , G01N30/7233 , G01N2030/8411
摘要： The present invention aims to provide a liquid chromatograph, an analysis system, and a gradient elution method, which are designed to permit a gradient change of eluent with higher precision and also permit a high sensitive detection or analysis. For attaining the object, there are provided: a liquid chromatograph having at least a liquid-feeding means 1 for flowing an eluent E at a predetermined flow rate, a sample-pouring means 9 for pouring a sample Sm into the eluent E, and a separation-column means 13 for separating a solute So contained in the sample Sm into components, comprising an eluent-selecting means 8 for forming branched flow paths 7 having predetermined volumes by dividing a flow path 3 of the eluent E fed from the liquid-feeding means 1, temporally storing eluents E1, E2, and soon in the branched flow paths 7, and pouring the sample Sm into the selected eluents E1, E2, and so on, and means for carrying out a gradient elution of a solute So; an analysis system comprising a mass spectrometer connected to the liquid chromatograph, and a gradient-elution method using the liquid chromatograph.
摘要翻译：本发明旨在提供一种液相色谱仪，分析系统和梯度洗脱方法，其被设计为允许更高精度的洗脱液梯度改变，并且还允许高灵敏度的检测或分析。为了达到上述目的，提供了一种液相色谱仪，其至少具有用于以预定流量流动洗脱液E的液体供给装置1，用于将样品Sm倾倒入洗脱液E的样品注入装置9，以及用于将包含在样品Sm中的溶质So分离成分量的分离柱装置13，包括用于形成具有预定体积的分支流路7的洗脱液选择装置8，其中通过将从进液方法1，在分支流路7中临时储存洗脱液E1，E2并且快速地将样品Sm注入到选定的洗脱液E1，E2等中，以及用于进行溶质So的梯度洗脱的装置; 包括与液相色谱仪连接的质谱仪的分析系统和使用液相色谱仪的梯度洗脱方法。

5. 发明授权

US07680609B2 Biopolymer automatic identifying method 失效
标题翻译：生物聚合物自动识别方法
公开(公告)号：US07680609B2
公开(公告)日：2010-03-16
申请号：US10526464
申请日：2003-09-04
申请人： Tohru Natsume , Hiroshi Nakayama
发明人： Tohru Natsume , Hiroshi Nakayama
IPC分类号： G01N27/62 , G01N27/70 , H01J49/26 , G01N33/483
CPC分类号： H01J49/0009 , Y10T436/143333 , Y10T436/24
摘要： The invention aims to provide a highly accurate automatic biopolymer determination technique utilizing mass spectrometry whereby calibration prior to measurement or the addition of an internal standard to a sample can be eliminated. The biopolymer automatic identifying method of the invention comprises: retrieving a candidate molecule by matching an observed mass value X obtained by mass spectrometry with a predetermined database; selecting an arbitrary number of candidate molecules with high similarity scores; calibrating the observed mass value X using the candidate molecule as an internal standard; calculating relative error Ec between a calibrated mass value Xc and a theoretical mass value M of the candidate molecule; determining the standard deviation SEc of the relative error; determining a tolerance Tc of database search from the standard deviation SEc; and repeating a database search based on the tolerance Tc.
摘要翻译：本发明旨在提供使用质谱法的高精度自动生物聚合物测定技术，由此可以消除在测量之前进行校准或向样品中添加内标物。本发明的生物聚合物自动识别方法包括：通过将通过质谱法获得的观察质量值X与预定数据库相匹配来检索候选分子; 选择具有高相似性分数的任意数量的候选分子; 使用候选分子作为内标校准观察到的质量值X; 计算校准质量值Xc与候选分子的理论质量值M之间的相对误差Ec; 确定相对误差的标准偏差SEc; 从标准偏差SEc确定数据库搜索的容差Tc; 并基于公差Tc重复数据库搜索。

6. 发明申请

US20080227694A1 Novel Interaction Between Proteins, and Therapeutic Agent for Disuse Muscular Atrophy or Method Associated with Disuse Muscular Atrophy Taking Advantage of Novel Interaction 失效
标题翻译：蛋白质之间的新型相互作用和用于消除肌肉萎缩的治疗剂或与消除肌肉萎缩相关的方法利用新颖的相互作用
公开(公告)号：US20080227694A1
公开(公告)日：2008-09-18
申请号：US10581969
申请日：2004-12-07
申请人： Tohru Natsume , Ken Watanabe
发明人： Tohru Natsume , Ken Watanabe
IPC分类号： A61K38/00 , C07K14/00 , G01N33/00 , A61P21/00
CPC分类号： G01N33/6887 , A61K38/1709 , C07K14/4702 , C12N15/113 , C12N2310/11 , C12N2310/14
摘要： [Problem] Providing a novel interaction between proteins.[Solution Means] It has been found that there is an interaction between proteins between proteasome and ZNF216 (or AWP1). It has also been found that there is an interaction between proteins between a polyubiquitin chain and ZNF216 (or AWP1). By utilizing this novel interaction between the proteins, a therapeutic agent for disuse muscular atrophy, and a method for screening the therapeutic agents for disuse muscular atrophy, a marker for disease diagnosis, a method for evaluating the risk of onset of the disuse muscular atrophy, etc., are provided.
摘要翻译： [问题]提供蛋白质之间的新颖相互作用。 [解决方案]已经发现蛋白酶体和ZNF216（或AWP1）之间的蛋白质之间存在相互作用。还发现多聚遍在蛋白链与ZNF216（或AWP1）之间的蛋白质之间存在相互作用。通过利用蛋白质之间的这种新的相互作用，用于消除肌肉萎缩的治疗剂，以及筛选用于不服用肌肉萎缩的治疗剂的方法，疾病诊断的标记物，用于评估滥用性肌肉萎缩发生风险的方法，等等。

7. 发明授权

US07066011B2 Liquid chromatograph and analysis system 失效
标题翻译：液相色谱和分析系统
公开(公告)号：US07066011B2
公开(公告)日：2006-06-27
申请号：US10479412
申请日：2001-04-08
申请人： Yoshi Yamauchi , Tohru Natsume , Toshiaki Isobe
发明人： Yoshi Yamauchi , Tohru Natsume , Toshiaki Isobe
IPC分类号： G01N1/00 , G01N30/00 , B01D15/08
CPC分类号： G01N30/34 , G01N30/7233 , G01N2030/8411
摘要： The present invention aims to provide a liquid chromatograph, an analysis system, and a gradient elution method, which are designed to permit a gradient change of eluent with higher precision and also permit a high sensitive detection or analysis. For attaining the object, there are provided: a liquid chromatograph having at least a liquid-feeding means for flowing an eluent E at a predetermined flow rate, a sample-pouring means for pouring a sample Sm into the eluent E, and a separation-column means for separating a solute So contained in the sample Sm into components, comprising an eluent-selecting means for forming branched flow paths having predetermined volumes by dividing a flow path of the eluent E fed from the liquid-feeding means, temporally storing eluents E1, E2, and soon in the branched flow paths, and pouring the sample Sm into the selected eluents E1, E2, and so on, and means for carrying out a gradient elution of a solute So; an analysis system comprising a mass spectrometer connected to the liquid chromatograph, and a gradient-elution method using the liquid chromatograph.
摘要翻译：本发明旨在提供一种液相色谱仪，分析系统和梯度洗脱方法，其被设计为允许更高精度的洗脱液梯度改变，并且还允许高灵敏度的检测或分析。为了实现该目的，提供了一种液相色谱仪，其至少具有用于以预定流速流动洗脱液E的液体供给装置，用于将样品Sm倾倒到洗脱液E中的样品注入装置，用于将包含在样品Sm中的溶质So分离成组分的柱装置，包括洗脱液选择装置，用于通过划分从进液装置供给的洗脱液E的流动路径形成具有预定体积的分支流路，暂时保存洗脱液E 在分支流动路径中，并将样品Sm倾倒入所选择的洗脱液E 1，E 2， 2等，以及用于进行溶质So的梯度洗脱的装置; 包括与液相色谱仪连接的质谱仪的分析系统和使用液相色谱仪的梯度洗脱方法。

8. 发明授权

US07700362B2 Method for screening therapeutic agents for disuse muscular atrophy using interaction between selected proteins and a polyubiquitin chain 失效
标题翻译：使用所选蛋白质与多聚遍在蛋白链之间的相互作用来筛选治疗剂用于不服用肌肉萎缩的方法
公开(公告)号：US07700362B2
公开(公告)日：2010-04-20
申请号：US10581969
申请日：2004-12-07
申请人： Tohru Natsume , Ken Watanabe
发明人： Tohru Natsume , Ken Watanabe
IPC分类号： H01L21/20
CPC分类号： G01N33/6887 , A61K38/1709 , C07K14/4702 , C12N15/113 , C12N2310/11 , C12N2310/14
摘要： A method for screening therapeutic agents for disuse muscular atrophy is provided that includes the steps of interacting a selected protein with a polyubiquitin chain in the presence of a candidate therapeutic agent, and determining the effect of the candidate on the binding strength between the protein and the polyubiquitin chain. The effect may be observed by color development on a substrate when the steps are carried out by way of an enzyme-linked immunosorbent assay, or by direct observation via NMR spectroscopy, X-ray crystal analysis, electron microscopy or surface plasmon resonance.
摘要翻译：提供了一种用于筛选用于不服用肌肉萎缩的治疗剂的方法，其包括在候选治疗剂存在下使选择的蛋白质与多聚遍在蛋白链相互作用的步骤，以及确定候选物对蛋白质与多聚遍在蛋白链。当通过酶联免疫吸附测定法或通过NMR光谱，X射线晶体分析，电子显微镜或表面等离子体共振直接观察时，可以通过底物上的显色来观察该效果。

9. 发明申请

US20090321052A1 Method of Producing Body Having Flow Path Formed Therein, and Body Having Flow Path Formed Therein 有权
标题翻译：在其中形成流路的身体的形成方法，以及在其中形成流路的身体
公开(公告)号：US20090321052A1
公开(公告)日：2009-12-31
申请号：US12085147
申请日：2006-11-17
申请人： Houkichi Yoshioka , Takahisa Yoshimura , Tohru Natsume
发明人： Houkichi Yoshioka , Takahisa Yoshimura , Tohru Natsume
IPC分类号： F28D15/00 , C25D5/02 , H05K7/20 , F28F7/00
CPC分类号： C25D1/02 , C25D5/02 , C25D5/10 , C25D7/00 , H01L23/473 , H01L2924/0002 , H01L2924/00
摘要： The present invention provides a water-cooled heat sink having an integrated structure, and having inside a precise, freely formed flow path, the water-cooled heat sink being produced without using a technique for pasting a plurality of metal sheets. In a water-cooled heat sink 1, a formed body 2 is provided outwardly, a flow path 3 for passage of a liquid is formed inwardly of the formed body 2, and an inlet 5 and an outlet 4 for the liquid, which communicate with the flow path 3, are formed in the main body of the heat sink 1. The entire formed body 2 of the heat sink 1 is integrally formed by thick coating layers applied by electroplating, and has no joints.
摘要翻译：本发明提供一种水冷式散热器，其具有一体结构，并且具有精确自由形成的流动路径内的水冷散热器，而不使用用于粘贴多个金属片的技术。在水冷散热器1中，成形体2向外侧设置，在成形体2的内侧形成有用于液体通过的流路3，以及用于液体的入口5和出口4，其与流路3形成在散热器1的主体中。散热器1的整体成形体2由通过电镀施加的厚涂层整体形成，并且没有接合部。

10. 发明申请

US20060100792A1 Biopolymer automatic identifying method 失效
标题翻译：生物聚合物自动识别方法
公开(公告)号：US20060100792A1
公开(公告)日：2006-05-11
申请号：US10526464
申请日：2003-09-04
申请人： Tohru Natsume , Hiroshi Nakayama
发明人： Tohru Natsume , Hiroshi Nakayama
IPC分类号： G06F19/00
CPC分类号： H01J49/0009 , Y10T436/143333 , Y10T436/24
摘要： The invention aims to provide a highly accurate automatic biopolymer determination technique utilizing mass spectrometry whereby calibration prior to measurement or the addition of an internal standard to a sample can be eliminated. The biopolymer automatic identifying method of the invention comprises: retrieving a candidate molecule by matching an observed mass value X obtained by mass spectrometry with a predetermined database; selecting an arbitrary number of candidate molecules with high similarity scores; calibrating the observed mass value X using the candidate molecule as an internal standard; calculating relative error Ec between a calibrated mass value Xc and a theoretical mass value M of the candidate molecule; determining the standard deviation SEc of the relative error; determining a tolerance Tc of database search from the standard deviation SEc; and repeating a database search based on the tolerance Tc.
摘要翻译：本发明旨在提供使用质谱法的高精度自动生物聚合物测定技术，由此可以消除在测量之前进行校准或向样品中添加内标物。本发明的生物聚合物自动识别方法包括：通过将通过质谱法获得的观察质量值X与预定数据库相匹配来检索候选分子; 选择具有高相似性分数的任意数量的候选分子; 使用候选分子作为内标校准观察到的质量值X; 计算校准质量值Xc与候选分子的理论质量值M之间的相对误差Ec; 确定相对误差的标准偏差S E S ; 从标准偏差S 确定数据库搜索的容差Tc; 并基于公差Tc重复数据库搜索。

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