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    Catalytically active recombinant memapsin and methods of use thereof
    1.
    发明申请
    Catalytically active recombinant memapsin and methods of use thereof 失效
    催化活性重组膜突触蛋白及其使用方法

    公开(公告)号：US20080112946A1

    公开(公告)日：2008-05-15

    申请号：US11888920

    申请日：2007-08-03

    申请人： Gerald Koelsch ,  Jordan J. N. Tang ,  Lin Hong ,  Arun K. Ghosh ,  Xinli Lin

    发明人： Gerald Koelsch ,  Jordan J. N. Tang ,  Lin Hong ,  Arun K. Ghosh ,  Xinli Lin

    IPC分类号： A61K38/46 ,  C12N9/52 ,  C12P21/04

    CPC分类号： C07K5/1021 ,  A61K38/00 ,  A61K39/00 ,  C07K1/1136 ,  C07K5/06026 ,  C07K5/06043 ,  C07K5/0806 ,  C07K2299/00 ,  C12N9/6421 ,  C12N9/6478 ,  Y02A90/26 ,  Y10S514/879

    摘要： Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1). The inhibition constant of OM99-2 is 1.6×10−9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bond to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.

    摘要翻译： 已经开发了用于生产纯化的，催化活性的重组突变蛋白2的方法。 已经确定了催化活性酶的底物和亚位点特异性。 底物和亚位点特异性信息用于设计可以抑制膜蛋白2功能的天然memapsin 2底物的底物类似物。底物类似物基于肽序列，显示与memapsin 2的天然肽底物相关。 底物类似物含有至少一个酰胺键的类似物，该类似物不能被膜蛋白2切割。开发了两个底物类似物合成的关键氨基酸残基位点处的等位基因，底物类似物OMR99- 1和OM99-2。 OM99-2基于由过渡态等电位羟基亚乙基取代的Leu-Ala肽键的八肽Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe（SEQ ID NO：28）（图1 ）。 OM99-2的抑制常数相对于重组前体蛋白2是1.6×10 -9 M。使用与该抑制剂的膜蛋白2键的结晶学来确定蛋白质的三维结构，以及 各种残留物在结合中的重要性。 本领域技术人员可以使用本信息来设计新的抑制剂，使用商业上可获得的有机化学和酶学方面熟悉的软件程序和技术来设计新的抑制剂2，可用于诊断和治疗和/或 预防阿尔茨海默病。

    Catalytically active recombinant memapsin and methods of use thereof
    2.
    发明授权
    Catalytically active recombinant memapsin and methods of use thereof 失效
    催化活性重组膜突触蛋白及其使用方法

    公开(公告)号：US07829669B2

    公开(公告)日：2010-11-09

    申请号：US11888920

    申请日：2007-08-03

    申请人： Gerald Koelsch ,  Jordan J. N. Tang ,  Lin Hong ,  Arun K. Ghosh ,  Xinli Lin

    发明人： Gerald Koelsch ,  Jordan J. N. Tang ,  Lin Hong ,  Arun K. Ghosh ,  Xinli Lin

    IPC分类号： C07K1/00

    CPC分类号： C07K5/1021 ,  A61K38/00 ,  A61K39/00 ,  C07K1/1136 ,  C07K5/06026 ,  C07K5/06043 ,  C07K5/0806 ,  C07K2299/00 ,  C12N9/6421 ,  C12N9/6478 ,  Y02A90/26 ,  Y10S514/879

    摘要： Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1). The inhibition constant of OM99-2 is 1.6×10−9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bond to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.

    摘要翻译： 已经开发了用于生产纯化的，催化活性的重组突变蛋白2的方法。 已经确定了催化活性酶的底物和亚位点特异性。 底物和亚位点特异性信息用于设计可以抑制膜蛋白2功能的天然memapsin 2底物的底物类似物。底物类似物基于肽序列，显示与memapsin 2的天然肽底物相关。 底物类似物含有至少一个酰胺键的类似物，该类似物不能被膜蛋白2切割。开发了两个底物类似物合成的关键氨基酸残基位点处的等位基因，底物类似物OMR99- 1和OM99-2。 OM99-2基于由过渡态等电位羟基亚乙基取代的Leu-Ala肽键的八肽Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe（SEQ ID NO：28）（图1 ）。 OM99-2的抑制常数为1.6×10-9M，与重组前胶原蛋白2相似。蛋白2的结构与该抑制剂结合使用，用于测定蛋白质的三维结构，以及各种残基的重要性 绑定。 本领域技术人员可以使用本信息来设计新的抑制剂，使用商业上可获得的有机化学和酶学方面熟悉的软件程序和技术来设计新的抑制剂2，可用于诊断和治疗和/或 预防阿尔茨海默病。

    Catalytically active recombinant memapsin and methods of use thereof
    3.
    发明授权
    Catalytically active recombinant memapsin and methods of use thereof 失效
    催化活性重组膜突触蛋白及其使用方法

    公开(公告)号：US06545127B1

    公开(公告)日：2003-04-08

    申请号：US09604608

    申请日：2000-06-27

    申请人： Jordan J. N. Tang ,  Xinli Lin ,  Gerald Koelsch ,  Lin Hong

    发明人： Jordan J. N. Tang ,  Xinli Lin ,  Gerald Koelsch ,  Lin Hong

    IPC分类号： G01N3348

    CPC分类号： C07K5/1021 ,  A61K38/00 ,  A61K39/00 ,  C07K1/1136 ,  C07K5/06026 ,  C07K5/06043 ,  C07K5/0806 ,  C07K2299/00 ,  C12N9/6421 ,  C12N9/6478 ,  Y02A90/26 ,  Y10S514/879

    摘要： Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1). The inhibition constant of OM99-2 is 1.6×10−9M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.

    摘要翻译： 已经开发了用于生产纯化的，催化活性的重组突变蛋白2的方法。 已经确定了催化活性酶的底物和亚位点特异性。 底物和亚位点特异性信息用于设计可以抑制膜蛋白2功能的天然memapsin 2底物的底物类似物。底物类似物基于肽序列，显示与memapsin 2的天然肽底物相关。 底物类似物含有至少一个酰胺键的类似物，该类似物不能被膜蛋白2切割。开发了两个底物类似物合成的关键氨基酸残基位点处的等位基因，底物类似物OMR99- 1和OM99-2。 OM99-2基于由过渡态等电位羟基亚乙基取代的Leu-Ala肽键的八肽Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe（SEQ ID NO：28）（图1 ）。 OM99-2的抑制常数为1.6×10 -9 M，与重组pro-memapsin2结合使用与此抑制剂结合的胶原蛋白2的结晶学，以确定蛋白质的三维结构，以及各种残基在结合中的重要性 。 本领域技术人员可以使用本信息来设计新的抑制剂，使用商业上可获得的有机化学和酶学方面熟悉的软件程序和技术来设计新的抑制剂2，可用于诊断和治疗和/或 预防阿尔茨海默病。

    Beta-secretase inhibitors and methods of use
    5.
    发明申请
    Beta-secretase inhibitors and methods of use 审中-公开
    β-分泌酶抑制剂和使用方法

    公开(公告)号：US20060234944A1

    公开(公告)日：2006-10-19

    申请号：US10493439

    申请日：2002-10-23

    申请人： Arun Ghosh ,  Jordan Tang ,  Geoffrey Bilcer ,  Wanpin Chang ,  Lin Hong ,  Gerald Koelsch ,  Jeff Loy ,  Robert Turner III

    发明人： Arun Ghosh ,  Jordan Tang ,  Geoffrey Bilcer ,  Wanpin Chang ,  Lin Hong ,  Gerald Koelsch ,  Jeff Loy ,  Robert Turner III

    IPC分类号： A61K38/08 ,  C07K7/06

    CPC分类号： C07K7/06 ,  C07K5/0207

    摘要： Compounds inhibit memapsin 2 β-secretase activity and selectively inhibit memapsin 2 β-secretase activity relative to memapsin 1 β-secretase activity. The compounds are employed in methods to inhibit memapsin 2 β-secretase activity, in the treatment of Alzheimer's disease, in the inhibition of hydrolysis of a β-secretase site of a β-amyloid precursor protein and to decrease β-amyloid protein in in vitro samples and in mammals. Proteins of memapsin 2 associated with compounds of the invention are crystallized.

    摘要翻译： 化合物抑制复合蛋白2的β-分泌酶活性，并相对于memapsin1β-分泌酶活性选择性地抑制memapsin2β-分泌酶活性。 该化合物用于抑制复合体蛋白酶2β-分泌酶活性，治疗阿尔茨海默氏病，抑制β-淀粉样蛋白前体蛋白的β-分泌酶位点的水解并在体外降低β-淀粉样蛋白的方法 样品和哺乳动物。 与本发明化合物相关的胶原蛋白2的蛋白质结晶。

    Devices, systems, and methods for improving image consistency
    6.
    发明授权
    Devices, systems, and methods for improving image consistency 失效
    用于提高图像一致性的设备，系统和方法

    公开(公告)号：US07680314B2

    公开(公告)日：2010-03-16

    申请号：US11539662

    申请日：2006-10-09

    申请人： Lin Hong

    发明人： Lin Hong

    IPC分类号： G06K9/00 ,  G06K9/34

    CPC分类号： G06T7/143

    摘要： Certain exemplary embodiments can comprise a method, which can comprise automatically rendering an improved image of a target object. The improved image obtained based upon a principal mode of the target object. The principal mode of the target object can be provided to an algorithm that is adapted to derive the improved image of the target object.

    摘要翻译： 某些示例性实施例可以包括一种方法，其可以包括自动呈现目标对象的改进的图像。 基于目标对象的主要模式获得的改进的图像。 可以将目标对象的主要模式提供给适于导出目标对象的改进图像的算法。

    Feature Processing For Lung Nodules In Computer Assisted Diagnosis
    7.
    发明申请
    Feature Processing For Lung Nodules In Computer Assisted Diagnosis 有权
    计算机辅助诊断中肺结节特征处理

    公开(公告)号：US20090041328A1

    公开(公告)日：2009-02-12

    申请号：US12170639

    申请日：2008-07-10

    申请人： Lin Hong ,  Christopher V. Alvino ,  Hong Shen

    发明人： Lin Hong ,  Christopher V. Alvino ,  Hong Shen

    IPC分类号： G06K9/62

    CPC分类号： G06T7/0012 ,  G06T2207/30061 ,  G06T2207/30064

    摘要： Feature processing is provided for lung nodules in computer-assisted diagnosis. A feature that may better distinguish nodules from background is extracted using a Hough transform. Rather than relying on a specific boundary shape, the Hough transform accumulates evidence associated with a region, such as a ring region. The accumulated evidence provides a feature score without requiring a nodule to fit a specific shape. In another approach, a background level is determined from extracted features. Rather than attempting to normalize an image prior to extraction, the features are normalized. The feature normalization and generalized Hough transform extraction may be used together or alone.

    摘要翻译： 在计算机辅助诊断中为肺结节提供特征处理。 使用霍夫变换提取可以更好地区分结节与背景的特征。 霍夫变换不是依赖于特定的边界形状，而是累积与区域相关联的证据，例如环形区域。 积累的证据提供了一个特征分数，而不需要结节来适应特定的形状。 在另一种方法中，从提取的特征确定背景级别。 在尝试在提取之前对图像进行归一化，而不是将特征归一化。 特征归一化和广义霍夫变换提取可以一起使用或单独使用。

    Methods and Apparatus for Automatic Body Part Identification and Localization
    8.
    发明申请
    Methods and Apparatus for Automatic Body Part Identification and Localization 审中-公开
    自动身体部位识别和定位的方法和装置

    公开(公告)号：US20080112605A1

    公开(公告)日：2008-05-15

    申请号：US11933518

    申请日：2007-11-01

    申请人： Lin Hong ,  Shen Hong

    发明人： Lin Hong ,  Shen Hong

    IPC分类号： A61B5/00

    CPC分类号： G06T7/74 ,  G06T2207/30004

    摘要： Methods and apparatus are disclosed for automatically identifying and locating body parts in medical imaging. To automatically identify body parts of in an image, an identification and location algorithm is used. This establishes a reference frame in relation to the image. Then, a location of the head in relation to the frame is established. After upper and lower boundaries of the head are determined, a neck section of the image is identified. The neck section is identified using the lower boundary of the head section. The location of the neck section is then found. A thorax cage section is found and located positively below the neck section. The abdomen and pelvis are identified together and ultimately separately located and identified.

    摘要翻译： 公开了用于在医学成像中自动识别和定位身体部位的方法和装置。 为了自动识别图像中的身体部位，使用识别和位置算法。 这建立了与图像相关的参考帧。 然后，建立头部相对于框架的位置。 在确定头部的上边界和下边界之后，识别图像的颈部。 使用头部的下边界识别颈部。 然后找到颈部的位置。 发现一个胸部保持架部分，并正确地位于颈部部分。 腹部和骨盆被一起识别，最终分开定位和识别。

    APPARATUS FOR ADJUSTING INCLINATION OF CHAIR BACKS
    10.
    发明申请
    APPARATUS FOR ADJUSTING INCLINATION OF CHAIR BACKS 有权
    调整椅背的装置

    公开(公告)号：US20050168029A1

    公开(公告)日：2005-08-04

    申请号：US10768592

    申请日：2004-01-30

    申请人： Lin Hong

    发明人： Lin Hong

    IPC分类号： A47C1/024 ,  A47C1/026 ,  A47C1/032 ,  A47C7/00 ,  A47C7/40 ,  G05G5/06

    CPC分类号： A47C1/03255 ,  A47C1/03238

    摘要： An apparatus for adjusting the inclination of a chair back, is disposed on the chassis at the bottom of a cushion and pivotally coupled to the middle of a base at the upper end of chair legs. A control rod has its middle predetermined position pivotally coupled to the base. A positioning plate has a bolt at its top surface and is disposed at the rear end of the base. A resilient component is pivotally coupled such that one end of the resilient component is hooked into an end of the control rod, and the other end of the resilient component being hooked into the bolt at the top surface of the positioning plate. When the control rod is turned to swing its end, the resilient component rotates, so that one of the resilient legs of the resilient component produces an elastic push onto the positioning plate. Thus the positioning plate contracts and moves to embed into or withdrawal from a latch groove disposed at the bottom rear side of the chassis. Therefore, the pushing force of a spring can be acted completely on the positioning plate and the positioning plate can move smoother, making operation easier and simpler.

    摘要翻译： 一种用于调节椅子背部倾斜度的装置设置在底座上的垫子的底部，并在椅腿的上端枢转地联接到基座的中部。 控制杆具有枢转地联接到基座的中间预定位置。 定位板在其顶面具有螺栓，并且设置在基座的后端。 弹性部件被枢转地联接，使得弹性部件的一端钩在控制杆的一端中，并且弹性部件的另一端被钩在定位板的顶表面处的螺栓中。 当控制杆转动以摆动其端部时，弹性部件旋转，使得弹性部件的弹性腿之一产生弹性推动到定位板上。 因此，定位板收缩并移动以嵌入到设置在底盘的后后侧的闩锁槽或从其中取出。 因此，弹簧的推力可以完全作用在定位板上，定位板可以更平稳地移动，使操作更简单。