公开(公告)号：WO1998023733A2

公开(公告)日：1998-06-04

申请号：PCT/US1997021940

申请日：1997-11-26

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  LOEB, Lawrence, A. ,  HOOD, Leroy ,  SUZUKI, Motoshi

IPC: C12N09/12

CPC classification number: C12N9/1252 ,  C12Q1/6858 ,  C12Q1/6883

Abstract: The present invention provides a method for identifying a thermostable polymerase having altered fidelity. The method consists of generating a random population of polymerase mutants by mutating at least one amino acid residue of a thermostable polymerase and screening the population for one or more active polymerase mutants by genetic selection. For example, the invention provides a method for identifying a thermostable polymerase having altered fidelity by mutating at least one amino acid residue in an active site O-helix of a thermostable polymerase. The invention also provides thermostable polymerases and nucleic acids encoding thermostable polymerases having altered fidelity, for example, high fidelity polymerases and low fidelity polymerases. The invention additionally provides a method for identifying one or more mutations in a gene by amplifying the gene with a high fidelity polymerase. The invention further provides a method for accurately copying repetitive nucleotide sequences using a high fidelity polymerase mutant. The invention also provides a method for diagnosing a genetic disease using a high fidelity polymerase mutant. The invention further provides a method for randomly mutagenizing a gene by amplifying the gene using a low fidelity polymerase mutant.

Abstract translation: 本发明提供用于鉴定具有改变的保真度的热稳定聚合酶的方法。 该方法包括通过突变热稳定聚合酶的至少一个氨基酸残基并通过遗传选择筛选一个或多个活性聚合酶突变体的群体来产生聚合酶突变体的随机群体。 例如，本发明提供了通过突变热稳定聚合酶的活性位点O-螺旋中的至少一个氨基酸残基来鉴定具有改变的保真度的耐热聚合酶的方法。 本发明还提供了具有改变的保真度的热稳定聚合酶和编码耐热聚合酶的核酸，例如高保真聚合酶和低保真度聚合酶。 本发明另外提供了通过用高保真度聚合酶扩增基因来鉴定基因中的一个或多个突变的方法。 本发明还提供了使用高保真聚合酶突变体准确地复制重复核苷酸序列的方法。 本发明还提供了使用高保真度聚合酶突变体来诊断遗传疾病的方法。 本发明还提供了通过使用低保真度聚合酶突变体扩增基因来随机诱变基因的方法。

公开(公告)号：WO1998011672A1

公开(公告)日：1998-03-19

申请号：PCT/US1997016372

申请日：1997-09-12

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  SUOMINEN, Edwin, A.

IPC: H04B01/26

CPC classification number: H04B1/16 ,  H03D3/007 ,  H03D3/009 ,  H03D7/165 ,  H04B1/06 ,  H04B1/10 ,  H04B1/26 ,  H04B1/30 ,  H04L25/067

Abstract: An RF tuner and tuning method employs analog quadrature mixing with a coarse-stepwise tunable local oscillator (24) to a near-baseband passband region, followed by A/D conversion of the I and Q signals (42, 44), correction of phase, group delay, and amplitude errors, image rejection, and translation to baseband by fixed frequency translation, stepwise channelized translation, or essentially continuously variable tuning over a given digital tuning range. The near-baseband passband region is sized and located such that alternating image rejection provides non-redundant and complete tuning coverage of a desired high frequency spectrum with a local oscillator step size equal to about twice the digital tuning range or about twice the number of channels digitally stepwise tunable times the channel width, effectively doubling the typical local oscillator step size.

Abstract translation: RF调谐器和调谐方法采用模拟正交混合与粗阶段可调本地振荡器（24）到近基带通带区域，接着进行I / Q信号（42,44）的A / D转换，校正相位 ，组延迟和幅度误差，图像抑制以及通过固定频率转换，逐步通道化转换或在给定的数字调谐范围内基本上连续可变的调谐到基带的转换。 近基带通带区域的大小和位置使得交替镜像抑制提供了所需高频谱的非冗余和完全调谐覆盖，本地振荡器步长大小等于数字调谐范围的大约两倍或者是通道数量的两倍 数字逐步可调谐时间通道宽度，有效地使典型的本地振荡器步长倍增。

公开(公告)号：WO1998004294A2

公开(公告)日：1998-02-05

申请号：PCT/US1997012977

申请日：1997-07-24

Applicant: NEORX CORPORATION ,  UNIVERSITY OF WASHINGTON

Inventor： NEORX CORPORATION ,  UNIVERSITY OF WASHINGTON ,  KASINA, Sudhakar ,  RENO, John, M. ,  FRITZBERG, Alan, R. ,  TAIT, Jonathan

IPC: A61K51/08

CPC classification number: C07K7/06 ,  A61K47/54 ,  A61K47/547 ,  A61K47/549 ,  A61K51/087 ,  A61K51/088 ,  A61K2123/00 ,  C07K1/13 ,  C07K14/4721

Abstract: Radiolabeled annexin and modified annexin conjugates useful for imaging vascular thrombi are described. Methods for making and using such radiolabeled annexin conjugates are also provided.

Abstract translation: 描述了可用于成像血管血栓的放射性标记的膜联蛋白和修饰的膜联蛋白缀合物。 还提供了制备和使用这种放射性标记的膜联蛋白缀合物的方法。

公开(公告)号：WO1997046664A1

公开(公告)日：1997-12-11

申请号：PCT/US1997009875

申请日：1997-06-06

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  SNOW, Alan ,  FUKUCHI, Ken-Ichiro ,  HASSELL, John

IPC: C12N05/00

CPC classification number: C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0306 ,  A01K2267/0312 ,  A01K2267/0318 ,  A01K2267/0356 ,  A01K2267/0362 ,  A61K49/0008 ,  C07K14/4711 ,  C12N2800/108 ,  C12N2830/008

Abstract: The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and an amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition.

Abstract translation: 本发明提供了表达编码转基因的全基因组的转基因非人动物。 还提供了表达perlecan和编码转基因淀粉样蛋白的双重转基因非人动物。 另外提供筛选改变淀粉样蛋白沉积速度或程度的化合物的方法。 该方法包括：（a）构建一个全基因组转基因动物; （b）向所述perlecan转基因动物施用有效量的测试化合物; 和（c）确定所述测试化合物是否改变淀粉样蛋白沉积的程度或速率。 最后，本发明提供了筛选改变淀粉样蛋白沉积速度或程度的化合物的方法。 该方法包括：（a）构建一个perlecan /淀粉样蛋白双转基因动物; （b）向所述perlecan /淀粉样蛋白双转基因动物施用有效量的测试化合物; 和（c）确定所述测试化合物是否改变淀粉样蛋白沉积的程度或速率。

公开(公告)号：WO1997030108A1

公开(公告)日：1997-08-21

申请号：PCT/US1997003340

申请日：1997-02-19

Applicant: VANDERBILT UNIVERSITY ,  UNIVERSITY OF WASHINGTON

Inventor： VANDERBILT UNIVERSITY ,  UNIVERSITY OF WASHINGTON ,  HOLT, Jeffrey, T. ,  JENSEN, Roy, A. ,  CLAIRE-KING, Marie ,  PAGE, David, L. ,  SZABO, Csilla, I. ,  JETTON, Thomas, L. ,  ROBINSON-BENION, Cheryl, L. ,  THOMPSON, Marilyn, E.

IPC: C08H01/00

CPC classification number: A61K49/0004 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4703 ,  C07K2319/00

Abstract: Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localises to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroplasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described. A method of screening for the receptors of the BRCA1 protein and BRCA2 proteins is also described.

Abstract translation: 家族性乳腺癌和卵巢癌的遗传分析表明，BRCA1是肿瘤抑制基因。 BRCA1基因编码190 kDa的蛋白质，与蛋白质的大豆蛋白家族具有序列同源性和生物化学类比。 通过经调节的分泌途径从内分泌细胞分泌颗粒，并被蛋白水解切割以产生生物活性肽。 BRCA1蛋白定位于分泌囊泡，并被证明是分泌的。 BRCA1的基因转移抑制乳腺和卵巢癌细胞的生长和肿瘤发生，但不抑制结肠或肺癌细胞或纤维板，这表明BRCA1编码组织特异性生长抑制剂。 因此，BRCA1是分泌的生长抑制剂，并且通过以前未被描述用于肿瘤抑制基因的机制起作用。 BRCA2乳腺癌和卵巢癌基因编码的蛋白质也包括一个颗粒蛋白，表明BRCA2蛋白也是分泌的肿瘤抑制因子。 还描述了使用BRCA1和BRCA蛋白和基因的治疗方法。 还描述了筛选BRCA1蛋白和BRCA2蛋白的受体的方法。

公开(公告)号：WO1997014711A1

公开(公告)日：1997-04-24

申请号：PCT/US1996016672

申请日：1996-10-18

Applicant: RECEPTAGEN CORPORATION ,  UNIVERSITY OF WASHINGTON ,  MORGAN, A., Charles, Jr. ,  WILBUR, D., Scott ,  PATHARE, Pradip, M.

Inventor： RECEPTAGEN CORPORATION ,  UNIVERSITY OF WASHINGTON

IPC: C07H23/00

CPC classification number: C07H23/00

Abstract: Vitamin B12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solubilizing linker.

Abstract translation: 公开了通过影响细胞表面受体转运途径来调节细胞表面受体的维生素B12受体调节剂。 维生素B12受体调节剂由共价结合的重新路由部分和通过水溶性接头连接的靶向部分组成。

公开(公告)号：WO1997006760A1

公开(公告)日：1997-02-27

申请号：PCT/US1996013235

申请日：1996-08-16

Applicant: PI MEDICAL CORPORATION ,  UNIVERSITY OF WASHINGTON ,  CORBETT, Scott, S., III ,  SWANSON, John, W. ,  MARTYNIUK, Jerry ,  CLARY, Thomas, R. ,  SPELMAN, Francis, A. ,  CLOPTON, Ben ,  VOIE, Arne, H. ,  JOLLY, Claude, N.

Inventor： PI MEDICAL CORPORATION ,  UNIVERSITY OF WASHINGTON

IPC: A61F11/04

CPC classification number: A61N1/0541 ,  A61B2018/00107

Abstract: A multi-electrode cochlear implant (10) is taught in which approximately twenty or more insulated metal wires (14, 16) are wound aaround a flexible tube (12). These wires (14, 16) are held in place with a further layer of dielectric insulating material (18). The insulation is selectively removed with a laser beam to form electrodes (20). Two or more layers or valences of wires (54, 58, 62) can be used, with the inner layer of wires (62) terminating distal to the outer layers (54, 58) to provide a stepwise approximation of the tapering of the scala tympani. A core (68) of shape memory material may be introduced into the tube (12), so that the implant will retain an effective shape after implantation.

Abstract translation: 教导了一种多电极耳蜗植入物（10），其中约二十个或更多个绝缘的金属线（14,16）围绕柔性管（12）缠绕。 这些电线（14,16）用另一层介电绝缘材料（18）保持就位。 用激光束选择性地去除绝缘体以形成电极（20）。 可以使用两层或更多层的电线（54,58,62），其中电线（62）的内层终止于外层（54,58）的远端，以提供斯卡拉锥度的逐步近似 定音鼓。 形状记忆材料的芯（68）可被引入到管（12）中，使得植入物将在植入后保持有效的形状。

公开(公告)号：WO1996036036A1

公开(公告)日：1996-11-14

申请号：PCT/US1996005431

申请日：1996-04-19

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  FURNESS, Thomas, A., III ,  MELVILLE, Charles, D. ,  TIDWELL, Michael, R.

IPC: G09G03/02

CPC classification number: G02B27/017 ,  G02B26/10 ,  G02B27/0172 ,  G02B2027/0116 ,  G02B2027/0118 ,  G02B2027/0132 ,  G02B2027/0138 ,  G02B2027/0187 ,  G02B2027/0198 ,  G09G3/001 ,  H04N9/3129

Abstract: A virtual retinal display utilizes photon generation and manipulation to create a panoramic, high resolution, color virtual image that is projected directly onto the retina of the eye. The virtual retinal display includes a source of photons, the photons being modulated with video information and scanned by a scanning system in a raster type of pattern directly onto the retina of the user's eye. A single, monofilament optical fiber (300) of very small diameter couples light from the photon generator (308, 314) to the scanning system (16) so as to provide to the scanning system a point source of light at the fiber's exit aperture (306). The photon generator may utilize coherent or non-coherent light. Further, the photon generator may utilize color light emitters so as to scan a colored virtual image directly onto the retina of the user's eye.

Abstract translation: 虚拟视网膜显示器利用光子产生和操纵来创建直接投影到眼睛的视网膜上的全景，高分辨率的彩色虚像。 虚拟视网膜显示器包括光子源，光子被视频信息调制，并以光栅类型的扫描系统直接扫描到用户的眼睛的视网膜上。 非常小直径的单个单丝光纤（300）将来自光子发生器（308,314）的光耦合到扫描系统（16），以向扫描系统提供光纤出射孔处的点光源（ 306）。 光子发生器可以利用相干或非相干光。 此外，光子发生器可以利用彩色发光器，以将有色虚拟图像直接扫描到用户的眼睛的视网膜上。

公开(公告)号：WO1996015149A3

公开(公告)日：1996-05-23

申请号：PCT/US1995014776

申请日：1995-11-09

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  CATTERALL, William, A. ,  SHENG, Zu-Hang

IPC: C07K14/705

公开(公告)号：WO1995033405A1

公开(公告)日：1995-12-14

申请号：PCT/US1995006259

申请日：1995-06-06

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  KEEFE, Douglas, H.

IPC: A61B05/12

CPC classification number: A61B5/121 ,  A61B5/12 ,  A61B5/7232 ,  G01H15/00 ,  G01N2291/02491 ,  G01N2291/02872 ,  Y10S128/925

Abstract: A system and method of measuring the linear and nonlinear response of an unknown acoustic termination uses a small probe assembly containing a sound source and microphone to determine the reflection function of the unknown acoustic termination. The probe assembly is used with a calibration tube to calculate an electrical signal that will provide a desired acoustic stimulus signal to the acoustic termination. The calibration tube is also used to characterize the signal processing properties of the sound source and microphone, as well as other associated signal processing circuits such as amplifiers, filters, and the like. The calibrated system is subsequently coupled to the unknown acoustic termination to deliver the acoustic stimulus signal. The reflection function is indicative of the power transferred to the unknown acoustic termination. The measurement of the linear transfer characteristic is applicable to any unknown acoustic termination such as a musical instrument or the auditory system. The probe assembly is sized to be positioned directly within the outer portion of the ear and measure the linear characteristics of the ear. The system is further able to measure the nonlinear transfer characteristics of the ear by measuring the linear response at multiple levels of the acoustic stimulus. The system is particularly useful in testing the response of the middle ear and inner ear of humans or other animals.

Abstract translation: 测量未知声音终端的线性和非线性响应的系统和方法使用包含声源和麦克风的小探头组件来确定未知声终端的反射功能。 探针组件与校准管一起使用以计算将向声学终端提供期望的声学刺激信号的电信号。 校准管还用于表征声源和麦克风以及诸如放大器，滤波器等的其它相关联的信号处理电路的信号处理特性。 随后校准的系统耦合到未知的声学终端以传送声学刺激信号。 反射函数表示传递到未知声终端的功率。 线性传递特性的测量适用于诸如乐器或听觉系统的任何未知的声学终止。 探针组件的尺寸设置成直接定位在耳朵的外部部分内并测量耳朵的线性特征。 该系统还能够通过测量声学刺激的多个级别的线性响应来测量耳朵的非线性传递特性。 该系统在测试人类或其他动物的中耳和内耳的反应方面特别有用。