公开(公告)号：US20060270841A1

公开(公告)日：2006-11-30

申请号：US10504446

申请日：2003-02-25

申请人： Amy Espeseth ,  Marc Ferrer ,  Osvaldo Flores ,  Daria Hazuda ,  James Inglese ,  Michael Miller ,  Bruce Register ,  Xiao-Ping Shi ,  Adam Simon ,  Paul Zuck

发明人： Amy Espeseth ,  Marc Ferrer ,  Osvaldo Flores ,  Daria Hazuda ,  James Inglese ,  Michael Miller ,  Bruce Register ,  Xiao-Ping Shi ,  Adam Simon ,  Paul Zuck

IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12P21/06 ,  C12N9/64

CPC分类号： C07K14/47 ,  C07K14/4702 ,  C07K14/4711 ,  C07K2319/00 ,  C07K2319/50 ,  G01N2500/10

摘要： The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and γ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.

摘要翻译： 本发明提供了DNA构建体，遗传工程化宿主细胞和用于鉴定淀粉样前体蛋白（APP）处理抑制剂的方法。 该方法提供了在单次测定中方便地鉴定β-分泌酶和γ-分泌酶抑制剂以及其它形式的APP处理。 该方法依赖于APP和转录因子的融合蛋白，其中APP处理释放转录因子，允许转录因子激活报告基因的转录。 抑制剂被鉴定为阻断或减少转录因子从融合蛋白释放的物质，从​​而导致报告基因读出的减少。

公开(公告)号：US20070219354A1

公开(公告)日：2007-09-20

申请号：US11714985

申请日：2007-03-07

申请人： Daria Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

发明人： Daria Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

IPC分类号： C07K16/00 ,  C07K14/00

CPC分类号： C07K7/06 ,  A01K2217/05 ,  A01K2267/0306 ,  A61K38/00 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/4711 ,  C07K16/18 ,  C12P21/06 ,  C12Q1/37 ,  G01N33/5088 ,  G01N33/6896 ,  G01N2500/00 ,  G01N2800/52

摘要： Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.

公开(公告)号：US20070292895A1

公开(公告)日：2007-12-20

申请号：US11803207

申请日：2007-05-14

申请人： Xiao-Ping Shi ,  Guoxin Wu ,  Jason Kahana ,  Adam Simon

发明人： Xiao-Ping Shi ,  Guoxin Wu ,  Jason Kahana ,  Adam Simon

IPC分类号： G01N33/573

CPC分类号： G01N33/6896 ,  G01N2333/948 ,  G01N2800/2821 ,  G01N2800/52

摘要： Methods and assays for detecting β-secretase (BACE-1) activity in body fluids or tissue extracts from individuals, particularly individuals who have Alzheimer's disease, are disclosed. A truncated form of BACE-1 was isolated that can be used as a biomarker for Alzheimer's disease.

摘要翻译： 公开了用于检测来自个体，特别是患有阿尔茨海默病的个体的体液或组织提取物中的β-分泌酶（BACE-1）活性的方法和测定法。 分离出截短形式的BACE-1，其可用作阿尔茨海默病的生物标志物。

公开(公告)号：US20050154434A1

公开(公告)日：2005-07-14

申请号：US10504830

申请日：2003-03-06

申请人： Adam Simon ,  Arthur Lifshey ,  Elena Fattori

发明人： Adam Simon ,  Arthur Lifshey ,  Elena Fattori

IPC分类号： A61N1/30 ,  A61M20060101 ,  A61M5/178 ,  A61N1/00 ,  A61N1/05 ,  A61N1/32

CPC分类号： A61N1/327 ,  A61M5/3291 ,  A61M5/3298 ,  A61M5/422 ,  A61M5/46 ,  A61N1/306 ,  A61N1/325

摘要： A treatment device is provided for applying electrical energy to biological tissue in conjunction with injecting a composition that advantageously diffuses through the tissue. An injector such as a syringe has a reservoir for the treatment composition and injection cannula. The cannula can function as an electrode, and one or more additional electrodes are provided as opposed electrodes. The electrodes can each have tissue penetrating needles, or one or more of the electrodes can have a surface bearing conductive contact part. The syringe or other injector and a drive unit that applies electrical power to the electrodes are operable simultaneously or in a sequence, and can be triggered by switches or automatically upon detection of the injection proceeding to a predetermined state. The treatment device preferably uses a disposable syringe received in a carrier and generally is provided with a non-threatening appearance by minimizing tissue penetration and potential high voltage aspects.

摘要翻译： 提供了一种处理装置，用于将电能施加到生物组织，同时注入有利于扩散通过组织的组合物。 诸如注射器的注射器具有用于治疗组合物和注射套管的储存器。 套管可以用作电极，并且提供一个或多个附加电极作为相对电极。 电极可以各自具有组织穿透针，或者一个或多个电极可以具有表面承载导电接触部分。 将注射器或其它注射器以及向电极施加电力的驱动单元可以同时或按顺序操作，并且可以由开关触发或者在检测到进入预定状态的注射时自动操作。 治疗装置优选使用容纳在载体中的一次性注射器，并且通常通过使组织穿透和潜在的高电压方面最小化而具有非威胁性外观。

公开(公告)号：US20070101449A1

公开(公告)日：2007-05-03

申请号：US10558656

申请日：2004-05-28

申请人： Richard Chen ,  Adam Simon ,  Thomas Vogt

发明人： Richard Chen ,  Adam Simon ,  Thomas Vogt

IPC分类号： A01K67/027 ,  C12N5/06

CPC分类号： C07K14/4711 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0312 ,  C07K16/18 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention provides transgenic animals having an amyloid precursor protein wherein the amino acids flanking the &bgr; secretase cleavage site are NF and EV. The invention also provides tissues and cell lines derived from such animals. The invention further provides methods of screening candidate compounds to determine whether the compounds can alter the rate of cleavage of amyloid precursor protein by &bgr; secretase.

摘要翻译： 本发明提供具有淀粉样前体蛋白质的转基因动物，其中β分泌酶切割位点侧翼的氨基酸为NF和EV。 本发明还提供了衍生自这些动物的组织和细胞系。 本发明进一步提供筛选候选化合物以确定化合物是否可以通过β分泌酶改变淀粉样蛋白前体蛋白的切割速率的方法。

公开(公告)号：US20230219504A1

公开(公告)日：2023-07-13

申请号：US17570721

申请日：2022-01-07

申请人： Adam Simon

发明人： Adam Simon

IPC分类号： B60R9/10

CPC分类号： B60R9/10

摘要： An attachment locks a bicycle rack and/or a bicycle to a vehicle. The attachment may have a rigid body with a first end adapted to attach to a portion of the bicycle rack and/or a bicycle, and a second end adapted for insertion into a trunk or hatch space of the vehicle. The first end may include a loop, clasp or pivot joint which attaches to the bicycle or bicycle rack. The second end may be provided with an angle section joined to the rigid body via a radius. The second end is thin and flat, to allow the second end to extend into the trunk space and remain captured in the trunk space by a closed trunk lid, without interfering with operation of the trunk lid. An anchor may extend through or project outwardly from the second end, to resist attempts to pull the attachment out of the trunk space by force. A trunk bar has a loop section and ends adapted to be secured into a trunk space.