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公开(公告)号：US06867197B1
公开(公告)日：2005-03-15
申请号：US09448312
申请日：1999-11-23
CPC分类号： C07D219/08 , A61K38/00 , A61K47/541 , A61K47/545 , C07K14/4711 , C07K14/4713 , C12N9/0053 , C12Q1/6806 , C12Q2527/101
摘要： The present invention relates to genetic mutations in mitochondrial cytochrome c oxidase genes that segregate with Alzheimer's disease (AD). The invention provides methods for detecting such mutations, as a diagnostic for Alzheimer's Disease, either before or after the onset of clinical symptoms. The invention further provides treatment of cytochrome c oxidase dysfunction.
摘要翻译： 本发明涉及与阿尔茨海默氏病（AD）分离的线粒体细胞色素c氧化酶基因中的遗传突变。 本发明提供了在临床症状发作之前或之后检测这种突变作为阿尔茨海默病诊断的方法。 本发明进一步提供细胞色素c氧化酶功能障碍的治疗。
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公开(公告)号：US06653094B2
公开(公告)日：2003-11-25
申请号：US09924313
申请日：2001-08-07
IPC分类号： C12Q132
CPC分类号： C12Q1/6883 , G01N33/6893 , G01N2800/042
摘要： The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.
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73.发明授权Compositions and mehtods for determining interactions of mitochondrial components, and for identifying agents that alter such interactions 失效用于确定线粒体组分相互作用的组合物和方法，以及用于鉴定改变这种相互作用的试剂公开(公告)号：US06562563B1
公开(公告)日：2003-05-13
申请号：US09434354
申请日：1999-11-03
申请人： Anne N. Murphy , William Clevenger , Sandra Eileen Wiley , Alexander Y. Andreyev , Luciano G. Frigeri , Gonul Velecelebi , Robert E. Davis
发明人： Anne N. Murphy , William Clevenger , Sandra Eileen Wiley , Alexander Y. Andreyev , Luciano G. Frigeri , Gonul Velecelebi , Robert E. Davis
IPC分类号： C12N500
CPC分类号： G01N33/5079 , C07K14/43595 , C07K2319/00 , C07K2319/21 , C07K2319/23 , C07K2319/50 , C07K2319/60 , C12N9/90 , C12N15/62 , G01N33/542
摘要： Compositions and methods are provided for identifying agents that alter mitochondrial membrane permeability transition. The screening methods generally detect agents that alter the interaction between the mitochondrial adenine nucleotide translocator and cyclophilin D. Such agents may be used, for example, in the treatment of a variety of conditions associated with altered mitochondrial function.
摘要翻译： 提供组合物和方法用于鉴定改变线粒体膜通透性转换的药剂。 筛选方法通常检测改变线粒体腺嘌呤核苷酸转运体和亲环蛋白D之间的相互作用的试剂。这种试剂可用于例如治疗与线粒体功能改变相关的多种病症。
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公开(公告)号：US06511966B2
公开(公告)日：2003-01-28
申请号：US09933911
申请日：2001-08-20
IPC分类号： A01N4304
CPC分类号： A61K31/155 , A61K31/00 , A61K31/05 , A61K31/06 , A61K31/136 , C07C39/08 , C07C39/11 , C07C39/19 , C07C69/017 , C07C215/78 , C07C215/80 , C07C217/84 , C07C279/18 , C07D215/20 , C07D311/72
摘要： The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus. Parkinson's Disease, neuronal and cardiac ischemia. Huntington's disease and stroke.
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公开(公告)号：US06489095B2
公开(公告)日：2002-12-03
申请号：US09098079
申请日：1998-06-15
IPC分类号： C12Q168
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/156 , C12Q2600/172
摘要： Compositions and methods based on quantification of extramitochondrial DNA (exmtDNA) sequences are provided that are useful for detecting the presence of or risk for having a disease associated with altered mitochondrial function, and for identifying agents suitable for treating such diseases. The exmtDNA sequences have strong homology to authentic mitochondrial DNA (mtDNA) sequences.
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公开(公告)号：US06291172B1
公开(公告)日：2001-09-18
申请号：US09302682
申请日：1999-04-30
IPC分类号： C12P1934
CPC分类号： C07D219/08 , A61K38/00 , C07K14/4711 , C07K14/4713 , C12N9/0053 , C12Q1/6806 , C12Q1/6883 , C12Q2600/156 , C12Q2527/101
摘要： The present invention relates to genetic mutations in mitochondrial genes that segregate with diabetes mellitus. The invention provides methods for detecting such mutations, as a diagnostic for diabetes mellitus, either before or after the onset of clinical symptoms. Examples of specific mutations in the ATP synthase 8/6 sequence and tRNALys sequence are given. The invention also provides treatments for dysfunctions due to genes for mitochondrial functions that segregate with diabetes mellitus. Cybrid cell lines are described which are useful as model systems for the study of the mitochondrial metabolic disorders that are associated with diabetes mellitus, and for identifying therapeutic compounds and treatments for this disease.
摘要翻译： 本发明涉及与糖尿病分离的线粒体基因中的遗传突变。 本发明提供在临床症状发作之前或之后检测这种突变作为糖尿病诊断的方法。 给出了ATP合酶8/6序列和tRNALys序列中特异性突变的实例。 本发明还提供了由于与糖尿病分离的线粒体功能的基因引起的功能障碍的治疗。 描述了杂交细胞系，其可用作研究与糖尿病相关的线粒体代谢紊乱的模型系统，并且用于鉴定该疾病的治疗化合物和治疗。
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77.发明授权Indicators of altered mitochondrial function in predictive methods for determining risk of type 2 diabetes mellitus 失效线粒体功能改变的指标，用于确定2型糖尿病风险的预测方法公开(公告)号：US06280966B1
公开(公告)日：2001-08-28
申请号：US09521407
申请日：2000-03-08
IPC分类号： C12Q132
CPC分类号： C12Q1/6883 , G01N33/6893 , G01N2800/042
摘要： The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, celullar responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.
摘要翻译： 本发明涉及用于早期检测人类发展中的2型糖尿病的风险的改进的诊断方法，以及用于治疗2型糖尿病的治疗药物的筛选测定法，通过比较一种或多种改变的 线粒体功能。 改变线粒体功能的指标包括线粒体酶和ATP生物合成因子等酶。 线粒体功能改变的其他指标包括线粒体质量，线粒体数量和线粒体DNA含量，细胞内钙升高和凋亡细胞的纤溶酶反应以及自由基生成。 还提供了用于治疗和分层人类患者的方法，这些方法涉及公开的改变的脑膜功能指标。
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公开(公告)号：US5290705A
公开(公告)日：1994-03-01
申请号：US820302
申请日：1992-01-13
申请人： Robert E. Davis
发明人： Robert E. Davis
CPC分类号： B01L3/5085 , B01L3/5088 , G01N21/03 , B01L2300/0822 , G01N2021/0346 , G01N21/35 , G01N21/3577
摘要： A specimen support for optical observation or analysis. The support comprises a disc-like member composed of a rigid material and having at least one unobstructed hole extending therethrough. When analyzing a liquid specimen, the disc is dipped in the liquid and the surface tension of the liquid will cause the liquid to bridge or span the hole. The support is then placed in a tray or holder and exposed to an infrared beam to generate an infrared spectrum.
摘要翻译： 光学观察或分析的样本支持。 支撑件包括由刚性材料构成并且具有延伸穿过其中的至少一个无障碍孔的盘状构件。 当分析液体样品时，将盘浸入液体中，并且液体的表面张力将导致液体桥接或跨越孔。 然后将支撑物放置在托盘或支架中并暴露于红外光束以产生红外光谱。
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公开(公告)号：US5064326A
公开(公告)日：1991-11-12
申请号：US533173
申请日：1990-06-04
申请人： Robert E. Davis , Frank R. England
发明人： Robert E. Davis , Frank R. England
IPC分类号： F16B21/07 , F16B21/18 , F16B23/00 , F16B31/02 , F16B37/14 , F16B39/30 , F16B41/00 , G01F15/00 , G01R11/24 , G09F3/03
CPC分类号： G09F3/0317 , F16B41/005 , G01F15/007 , G01R11/24 , F16B21/073 , F16B21/183 , F16B23/00 , F16B31/021 , F16B37/14 , F16B39/30 , Y10S411/91 , Y10T292/51
摘要： Tamper proof service bolts for sealing boxcars, automobile hoods, gates and other enclosures, as well as gas and electric meters, railroad switches and the like. In a first preferred embodiment the tamper proof service bolts are characterized by special head service bolts, each having a base member and a collar secured to the base member by means of a connecting bolt having a specialized head recess for receiving a corresponding tool which is required for removing the connecting bolt and the collar from the base member. In another preferred embodiment of the invention retainer clip service bolts are provided, wherein a retainer clip is adapted to mount on each base member and in the collar when the collar is fitted over the base member, to secure the collar on the base member. In still another preferred embodiment a sacrifice head service bolt is provided where the collar is fitted on the base member and a sacrifice head having a thin, frangible neck is threaded on the base member, such that the bottom element of the sacrifice head is countersunk in the collar when the top element of the sacrifice head is stripped from the bottom element at the frangible neck. A cross-thread nipple service bolt is also provided, wherein the base member is fitted with an upward-standing, threaded stud for engaging dissimilar threads in a cross-thread collar such that the threaded nipple is irreversibly cross-threaded into the cross-thread collar.
摘要翻译： 用于密封箱车，汽车罩，门和其他外壳的防篡改螺栓，以及气体和电表，铁路开关等。 在第一优选实施例中，防篡改维修螺栓的特征在于具有特殊的头部维修螺栓，每个螺栓具有基座构件和通过具有专用头部凹槽的连接螺栓固定到基座构件的轴环，用于接收所需的相应工具 用于从基座构件移除连接螺栓和套环。 在本发明的另一个优选实施例中，提供固定夹维护螺栓，其中当套环安装在基座构件上时，保持夹适于安装在每个基座构件上和套环中，以将套环固定在基座构件上。 在又一优选实施例中，提供了牺牲头维修螺栓，其中套环安装在基座构件上，并且具有薄的易碎颈部的牺牲头在基座构件上螺纹连接，使得牺牲头的底部元件埋入 当在易碎的颈部从牺牲头部的顶部元件从底部元件剥离时的领子。 还提供十字螺纹接头维修螺栓，其中，所述基座部件装配有向上的螺纹螺栓，用于接合十字螺纹轴环中的不同螺纹，使得螺纹接头不可逆地交叉螺纹到十字螺纹 领。
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公开(公告)号：US5039062A
公开(公告)日：1991-08-13
申请号：US535554
申请日：1990-06-11
申请人： Frank R. England , Robert E. Davis
发明人： Frank R. England , Robert E. Davis
IPC分类号： F16K35/06
CPC分类号： F16K35/06 , Y10T137/7256 , Y10T70/5615 , Y10T70/5805
摘要： A tamper-proof valve which includes a valve body fitted with a transverse bore, an entry port and outlet port communicating with the transverse bore and an inner body seat for receiving a tapered inner body having a notch adapted for manipulation in alignment with the entry port and outlet port in open configuration and transverse to the entry port and outlet port, in closed configuration. A plug is provided on the top of the inner body for seating one end of a spring which is slidably encased in a collet. A square key is also slidably disposed in one end of the collet and is adapted to seat in a key seat provided in a top valve assembly which mounts on the valve body. An allen screw having a tamper-proof tool receptacle is threaded in the top valve assembly in alignment with the key, such that a special tool may be inserted in the allen screw tool receptacle and the allen screw rotated in the clockwise direction (when viewing the valve body from the top) to seat against the key, compress the spring inside the collet, remove the key from the key seat located in the top valve assembly and facilitate rotation of the top valve assembly independently of the inner body. Rotation of the allen screw in the opposite, or counterclockwise direction allows the spring to force the key upwardly into the key seat and facilitate opening and closing the inner body and the valve body in concert.
摘要翻译： 一种防窜流阀，其包括装配有横向孔的阀体，与所述横向孔连通的进入口和出口端口以及用于接纳锥形内部主体的内部主体，所述锥形内部主体具有适于与所述入口端口对准的操作的凹口 并且出口处于打开配置并横向入口和出口，处于关闭状态。 在内体的顶部设有塞子，用于将可滑动地装在筒夹中的弹簧的一端固定。 方形键也可滑动地设置在夹头的一端中，并且适于安置在安装在阀体上的顶阀组件中设置的钥匙座中。 具有防篡改工具容器的内六角螺丝与顶部阀组件螺纹连接，与钥匙对准，使得特殊工具可以插入螺钉工具插座中，并且三角螺丝沿顺时针方向旋转（当观察 阀体从顶部）靠在钥匙上，压缩夹头内的弹簧，从位于顶部阀门组件中的钥匙座上卸下钥匙，便于独立于内部主体旋转顶部阀门组件。 内六角螺杆以相反或逆时针方向的旋转允许弹簧将钥匙向上推入钥匙座，并有助于使内体和阀体协调地打开和关闭。
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