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11. 发明申请

WO1995012171A2 METHOD AND APPARATUS FOR ADAPTIVE CONTROL OF HUMAN-MACHINE SYSTEMS EMPLOYING DISTURBANCE RESPONSE 审中-公开
标题翻译：人机系统自适应控制的方法与装置应对干扰响应
公开(公告)号：WO1995012171A2
公开(公告)日：1995-05-04
申请号：PCT/US1994012179
申请日：1994-10-24
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , BELL, David, A. , BELL, Lon, E. , LEVINE, Simon , KOREN, Yoram
IPC分类号： G06F17/00
CPC分类号： B60W40/08 , A61G5/04 , A61G2203/14 , B60W2300/38 , Y10S180/907 , Y10S297/04 , Y10S706/905
摘要： Adaptive control of a system with a human in the loop is accomplished by sensing human operator reactions to a disturbance in the system and characterizing the operator response to the disturbance. The operator response is characterized in one of several forms by predicting a response based on a model quantifying a response based on statistics or merely measuring a response for accumulation of data to be employed by an artificial intelligent system. The disturbance which provides the human operator reaction, is applied or occurs naturally based on other stimulus and is measured by the system. Quantifying the results of the disturbance and the operator response comparison allows selection of a control mode by identifying one or more categories of reactions response or a graduated modification of the control law employed in the system. Various modes or categories for control of the system incorporate different sensitivities on a macro scale or an entirely different control algorithm. Graduated adaptation alters sensitivity or other perimeters in the system at a micro level incrementally throughout given ranges of control.
摘要翻译：通过感测人类操作员对系统中的干扰的反应并表征操作者对干扰的响应来实现对环路中的人的系统的自适应控制。操作员响应以几种形式之一表征，通过基于基于统计量量化响应的模型来预测响应，或者仅测量人造智能系统将要使用的数据的累积响应。提供人员操作反应的干扰，以其他刺激为基础自然发生，并由系统测量。量化干扰的结果和操作者响应比较允许通过识别系统中使用的控制规则的一个或多个类别的反应响应或分级修改来选择控制模式。用于系统控制的各种模式或类别在宏观尺度或完全不同的控制算法上包含不同的灵敏度。渐变自适应在给定的控制范围内以微观级别改变系统中的灵敏度或其他周长。

12. 发明申请

WO1994029436A1 METHODS FOR SELECTIVELY STIMULATING PROLIFERATION OF T CELLS 审中-公开
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：WO1994029436A1
公开(公告)日：1994-12-22
申请号：PCT/US1994006255
申请日：1994-06-03
申请人： THE UNITED STATES OF AMERICA represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION
发明人： THE UNITED STATES OF AMERICA represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION , JUNE, Carl, H. , THOMPSON, Craig, B. , NABEL, Gary, J. , GRAY, Gary, S. , RENNERT, Paul, D.
IPC分类号： C12N05/08
CPC分类号： C12N5/0636 , A61K35/17 , A61K38/00 , A61K48/00 , C07K14/70532 , C07K16/2809 , C07K16/2818 , C07K16/2896 , C07K2317/34 , C07K2317/74 , C12N2501/51 , C12N2501/515 , C12N2501/599
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。通过本发明方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

13. 发明申请

WO1994029342A1 CELL SURFACE LAMP EXPRESSION AND SELECTIN-DEPENDENT ADHESION 审中-公开
标题翻译：细胞表面表达和选择性依赖性粘附
公开(公告)号：WO1994029342A1
公开(公告)日：1994-12-22
申请号：PCT/US1994006493
申请日：1994-06-08
申请人： LA JOLLA CANCER RESEARCH FOUNDATION , THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , SAWADA, Ritsuko , LOWE, John, B. , FUKUDA, Minoru
IPC分类号： C07K13/00
CPC分类号： C07K14/705 , A61K38/00 , C07K14/47
摘要： The present invention provides novel purified human lysosomal membrane sialoglycoproteins. These novel human proteins, lamp-1 and lamp-2, are highly glycosylated and are the major carriers of polylactosaminoglycan, when expressed on the cell surface participate in various cellular adhesion interactions. Further provided by the present invention are methods of modifying biological functions mediated by the regulatory activity of selectin receptors, methods of alleviating pathologic conditions mediated by lamp-derived polypeptide and selectin receptor interactions. Isolated nucleid acids encoding the novel lamp-1 amd lamp-2 glycoproteins and soluble lamp-derived polypeptides are provided, as well as vectors containing the nucleic acids and recombinant host cells transformed with such vectors. This invention provides antisense oligonucleotides capable of binding specifically to mRNA molecules encoding human lamp-derived polypeptides. The present invention provides monoclonal antibodies to the soluble lamp-derived polypeptides. Methods of detecting the presence of activated selectin receptors on platelets and endothelial cell surfaces are also provided.
摘要翻译：本发明提供新型纯化的人溶酶体膜唾液酸糖蛋白。这些新型人类蛋白质灯1和灯2高度糖基化，并且是在细胞表面上表达时参与多种细胞粘附相互作用的聚乳糖胺聚糖的主要载体。本发明还提供了改变由选择素受体的调节活性介导的生物功能的方法，减轻由灯衍生的多肽介导的病理状况的方法和选择素受体相互作用。提供编码新型灯-1-amd灯2糖蛋白和可溶性灯衍生多肽的分离的核酸，以及含有用这些载体转化的核酸和重组宿主细胞的载体。本发明提供能够特异性结合编码人类灯衍生多肽的mRNA分子的反义寡核苷酸。本发明提供了针对可溶性灯衍生多肽的单克隆抗体。还提供了检测血小板和内皮细胞表面上活化的选择素受体的存在的方法。

14. 发明申请

WO1994028938A1 ADENOVIRUS VECTORS FOR GENE THERAPY SPONSORSHIP 审中-公开
标题翻译：腺病毒载体为基因治疗赞助
公开(公告)号：WO1994028938A1
公开(公告)日：1994-12-22
申请号：PCT/US1994006338
申请日：1994-06-06
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , WILSON, James, M. , ENGELHARDT, John
IPC分类号： A61K48/00
CPC分类号： C12N15/86 , A01K67/027 , A01K67/0271 , A01K2217/05 , A01K2267/03 , A61K38/00 , A61K48/00 , A61L27/38 , B82Y5/00 , C07K14/4712 , C07K16/18 , C07K16/28 , C12N15/8509 , C12N2710/10343
摘要： The present invention comprises an improved adenovirus vector and methods for making and using such vectors. The adenovirus vectors of the present invention retain at least a portion of the adenoviral E3 region, carry a deletion of at least a portion of the adenoviral E1 region. Vectors of the present invention preferably also include an additional deletion to accommodate a transgene and/or other mutations which result in reduced expression or over-expression of adenoviral protein and/or reduced viral replication. The vectors of the present invention further include a transgene operatively-linked thereto. By reducing or eliminating viral replication and viral protein expression, the immune response of the infected host to the virus and viral protein is decreased and persistence of transgene expression can be increased. The adenovirus vectors of the present invention are thus particularly useful in gene transfer and therapy.
摘要翻译：本发明包括改良的腺病毒载体和用于制备和使用这些载体的方法。本发明的腺病毒载体保留腺病毒E3区域的至少一部分，携带至少部分腺病毒E1区域的缺失。本发明的载体优选还包括另外的缺失以适应导致腺病毒蛋白质的表达或过度表达和/或减少的病毒复制的转基因和/或其它突变。本发明的载体还包括与其可操作地连接的转基因。通过减少或消除病毒复制和病毒蛋白表达，感染的宿主对病毒和病毒蛋白的免疫应答降低，可以增加转基因表达的持续性。因此，本发明的腺病毒载体特别可用于基因转移和治疗。

15. 发明申请

WO1994026447A1 METHOD AND APPARATUS FOR RAPIDLY SOLIDIFIED INGOT PRODUCTION 审中-公开
标题翻译：用于快速固化生产的方法和装置
公开(公告)号：WO1994026447A1
公开(公告)日：1994-11-24
申请号：PCT/US1994005516
申请日：1994-05-17
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , GHOSH, Amit, K.
IPC分类号： B22F09/00
CPC分类号： B22D27/08
摘要： An apparatus and method for producing a rapidly solidified ingot characterized by a fine scale microstructure capable of precipitating uniformly dispersed fine particles. A charge of material (26) is placed in a crucible (14) and heated by a furnace (12) to melt the charge (26). The melt is discharged from the crucible (14) in a stream (74) along a pouring axis. An ingot mold (16) is oriented at an angle with respect to the pouring axis so that the stream (74) is received in the mold (16). As the melt is being poured into the mold (16), the mold (16) is rotated about its central axis at a predetermined speed to continuously shear, both circumferentially and downwardly, a thin layer of melt (78) from the stream (74) as the stream contacts the sidewall surfaces of the mold (16). The thin layer (78) is rapidly solidified by the rapid extraction of heat through the mold (16) and is formed, as said ingot mold (16) fills and successive layers are solidified, into an ingot having a fine microstructure capable of developing uniformly dispersed fine particles.
摘要翻译：一种用于生产快速固化锭的装置和方法，其特征在于能够使均匀分散的细颗粒沉淀的微细尺度微结构。将材料（26）装入坩埚（14）中并通过炉（12）加热以熔化电荷（26）。熔体沿着倾倒轴线从坩埚（14）排出。锭模具（16）相对于倾倒轴线成一角度定向，使得料流（74）被容纳在模具（16）中。当熔体被浇注到模具（16）中时，模具（16）以预定的速度围绕其中心轴线旋转，以连续地从流（74）连续地剪切薄层的熔体（78）），因为流接触模具（16）的侧壁表面。通过快速提取热量通过模具（16）快速固化薄层（78），并且当所述锭模（16）填充并连续层固化时，其形成为具有均匀显影的精细微结构的锭分散细颗粒。

16. 发明申请

WO1993022331A1 HUMAN CRABP-I AND CRABP-II 审中-公开
标题翻译：人CRABP-I和CRABP-II
公开(公告)号：WO1993022331A1
公开(公告)日：1993-11-11
申请号：PCT/US1993003936
申请日：1993-04-27
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , ASTROM, Anders , VOORHEES, John, J. , PETTERSON, Ulrika , TAVAKKOL, Amir
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C07H21/04
CPC分类号： C12Q1/6897 , C07K14/70567 , G01N2333/70567 , G01N2500/00
摘要： The sequences encoding two isoforms of human cellular retinoic acid binding proteins, CRABP-I and CRABP-II, have been cloned and sequenced and are set forth with their corresponding amino acid sequences in SEQ ID NOS. 1-4. The indentification of human CRABP nucleic and amino acid sequences provides the basis for the construction of recombinant human CRABP vectors and expression constructs. Human CRABP can also be synthesized or produced ex vivo, e.g. in bacterial or other production systems. Ligand binding assays, including recombinant and chimeric receptor reporter assays, and direct and competition hybridization assays employing the human CRABP sequences herein described can be used to test drugs for retinoic induction and tissue specificity for pathologies in which retinoids are implicated. Immunoassays utilizing antibodies or binding fragments produced to human CRABP can also be used to test patient tissues for the presence and levels of CRABP for diagnosis and to monitor treatment. The indentification of the nucleic and amino acids sequences for human CRABP-I and CRABP-II also contributes to the elucidation of the function and interaction of the retinoid-binding proteins. The CRABP-II gene, isolated from a human placenta genomic library, spans 6 kilobases and includes 4 exons. One major transcription initiation site was mapped to an A residue 137 nucleotides upstream of the ATG initiation codon. CRABP-II mRNA was rapidly induced within 2-6 hours in culture by retinoic acid, primarily due to an increased rate of transcription which required on-going synthesis. The human CRABP-II gene is thus apparently transcriptionally regulated by a newly synthesized regulator protein. Once the CRABP-II is produced, message stabilization may provide means by which elevated CRABP-II in mRNA is maintained.
摘要翻译：编码人类细胞视黄酸结合蛋白（CRABP-1和CRABP-II）的两种同工型的序列已被克隆并测序，并以SEQ ID NOS中相应的氨基酸序列进行阐述。 1-4。人类CRABP核酸和氨基酸序列的鉴定提供了构建重组人类CRABP载体和表达构建体的基础。人类CRABP也可以离体合成或产生，例如，在细菌或其他生产系统中。配体结合测定法，包括重组和嵌合受体报告基因测定，以及使用本文所述的人类CRABP序列的直接和竞争杂交测定法，可用于检测视黄酸诱导药物和组胺特异性，其中涉及类维生素A。利用针对人类CRABP产生的抗体或结合片段的免疫测定法也可用于测试患者组织中CRABP的存在和水平以进行诊断和监测治疗。人CRABP-1和CRABP-II的核酸和氨基酸序列的鉴定也有助于阐明类视黄醇结合蛋白的功能和相互作用。从人胎盘基因组文库分离的CRABP-II基因跨越6千碱基并且包括4个外显子。一个主要的转录起始位点被映射到ATG起始密码子上游137个核苷酸的A残基。 CRABP-II mRNA在视黄酸培养2-6小时内迅速诱导，主要是由于需要持续合成的转录速率增加。因此，人类CRABP-II基因显然被新合成的调节蛋白转录调节。一旦CRABP-II产生，信号稳定可以提供维持mRNA中升高的CRABP-II的方式。

17. 发明申请

WO1993019767A1 CD28 PATHWAY IMMUNOREGULATION 审中-公开
标题翻译： CD28路径免疫法
公开(公告)号：WO1993019767A1
公开(公告)日：1993-10-14
申请号：PCT/US1993003155
申请日：1993-04-06
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , THOMPSON, Craig, B. , JUNE, Carl, H.
IPC分类号： A61K37/00
CPC分类号： C12N5/0636 , A61K31/395 , A61K35/17 , A61K38/2013 , A61K38/45 , A61K38/465 , A61K2039/505 , A61K2039/5158 , C07K14/70521 , C07K16/00 , C07K16/2806 , C07K16/2809 , C07K16/2812 , C07K16/2815 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/289 , C07K16/2896 , C07K2317/54 , C07K2317/73 , C07K2317/74 , C07K2319/30 , C12N2501/51 , C12N2501/515 , A61K2300/00
摘要： Immunotherapy of the present invention involves the regulation of the T cell immune response through the activation or suppression/inactivation of the CD28 pathway. Induction of activated T cell lymphokine production occurs upon stimulatory binding of the CD28 surface receptor molecule, even in the presence of conventional immunosuppressants. Inhibition of CD28 receptor binding to an appropriate stimulatory ligand or inactivation of the CD28 signal transduction pathway through other means down-regulates CD28-pathway related T cell lymphokine production and its resulting effects.
摘要翻译：本发明的免疫治疗涉及通过CD28途径的激活或抑制/失活调节T细胞免疫应答。活化的T细胞淋巴因子产生的诱导发生在CD28表面受体分子的刺激结合后，即使在常规免疫抑制剂的存在下也是如此。抑制CD28受体结合适当的刺激配体或通过其他方式灭活CD28信号转导通路下调CD28通路相关T细胞淋巴因子的产生及其结果。

18. 发明申请

WO1993017696A1 METHOD FOR KIDNEY TUBULOGENESIS 审中-公开
标题翻译： KIDNEY TUBULOGENESIS的方法
公开(公告)号：WO1993017696A1
公开(公告)日：1993-09-16
申请号：PCT/US1993001666
申请日：1993-03-02
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , HUMES, H., David
IPC分类号： A61K37/00
CPC分类号： C12N5/0687 , A61K35/12 , A61K48/00 , C12N5/0686 , C12N2501/11 , C12N2501/15 , C12N2501/385 , C12N2502/28 , C12N2510/00 , C12N2533/54 , Y10S623/915
摘要： Methods, including culture media conditions, which provide for isolation and purification of renal tubule stem cells and for in vitro kidney tubulogenesis are disclosed. The methods rely on culturing adult kidney cells in a culture media treated with combinations of transforming growth factor- beta 1, epidermal growth factor, and all-trans retinoic acid.
摘要翻译：公开了包括提供肾小管干细胞分离和纯化以及体外肾细胞发生的方法，包括培养基条件。该方法依赖于在转化生长因子-β1，表皮生长因子和全反式视黄酸组合处理的培养基中培养成年肾细胞。

19. 发明申请

WO1993017240A1 SELF REGULATING BLOOD PUMP 审中-公开
标题翻译：自我调节血液泵
公开(公告)号：WO1993017240A1
公开(公告)日：1993-09-02
申请号：PCT/US1992008635
申请日：1992-10-09
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , MONTOYA, Jean, Patrick , MERZ, Scott, Isaac , BARLETT, Robert, Hawes
IPC分类号： F04B43/08
CPC分类号： F04B43/1215 , F04B43/0072 , F16L11/085 , F16L11/12
摘要： A peristaltic pump (20) having controlled suction. In one embodiment, the pump includes a tubing (38) which is collapsed when the internal pressure of the tubing (38) is equal to or less than ambient. In this state, the pump (20) is unable to generate negative pressures. An air-tight housing (100) may be provided over the tubing (38) and connected to a vacuum source (102). Upon a vacuum being applied, the tubing (38) is capable of controllably producing negative pressures, allowing the pump (20) to be operated as a suction pump. In another embodiment the tubing (38) exhibits a variable cross-sectional width.

20. 发明申请

WO1992007867A1 POLYSUBSTITUTED BENZIMIDAZOLES AS ANTIVIRAL AGENTS 审中-公开
标题翻译：多元苯并咪唑作为抗病毒剂
公开(公告)号：WO1992007867A1
公开(公告)日：1992-05-14
申请号：PCT/US1991008124
申请日：1991-10-31
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , TOWNSEND, Leroy, B. , DRACH, John, C.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C07H17/02
CPC分类号： A61K31/70 , A61K31/415 , A61K31/4184 , A61K31/52 , A61K31/7056 , C07D235/24 , C07D235/26 , C07D235/30 , C07H19/052 , Y10S514/934 , A61K2300/00
摘要： This invention relates to novel polysubstituted benzimidazoles and compositions and their use in the treatment of viral infections. The polysubstituted benzimidazoles and compositions of the present invention exhibit antiviral properties against viruses of the herpes family, particularly human cytomegalovirus (HCMV) and herpes simplex viruses (HSV).

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