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81. 发明申请

WO1993019743A1 METHOD OF TREATMENT OF HYPERPIGMENTATION IN BLACK SKIN WITH RETINOIC ACID AND METHOD OF LIGHTENING BLACK SKIN WITH RETINOIC ACID 审中-公开
标题翻译：治疗黑皮肤高脂肪酸的方法及其制备方法
公开(公告)号：WO1993019743A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002711
申请日：1993-03-31
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , VOORHEES, John, J. , ELLIS, Charles, N. , GRIFFITHS, Christopher, E., M.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K31/07
CPC分类号： A61Q19/02 , A61K8/49 , A61K8/494 , A61K8/671 , A61K31/07 , A61K31/20 , A61K31/203 , A61K31/41 , A61K31/415 , A61K31/495 , A61K2800/782 , A61K2300/00
摘要： Hyperpigmentation of black skin may be treated by topical application of retinoic acid to the skin. Topical application of retinoic acid is also effective for lightening normal black skin.
摘要翻译：黑皮肤色素沉着过度可能会通过局部应用视黄酸来治疗皮肤。视黄酸的局部应用对于减轻正常的黑色皮肤也是有效的。

82. 发明申请

WO1993019729A1 RETINOIC ACID AS A SKIN TANNING AGENT IN PERSONS OF LIGHT SKIN COLOR 审中-公开
标题翻译：作为轻皮肤颜色的皮肤TANNING代理的反义酸
公开(公告)号：WO1993019729A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002712
申请日：1993-03-31
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , VOORHEES, John, J. , GRIFFITHS, Christopher, E., M. , ELLIS, Charles, N.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K07/42
CPC分类号： A61Q19/04 , A61K8/671 , A61K31/07 , A61K31/20 , Y10S514/844 , Y10S514/847 , Y10S514/944
摘要： Topical application of retinoic acid is effective for increasing the tyrosinase activity in the skin of people having light skin. Thus, topical application of retinoic acid may be used to effect a suntan in people having light skin and as a consequence protect against photodamage.

83. 发明申请

WO1993018132A1 METHODS, COMPOSITIONS AND DEVICES FOR MAINTAINING AND GROWING HUMAN STEM AND/OR HEMATOPOIETIC CELLS 审中-公开
标题翻译：用于维持和培养人类干细胞和/或血细胞分化细胞的方法，组合物和装置
公开(公告)号：WO1993018132A1
公开(公告)日：1993-09-16
申请号：PCT/US1993001803
申请日：1993-03-04
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , PALSSON, Bernhard, O. , EMERSON, Stephen, G. , SCHWARTZ, Richard, M.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C12M03/00
CPC分类号： C12M25/02 , C12M29/10 , C12M35/08
摘要： Methods, compositions and devices are provided for the growth of human stem and/or hematopoietic cells in culture. Bioreactors (106) are provided in which diverse cell types are simultaneously-cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor (106) while removing undesirable metabolic products. This simultaneous culture of multiple cell types successfully reconstructs hematopoietic tissue ex vivo. Optionally, at least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. Means are provided for maintaining the stromal cells (112) and hematopoietic cells (110) separately, and to allow for harvesting of both the adherent (110, 112) and non-adherent cells (114).
摘要翻译：提供了用于培养人类干细胞和/或造血细胞生长的方法，组合物和装置。提供生物反应器（106），其中不同的细胞类型在适当水平的营养物和生长因子的存在下同时培养，基本上连续保持在生物反应器（106）中，同时除去不需要的代谢产物。这种多细胞类型的同时培养成功地重建造血组织。任选地，通过转染的基质细胞，特别是异源细胞的排泄提供至少一种生长因子。提供了用于分别维持基质细胞（112）和造血细胞（110）并且允许收集粘附（110,112）和非粘附细胞（114）的装置。

84. 发明申请

WO1993011265A1 METHOD FOR GENERATING CHROMOSOME REGION-SPECIFIC PROBES 审中-公开
标题翻译：用于产生染色体区域特异性探针的方法
公开(公告)号：WO1993011265A1
公开(公告)日：1993-06-10
申请号：PCT/US1992010429
申请日：1992-12-03
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , TRENT, Jeffrey, M. , MELTZER, Paul, S.
IPC分类号： C12Q01/68
CPC分类号： C12N15/1093 , C12Q1/6841 , C12Q1/6853 , C12Q1/6876 , C12Q2600/156 , G01T1/1648 , G21K1/025
摘要： The present invention provides rapid, reproducible procedures for generating chromosome region-specific probes (CRSPs) for diagnostic and research applications. Region-specific probes are provided by direct in vitro enzymatic amplification (PCR) of microdissected chromosomal or hyridized DNA from the chromosomal region of interest, followed by labelling for in situ hybridization to metaphase chromosomes and interphase nuclei. CRSP specificity can be further enhanced using a linker-based strategy, wherein linkered DNA (LDNA) sequences prepared from DNA libraries are hybridized to chromosomal DNA in situ, microdissected from the chromosomal region of interest and then directly amplified using the linker as primer. These procedures make it possible to generate a vast number of chromosome region-specific probes without microchemical manipulation after dissection and provide means for identifying cryptic chromosomal alterations previously not amenable to routine cytogenetic analysis. Probes generated by the methods of the present invention can also be used for screening any DNA library of interest.
摘要翻译：本发明提供用于产生用于诊断和研究应用的染色体区特异性探针（CRSP）的快速，可再现的程序。区域特异性探针通过目的染色体区域的显微切割染色体或杂交DNA的直接体外酶扩增（PCR）提供，然后进行标记用于中期染色体和间期核的原位杂交。可以使用基于接头的策略进一步提高CRSP特异性，其中由DNA文库制备的接头DNA（LDNA）序列原位杂交到染色体DNA，并从感兴趣的染色体区域显微切割，然后使用接头作为引物直接扩增。这些程序使得可以在解剖后产生大量的染色体区域特异性探针而不进行微量化学操作，并提供用于鉴定以前不适合于常规细胞遗传学分析的隐性染色体改变的方法。通过本发明的方法产生的探针也可以用于筛选目的的任何DNA文库。

85. 发明申请

WO1993007265A1 TREATMENT OF CYSTIC FIBROSIS 审中-公开
标题翻译： CYSTIC FIBROSIS的治疗
公开(公告)号：WO1993007265A1
公开(公告)日：1993-04-15
申请号：PCT/US1992008346
申请日：1992-09-30
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , COLLINS, Francis, S. , DRUMM, Mitchell, L. , DAWSON, David, C. , WILKINSON, Daniel, W.
IPC分类号： C12N15/00
CPC分类号： A61K45/06 , A61K38/00 , C07K14/4712
摘要： Cystic fibrosis (CF), a lethal genetic disease associated with a defect in Cl transport, is caused by mutations in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR). Surprisingly, not only wild type CFTR, but several naturally-occurring CFTR mutants carrying a defect in the first nucleotide binding fold (NFB1) all expressed cAMP-activatable Cl currents. Treatment of the CFTR mutants with appropriate concentrations of methylxanthine phosphodiesterase inhibitor (which increases cAMP levels) activated Cl conductance to near wild type levels. The present invention thus provides a new avenue for treating cystic fibrosis by the administration of therapeutically effective amounts of compounds which elevate cAMP levels. Dosage and patient responsiveness to treatment, as well as relative efficacies of the compounds being or to be administered can also be determined in accordance with the methods of present invention.
摘要翻译：囊性纤维化（CF）是与C1转运缺陷相关的致命遗传疾病，由编码囊性纤维化跨膜传导调节因子（CFTR）的基因突变引起。令人惊讶的是，不仅野生型CFTR，而是在第一核苷酸结合折叠（NFB1）中携带缺陷的几种天然存在的CFTR突变体都表达cAMP可激活的Cl电流。用适当浓度的甲基黄嘌呤磷酸二酯酶抑制剂（其增加cAMP水平）处理CFTR突变体将Cl电导活化到接近野生型水平。因此，本发明通过施用治疗有效量的提高cAMP水平的化合物来提供治疗囊性纤维化的新途径。治疗的剂量和患者反应性以及正在或将被给予的化合物的相对功效也可以根据本发明的方法来确定。

86. 发明申请

WO1991012838A1 IMPLANTABLE INFUSION DEVICE 审中-公开
标题翻译：可植入式输液装置
公开(公告)号：WO1991012838A1
公开(公告)日：1991-09-05
申请号：PCT/US1991001414
申请日：1991-03-01
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , ENSMINGER, William, D. , KNOL, James, A. , ANDREWS, James, C.
IPC分类号： A61M05/178
CPC分类号： A61M39/0606 , A61M39/0208 , A61M2039/0211 , A61M2039/062 , A61M2039/0633 , A61M2039/064 , A61M2039/0653 , A61M2039/0666 , A61M2039/0686
摘要： An infusion port (10) for implantation adapted for providing repeated access to specific tissue within a patient and communicating with the tissue by an internal implanted catheter (52). The infusion ports according to this invention incorporate an enlarged entrance orifice (13) with a funnel shaped internal cavity which narrows down to a reduced diameter passageway (18). An articulating catheter valve (24) is provided within the passageway which normally prevents the flow of fluids through the valve but can be penetrated by an external introduced filament (32) such as a catheter. After implantation, an external filament (32) which is introduced into the port (10) is guided by the port internal cavity into registry with the catheter valve (24). Continued feeding of the filament (32) causes the catheter to pass through the valve (24). Thereafter, when a catheter (32) is inserted, therapeutic agents infused within the patient, or body fluids can be withdrawn. Alternate embodiments disclose various valve concepts (56) and means for providing a change in direction of an introduced filament inserted through the infusion device. Additional embodiments disclose the concepts of providing an antimicrobial fluid bath (98) within the device for prevention of infection and various approaches for securely connecting an internal catheter (52) to an infusion port.

87. 发明申请

WO1990006568A1 SILICON TACTILE IMAGING ARRAY AND METHOD OF MAKING SAME 审中-公开
标题翻译：硅手机成像阵列及其制作方法
公开(公告)号：WO1990006568A1
公开(公告)日：1990-06-14
申请号：PCT/US1989005571
申请日：1989-12-08
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , WISE, Kensall, D. , SUZUKI, Kenichiro , NAJAFI, Khalil
IPC分类号： G08C19/10
CPC分类号： B25J13/084 , G01L1/148 , G06F3/044 , G06F2203/04103
摘要： A high-performance single-crystal silicon tactile imaging array (22) organized in a X-Y matrix of capacitor elements. Metallic column lines are formed on a glass support substrate (32), while the row lines (34, RO-R31) are formed from a contiguous chain of doubly-supported bridge structures (70), with one such structure (70) for each sensing element (38). All of the bridge structures are simultaneously fabricated from a single-crystal silicon semiconductor wafer (150) using a two-step boron diffusion process, followed by a silicon-to-glass electrostatic bonding step and subsequent unmasked wafer dissolution. Each bridge structure (70) has a thick center plate (72) for the sense capacitor supported by thinner beams (74, 76) connected to adjacent row single-crystal silicon support rails (78, 80) bonded to the glass substrate (32). The resulting imager (22) is rugged, of high resolution and high density, and is inherently stable over time and temperature.

88. 发明申请

WO1989011491A1 ANTIBODIES TO HUMAN MAMMARY CELL GROWTH INHIBITOR AND METHODS OF PRODUCTION AND USE 审中-公开
标题翻译：人类细胞生长抑制剂的抗体及其生产和使用方法
公开(公告)号：WO1989011491A1
公开(公告)日：1989-11-30
申请号：PCT/US1989002215
申请日：1989-05-22
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , ERVIN, Paul, R., Jr. , WICHA, Max, S. , KAMINSKI, Mark, S. , CODY, Robert, L.
IPC分类号： C07K15/00
CPC分类号： G01N33/57415 , A61K38/00 , C07K14/475 , C07K16/22
摘要： Polyclonal antibody from animal antiserum and monoclonal antibodies produced by hybridoma cell lines bind to a mammary cell specific growth inhibitor secreted by NHMC. When purified by affinity monoclonal antibody chromatography, the inhibitor of the present invention exhibits peaks of activity at about 47,000 and about 63,000-67,000, as measured by SDS-PAGE. The growth inhibitor is present in the sera of normal females, but is absent or present in decreased levels in the sera of normal males and female breast cancer patients. Binding assays of the antibody to the inhibitor can be used to diagnose the presence of breast cancer, to screen for those at high risk breast cancer, and to monitor patient levels of inhibitor in mammary tissue and serum during treatment.
摘要翻译：来自动物抗血清的多克隆抗体和由杂交瘤细胞系产生的单克隆抗体结合到由NHMC分泌的乳腺细胞特异性生长抑制剂。当通过亲和单克隆抗体色谱法纯化时，本发明的抑制剂通过SDS-PAGE测量显示约47,000和约63,000-67,000的活性峰。生长抑制剂存在于正常女性的血清中，但在正常男性和女性乳腺癌患者的血清中不存在或呈现降低的水平。抗体对抑制剂的结合分析可用于诊断乳腺癌的存在，筛选高危乳腺癌患者，并监测治疗期间乳腺组织和血清中的抑制剂水平。

89. 发明申请

WO1998028422A1 RAIDD, A NOVEL CELL DEATH ADAPTOR MOLECULE 审中-公开
标题翻译： RAIDD，一个新的细胞死亡适配器分子
公开(公告)号：WO1998028422A1
公开(公告)日：1998-07-02
申请号：PCT/US1997023548
申请日：1997-12-19
申请人： HUMAN GENOME SCIENCES, INC. , THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： HUMAN GENOME SCIENCES, INC. , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , DIXIT, Vishva, M. , NI, Jian
IPC分类号： C12N15/12
CPC分类号： C12N9/6475 , A61K38/00 , C07K14/7151 , C12N2799/026 , G01N33/5008 , G01N33/68 , G01N2510/00
摘要： The present invention relates to a novel molecule involved in the process of apoptosis. In particular, isolated nucleic acid molecules are provided encoding the human RAIDD protein and splice variants thereof - referred to as RAIDD-SV1 and RAIDD-SV2. RAIDD polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of RAIDD activity.
摘要翻译：本发明涉及参与凋亡过程的新型分子。特别地，提供了分离的核酸分子，其编码人类RAIDD蛋白及其剪接变体 - 称为RAIDD-SV1和RAIDD-SV2。还提供了RAIDD多肽，载体，宿主细胞和用于制备它们的重组方法。本发明还涉及用于鉴定RAIDD活性的激动剂和拮抗剂的筛选方法。

90. 发明申请

WO1998010159A1 OPTIMIZED GEOMETRIES OF FIBER REINFORCEMENTS OF CEMENT, CERAMIC AND POLYMERIC BASED COMPOSITES 审中-公开
标题翻译：水泥，陶瓷和聚合物复合材料纤维增强优化几何
公开(公告)号：WO1998010159A1
公开(公告)日：1998-03-12
申请号：PCT/US1997015434
申请日：1997-09-03
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , NAAMAN, Antoine, E.
IPC分类号： E04C05/01
CPC分类号： C04B35/80 , B29C70/16 , E04C5/012 , E04C5/03 , E04C5/073 , Y10T428/2902 , Y10T428/2907 , Y10T428/2913 , Y10T428/2964 , Y10T428/2967 , Y10T428/2973
摘要： Fibers, continuous or discontinuous, and bars having optimized geometries for use in the reinforcement of cement, ceramic and polymeric based matrices are claimed. The geometries are designed to increase the ratio of surface area available for bond between the fiber and the matrix to the cross-sectional area of fiber. In the case of a continuous reinforcement comprised of a single fiber or a bar made out of a bundle of fibers, such as is the case in reinforced and prestressed concrete, increasing the surface area available for bond leads to a decrease in crack width, development length, and transfer length. The fibers or bars are also configured to be amenable for twisting or to have spiral like deformations along their longitudinal axis to further develop the mechanical component of bond between the fibers and the matrix. Additional methods of mechanical bond enhancement, such as crimping and/or addition of anchorages, such as hooked ends, paddles, buttons, etc., can be applied to the claimed fibers to further improve their bond characteristics.
摘要翻译：声称连续或不连续的纤维和具有优化几何形状的棒用于水泥，陶瓷和聚合物基质的增强。几何形状被设计成增加可用于纤维和基体之间的结合的表面积与纤维的横截面面积的比率。在由纤维束制成的单根纤维或棒制成的连续加固的情况下，例如在增强和预应力混凝土中的情况，增加可用于粘结的表面积导致裂缝宽度的减小，开发长度和传送长度。纤维或条还被构造成适于扭曲或沿其纵向轴线具有螺旋形变形，以进一步发展纤维和基质之间的机械结合部分。附加的机械结合增强方法，例如压接和/或添加锚固件，例如钩形端部，桨叶，钮扣等，可以应用于要求保护的纤维，以进一步改善它们的粘合特性。

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