公开(公告)号：US20070174221A1

公开(公告)日：2007-07-26

申请号：US11623639

申请日：2007-01-16

申请人： Bernhard Sendhoff ,  Yaochu Jin ,  Edward Tsang ,  Qingfu Zhang ,  Aimin Zhou

发明人： Bernhard Sendhoff ,  Yaochu Jin ,  Edward Tsang ,  Qingfu Zhang ,  Aimin Zhou

IPC分类号： G06F15/18

CPC分类号： G06N3/126 ,  G06F2217/08

摘要： A system and method for combining the model-based and genetics-based methods are combined according to a convergence criterion. When the population is not converged, the genetics-based approach is used, and when the population is converged, the model-based method is used to generate offspring. The algorithm benefits from using a model-based offspring generation only when the population shows a certain degree of regularity, i.e., converged in a stochastic sense. In addition, a more sophisticated method to construct the stochastic part of the model can be used. Also a biased Gaussian noise (the mean of the noise is not zero), as well as a white Gaussian noise (the mean of the noise is zero) can be preferably used for the stochastic part of the model.

摘要翻译： 将基于模型和基于遗传学的方法组合的系统和方法根据收敛标准进行组合。 当人口不融合时，使用基于遗传学的方法，当人口聚合时，使用基于模型的方法来产生后代。 只有当人口显示一定程度的规律性，即以随机意义收敛时，该算法才有益于使用基于模型的后代。 此外，可以使用更复杂的构建模型的随机部分的方法。 偏置的高斯噪声（噪声的平均值也不是零），以及白高斯噪声（噪声的平均值为零）也可以优选地用于模型的随机部分。

公开(公告)号：US5972678A

公开(公告)日：1999-10-26

申请号：US479895

申请日：1995-06-07

申请人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

发明人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

IPC分类号： C12N9/22 ,  C12N15/55

CPC分类号： C12N9/22

摘要： Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide. Analysis of aligned murine and human 2-5A-dependent RNase sequences revealed several features, including similarity to RNase E which is implicated in the control of mRNA stability in E. coli. A duplicated phosphate-binding loop motif is determined by deletion analysis and site-directed mutagenesis to function in the binding of 2-5A.

摘要翻译： 分离的2-5A依赖性核糖核酸酶，由5'-磷酸化，2'，5'-连接的寡聚腺苷酸（2-5A）活化的干扰素诱导的酶，并且涉及干扰素作用和基本控制的分子机制 公开了哺乳动物细胞中RNA稳定性及其编码序列。 还公开了克隆和分析鼠和人2-5A依赖性核糖核酸酶的表达。 在体外产生的重组人2-5A依赖性核糖核酸酶结合激活亲和基质2-5A-纤维素，导致核糖核酸酶活性。 2-5A依赖性核糖核酸酶的重组和天然存在形式的2-5A结合特性基本相同。 通过测量用干扰素和放线菌酮处理的细胞中的mRNA水平来证明干扰素诱导2-5A依赖性RNA酶表达。 分析对齐的鼠和人2-5A依赖性核糖核酸酶序列揭示了几个特征，包括与核糖核酸酶E的相似性，其涉及大肠杆菌中mRNA稳定性的控制。 通过缺失分析和定点诱变来确定复制的磷酸结合环基序在2-5A的结合中起作用。

公开(公告)号：US5877019A

公开(公告)日：1999-03-02

申请号：US701005

申请日：1996-08-21

申请人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

发明人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

IPC分类号： C12N9/22 ,  C12N5/16

CPC分类号： C12N9/22

摘要： 2-5A-dependent RNase, an endoribonuclease that requires 5'-phosphorylated 2',5'-linked oligoadenylates (2-5A), functions in the molecular mechanism of interferon action. Recombinant, 2-5A-dependent RNase was expressed to high levels (at least 10% of the soluble protein) in insect cells by infecting with baculovirus containing human cDNA to 2-5A-dependent RNase. In contrast, there was no 2-5A-dependent RNase present in control insect cells infected with nonrecombinant baculovirus. The purified, recombinant enzyme eluted from a gel-filtration column as a monomer that showed potent and highly specific, 2-5A-dependent RNase activity. Precise activitor requirements were determined using the purified enzyme of a variety of 2',5'-linked oligonucleotides. The activated enzyme was capable of cleaving both poly(rU) and, to a lesser extent, poly(rA) but not poly(rC), poly(rG), or poly(dT. Interestingly, poly(rU) was cleaved to a series of discrete products ranging between 5 and 22 nucleotides in length. Furthermore, whereas manganese and magnesium stimulated 2-5A-dependent RNase activity, the enzyme was capable of cleaving RNA in the absence of divalent cations.

摘要翻译： 2-5A依赖性核糖核酸酶，需要5'磷酸化2'，5'-连接的寡聚腺苷酸（2-5A）的内切核糖核酸酶，在干扰素作用的分子机制中起作用。 通过将含有人cDNA的杆状病毒感染至2-5A依赖性核糖核酸酶，将重组的2-5A依赖性核糖核酸酶表达为昆虫细胞中的高水平（至少10％的可溶性蛋白质）。 相反，在非重组杆状病毒感染的对照昆虫细胞中不存在2-5A依赖的核糖核酸酶。 纯化的重组酶以凝胶过滤柱作为单体洗脱，其显示出有效和高度特异性的2-5A依赖性核糖核酸酶活性。 使用各种2'，5'-连接的寡核苷酸的纯化酶确定精确的活化剂要求。 活化的酶能够切割聚（rU），并且在较小程度上能够切割聚（rA）而不是聚（rC），聚（rG）或聚（dT）。有趣的是，聚（rU）被切割成 一系列离散产品的长度为5至22个核苷酸，此外，锰和镁刺激了2-5A依赖性核糖核酸酶活性，但该酶能够在不存在二价阳离子的情况下切割RNA。

公开(公告)号：US5840577A

公开(公告)日：1998-11-24

申请号：US462481

申请日：1995-06-05

申请人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

发明人： Robert H. Silverman ,  Bret A. Hassel ,  Aimin Zhou

IPC分类号： C12N9/22 ,  C12N15/55 ,  C12N5/00

CPC分类号： C12N9/22

摘要： Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide. Analysis of aligned murine and human 2-5A-dependent RNase sequences revealed several features, including similarity to RNase E which is implicated in the control of mRNA stability in E. coli. A duplicated phosphate-binding loop motif is determined by deletion analysis and site-directed mutagenesis to function in the binding of 2-5A.

摘要翻译： 分离的2-5A依赖性核糖核酸酶，由5'-磷酸化，2'，5'-连接的寡聚腺苷酸（2-5A）活化的干扰素诱导的酶，并且涉及干扰素作用和基本控制的分子机制 公开了哺乳动物细胞中RNA稳定性及其编码序列。 还公开了克隆和分析鼠和人2-5A依赖性核糖核酸酶的表达。 在体外产生的重组人2-5A依赖性核糖核酸酶结合激活亲和基质2-5A-纤维素，导致核糖核酸酶活性。 2-5A依赖性核糖核酸酶的重组和天然存在形式的2-5A结合特性基本相同。 通过测量用干扰素和放线菌酮处理的细胞中的mRNA水平来证明干扰素诱导2-5A依赖性RNA酶表达。 分析对齐的鼠和人2-5A依赖性核糖核酸酶序列揭示了几个特征，包括与核糖核酸酶E的相似性，其涉及大肠杆菌中mRNA稳定性的控制。 通过缺失分析和定点诱变来确定复制的磷酸结合环基序在2-5A的结合中起作用。

公开(公告)号：US08802895B2

公开(公告)日：2014-08-12

申请号：US12906315

申请日：2010-10-18

申请人： Bin Su ,  Aimin Zhou ,  Yan Xu

发明人： Bin Su ,  Aimin Zhou ,  Yan Xu

IPC分类号： C07C303/00

CPC分类号： C07C311/08 ,  C07C2601/08 ,  C07D261/18 ,  C07D307/68 ,  C07D317/60 ,  C07D333/38

摘要： The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), Ra is a benzyl group with alkyl and/or alkoxy; Rb is selected from H and alkyl groups; Rf is an alkyl; and R3 is selected from a substituted phenyl, a heterocyclic group, and wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group.

摘要翻译： 本发明提供式（I）化合物，其药物组合物，制备用于治疗癌症的药物的方法和治疗癌症的方法。 本发明表现出对癌症的优点，例如在更广泛的癌症上显着更高的效力和有效性。 在式（I）中，R a为具有烷基和/或烷氧基的苄基; Rb选自H和烷基; Rf是烷基; 并且R 3选自取代的苯基，杂环基，并且其中R c选自稠环，稠环和任何二价环状基团。

公开(公告)号：US07739206B2

公开(公告)日：2010-06-15

申请号：US11623639

申请日：2007-01-16

申请人： Bernhard Sendhoff ,  Yaochu Jin ,  Edward Tsang ,  Qingfu Zhang ,  Aimin Zhou

发明人： Bernhard Sendhoff ,  Yaochu Jin ,  Edward Tsang ,  Qingfu Zhang ,  Aimin Zhou

IPC分类号： G06F15/18 ,  G06N3/00 ,  G06N3/12

CPC分类号： G06N3/126 ,  G06F2217/08

摘要： A system and method for combining the model-based and genetics-based methods are combined according to a convergence criterion. When the population is not converged, the genetics-based approach is used, and when the population is converged, the model-based method is used to generate offspring. The algorithm benefits from using a model-based offspring generation only when the population shows a certain degree of regularity, i.e., converged in a stochastic sense. In addition, a more sophisticated method to construct the stochastic part of the model can be used. Also a biased Gaussian noise (the mean of the noise is not zero), as well as a white Gaussian noise (the mean of the noise is zero) can be preferably used for the stochastic part of the model.

摘要翻译： 将基于模型和基于遗传学的方法组合的系统和方法根据收敛标准进行组合。 当人口不融合时，使用基于遗传学的方法，当人口聚合时，使用基于模型的方法来产生后代。 只有当人口显示一定程度的规律性，即以随机意义收敛时，该算法才有益于使用基于模型的后代。 此外，可以使用更复杂的构建模型的随机部分的方法。 偏置的高斯噪声（噪声的平均值也不是零），以及白高斯噪声（噪声的平均值为零）也可以优选地用于模型的随机部分。

公开(公告)号：US6028243A

公开(公告)日：2000-02-22

申请号：US943956

申请日：1997-10-03

申请人： Robert H. Silverman ,  Aimin Zhou

发明人： Robert H. Silverman ,  Aimin Zhou

IPC分类号： C12N9/22 ,  C12N15/85 ,  C12N15/11 ,  A01K67/00 ,  G01N33/00

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  C12N9/22 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  C12N2517/02

摘要： The present invention provides a mutant, non-human mammal, particularly a mutant mouse, having a homozygous disruption in the RNase L gene thereof. Since the homozygous disruption in the RNase L gene leads to minimal if any production of RNase L in the mutant mammals, such mutant mammals are useful for assessing the effect of antiviral drugs on the induction, synthesis, or activation of RNase L. The present invention also relates to mutant, non-human, embryonic stem cell lines having a heterozygous disruption of the RNase L gene thereof, to isolated mammalian cells having a homozygous disruption in the RNase L gene thereof, and to a DNA construct comprising a DNA sequence of a disrupted coding exon of a RNase L gene.

摘要翻译： 本发明提供了在其RNase L基因中具有纯合破坏的突变型非人哺乳动物，特别是突变型小鼠。 由于RNase L基因中的纯合性破坏导致突变哺乳动物中RNA酶L的任何产生都是最小的，所以这种突变的哺乳动物可用于评估抗病毒药物对RNA酶L的诱导，合成或活化的影响。本发明 还涉及其具有RNase L基因的杂合破坏的突变体，非人胚胎干细胞系与其在RNA酶L基因中具有纯合破裂的分离的哺乳动物细胞，以及包含DNA序列的DNA构建体 核糖核酸酶L基因的破坏编码外显子。

公开(公告)号：US20130102011A1

公开(公告)日：2013-04-25

申请号：US13618005

申请日：2012-09-14

申请人： Aimin Zhou ,  Hongli Liu ,  Chun Zeng

发明人： Aimin Zhou ,  Hongli Liu ,  Chun Zeng

IPC分类号： G01N33/68

CPC分类号： G01N33/6893 ,  G01N33/57438 ,  G01N33/57488 ,  G01N2333/948 ,  G01N2800/50

摘要： Diagnostic tests for characterizing a test subject's risk of developing or having cancer, based on determining the level of LRG1 and/or CD13 in a bodily sample obtained from a test subject are described. Levels of LRG1 and/or CD13 are then compared to a predetermined value that is derived from measurements of the levels of LRG1 and/or CD13 in comparable bodily samples obtained from control subjects. Such comparison characterizes the test subject's risk of developing or having cancer.

摘要翻译： 描述了基于确定从测试对象获得的身体样品中的LRG1和/或CD13的水平来表征测试对象发展或患有癌症的风险的诊断测试。 然后将LRG1和/或CD13的水平与从对照受试者获得的可比较的身体样品中的LRG1和/或CD13的水平的测量结果中得出的预定值进行比较。 这种比较表征了测试对象发展或患癌症的风险。

公开(公告)号：US20120095092A1

公开(公告)日：2012-04-19

申请号：US12906315

申请日：2010-10-18

申请人： Bin Su ,  Aimin Zhou ,  Yan Xu

发明人： Bin Su ,  Aimin Zhou ,  Yan Xu

IPC分类号： A61K31/357 ,  C07C311/08 ,  A61K31/18 ,  C07D317/46 ,  A61P35/00 ,  A61P35/02

CPC分类号： C07C311/08 ,  C07C2601/08 ,  C07D261/18 ,  C07D307/68 ,  C07D317/60 ,  C07D333/38

摘要： The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), Ra is a benzyl group with alkyl and/or alkoxy; Rb is selected from H and alkyl groups; Rf is an alkyl; and R3 is selected from a substituted phenyl, a heterocyclic group, and wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group.

摘要翻译： 本发明提供式（I）化合物，其药物组合物，制备用于治疗癌症的药物的方法和治疗癌症的方法。 本发明表现出对癌症的优点，例如在更广泛的癌症上显着更高的效力和有效性。 在式（I）中，R a为具有烷基和/或烷氧基的苄基; Rb选自H和烷基; Rf是烷基; 并且R 3选自取代的苯基，杂环基，并且其中R c选自稠环，稠环和任何二价环状基团。

公开(公告)号：US06762038B1

公开(公告)日：2004-07-13

申请号：US09393028

申请日：1999-09-09

申请人： Robert H. Silverman ,  Bryan R. G. Williams ,  Fulvia Terenzi ,  Aimin Zhou ,  Sandy Der

发明人： Robert H. Silverman ,  Bryan R. G. Williams ,  Fulvia Terenzi ,  Aimin Zhou ,  Sandy Der

IPC分类号： C12P2106

CPC分类号： C07K14/005 ,  C12N2710/10322 ,  C12P21/02

摘要： Mammalian somatic cells having a homozygous disruption in the gene which encodes the endonbonuclease RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase PKR are provided. Methods for producing enhanced levels of recombinant proteins in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption in the PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein. In another aspect the methods employ mutant cells hating a homozygous disruption in the PKR gene, i.e. PKR null cells.

摘要翻译： 提供了在编码内切核糖核酸酶RNA酶L的基因中具有纯合破坏并编码编码双链RNA依赖性激酶PKR的基因中的均匀中断的哺乳动物体细胞。 还提供了在哺乳动物细胞系统中产生增强水平的重组蛋白的方法。 在一个方面，该方法使用在RNase L基因中具有纯合破坏的细胞和PKR基因中的纯合破坏，并且包括用编码所需外源蛋白质的核酸或多核苷酸转染细胞; 在细胞中表达外源蛋白; 并从转染的细胞中分离外源蛋白。 在另一方面，该方法使用用编码所需外源蛋白的核酸转染的RNase L无效细胞。 在另一方面，所述方法使用突变细胞，其憎恨PKR基因中的纯合破坏，即PKR无效细胞。