公开(公告)号：US5134701A

公开(公告)日：1992-07-28

申请号：US310153

申请日：1989-02-10

Applicant: David C. Mueller ,  Steven R. Williams ,  Nabil M. Abu-Jbara

Inventor： David C. Mueller ,  Steven R. Williams ,  Nabil M. Abu-Jbara

IPC: G06F11/28 ,  G06F9/38 ,  G06F11/34 ,  G06F11/36

CPC classification number: G06F11/3636 ,  G06F11/348 ,  G06F11/3644 ,  G06F11/3652

Abstract: The test apparatus for monitoring the operation of a processor that has multiple instruction fetch capability monitors the instruction memory to record the sequence of program instructions that are retrieved by the processor from program memory. The test apparatus determines when a jump operation is executed and determines the target of the jump oepration by inserting a break point instruction in place of one of the two program instructions that is retrieved by the processor from program memory. This instruction substitution is accomplished by an instruction jamming circuit that forces the break point instruction onto the processor data bus as part of the program instruction fetch cycle in lieu of one of the instruction retrieved as part of the execution of the jump instruction. If the break point operation is executed, then the target address of the jump operation is the address location that contains the break point instruction that was substituted for one of the program instructions retrieved from the instruction memory. In this case, the test apparatus responds to the execution of the break point instruction by replacing the program instruction originally retrieved from program memory and substituted for by the break point instruction. Thus, the break point instruction acts as a flag to indicate that this address is the target address of the jump instruction. If the break point instruction is not executed by the processor, it is because the jump instruction target address is the location that contains the other retrieved program instruction.

Abstract translation: 用于监视具有多个指令获取能力的处理器的操作的测试装置监视指令存储器以记录由处理器从程序存储器检索的程序指令序列。 测试装置确定何时执行跳转操作并且通过插入断点指令来代替由处理器从程序存储器中检索的两个程序指令中的一个程序指令来确定跳转检测的目标。 该指令替换由指令干扰电路实现，该指令干扰电路将断点指令强制到处理器数据总线上，作为程序指令获取周期的一部分，代替作为跳转指令的执行的一部分检索的指令之一。 如果执行断点操作，则跳转操作的目标地址是包含用于替换从指令存储器检索的程序指令之一的断点指令的地址位置。 在这种情况下，测试装置通过替换原来从程序存储器检索并由断点指令代替的程序指令来响应中断点指令的执行。 因此，断点指令用作标志以指示该地址是跳转指令的目标地址。 如果处理器不执行断点指令，则是因为跳转指令目标地址是包含其他检索到的程序指令的位置。

公开(公告)号：US07732586B2

公开(公告)日：2010-06-08

申请号：US11748432

申请日：2007-05-14

Applicant: David W. Martin, Jr. ,  Andrew C. Jamieson ,  Dean M. Scholl ,  Steven R. Williams

Inventor： David W. Martin, Jr. ,  Andrew C. Jamieson ,  Dean M. Scholl ,  Steven R. Williams

IPC: C07H21/04 ,  C12P21/04

CPC classification number: C07K14/21 ,  C07K2319/35 ,  C07K2319/74

Abstract: Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of Pseudomonas aeruginosa, are disclosed. The bacteriocins are modified at the ends of their tail fibers in a region responsible for binding specificity and affinity to their cognate binding partners, or receptors, such as those on the surface of bacteria. Methods for the use of the modified bacteriocins, such as to bind receptors, including virulence or fitness factors, on the surfaces of bacteria, are also described.

Abstract translation: 公开了天然存在的细菌素的修饰形式，例如铜绿假单胞菌的R型py虫。 细菌素在其尾纤维的末端被修饰，负责对其同源结合配偶体或受体（例如细菌表面上的那些）的结合特异性和亲和力。 还描述了在细菌表面上使用修饰的细菌素，例如结合受体（包括毒力或适应因子）的方法。

公开(公告)号：US07700729B2

公开(公告)日：2010-04-20

申请号：US11929867

申请日：2007-10-30

Applicant: Dean M. Scholl ,  Steven R. Williams

Inventor： Dean M. Scholl ,  Steven R. Williams

IPC: C07K14/00 ,  C12P21/04

CPC classification number: C07K14/21 ,  C07K2319/35 ,  C07K2319/74

Abstract: Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of Pseudomonas aeruginosa, are disclosed as are methods for producing them in GRAS organisms. The bacteriocins are modified at the ends of their tail fibers in a region responsible for binding specificity and affinity to their cognate binding partners, or receptors, such as those on the surface of bacteria. Methods for the use of the modified bacteriocins, such as to bind receptors, including virulence or fitness factors, on the surfaces of bacteria, are also described.

Abstract translation: 公开了天然存在的细菌素的修饰形式，例如绿脓假单胞菌的R型py霉素，作为在GRAS生物体中生产它们的方法。 细菌素在其尾纤维的末端被修饰，负责对其同源结合配偶体或受体（例如细菌表面上的那些）的结合特异性和亲和力。 还描述了在细菌表面上使用修饰的细菌素，例如结合受体（包括毒力或健康因子）的方法。

公开(公告)号：US08673291B2

公开(公告)日：2014-03-18

申请号：US13117467

申请日：2011-05-27

Applicant: Dean M. Scholl ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, Jr.

Inventor： Dean M. Scholl ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, Jr.

IPC: C12N1/20 ,  C12N7/00 ,  C07H21/00 ,  C07K14/00

CPC classification number: C07K14/33

Abstract: This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous human pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous producer cells that, unlike C. difficile, do not die in the presence of oxygen. Disclosed also is the specific gene of the isolated gene cluster that determines the killing spectrum of the R-type bacteriocin and the demonstration that the killing spectra of diffocins can be altered by engineering orf1374 of the diffocin genetic locus. This invention offers a potent bactericidal agent and a means to make it in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.

Abstract translation: 本公开涉及发现和分离编码特异性杀伤艰难梭菌（Clostridium difficile bacteria），危险人类病原体的R型高分子量细菌素的整个基因簇。 还公开了在无害生物细胞中生产R型细菌素的方法，其与艰难梭菌不同，不在氧的存在下死亡。 还公开了分离的基因簇的特异性基因，其确定了R型细菌素的杀伤谱，并且证明了可以通过工程化的diffocin遗传基因座的orf1374改变diffocins的杀伤谱。 本发明提供了一种有效的杀菌剂和一种使其成为在肠胃环境中选择性杀死艰难梭菌的细菌的手段，在这些细菌中它们可能会对受感染的病人或农场动物造成极大的伤害甚至死亡。

公开(公告)号：US08473478B2

公开(公告)日：2013-06-25

申请号：US09957459

申请日：2001-09-21

Applicant: Warren Roach ,  Steven R. Williams ,  Troy J. Reiber ,  Steven C. Burdine

Inventor： Warren Roach ,  Steven R. Williams ,  Troy J. Reiber ,  Steven C. Burdine

IPC: G06F17/30

CPC classification number: G06F17/30073 ,  G06F11/1461 ,  G06F17/30067 ,  G06F17/30917

Abstract: A method for archiving files includes determining when a change in an operating file is imminent, capturing the operating file immediately before the change in the operating file occurs, if the operating file has not already been captured; and capturing the operating file immediately after the change in the operating file has occurred.

公开(公告)号：US20110293566A1

公开(公告)日：2011-12-01

申请号：US13117467

申请日：2011-05-27

Applicant: Dean M. SCHOLL ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, JR.

Inventor： Dean M. SCHOLL ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, JR.

IPC: A61K38/16 ,  C07K14/33 ,  C12P21/02 ,  A61K35/00 ,  C12N15/74 ,  C12N1/21 ,  C07H21/04 ,  A61P31/04

CPC classification number: C07K14/33

Abstract: This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous human pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous producer cells that, unlike C. difficile, do not die in the presence of oxygen. Disclosed also is the specific gene of the isolated gene cluster that determines the killing spectrum of the R-type bacteriocin and the demonstration that the killing spectra of diffocins can be altered by engineering orf1374 of the diffocin genetic locus. This invention offers a potent bactericidal agent and a means to make it in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.

Abstract translation: 本公开涉及发现和分离编码特异性杀伤艰难梭菌（Clostridium difficile bacteria），危险人类病原体的R型高分子量细菌素的整个基因簇。 还公开了在无害生物细胞中生产R型细菌素的方法，其与艰难梭菌不同，不在氧的存在下死亡。 还公开了分离的基因簇的特异性基因，其确定了R型细菌素的杀伤谱，并且证明了可以通过工程化的diffocin遗传基因座的orf1374改变diffocins的杀伤谱。 本发明提供了一种有效的杀菌剂和一种使其成为在肠胃环境中选择性杀死艰难梭菌的细菌的手段，在这些细菌中它们可能会对受感染的病人或农场动物造成极大的伤害甚至死亡。

公开(公告)号：US20110183893A1

公开(公告)日：2011-07-28

申请号：US12982827

申请日：2010-12-30

Applicant: David W. MARTIN, JR. ,  Steven R. Williams

Inventor： David W. MARTIN, JR. ,  Steven R. Williams

IPC: A61K38/17 ,  C07K14/435 ,  C07K16/46 ,  C40B40/10 ,  C07H21/04 ,  A61P31/12 ,  A61P35/00

CPC classification number: C07K14/70539 ,  A61K38/1774 ,  C07K2319/33 ,  Y02A50/389 ,  Y02A50/393

Abstract: This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their α1-α2 platform domain, to the intended target cell specifically. The α1-α2 domain is contiguous with a heterologous α3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the α3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified α3 domain of a MIC protein.

Abstract translation: 本发明描述了通过连接单价MICA或MICB蛋白（即它们的α1-α2平台结构域）的NKG2D结合部分可以激活NK细胞和某些T细胞以攻击特异性细胞靶细胞的可溶性，一价，非天然蛋白质分子， 具体到目的细胞。 α1-α2结构域与已经被遗传修饰的异源α3结构域连续，直接或间接地结合到靶细胞的细胞外方面，从而作为靶向结构域。 在α3结构域内产生非天然和非末端靶向基序的遗传修饰可以包括MIC蛋白质的一部分抗体，另一蛋白质分子或其部分，肽或非天然修饰的α3结构域 。

公开(公告)号：US5574205A

公开(公告)日：1996-11-12

申请号：US175469

申请日：1993-12-30

Applicant: Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona L. A. De Rafael

Inventor： Raju Kucherlapati ,  Beverly H. Koller ,  Oliver Smithies ,  Robert B. Dubridge ,  Gary Greenburg ,  Daniel J. Capon ,  Steven R. Williams ,  Mariona L. A. De Rafael

IPC: A01K67/027 ,  A61K35/12 ,  A61K38/21 ,  A61K45/00 ,  C07H21/04 ,  C07K14/74 ,  C12N5/02 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/85 ,  C12Q1/68 ,  G01N33/53 ,  A61K48/00 ,  A61K49/00 ,  C12N5/00

CPC classification number: A01K67/0271 ,  A01K67/0275 ,  A01K67/0276 ,  C07K14/70539 ,  C12N15/00 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/025 ,  A01K2267/03 ,  A01K2267/0381

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract translation: 同源重组用于灭活基因，特别是与MHC抗原相关的基因。 特别地，每个β2-微球蛋白基因和IFN-γR基因被灭活以减少或消除功能性MHC抗原的表达。 所得细胞可用作通用供体细胞。 此外，胚胎干细胞可以通过同源重组来修饰，用于产生嵌合或转基因哺乳动物宿主，其可以用作通用供体器官的来源，或作为药物和移植疗法的模型。 还描述了在非转化的哺乳动物体细胞中同源重组的方法。