公开(公告)号：US06303303B1

公开(公告)日：2001-10-16

申请号：US09190756

申请日：1998-11-12

申请人： Ronald J. Green ,  Vrijmoed Chi ,  Rodney D. Gilchrist ,  Gregory Dee ,  John K. Stevens

发明人： Ronald J. Green ,  Vrijmoed Chi ,  Rodney D. Gilchrist ,  Gregory Dee ,  John K. Stevens

IPC分类号： C12Q168

CPC分类号： G01N27/44721 ,  G01N27/44717 ,  G06F19/18 ,  G06F19/22 ,  Y10T436/143333

摘要： Normalization of experimental fragment patterns for nucleic acid polymers having putatively known sequences starts with obtaining at least one raw fragment pattern for the experimental sample. The raw fragment pattern represents the positions of a selected nucleic acid base within the polymer as a function of migration time or distance. This raw fragment pattern is conditioned using conventional baseline correction and noise reduction technique to yield a clean fragment pattern. The clean fragment pattern is then evaluated to determine one or more “normalization coefficients.” These normalization coefficients reflect the displacement, stretching or shrinking, and rate of stretching or shrinking of the clean fragment, or segments thereof, which are necessary to obtain a suitably high degree of correlation between the clean fragment pattern and a standard fragment pattern which represents the positions of the selected nucleic acid base within a standard polymer actually having the known sequence as a function of migration time or distance. The normalization coefficients are then applied to the clean fragment pattern to produce a normalized fragment pattern which is used for base-calling in a conventional manner. This method may be implemented in an apparatus comprising a computer processor programmed to determine normalization coefficients for an experimental fragment pattern. This computer may be separate from the electrophoresis apparatus, or part of an integrated unit.

摘要翻译： 具有推定已知序列的核酸聚合物的实验片段模式的归一化从获得实验样品的至少一个原始片段图案开始。 原始片段图案表示聚合物内所选择的核酸碱基作为迁移时间或距离的函数的位置。 使用常规的基线校正和降噪技术调节该原始片段模式以产生干净的片段模式。 然后评估干净的片段模式以确定一个或多个“归一化系数”。 这些归一化系数反映了清洁片段或其片段的位移，拉伸或缩小以及拉伸或收缩速率，这些片段或片段是清洁片段图案与标示片段图案之间适当高程度的相关性所必需的， 实际上具有已知序列的标准聚合物内所选核酸碱基的位置作为迁移时间或距离的函数。 然后将归一化系数应用于干净的片段模式以产生用于以常规方式的基本呼叫的归一化的片段模式。 该方法可以在包括被编程为确定实验片段模式的归一化系数的计算机处理器的装置中实现。 该计算机可以与电泳装置或集成单元的一部分分开。

公开(公告)号：US6071726A

公开(公告)日：2000-06-06

申请号：US765626

申请日：1996-12-27

申请人： Eleftherios Diamandis ,  James M. Dunn ,  John K. Stevens

发明人： Eleftherios Diamandis ,  James M. Dunn ,  John K. Stevens

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/04 ,  G01N33/53

CPC分类号： C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/6886 ,  C12Q1/686 ,  C12Q1/6869 ,  C12Q2600/16

摘要： Rapid and cost effective diagnosis of p53 mutations of a sample of patients is achieved by employing a selected plurality of diagnostic tools, in a hierarchy of increasing accuracy and cost per tool, in which each tool detects essentially no false positives. Diagnostic tests that may be included among the plurality of tests selected include, in order of increasing accuracy and cost:(a) immunoassays,(b) analysis of DNA from a patient sample by quantitative amplification of p53 exons using amplification primers complementary to intron regions flanking each exon and examination of the length or quantity of each amplified fragment for nucleotide insertions or deletions relative to the normal p53 gene. Preferably, the amplification primers are multiplexed so that more than one DNA fragment is amplified in a single vessel, using sets of primers which provide gene fragments of distinctive lengths when used to amplify a normal p53 gene; and(c) analysis of DNA from a patient sample by DNA sequencing of the p53 gene beginning with the sequencing of those regions most likely to harbor point mutations, and proceeding to sequence regions less likely to harbor point mutations.

摘要翻译： PCT No.PCT / US95 / 08605 Sec。 371日期1996年12月27日第 102（e）日期1996年12月27日PCT提交1995年7月7日PCT公布。 公开号WO96 / 01909 日期1996年1月25日通过使用所选择的多种诊断工具，以提高每个工具的精度和成本的层次结构实现对患者样本的p53突变的快速和成本有效的诊断，其中每个工具基本上不检测到假阳性。 可以包括在所选择的多个测试中的诊断测试包括：提高准确性和成本的顺序：（a）免疫测定，（b）使用与内含子区域互补的扩增引物定量扩增p53外显子来分析来自患者样品的DNA 侧翼于每个外显子，并检查每个扩增片段的长度或数量，用于相对于正常p53基因的核苷酸插入或缺失。 优选地，扩增引物被多重化，使得在单个容器中扩增多于一个DNA片段，使用提供用于扩增正常p53基因的特异长度的基因片段的引物组; 和（c）通过对最可能存在点突变的那些区域的测序开始的p53基因的DNA测序从患者样品中分析DNA，并且进行到不太可能存在点突变的序列区域。

公开(公告)号：US5853979A

公开(公告)日：1998-12-29

申请号：US497202

申请日：1995-06-30

申请人： Ronald J. Green ,  Vrijmoed Chi ,  Rodney D. Gilchrist ,  Gregory Dee ,  John K. Stevens

发明人： Ronald J. Green ,  Vrijmoed Chi ,  Rodney D. Gilchrist ,  Gregory Dee ,  John K. Stevens

IPC分类号： C12Q1/68 ,  G01N27/447 ,  C12Q1/70 ,  G01N33/48 ,  G06K9/00

CPC分类号： G01N27/44721 ,  G01N27/44717 ,  G06F19/18 ,  G06F19/22 ,  Y10T436/143333

摘要： Normalization of experimental fragment patterns for nucleic acid polymers having putatively known sequences starts with obtaining at least one raw fragment pattern for the experimental sample. The raw fragment pattern represents the positions of a selected nucleic acid base within the polymer as a function of migration time or distance. This raw fragment pattern is conditioned using conventional baseline correction and noise reduction technique to yield a clean fragment pattern. The clean fragment pattern is then evaluated to determine one or more "normalization coefficients." These normalization coefficients reflect the displacement, stretching or shrinking, and rate of stretching or shrinking of the clean fragment, or segments thereof, which are necessary to obtain a suitably high degree of correlation between the clean fragment pattern and a standard fragment pattern which represents the positions of the selected nucleic acid base within a standard polymer actually having the known sequence as a function of migration time or distance. The normalization coefficients are then applied to the clean fragment pattern to produce a normalized fragment pattern which is used for base-calling in a conventional manner. This method may be implemented in an apparatus comprising a computer processor programmed to determine normalization coefficients for an experimental fragment pattern. This computer may be separate from the electrophoresis apparatus, or part of an integrated unit.

摘要翻译： 具有推定已知序列的核酸聚合物的实验片段模式的归一化从获得实验样品的至少一个原始片段图案开始。 原始片段图案表示聚合物内所选择的核酸碱基作为迁移时间或距离的函数的位置。 使用常规的基线校正和降噪技术调节该原始片段模式以产生干净的片段模式。 然后评估干净的片段模式以确定一个或多个“归一化系数”。 这些归一化系数反映了清洁片段或其片段的位移，拉伸或缩小以及拉伸或收缩速率，这些片段或片段是清洁片段图案与标示片段图案之间适当高程度的相关性所必需的， 实际上具有已知序列的标准聚合物内所选核酸碱基的位置作为迁移时间或距离的函数。 然后将归一化系数应用于干净的片段模式以产生用于以常规方式的基本呼叫的归一化的片段模式。 该方法可以在包括被编程为确定实验片段模式的归一化系数的计算机处理器的装置中实现。 该计算机可以与电泳装置或集成单元的一部分分开。

公开(公告)号：US5776767A

公开(公告)日：1998-07-07

申请号：US570994

申请日：1995-12-12

申请人： John K. Stevens ,  James M. Dunn ,  Gregory Dee ,  James W. Cassidy

发明人： John K. Stevens ,  James M. Dunn ,  Gregory Dee ,  James W. Cassidy

IPC分类号： G01N27/447 ,  G06F19/00 ,  C12M3/00

CPC分类号： G01N27/44782

摘要： A virtual DNA sequencer combines a plurality of individual DNA sequencers. Samples of DNA or other nucleic acid from subjects are prepared and allocated in real time to particular lanes or sets of lanes in electrophoresis plates of the individual sequencers, with records kept of the allocations. The data resulting from the electrophoresis runs is collected and collated according to the identities of the subjects. The individual sequencers are networked, and each individual sequencer is preferably equipped with a data buffer large enough to accommodate all or substantially all of a data run, thus protecting the virtual sequencer from loss of valuable data in the event that the network is disrupted for some portion of the time of the data run. In this way, a plurality of sequencers is virtually the same as a single sequencer with a very large number of tracks each of which can run for a much longer sequencing run than an individual sequencer.

摘要翻译： 虚拟DNA测序仪组合了多个单独的DNA测序仪。 来自受试者的DNA或其他核酸的样品被制备并实时分配到各个定序器的电泳板中的特定泳道或泳道组，并保存有分配记录。 根据受试者的身份收集和整理电泳运行产生的数据。 各个顺控程序被联网，并且每个单独的定序器优选地配备有足够大的数据缓冲器，以容纳所有或基本上所有的数据运行，从而在网络被中断的情况下保护虚拟定序器免于丢失有价值的数据 部分时间的数据运行。 以这种方式，多个定序器与具有非常大数量的轨道的单个定序器几乎相同，每个轨道可以运行比单个定序器更长的排序运行。

公开(公告)号：US4603495A

公开(公告)日：1986-08-05

申请号：US652040

申请日：1984-09-19

申请人： John K. Stevens

发明人： John K. Stevens

IPC分类号： G06K17/00 ,  G09B23/28 ,  G09F3/04

CPC分类号： G09B23/285 ,  G06K17/0022

摘要： The invention provides an alphanumeric display module of four controllable cells, each constituted by electrically selectable elements that is able to provide significantly increased vocabulary of words considered essential for merchandising, such as "SAVE" and "BUY", displayed in an acceptable unambiguous manner, while requiring less than 40 electric control lines, so that currently available 40 terminal memory storage devices can be employed in a simple and economical control circuit. The first two cells are of conventional "figure 8" configuration, each employing seven controllable elements. The third cell includes an upward right inclined element in its lower half thus, for example, removing ambiguity between "U" and "V", while the fourth cell includes an additional vertical stroke of two separate elements between and parallel to the existing vertical strokes to permit, for example, acceptable display of "T" and "Y" and "W". A selectable decimal period is provided at least between the second and third cells, and another may be provided between the third and fourth cells. A fifth cell can be provided consisting of a percentage sign and a cents sign having an oblique stroke in common. All of the thirty five elements can be controlled using only thirty six control lines, so that four are still available for basic control purposes, i.e., ground, power input, clock input and display backplane. It is also possible to provide the second cell with a downward right inclined element in the upper half to permit display of an unambiguous "N" and consequent display of the word "NEW".

摘要翻译： 本发明提供了四个可控单元的字母数字显示模块，每个可控单元由电可选元件构成，其能够提供显着增加的以可接受的明确方式显示的商品销售所必需的词汇，例如“保存”和“购买” 同时需要少于40个电气控制线，使得当前可用的40个终端存储器件可以用于简单和经济的控制电路中。 前两个电池是常规的“图8”配置，每个电池采用七个可控元件。 第三单元在其下半部包括向上的右倾斜元件，因此例如消除“U”和“V”之间的模糊，而第四单元包括在现有垂直笔画之间并平行于两个独立元件的附加垂直行程 以允许例如可接受地显示“T”和“Y”和“W”。 至少在第二和第三小区之间提供可选择的十进制周期，并且可以在第三和第四小区之间提供另一个小时。 可以提供由百分比符号和具有普通斜行程的分号组成的第五单元。 只能使用三十六条控制线来控制三十五个元件，所以四个仍然可用于基本控制，即接地，电源输入，时钟输入和显示背板。 还可以在第二单元格的上半部分提供向下的右倾斜元件，以允许显示一个明确的“N”并随之显示单词“NEW”。

公开(公告)号：US07902962B2

公开(公告)日：2011-03-08

申请号：US12642388

申请日：2009-12-18

申请人： John K. Stevens ,  Robert J. Griffin ,  Alexander Tkanchenko

发明人： John K. Stevens ,  Robert J. Griffin ,  Alexander Tkanchenko

IPC分类号： H04Q5/22

CPC分类号： H01Q7/00 ,  G06K7/10336 ,  H01Q1/2208

摘要： A cart has at least three wheels. It has one or more loop antennas, and a radio transceiver connected with the antennas. The antennas and transceiver operate at a frequency lower than 1 megahertz. The loop antennas are each at least 0.2 square meters in area. The cart is moved to an area such as a room, and the transceiver communicates with various RF tags in the room. Because of the antenna configuration, the portion of spectrum employed, and the power levels used, the cart is able to communicate with most if not all of the RF tags in the room. The cart can then be moved to another area such as another room, and the process repeated. In this way an inventory of tags can be made without expensive permanently installed infrastructure. The system is robust against interferers such as large metal objects and intervening objects.

摘要翻译： 车子至少有三个轮子。 它具有一个或多个环形天线，以及与天线连接的无线电收发器。 天线和收发器工作频率低于1兆赫兹。 环形天线的面积至少为0.2平方米。 将推车移动到诸如房间的区域，并且收发器与房间中的各种RF标签通信。 由于天线配置，采用的频谱部分和使用的功率电平，车可以与室内的大多数（如果不是全部）RF标签通信。 然后可以将推车移动到另一区域，例如另一房间，并重复该过程。 以这种方式，可以制作标签的库存，而不需要昂贵的永久安装的基础设施。 该系统对于诸如大型金属物体和居间物体的干扰源是强大的。

公开(公告)号：US20100245046A1

公开(公告)日：2010-09-30

申请号：US12642388

申请日：2009-12-18

申请人： John K. Stevens ,  Robert J. Griffin ,  Alexander Tkanchenko

发明人： John K. Stevens ,  Robert J. Griffin ,  Alexander Tkanchenko

IPC分类号： H04Q5/22

CPC分类号： H01Q7/00 ,  G06K7/10336 ,  H01Q1/2208

摘要： A cart has at least three wheels. It has one or more loop antennas, and a radio transceiver connected with the antennas. The antennas and transceiver operate at a frequency lower than 1 megahertz. The loop antennas are each at least 0.2 square meters in area. The cart is moved to an area such as a room, and the transceiver communicates with various RF tags in the room. Because of the antenna configuration, the portion of spectrum employed, and the power levels used, the cart is able to communicate with most if not all of the RF tags in the room. The cart can then be moved to another area such as another room, and the process repeated. In this way an inventory of tags can be made without expensive permanently installed infrastructure. The system is robust against interferers such as large metal objects and intervening objects.

摘要翻译： 车子至少有三个轮子。 它具有一个或多个环形天线，以及与天线连接的无线电收发器。 天线和收发器工作频率低于1兆赫兹。 环形天线的面积至少为0.2平方米。 将推车移动到诸如房间的区域，并且收发器与房间中的各种RF标签通信。 由于天线配置，采用的频谱部分和使用的功率电平，车可以与室内的大多数（如果不是全部）RF标签通信。 然后可以将推车移动到另一区域，例如另一房间，并重复该过程。 以这种方式，可以制作标签的库存，而不需要昂贵的永久安装的基础设施。 该系统对于诸如大型金属物体和居间物体的干扰源是强大的。

公开(公告)号：US06820805B2

公开(公告)日：2004-11-23

申请号：US10297246

申请日：2002-12-03

申请人： John K. Stevens

发明人： John K. Stevens

IPC分类号： G06F1760

CPC分类号： G06Q10/08 ,  G06Q10/087 ,  G07B2017/00209 ,  G07C9/00571 ,  G07F17/0042 ,  G07F17/12

摘要： Openings and closings of a secured storage receptacle (60) are logged to record the transfer of items. The system gains access to a signal-transmitting receptacle; transmits a first confirmation signal to a mobile transmission node (61); processes the first confirmation signal at the mobile transmission node (61); transmits a second confirmation signal to a central server (64); and notifies a consumer of the delivery with an electronic message (66). This process allows the transfer of items by a delivery confirmation signals to be received from the signal-transmitting receptable (60). The signal transmitted from the signal-transmitting receptable (60) is coupled to the opening and closing of the storage box.

摘要翻译： 记录安全存储容器（60）的打开和关闭以记录物品的转移。 系统可以访问信号传输插座; 向移动发送节点（61）发送第一确认信号; 在移动传输节点（61）处理第一确认信号; 向中央服务器（64）发送第二确认信号; 并用电子消息通知消费者交货（66）。 该过程允许通过传送确认信号传送项目以从信号发送接收端（60）接收。 从信号发送接收器（60）发送的信号耦合到存储盒的打开和关闭。

公开(公告)号：US06270963B1

公开(公告)日：2001-08-07

申请号：US08750232

申请日：1996-11-29

申请人： John K. Stevens ,  James M. Dunn ,  Denis Capatos ,  David E. Matthews

发明人： John K. Stevens ,  James M. Dunn ,  Denis Capatos ,  David E. Matthews

IPC分类号： C12Q168

CPC分类号： C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/16

摘要： A hierarchy of at least two assay techniques is utilized in testing for disease-associated mutations. The first assay in the hierarchy is selected to provide a highly specific test for the existence of the disease-associated mutation, although the accuracy of the test need not be high. The final assay in the hierarchy is selected to provide a highly accurate and highly specific test for the existence of the disease associated mutation. Intermediate tests of progressively greater accuracy may also be included in the hierarchy. Once the hierarchy has been selected for a given mutation-associated disease, a patient sample is analyzed the patient sample using the first, lowest accuracy assay in the hierarchy. If the result of the first assay is negative for the presence of a disease-associated mutation, then the next assay in the hierarchy is performed. This process is repeated until the final assay has been performed on all samples which gave negative results when tested by all less-accurate assays in the hierarchy. The test may be used for diagnosis and targeted screening for p53 mutations and mutations in the RB1 gene.

摘要翻译： 使用至少两种测定技术的层次来测试疾病相关突变。 选择层次结构中的第一个测定法为疾病相关突变的存在提供高度特异性的测试，尽管测试的准确性不需要很高。 选择层次结构中的最终测定法为疾病相关突变的存在提供高度准确和高度特异性的检验。 渐进更高精度的中间测试也可能包含在层次结构中。 一旦为给定的突变相关疾病选择了层次结构，则使用层次结构中的第一种最低精度的分析方法对患者样本进行分析。 如果第一次测定的结果对于存在疾病相关突变是阴性的，则进行层次结构中的下一个测定。 重复此过程，直到对所有样品进行最终测定，当通过层次结构中的所有较不准确的测定进行测试时，会产生阴性结果。 该检测可用于诊断和靶向筛选p53突变和RB1基因突变。

公开(公告)号：US5834189A

公开(公告)日：1998-11-10

申请号：US577858

申请日：1995-12-22

申请人： John K. Stevens ,  James M. Dunn ,  James Leushner ,  Ronald J. Green

发明人： John K. Stevens ,  James M. Dunn ,  James Leushner ,  Ronald J. Green

IPC分类号： C12N15/09 ,  C12Q1/68 ,  G01N27/447 ,  C12P19/34

CPC分类号： C12Q1/6858 ,  C12Q1/6869 ,  C12Q1/6881 ,  C12Q1/6883 ,  C12Q1/689 ,  G01N27/44721 ,  C12Q2600/156 ,  C12Q2600/16

摘要： The allelic type of a polymorphic genetic locus in a sample is identified by first combining the sample with a sequencing reaction mixture containing a polymerase, nucleotide feedstocks, one type of chain terminating nucleotide and a sequencing primer to form a plurality of oligonucleotide fragments of differing lengths, and then evaluating the length of the oligonucleotide fragments. As in a standard sequencing procedure, the lengths of the fragments indicate the positions of the type of base corresponding to the chain terminating nucleotide in the extended primer. Instead of performing and evaluating four concurrent reactions, one for each type of chain terminating nucleotide, however, the sample is concurrently combined with at most three, and preferably only one, sequencing reaction mixtures containing different types of chain terminating nucleotides. The information obtained from this test is evaluated prior to performing any additional tests on the sample. In many cases, evaluation of the positions of only a single base using one sequencing reaction will allow for allelic typing of the sample.

摘要翻译： 通过首先将样品与含有聚合酶，核苷酸原料，一种类型的终止核苷酸和测序引物的测序反应混合物合并，形成不同长度的多个寡核苷酸片段，来鉴定样品中多态性遗传位点的等位基因型 ，然后评估寡核苷酸片段的长度。 如在标准测序程序中，片段的长度表示对应于延伸引物中的链终止核苷酸的碱基类型的位置。 然而，代替执行和评估四种并发反应，每种类型的链终止核苷酸一个样品同时与至多三个，优选仅一个含有不同类型的链终止核苷酸的测序反应混合物组合。 在对样品进行任何额外的测试之前，先评估从该测试获得的信息。 在许多情况下，使用一个测序反应评估仅一个碱基的位置将允许样品的等位基因分型。