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    ENHANCED PROMOTERS FOR SYNTHESIS OF SMALL HAIRPIN RNA
    1.
    发明申请
    ENHANCED PROMOTERS FOR SYNTHESIS OF SMALL HAIRPIN RNA 审中-公开
    用于合成小毛发RNA的增强促进剂

    公开(公告)号：WO2005007875A3

    公开(公告)日：2008-04-10

    申请号：PCT/US2004023215

    申请日：2004-07-19

    Applicant: UNIV MASSACHUSETTS ,  XU ZUOSHANG ,  XIA XUGANG

    Inventor： XU ZUOSHANG ,  XIA XUGANG

    IPC: A61K31/70 ,  C07H21/02 ,  C07H21/04 ,  C12N5/00 ,  C12N9/22 ,  C12N15/11 ,  C12Q20060101 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

    CPC classification number: C12N15/111 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2330/30

    Abstract: The present invention provides compositions for RNA interference and methods of use thereof. In particular, the invention provides small hairpin RNAs (shRNAs) having modified promoters, including the Pol III U6 promoter, which may be used to increase the potency of shRNA by increasing the expression level. Modifications include constructs with a Pol II enhancer, such as the cytomegalovirus (CMV) enhancer, immediate-early promoter near the Pol III, e.g., U6 promoter, either upstream or downstream from the shRNA sequence and in either forward or backward orientation. Such constructs are useful for increasing the expression of the shRNA, thereby enhancing inhibition of a single nucleotide mismatched mutant allele. Functional and genomic and proteomic methods are featured. Therapeutic methods are also featured.

    Abstract translation: 本发明提供了用于RNA干扰的组合物及其使用方法。 特别地，本发明提供具有修饰的启动子的小发夹RNA（shRNA），其包括Pol III U6启动子，其可用于通过增加表达水平来增加shRNA的效力。 修饰包括具有Pol II增强子的构建体，例如巨细胞病毒（CMV）增强子，在Pol III附近的即时早期启动子，例如U6启动子，位于shRNA序列的上游或下游以及向前或向后的方向。 这种构建体可用于增加shRNA的表达，从而增强对单核苷酸错配突变体等位基因的抑制。 功能和基因组和蛋白质组学方法。 还介绍了治疗方法。

    NUCLEIC ACID HYBRIDIZATION METHODS
    5.
    发明申请
    NUCLEIC ACID HYBRIDIZATION METHODS 审中-公开
    核酸混合方法

    公开(公告)号：WO2005049848A3

    公开(公告)日：2007-06-14

    申请号：PCT/US2004037472

    申请日：2004-11-10

    Applicant: GENEOHM SCIENCES INC ,  CROTHERS DONALD M

    Inventor： CROTHERS DONALD M

    IPC: C12Q1/68 ,  C07H21/04 ,  C12P19/34 ,  C12Q20060101

    CPC classification number: C12Q1/6837 ,  C12Q2565/543 ,  C12Q2531/125 ,  C12Q2521/531

    Abstract: Disclosed herein are methods of destabilizing double-stranded nucleic acid hybridization using an enzyme comprising DNA N-glycosylase activity. Also disclosed herein is the detection of a double-stranded target DNA wherein the hybridization of duplex strands has been at least partially disrupted thereby permitting invasion of a probe strand. Also disclosed herein are methods of using an enzyme comprising DNA N-glycosylase activity to generate single-stranded circular nucleic acids.

    Abstract translation: 本文公开了使用包含DNA N-糖基化酶活性的酶使双链核酸杂交失稳的方法。 本文还公开了双链靶DNA的检测，其中双链体的杂交已被至少部分地破坏从而允许侵入探针链。 本文还公开了使用包含DNA N-糖基化酶活性的酶以产生单链环状核酸的方法。

    METHODS FOR IDENTIFYING A PATIENT AS A CANDIDATE FOR TREATMENT WITH A LONG ACTING BETA AGONIST AND FOR PREDICTING A PATIENT'S RESPONSE TO LONG ACTING BETA2 AGONIST THERAPY BY ANALYSING POLYMORPHISMS IN THE BETA2-ADRENERGIC RECEPTOR GENE
    7.
    发明申请
    METHODS FOR IDENTIFYING A PATIENT AS A CANDIDATE FOR TREATMENT WITH A LONG ACTING BETA AGONIST AND FOR PREDICTING A PATIENT'S RESPONSE TO LONG ACTING BETA2 AGONIST THERAPY BY ANALYSING POLYMORPHISMS IN THE BETA2-ADRENERGIC RECEPTOR GENE 审中-公开
    用于将患者鉴定为用于治疗长期作用的激动剂的候选药物的方法，以及通过分析BETA2-二倍体受体基因中的多态性来预测患者对长期治疗BETA2激动剂治疗的反应的方法

    公开(公告)号：WO2006031181A8

    公开(公告)日：2007-03-01

    申请号：PCT/SE2005001317

    申请日：2005-09-12

    Applicant: ASTRAZENECA AB ,  AMBROSE HELEN JEAN ,  GOLDMAN MITCHELL JOEL

    Inventor： AMBROSE HELEN JEAN ,  GOLDMAN MITCHELL JOEL

    IPC: C12Q1/68 ,  C07K14/705 ,  C12Q20060101

    CPC classification number: C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/172

    Abstract: The invention relates to a method for identifying a patient as a candidate for treatment with a long acting beta agonist comprises isolating a biological sample from a patient and identifying the presence or absence of at least one haplotype C in the beta2 -adrenergic receptor gene. The presence of at least one haplotype C in a patient sample indicates that patient is a good candidate for treatment. For example, the patient may have a respiratory disease, preferably an obstructive airway disease, and most preferably, COPD or asthma. The invention also related to a method for predicting an asthma patient's response to long acting beta2 agonist therapy comprising detecting polymorphisms in the beta2-adrenergic receptor gene.

    Abstract translation: 本发明涉及用于鉴定患者作为用长效β激动剂治疗的候选物的方法，包括从患者中分离生物样品并鉴定β2-肾上腺素能受体基因中至少一个单体型C的存在或不存在。 在患者样品中存在至少一个单体型C表明患者是治疗的良好候选者。 例如，患者可能具有呼吸系统疾病，优选阻塞性气道疾病，最优选COPD或哮喘。 本发明还涉及预测哮喘患者对长效β2激动剂治疗的反应的方法，包括检测β2-肾上腺素能受体基因中的多态性。

    TERMINAL-PHOSPHATE-LABELED NUCLEOTIDES AND METHODS OF USE
    8.
    发明申请
    TERMINAL-PHOSPHATE-LABELED NUCLEOTIDES AND METHODS OF USE 审中-公开
    终端磷酸酯标记的核苷酸和使用方法

    公开(公告)号：WO2004072297A3

    公开(公告)日：2007-01-18

    申请号：PCT/US2004002785

    申请日：2004-01-30

    Applicant: AMERSHAM BIOSCIENCES CORP ,  FULLER CARL ,  KUMAR SHIV ,  SOOD ANUP ,  NELSON JOHN

    Inventor： FULLER CARL ,  KUMAR SHIV ,  SOOD ANUP ,  NELSON JOHN

    IPC: C12Q1/68 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  C12Q20060101 ,  C12Q1/00 ,  C12Q1/42 ,  G01N33/52 ,  G01N33/58

    CPC classification number: C12Q1/6823 ,  C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  C12Q1/6816 ,  C12Q1/6851 ,  C12Q2521/525

    Abstract: The present invention relates to improved methods of detecting a target using a labeled substrate or substrate analog. The methods comprise reacting the substrate or substrate analog in an enzyme-catalyzed reaction which produces a labeled moiety with independently detectable signal only when such substrate or substrate analog reacts. The present invention, in particular, describes methods of detecting a nucleic acid in a sample, based on the use of terminal-phosphate-labeled nucleotides as substrate for nucleic acid polymerases. The methods provided by this invention utilize a nucleoside polyphosphate, dideoxynucleoside polyphosphate, or deoxynucleoside polyphosphate analogue which has a colorimetric dye, chemiluminescent, or fluorescent moiety, a mass tag or an electrochemical tag attached to the terminal-phosphate. When a nucleic acid polymerase uses this analogue as a substrate, an enzyme-activatable label would be present on the inorganic polyphosphate by-product of phosphoryl transfer. Cleavage of the polyphosphate product of phosphoryl transfer via phosphatase leads to a detectable change in the label attached thereon. When the polymerase assay is performed in the presence of a phosphatase, there is provided a convenient method for real-time monitoring of DNA or RNA synthesis and detection of a target nucleic acid.

    Abstract translation: 本发明涉及使用标记的底物或底物类似物检测靶的改进方法。 所述方法包括在酶催化的反应中使底物或底物类似物反应，其仅在这种底物或底物类似物反应时产生具有独立可检测信号的标记部分。 本发明特别地描述了基于使用末端磷酸酯标记的核苷酸作为核酸聚合酶的底物来检测样品中核酸的方法。 本发明提供的方法利用了具有比色染料，化学发光或荧光部分的核苷多磷酸，双脱氧核苷多聚磷酸酯或脱氧核苷多聚磷酸酯类似物，连接至末端磷酸酯的质量标签或电化学标签。 当核酸聚合酶使用该类似物作为底物时，酶活性标记将存在于磷酸转移的无机多磷酸盐副产物上。 通过磷酸酶切割磷酸转移的多磷酸盐产物导致附着在其上的标记物的可检测的变化。 当在磷酸酶的存在下进行聚合酶测定时，提供了用于实时监测DNA或RNA合成和检测靶核酸的方便的方法。

    METHOD OF MAKING CARBON NANOTUBE ARRAYS, AND THERMAL INTERFACES USING SAME
    10.
    发明申请
    METHOD OF MAKING CARBON NANOTUBE ARRAYS, AND THERMAL INTERFACES USING SAME 审中-公开
    制备碳纳米管阵列的方法和使用相同的热界面

    公开(公告)号：WO2005052179A3

    公开(公告)日：2006-08-24

    申请号：PCT/US2004026173

    申请日：2004-08-11

    Applicant: UNIV JOHNS HOPKINS ,  OSIANDER ROBERT ,  SAMPLE JENNIFER L

    Inventor： OSIANDER ROBERT ,  SAMPLE JENNIFER L

    IPC: F28F27/00 ,  B32B9/00 ,  C01B31/02 ,  C12Q20060101 ,  C23C16/26 ,  H01L21/00 ,  H01L23/373

    CPC classification number: B82Y30/00 ,  B82Y40/00 ,  C01B32/162 ,  C01B2202/02 ,  C01B2202/08 ,  C01B2202/34 ,  C01B2202/36 ,  F28F13/00 ,  F28F2013/006 ,  F28F2013/008 ,  F28F2255/20 ,  H01L23/373 ,  H01L2924/0002 ,  Y10S977/734 ,  Y10S977/742 ,  Y10S977/939 ,  Y10T428/265 ,  Y10T428/30 ,  H01L2924/00

    Abstract: Thermal interfaces and methods include an array of carbon nanotubes aligned substantively perpendicularly from a substrate. One method includes arranging metal catalyst particles (732) with a particular ligand (734) on a fluid surface (722) of a Langmuir-Blodgett trough (710). This forms uniformly spaced particles (744) with spacing based on the particular ligand (734) . The uniformly spaced metal catalyst particles (744) are deposited on a substrate and carbon nanotubes are grown on the particles using chemical vapor deposition. A highly efficient thermal interface can be produced with a carbon nanotube packing ratio greater than fifty percent and used in a thermal switch or other device. In some methods, commercially available nanotubes (842) are condensed on a substrate using carbon nanotubes with terminal carboxylic acids (844) in solution and an amine monolayer (810) on the substrate. Pretreatment of the nanotubes (250) in a switch by applying heavy pressure between two surfaces (210, 220) results in good thermal conductivity between those surfaces (210, 220) at smaller operating pressures.

    Abstract translation: 热界面和方法包括从衬底基本上垂直排列的碳纳米管阵列。 一种方法包括将具有特定配体（734）的金属催化剂颗粒（732）布置在Langmuir-Blodgett槽（710）的流体表面（722）上。 这形成具有基于特定配体（734）的间隔的均匀间隔的颗粒（744）。 将均匀间隔的金属催化剂颗粒（744）沉积在基底上，并且使用化学气相沉积在颗粒上生长碳纳米管。 可以生产具有大于百分之五十的碳纳米管填充率的高效热界面，并且用于热开关或其他装置中。 在一些方法中，将市售的纳米管（842）在溶液中使用具有末端羧酸（844）的碳纳米管和基材上​​的胺单层（810）在基材上冷凝。 通过在两个表面（210,220）之间施加重的压力来对开关中的纳米管（250）进行预处理，在较小的操作压力下，在这些表面（210,220）之间导致良好的导热性。

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