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公开(公告)号：US08232060B2
公开(公告)日：2012-07-31
申请号：US12584353
申请日：2009-09-03
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。
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公开(公告)号：US20120171696A1
公开(公告)日：2012-07-05
申请号：US13366679
申请日：2012-02-06
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： G01N33/573 , C12Q1/48
CPC分类号： G01N33/574 , A61K38/00 , C07K2319/00 , C12N9/1205 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156 , G01N33/57484 , G01N2333/9121 , Y10T436/117497
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.
摘要翻译： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够筛选抑制蛋白质的化合物的方法，以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法。
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公开(公告)号：US08168383B2
公开(公告)日：2012-05-01
申请号：US12589176
申请日：2009-10-19
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
CPC分类号： G01N33/574 , A61K38/00 , C07K2319/00 , C12N9/1205 , C12Q1/6886 , C12Q2600/136 , C12Q2600/156 , G01N33/57484 , G01N2333/9121 , Y10T436/117497
摘要： Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.
摘要翻译： 涉及染色体2的新型基因缺失和易位导致融合蛋白的结合，其部分的间变型淋巴瘤激酶（ALK）激酶与部分二级蛋白结合，已经在人类实体瘤中被鉴定。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变多肽的载体，用于检测其的探针，分离的突变多肽和用于检测融合和截短的多肽的试剂。 本发明还提供了用于确定生物样品中这些突变体多肽的存在的方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变多核苷酸或多肽特征的癌症进展抑制方法。
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公开(公告)号：US20110223609A1
公开(公告)日：2011-09-15
申请号：US12584353
申请日：2009-09-03
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。
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公开(公告)号：US20100304382A1
公开(公告)日：2010-12-02
申请号：US12714457
申请日：2010-02-27
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。
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公开(公告)号：US07700339B2
公开(公告)日：2010-04-20
申请号：US11787132
申请日：2007-04-13
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： C12N15/63 , C12N15/00 , C12N1/21 , C12N5/10 , C12P21/00 , C12Q1/68 , C07H21/00 , C12N9/12 , C12Q1/48 , C07K14/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
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公开(公告)号：US20090156475A1
公开(公告)日：2009-06-18
申请号：US11787132
申请日：2007-04-13
申请人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
发明人： Klarisa Rikova , Herbert Haack , Laura Sullivan , Ailan Guo , Anthony Possemato , Joan MacNeill , Ting-Lei Gu , Jian Yu
IPC分类号： A61K38/16 , C07H21/04 , C12N15/74 , C07K14/00 , C07K16/00 , G01N33/53 , C12Q1/68 , A61P35/00
CPC分类号： C12Q1/6886 , A61K31/713 , A61K38/00 , C07K14/47 , C07K2319/00 , C12N9/12 , C12N9/1205 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Y207/10001 , G01N33/57423 , G01N33/57484 , G01N33/6893 , G01N2333/912 , G01N2333/9121
摘要： In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译： 根据本发明，现在已经在人类实体肿瘤中鉴定了涉及染色体2的新基因缺失和易位，导致将部分间变性淋巴瘤激酶（ALK）激酶与部分二级蛋白结合的融合蛋白。 非小细胞肺癌（NSCLC）。 次级蛋白包括棘皮动物微管相关蛋白样4（EML-4）和TRK-融合基因（TFG）。 确认了保留ALK酪氨酸激酶活性的EML4-ALK融合蛋白，以驱动以这种突变为特征的NSCLC的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变ALK激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的这种新的融合蛋白的鉴定使得能够确定生物样品中这些突变型ALK激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及用于突变突变型多核苷酸特征的癌症进展抑制方法 或多肽，其也由本发明提供。
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18.发明申请公开(公告)号：US20130224869A1
公开(公告)日：2013-08-29
申请号：US13817911
申请日：2011-08-12
申请人： David Perrett , Nanda Kishore Nayuni , Paul Ellwood , Richard Maskell , Alasdair Hayden Wright , Sarah Thompson , Laura Sullivan
发明人： David Perrett , Nanda Kishore Nayuni , Paul Ellwood , Richard Maskell , Alasdair Hayden Wright , Sarah Thompson , Laura Sullivan
IPC分类号： G01N33/68
CPC分类号： G01N33/6839 , G01N21/6428 , G01N21/6456 , G01N21/94
摘要： An imaging system (10) and associated method for detection of protein contamination on a surgical instrument (100) that has been treated with a fluorescing stain, wherein fluorophors in the stain are capable of emitting light of an emitted type when both excited by light of an excitation type and in contact with a protein are provided. The system comprises a light tight chamber (14) for receiving the instrument (100). Inside the chamber (14) are both visible light sources (20) and excitation light sources (22) for respectively illuminating the chamber with visible and excitation type light. A digital camera (30) is able to capture a first image of the instrument (100) as illuminated by the visible light, and a second image, of patterns of fluorescence produced by the fluorophors in the stain corresponding to protein contamination. The first and second images are combined to produce a composite image of the instrument (100) highlighting the areas of protein contamination. Associated software can be used to analyse the images so as to determine a level of protein contamination.
摘要翻译： 一种成像系统（10）和用于检测已经用荧光染色剂处理的外科器械（100）上的蛋白污染的相关方法，其中染色体中的荧光体能够发射发射的光，当两者都被光 提供了与蛋白质接触的激发型。 该系统包括用于接收仪器（100）的不透光室（14）。 在室（14）内部是可见光源（20）和激发光源（22），用于分别用可见光和激发型光照射室。 数字照相机（30）能够捕获由可见光照射的仪器（100）的第一图像，以及第二图像，其中荧光体在染色体中产生的与蛋白质污染相对应的荧光图案。 组合第一和第二图像以产生突出蛋白质污染区域的仪器（100）的合成图像。 相关软件可用于分析图像，以确定蛋白质污染水平。
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公开(公告)号：US09664686B2
公开(公告)日：2017-05-30
申请号：US13817911
申请日：2011-08-12
申请人： David Perrett , Nanda Kishore Nayuni , Paul Ellwood , Richard Maskell , Alasdair Hayden Wright , Sarah Thompson , Laura Sullivan
发明人： David Perrett , Nanda Kishore Nayuni , Paul Ellwood , Richard Maskell , Alasdair Hayden Wright , Sarah Thompson , Laura Sullivan
CPC分类号： G01N33/6839 , G01N21/6428 , G01N21/6456 , G01N21/94
摘要： An imaging system (10) and associated method for detection of protein contamination on a surgical instrument (100) that has been treated with a fluorescing stain, wherein fluorophors in the stain are capable of emitting light of an emitted type when both excited by light of an excitation type and in contact with a protein are provided. The system comprises a light tight chamber (14) for receiving the instrument (100). Inside the chamber (14) are both visible light sources (20) and excitation light sources (22) for respectively illuminating the chamber with visible and excitation type light. A digital camera (30) is able to capture a first image of the instrument (100) as illuminated by the visible light, and a second image, of patterns of fluorescence produced by the fluorophors in the stain corresponding to protein contamination. The first and second images are combined to produce a composite image of the instrument (100) highlighting the areas of protein contamination. Associated software can be used to analyse the images so as to determine a level of protein contamination.
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公开(公告)号：US20050193934A1
公开(公告)日：2005-09-08
申请号：US11056994
申请日：2005-02-11
申请人： Laura Sullivan
发明人： Laura Sullivan
IPC分类号： A01C1/00
CPC分类号： A01C7/02
摘要： An apparatus and method for arranging plants. The apparatus being a planting guide comprising a flat sheet; a plurality of markings arranged about a point on the sheet; and indicia corresponding and adjacent to each of the markings, indicating distance of the marking relative to the point on the sheet. The planting guide having a plurality of markings being set out with the markings facing up; a plurality of plants being placed on the planting guide within one of the markings; and the plants configured.
摘要翻译： 一种用于布置植物的装置和方法。 该装置是包括平板的种植导向器; 围绕片材上的点布置的多个标记; 和与每个标记相对并相邻的标记，指示标记相对于纸张上的点的距离。 具有多个标记的种植引导件，其标记面朝上设置; 将多个植物放置在所述标记之一内的所述种植引导件上; 并配置植物。
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