ATE186598T1 - Homogene immunoassays unter verwendung von mutanten glucose-6-phosphatdehydrogenasen - Google Patents
Homogene immunoassays unter verwendung von mutanten glucose-6-phosphatdehydrogenasenInfo
- Publication number
- ATE186598T1 ATE186598T1 AT94923147T AT94923147T ATE186598T1 AT E186598 T1 ATE186598 T1 AT E186598T1 AT 94923147 T AT94923147 T AT 94923147T AT 94923147 T AT94923147 T AT 94923147T AT E186598 T1 ATE186598 T1 AT E186598T1
- Authority
- AT
- Austria
- Prior art keywords
- g6pdh
- enzymes
- precursor
- subject
- substitution
- Prior art date
Links
- 238000003018 immunoassay Methods 0.000 title abstract 2
- 108020005199 Dehydrogenases Proteins 0.000 title 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 title 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 abstract 8
- 108010029731 6-phosphogluconolactonase Proteins 0.000 abstract 8
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 abstract 8
- 102000004190 Enzymes Human genes 0.000 abstract 7
- 108090000790 Enzymes Proteins 0.000 abstract 7
- 239000002243 precursor Substances 0.000 abstract 4
- 238000006467 substitution reaction Methods 0.000 abstract 3
- 235000001014 amino acid Nutrition 0.000 abstract 2
- 150000001413 amino acids Chemical class 0.000 abstract 2
- 239000012491 analyte Substances 0.000 abstract 2
- 235000018417 cysteine Nutrition 0.000 abstract 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 abstract 2
- 230000037430 deletion Effects 0.000 abstract 2
- 238000012217 deletion Methods 0.000 abstract 2
- 230000037431 insertion Effects 0.000 abstract 2
- 238000003780 insertion Methods 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 230000035772 mutation Effects 0.000 abstract 2
- 108020004414 DNA Proteins 0.000 abstract 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 abstract 1
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract 1
- 238000010276 construction Methods 0.000 abstract 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 abstract 1
- 230000001419 dependent effect Effects 0.000 abstract 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 abstract 1
- 230000009870 specific binding Effects 0.000 abstract 1
- 239000013598 vector Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
- C12Q1/28—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/535—Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/581—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/902—Oxidoreductases (1.)
- G01N2333/904—Oxidoreductases (1.) acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmacology & Pharmacy (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/044,857 US6455288B1 (en) | 1993-04-08 | 1993-04-08 | Homogeneous immunoassays using mutant glucose-6-phosphate dehydrogenases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE186598T1 true ATE186598T1 (de) | 1999-11-15 |
Family
ID=21934701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT94923147T ATE186598T1 (de) | 1993-04-08 | 1994-04-07 | Homogene immunoassays unter verwendung von mutanten glucose-6-phosphatdehydrogenasen |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6455288B1 (de) |
| EP (1) | EP0710360B1 (de) |
| JP (1) | JP4223546B2 (de) |
| AT (1) | ATE186598T1 (de) |
| CA (1) | CA2160115A1 (de) |
| DE (1) | DE69421617T2 (de) |
| ES (1) | ES2139087T3 (de) |
| WO (1) | WO1994024559A2 (de) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5741715A (en) * | 1995-05-30 | 1998-04-21 | Roche Diagnostic Systems, Inc. | Quinidine immunoassay and reagents |
| EP0983509B1 (de) | 1997-05-14 | 2005-08-17 | Biosite Diagnostics Inc. | Schnelle bestimmung des verhältnisses von biologischen molekülen |
| US6306616B1 (en) | 1998-03-27 | 2001-10-23 | Microgenics Corporation | Adsorption type confirmatory assays |
| RU2153674C2 (ru) * | 1998-07-28 | 2000-07-27 | Красноярская государственная медицинская академия | Способ прогноза развития послеоперационных осложнений в виде генерализованной гнойной хирургической инфекции |
| JP2002065283A (ja) * | 2000-06-12 | 2002-03-05 | Wako Pure Chem Ind Ltd | ハイブリッド酵素およびその用途 |
| US7560239B2 (en) * | 2002-06-04 | 2009-07-14 | Lin-Zhi International Inc. | Homogeneous enzyme immunoassay for simultaneous detection of multiple analytes |
| US20050130243A1 (en) * | 2003-12-15 | 2005-06-16 | Zheng Yi F. | Assay for entactogens |
| US7022492B2 (en) * | 2003-12-15 | 2006-04-04 | Dade Behring Inc. | Ecstasy haptens and immunogens |
| US6991911B2 (en) * | 2003-12-15 | 2006-01-31 | Dade Behring Inc. | Assay for entactogens |
| US7115383B2 (en) * | 2004-03-22 | 2006-10-03 | Dade Behring Inc. | Assays for amphetamine and methamphetamine |
| US7037669B2 (en) * | 2004-03-22 | 2006-05-02 | Dade Behring Inc. | Assays for amphetamine and methamphetamine using stereospecific reagents |
| US7279340B2 (en) * | 2004-04-07 | 2007-10-09 | Dade Behring Inc. | Synthesis and application of procainamide analogs for use in an immunoassay |
| US20060046273A1 (en) * | 2004-08-27 | 2006-03-02 | Lin-Zhi International Inc. | Homogeneous enzyme immunoassay for oral fluid |
| US7189582B2 (en) | 2005-04-27 | 2007-03-13 | Dade Behring Inc. | Compositions and methods for detection of sirolimus |
| US8507280B2 (en) * | 2006-08-18 | 2013-08-13 | Ortho-Clinical Diagnostics, Inc. | Method of normalizing surface tension of a sample fluid |
| US8828665B2 (en) | 2007-02-16 | 2014-09-09 | Ark Diagnostics, Inc. | Compounds and methods for use in detecting gabapentin |
| US7790401B2 (en) | 2007-08-06 | 2010-09-07 | Siemens Healthcare Diagnostics | Methods for detection of immunosuppressant drugs |
| US7910378B2 (en) | 2007-12-14 | 2011-03-22 | Siemens Healthcare Diagnostics Inc. | Methods for detection of hydrophobic drugs |
| US20090226900A1 (en) * | 2008-03-05 | 2009-09-10 | Helicos Biosciences Corporation | Methods for Reducing Contaminants in Nucleic Acid Sequencing by Synthesis |
| US8647642B2 (en) | 2008-09-18 | 2014-02-11 | Aviex Technologies, Llc | Live bacterial vaccines resistant to carbon dioxide (CO2), acidic PH and/or osmolarity for viral infection prophylaxis or treatment |
| WO2010048423A1 (en) | 2008-10-24 | 2010-04-29 | Ark Diagnostics, Inc. | Levetiracetam immunoassays |
| SG177613A1 (en) | 2009-07-10 | 2012-03-29 | Linzy O Scott Iii | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
| US8329424B2 (en) | 2010-06-25 | 2012-12-11 | Siemens Healthcare Diagnostics | Reduction in false results in assay measurements |
| US8771964B2 (en) | 2012-02-02 | 2014-07-08 | Siemens Healthcare Diagnostics Inc. | Compositions and methods for detection of methadone metabolite |
| US9658218B2 (en) | 2012-05-07 | 2017-05-23 | Siemens Healthcare Diagnostics Inc. | Determination of total analyte concentration |
| US9121859B2 (en) | 2012-12-04 | 2015-09-01 | Siemens Healthcare Diagnostics Inc. | Compounds and methods for determination of FKBP-binding immunosuppressant drugs |
| EP2945942B1 (de) | 2013-01-18 | 2018-05-09 | ARK Diagnostics, Inc. | Voriconazol-immunoassays |
| EP2956444B1 (de) | 2013-02-13 | 2018-05-30 | ARK Diagnostics, Inc. | Posaconazol-immunoassays |
| CA2923140C (en) | 2013-09-05 | 2023-09-26 | Idexx Laboratories, Inc. | Methods for detecting renal disease |
| WO2015067302A1 (en) | 2013-11-05 | 2015-05-14 | Ecole Polytechnique Federale De Lausanne (Epfl) | Sensor molecules and uses thereof |
| WO2015094852A2 (en) | 2013-12-17 | 2015-06-25 | Siemens Healthcare Diagnostics Inc. | Preparation of multi-hapten mutant g6pdh conjugates and their use for detection of multiple analytes |
| CN107003304A (zh) | 2014-12-17 | 2017-08-01 | 西门子医疗保健诊断公司 | 用于羟考酮和羟吗啡酮的测定法的缀合物 |
| EP3259593B1 (de) | 2015-02-20 | 2022-10-05 | IDEXX Laboratories, Inc. | Homogener immunoassay mit kompensation für hintergrundsignal |
| EP3265074B1 (de) | 2015-03-03 | 2020-08-12 | ARK Diagnostics, Inc. | Pregabalinimmunoassays |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| MX2020003523A (es) | 2017-10-19 | 2020-07-22 | Idexx Lab Inc | Deteccion de dimetilarginina simetrica. |
| CN110174363A (zh) * | 2019-01-09 | 2019-08-27 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
| US10745492B1 (en) | 2019-04-03 | 2020-08-18 | Ark Diagnostics, Inc. | Antibodies to symmetrically dimethylated arginine analytes and use thereof |
| CN110078711B (zh) * | 2019-04-19 | 2020-09-18 | 北京九强生物技术股份有限公司 | 一种卡马西平衍生物及其在免疫检测中的用途 |
| CN110054620B (zh) * | 2019-04-19 | 2021-01-26 | 北京九强生物技术股份有限公司 | 一种苯巴比妥衍生物及其在免疫检测中的用途 |
| CN115684613B (zh) * | 2019-07-04 | 2026-03-31 | 北京九强生物技术股份有限公司 | 丙戊酸检测试剂盒 |
| US20210048436A1 (en) | 2019-08-15 | 2021-02-18 | Psychemedics Corporation | Homogeneous enzyme immunoassay for keratinized structures |
| US12517120B2 (en) | 2020-01-07 | 2026-01-06 | Beijing Strong Biotechnologies, Inc. | Glucose-6-phosphate dehydrogenase mutant and use thereof in preparing detection reagent |
| EP4662205A1 (de) | 2023-02-10 | 2025-12-17 | Siemens Healthcare Diagnostics, Inc. | Derivate, immunogene und antikörper und deren verwendung beim nachweis von verbindungen der ecstasy-klasse |
| WO2026030017A1 (en) * | 2024-07-30 | 2026-02-05 | Siemens Healthcare Diagnostics Inc. | Nitazene analogs and conjugates and methods of production and use thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3817837A (en) | 1971-05-14 | 1974-06-18 | Syva Corp | Enzyme amplification assay |
| US3935074A (en) | 1973-12-17 | 1976-01-27 | Syva Company | Antibody steric hindrance immunoassay with two antibodies |
| US4233401A (en) | 1977-07-14 | 1980-11-11 | Syva Company | Antienzyme homogeneous competitive binding assay |
| IT1199088B (it) * | 1984-03-09 | 1988-12-30 | Miles Italiana | Saggio di legame specifico mediante impiego di anti-g6pdh come marcante |
| US4727022A (en) | 1984-03-14 | 1988-02-23 | Syntex (U.S.A.) Inc. | Methods for modulating ligand-receptor interactions and their application |
| US4622294A (en) * | 1985-02-08 | 1986-11-11 | Kung Viola T | Liposome immunoassay reagent and method |
| DE3711881A1 (de) * | 1987-04-08 | 1988-10-27 | Merck Patent Gmbh | Verfahren zur herstellung von glucosedehydrogenase aus bacillus megaterium |
| JPH0286779A (ja) * | 1988-09-22 | 1990-03-27 | Amano Pharmaceut Co Ltd | 改良型組換えdna、それを含む形質転換体及びそれを用いた耐熱性グルコースデヒドロゲナーゼの製造法 |
| DE4024158A1 (de) | 1990-07-30 | 1992-02-06 | Boehringer Mannheim Gmbh | Klonierung und ueberexpression von glucose-6-phosphat-dehydrogenase aus leuconostoc dextranicus |
| JP2850515B2 (ja) * | 1990-09-25 | 1999-01-27 | 東洋紡績株式会社 | グルコースデヒドロゲナーゼおよびその製造法 |
| US5244796A (en) | 1990-10-12 | 1993-09-14 | Syracuse University | Cloned leuconostoc mesenteroides glucose-6-phosphate dehydrogenase genes and method of making glucose-6-phospate dehydrogenase |
| DE69132238T2 (de) | 1990-11-20 | 2000-12-21 | Dade Behring Marburg Gmbh | Verfahren zur Stabilisierung von Enzym-Konjugaten |
-
1993
- 1993-04-08 US US08/044,857 patent/US6455288B1/en not_active Expired - Lifetime
-
1994
- 1994-04-07 CA CA002160115A patent/CA2160115A1/en not_active Abandoned
- 1994-04-07 DE DE69421617T patent/DE69421617T2/de not_active Expired - Lifetime
- 1994-04-07 AT AT94923147T patent/ATE186598T1/de active
- 1994-04-07 JP JP52322794A patent/JP4223546B2/ja not_active Expired - Lifetime
- 1994-04-07 EP EP94923147A patent/EP0710360B1/de not_active Expired - Lifetime
- 1994-04-07 ES ES94923147T patent/ES2139087T3/es not_active Expired - Lifetime
- 1994-04-07 WO PCT/US1994/003437 patent/WO1994024559A2/en not_active Ceased
-
1995
- 1995-05-22 US US08/445,464 patent/US6090567A/en not_active Expired - Lifetime
- 1995-05-22 US US08/445,463 patent/US6033890A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69421617T2 (de) | 2000-03-02 |
| ES2139087T3 (es) | 2000-02-01 |
| EP0710360B1 (de) | 1999-11-10 |
| WO1994024559A3 (en) | 1995-01-26 |
| WO1994024559A2 (en) | 1994-10-27 |
| US6033890A (en) | 2000-03-07 |
| JP4223546B2 (ja) | 2009-02-12 |
| EP0710360A1 (de) | 1996-05-08 |
| JPH08510638A (ja) | 1996-11-12 |
| DE69421617D1 (de) | 1999-12-16 |
| US6455288B1 (en) | 2002-09-24 |
| US6090567A (en) | 2000-07-18 |
| CA2160115A1 (en) | 1994-10-27 |
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