CO6511214A2 - Detección del evento das 40278 9 de aad 1 - Google Patents
Detección del evento das 40278 9 de aad 1Info
- Publication number
- CO6511214A2 CO6511214A2 CO12039002A CO12039002A CO6511214A2 CO 6511214 A2 CO6511214 A2 CO 6511214A2 CO 12039002 A CO12039002 A CO 12039002A CO 12039002 A CO12039002 A CO 12039002A CO 6511214 A2 CO6511214 A2 CO 6511214A2
- Authority
- CO
- Colombia
- Prior art keywords
- detection
- present
- event
- aad
- plants
- Prior art date
Links
- 238000001514 detection method Methods 0.000 title abstract 4
- 101710096655 Probable acetoacetate decarboxylase 1 Proteins 0.000 title abstract 2
- 241000196324 Embryophyta Species 0.000 abstract 2
- 240000008042 Zea mays Species 0.000 abstract 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 abstract 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 abstract 2
- 238000003556 assay Methods 0.000 abstract 2
- 235000005822 corn Nutrition 0.000 abstract 2
- 101100442689 Caenorhabditis elegans hdl-1 gene Proteins 0.000 abstract 1
- 241001057636 Dracaena deremensis Species 0.000 abstract 1
- 238000002944 PCR assay Methods 0.000 abstract 1
- 238000004458 analytical method Methods 0.000 abstract 1
- 230000002363 herbicidal effect Effects 0.000 abstract 1
- 239000004009 herbicide Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 102000040430 polynucleotide Human genes 0.000 abstract 1
- 108091033319 polynucleotide Proteins 0.000 abstract 1
- 239000002157 polynucleotide Substances 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 238000004448 titration Methods 0.000 abstract 1
- 230000009466 transformation Effects 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8261—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
- C12N15/8271—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance
- C12N15/8274—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for herbicide resistance
-
- 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.)
- C12N9/0069—Oxidoreductases (1.) acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)
-
- 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.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Cultivation Of Plants (AREA)
- Pretreatment Of Seeds And Plants (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23524809P | 2009-08-19 | 2009-08-19 | |
| US23736610P | 2010-04-23 | 2010-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CO6511214A2 true CO6511214A2 (es) | 2012-08-31 |
Family
ID=43607318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CO12039002A CO6511214A2 (es) | 2009-08-19 | 2012-03-06 | Detección del evento das 40278 9 de aad 1 |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JP5771208B2 (enExample) |
| KR (1) | KR101772638B1 (enExample) |
| CN (1) | CN102575299B (enExample) |
| AU (1) | AU2010284286B2 (enExample) |
| CA (1) | CA2771581C (enExample) |
| CL (1) | CL2012000410A1 (enExample) |
| CO (1) | CO6511214A2 (enExample) |
| IL (1) | IL218175A (enExample) |
| IN (1) | IN2012DN01800A (enExample) |
| MX (1) | MX336072B (enExample) |
| NZ (1) | NZ598598A (enExample) |
| RU (1) | RU2577143C2 (enExample) |
| WO (1) | WO2011022471A1 (enExample) |
| ZA (1) | ZA201201210B (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8598413B2 (en) * | 2009-08-19 | 2013-12-03 | Dow AgroSciecnes, LLC. | AAD-1 event DAS-40278-9, related transgenic corn lines, event-specific identification thereof, and methods of weed control involving AAD-1 |
| CA2771538C (en) | 2009-08-19 | 2019-06-04 | Dow Agrosciences Llc | Aad-1 event das-40278-9, related transgenic corn lines, and event-specific identification thereof |
| TWI667347B (zh) | 2010-12-15 | 2019-08-01 | 瑞士商先正達合夥公司 | 大豆品種ｓｙｈｔ０ｈ２及偵測其之組合物及方法 |
| WO2015142571A1 (en) * | 2014-03-20 | 2015-09-24 | Monsanto Technology Llc | Transgenic maize event mon 87419 and methods of use thereof |
| CA3047050A1 (en) | 2016-12-22 | 2018-06-28 | Syngenta Participations Ag | Polymorphs |
| GB201622007D0 (en) | 2016-12-22 | 2017-02-08 | And See Cambridge Display Tech Ltd Syngenta Participations Ag | Polymorphs |
| UY37623A (es) | 2017-03-03 | 2018-09-28 | Syngenta Participations Ag | Derivados de oxadiazol tiofeno fungicidas |
| WO2018177880A1 (en) | 2017-03-31 | 2018-10-04 | Syngenta Participations Ag | Fungicidal compositions |
| CA3055680A1 (en) | 2017-03-31 | 2018-10-04 | Syngenta Participations Ag | Fungicidal compositions |
| WO2018185013A1 (en) | 2017-04-03 | 2018-10-11 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| BR112019020819B1 (pt) | 2017-04-05 | 2023-12-05 | Syngenta Participations Ag | Composto de fórmula (i), composição agroquímica, método para controlar ou prevenir a infestação de plantas úteis por micro-organismos fitopatogênicos e uso de um composto de fórmula (i) |
| BR112019020734B1 (pt) | 2017-04-05 | 2023-12-05 | Syngenta Participations Ag | Compostos derivados de oxadiazol, composição agroquímica, método para controlar ou prevenir a infestação de plantas úteis por microrganismos fitopatogênicos e uso dos referidos compostos |
| BR112019021019B1 (pt) | 2017-04-05 | 2023-12-05 | Syngenta Participations Ag | Compostos derivados de oxadiazol microbiocidas, composição agrícola, método para controlar ou prevenir a infestação de plantas úteis por microrganismos fitopatogênicos e uso de um composto derivado de oxadiazol |
| WO2018184984A1 (en) | 2017-04-05 | 2018-10-11 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| WO2018184982A1 (en) | 2017-04-05 | 2018-10-11 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| BR112019020739B1 (pt) | 2017-04-05 | 2023-12-19 | Syngenta Participations Ag | Compostos derivados de oxadiazol microbiocidas e seu uso, composição agroquímica, método para controlar ou prevenir a infestação de plantas úteis por microrganismos fitopatogênicos |
| WO2018185211A1 (en) | 2017-04-06 | 2018-10-11 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| CN110709395A (zh) | 2017-06-02 | 2020-01-17 | 先正达参股股份有限公司 | 杀微生物的噁二唑衍生物 |
| WO2018219773A1 (en) | 2017-06-02 | 2018-12-06 | Syngenta Participations Ag | Fungicidal compositions |
| EP3638032A1 (en) | 2017-06-14 | 2020-04-22 | Syngenta Participations AG | Fungicidal compositions |
| US20200315176A1 (en) | 2017-06-28 | 2020-10-08 | Syngenta Participations Ag | Fungicidal compositions |
| BR112020000465B1 (pt) | 2017-07-11 | 2024-02-20 | Syngenta Participations Ag | Derivados oxadiazol microbiocidas |
| WO2019011926A1 (en) | 2017-07-11 | 2019-01-17 | Syngenta Participations Ag | MICROBIOCIDE OXADIAZOLE DERIVATIVES |
| WO2019011928A1 (en) | 2017-07-11 | 2019-01-17 | Syngenta Participations Ag | MICROBIOCIDE OXADIAZOLE DERIVATIVES |
| WO2019011929A1 (en) | 2017-07-11 | 2019-01-17 | Syngenta Participations Ag | MICROBIOCIDE OXADIAZOLE DERIVATIVES |
| WO2019012001A1 (en) | 2017-07-12 | 2019-01-17 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| BR112020000371A2 (pt) | 2017-07-12 | 2020-07-14 | Syngenta Participations Ag | derivados de oxadiazol microbiocidas |
| BR112020000463A2 (pt) | 2017-07-13 | 2020-07-21 | Syngenta Participations Ag | derivados oxadiazol microbiocidas |
| UY37912A (es) | 2017-10-05 | 2019-05-31 | Syngenta Participations Ag | Derivados de picolinamida fungicidas que portan grupos terminales heteroarilo o heteroariloxi |
| UY37913A (es) | 2017-10-05 | 2019-05-31 | Syngenta Participations Ag | Derivados de picolinamida fungicidas que portan un grupo terminal cuaternario |
| BR112020009659A2 (pt) | 2017-11-15 | 2020-11-10 | Syngenta Participations Ag | derivados picolinamida microbiocidas |
| CN112020503A (zh) | 2018-04-26 | 2020-12-01 | 先正达参股股份有限公司 | 杀微生物的噁二唑衍生物 |
| CN112351981A (zh) | 2018-06-29 | 2021-02-09 | 先正达农作物保护股份公司 | 杀微生物的噁二唑衍生物 |
| EP3818058A1 (en) | 2018-07-02 | 2021-05-12 | Syngenta Crop Protection AG | 3-(2-thienyl)-5-(trifluoromethyl)-1,2,4-oxadiazole derivatives as agrochemical fungicides |
| CN112689631A (zh) | 2018-07-16 | 2021-04-20 | 先正达农作物保护股份公司 | 杀微生物的噁二唑衍生物 |
| CN113195462A (zh) | 2018-10-17 | 2021-07-30 | 先正达农作物保护股份公司 | 杀微生物的噁二唑衍生物 |
| AR116628A1 (es) | 2018-10-18 | 2021-05-26 | Syngenta Crop Protection Ag | Compuestos microbiocidas |
| WO2020165403A1 (en) | 2019-02-15 | 2020-08-20 | Syngenta Crop Protection Ag | Phenyl substituted thiazole derivatives as microbiocidal compounds |
| TWI877139B (zh) | 2019-02-20 | 2025-03-21 | 瑞士商先正達農作物保護公司 | 特特拉姆酸衍生物之用途 |
| GB201903942D0 (en) | 2019-03-22 | 2019-05-08 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| CA3132321A1 (en) | 2019-04-10 | 2020-10-15 | Clemens Lamberth | Fungicidal compositions |
| WO2020208095A1 (en) | 2019-04-10 | 2020-10-15 | Syngenta Crop Protection Ag | Microbiocidal picolinamide derivatives |
| BR112021026861A2 (pt) | 2019-07-05 | 2022-02-22 | Syngenta Crop Protection Ag | Derivados de picolinamida microbiocidas |
| GB201910037D0 (en) | 2019-07-12 | 2019-08-28 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| KR20220151177A (ko) | 2020-03-05 | 2022-11-14 | 신젠타 크롭 프로텍션 아게 | 살진균 조성물 |
| UY39115A (es) | 2020-03-05 | 2021-10-29 | Syngenta Crop Protection Ag | Mezclas fungicidas de derivados de arilo metoxiacrilato |
| GB202006399D0 (en) | 2020-04-30 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| GB202006386D0 (en) | 2020-04-30 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal Compounds |
| GB202006480D0 (en) | 2020-05-01 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| GB202006606D0 (en) | 2020-05-05 | 2020-06-17 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| GB202014840D0 (en) | 2020-09-21 | 2020-11-04 | Syngenta Crop Protection Ag | Microbiocidal compounds |
| KR102383881B1 (ko) * | 2020-10-16 | 2022-04-06 | 국립생태원 | 유전자변형 옥수수의 동시 검출 방법 |
| PY21104302A (es) | 2020-11-27 | 2022-08-09 | Syngenta Crop Protection Ag | Composición plaguicida |
| PY21103556A (es) | 2020-12-02 | 2023-05-03 | Syngenta Crop Protection Ag | Composiciones fungicidas |
| WO2022117650A1 (en) | 2020-12-02 | 2022-06-09 | Syngenta Crop Protection Ag | Fungicidal compositions |
| PY2219081A (es) | 2021-03-19 | 2022-09-27 | Syngenta Crop Protection Ag | Composiciones plaguicidas |
| WO2022233869A1 (en) | 2021-05-04 | 2022-11-10 | Syngenta Crop Protection Ag | Use of clethodim for insect control |
| MX2024000074A (es) | 2021-07-02 | 2024-02-23 | Syngenta Crop Protection Ag | Uso de fluazifop-p-butilo para control de insectos. |
| WO2026146027A1 (en) | 2025-01-03 | 2026-07-09 | Syngenta Crop Protection Ag | Fungicidal compositions |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245974B1 (en) * | 1997-08-06 | 2001-06-12 | North Carolina State University | Matrix attachment regions |
| AR042145A1 (es) * | 2002-11-27 | 2005-06-08 | Dow Agrociences Llc | Produccion de inmunoglobulinas en plantas con una fucocilacion reducida |
| PL1708560T3 (pl) * | 2003-12-15 | 2015-10-30 | Monsanto Technology Llc | Roślina kukurydzy MON88017 oraz kompozycje i sposoby ich wykrywania |
| PL2308976T5 (pl) * | 2004-04-30 | 2017-10-31 | Dow Agrosciences Llc | Nowe geny odporności na herbicydy |
| RU2270254C2 (ru) * | 2004-04-30 | 2006-02-20 | Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук | Способ идентификации трансгенных последовательностей днк в растительном материале и продуктах на его основе, набор олигонуклеотидов и биочип для осуществления этого способа |
| EP2147012A4 (en) * | 2007-05-17 | 2011-03-02 | Monsanto Technology Llc | MAISPOYLMORPHISMS AND METHOD FOR THEIR GENOTYPIZATION |
| CA2771538C (en) * | 2009-08-19 | 2019-06-04 | Dow Agrosciences Llc | Aad-1 event das-40278-9, related transgenic corn lines, and event-specific identification thereof |
| US8598413B2 (en) * | 2009-08-19 | 2013-12-03 | Dow AgroSciecnes, LLC. | AAD-1 event DAS-40278-9, related transgenic corn lines, event-specific identification thereof, and methods of weed control involving AAD-1 |
-
2010
- 2010-08-18 IN IN1800DEN2012 patent/IN2012DN01800A/en unknown
- 2010-08-18 WO PCT/US2010/045871 patent/WO2011022471A1/en not_active Ceased
- 2010-08-18 CN CN201080047115.6A patent/CN102575299B/zh active Active
- 2010-08-18 RU RU2012110253/10A patent/RU2577143C2/ru not_active IP Right Cessation
- 2010-08-18 KR KR1020127006871A patent/KR101772638B1/ko not_active Expired - Fee Related
- 2010-08-18 JP JP2012525662A patent/JP5771208B2/ja not_active Expired - Fee Related
- 2010-08-18 MX MX2012002076A patent/MX336072B/es unknown
- 2010-08-18 AU AU2010284286A patent/AU2010284286B2/en not_active Ceased
- 2010-08-18 CA CA2771581A patent/CA2771581C/en active Active
- 2010-08-18 NZ NZ598598A patent/NZ598598A/en not_active IP Right Cessation
-
2012
- 2012-02-16 IL IL218175A patent/IL218175A/en not_active IP Right Cessation
- 2012-02-16 CL CL2012000410A patent/CL2012000410A1/es unknown
- 2012-02-17 ZA ZA2012/01210A patent/ZA201201210B/en unknown
- 2012-03-06 CO CO12039002A patent/CO6511214A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN102575299A (zh) | 2012-07-11 |
| IN2012DN01800A (enExample) | 2015-06-05 |
| BR112012003873A2 (pt) | 2016-11-22 |
| MX336072B (es) | 2016-01-06 |
| ZA201201210B (en) | 2012-10-31 |
| AU2010284286B2 (en) | 2015-08-20 |
| JP2013505706A (ja) | 2013-02-21 |
| WO2011022471A1 (en) | 2011-02-24 |
| JP5771208B2 (ja) | 2015-08-26 |
| RU2012110253A (ru) | 2013-09-27 |
| HK1173194A1 (zh) | 2013-05-10 |
| AU2010284286A1 (en) | 2012-03-29 |
| MX2012002076A (es) | 2012-03-21 |
| CA2771581C (en) | 2018-05-01 |
| NZ598598A (en) | 2014-05-30 |
| IL218175A0 (en) | 2012-07-31 |
| CL2012000410A1 (es) | 2012-10-19 |
| IL218175A (en) | 2017-04-30 |
| CA2771581A1 (en) | 2011-02-24 |
| KR20120053038A (ko) | 2012-05-24 |
| RU2577143C2 (ru) | 2016-03-10 |
| KR101772638B1 (ko) | 2017-08-31 |
| CN102575299B (zh) | 2015-09-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2012002076A (es) | Deteccion de evento de ariloxialcanoato dioxigenasa-1 das-40278-9. | |
| Wigfield et al. | Students’ achievement values, goal orientations, and interest: Definitions, development, and relations to achievement outcomes | |
| AR077890A1 (es) | Evento das-40278-9 del gen aad -1 que codifica la proteina ariloxialcanoato dioxigenasa, lineas transgenicas de maiz relacionadas, e identificacion evento-especifico de las mismas | |
| BR112012021202A2 (pt) | aparelho e metodos para preparacao, reacao e deteccao integradas de amostras | |
| UY37586A (es) | Plantas y semillas de soja correspondientes al evento transgénico mon87701 y métodos de detección del mismo | |
| WO2012021795A3 (en) | Pancreatic cancer biomarkers and uses thereof | |
| WO2012083240A3 (en) | Oligonucleotide array for tissue typing | |
| WO2007114986A3 (en) | Cooperative probes and methods of using them | |
| WO2009043050A3 (en) | Optical assay system with a multi-probe imaging array | |
| EP4697020A3 (en) | Compositions and methods for analyte detection | |
| WO2012019193A3 (en) | Assay systems for genetic analysis | |
| EP2057181A4 (en) | METHOD AND SUBSTANCES FOR ISOLATING AND DETECTING SMALL POLYNUCLEOTIDES | |
| GB201303939D0 (en) | Droplet-Based assay system | |
| EA201291001A1 (ru) | Способы измерения ферментативной активности, полезные при определении жизнеспособности клеток в неочищенных образцах | |
| WO2012018741A3 (en) | Pressurizable cartridge for polymerase chain reactions | |
| WO2009121032A3 (en) | Sample preparation devices and methods for processing analytes | |
| ES2638294T3 (es) | Método de detección de cáncer | |
| CO6561770A2 (es) | Detecciòn del evento de soja aad-12 416 | |
| ES2686300T3 (es) | Asociación de variaciones genéticas raras recurrentes con el trastorno por déficit de atención e hiperactividad (TDAH) y procedimientos de uso de las mismas para el diagnóstico y tratamiento del mismo | |
| WO2011132061A3 (en) | Methylation profiling of dna samples | |
| WO2011046614A3 (en) | Methods and systems for phylogenetic analysis | |
| WO2008073895A3 (en) | Methods and devices for testing saliva | |
| WO2009099905A3 (en) | Molecular signatures and biomarkers associated with melanoma and methods of use thereof | |
| BR112013004278A2 (pt) | tintas de reagente enzimático para uso em tiras de teste tendo um código de calibração predeterminado | |
| WO2012083274A3 (en) | Methods for diagnosis, prognosis and methods of treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC | Application refused |