CA2744804C - Synaptic vesicle cycling assays and systems - Google Patents
Synaptic vesicle cycling assays and systems Download PDFInfo
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- CA2744804C CA2744804C CA2744804A CA2744804A CA2744804C CA 2744804 C CA2744804 C CA 2744804C CA 2744804 A CA2744804 A CA 2744804A CA 2744804 A CA2744804 A CA 2744804A CA 2744804 C CA2744804 C CA 2744804C
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2254458A1 (en) * | 2008-02-04 | 2010-12-01 | Bayer HealthCare, LLC | Semiconductor based analyte sensors and methods |
| US9217155B2 (en) | 2008-05-28 | 2015-12-22 | University Of Massachusetts | Isolation of novel AAV'S and uses thereof |
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| EP3095853B1 (en) * | 2014-01-16 | 2019-01-30 | Hamamatsu Photonics K.K. | Cell observation device, electrostimulation device, and cell observation method |
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| US10370432B2 (en) | 2014-10-03 | 2019-08-06 | University Of Massachusetts | Heterologous targeting peptide grafted AAVS |
| EP3200830B1 (en) | 2014-10-03 | 2020-09-09 | University of Massachusetts | High efficiency library-identified aav vectors |
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| US10457940B2 (en) | 2016-09-22 | 2019-10-29 | University Of Massachusetts | AAV treatment of Huntington's disease |
| CA3040483A1 (en) | 2016-10-13 | 2018-04-19 | University Of Massachusetts | Aav capsid designs |
| EP3622073A4 (en) | 2017-05-09 | 2021-01-06 | University of Massachusetts | METHOD FOR TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) |
| US11739330B2 (en) | 2017-09-22 | 2023-08-29 | University Of Massachusetts | SOD1 dual expression vectors and uses thereof |
| JP2021520811A (ja) | 2018-04-13 | 2021-08-26 | ユニバーシティ オブ マサチューセッツ | ヘキソサミニダーゼアルファおよびベータサブユニットをコードしているバイシストロニックａａｖベクターならびにその使用 |
| JP7065433B2 (ja) * | 2018-08-14 | 2022-05-12 | 日本電信電話株式会社 | 電極及びその製造方法、並びに積層体 |
| EP3861121A4 (en) | 2018-10-05 | 2022-08-24 | University of Massachusetts | RAAV VECTORS FOR THE TREATMENT OF GM1 AND GM2 GANGLIOSIDOSIS |
| IL289749B1 (en) * | 2019-07-16 | 2026-02-01 | Meso Scale Technologies Llc | Testing instruments, methods and reagents |
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| EP4271789A4 (en) * | 2020-12-31 | 2024-11-27 | Q-State Biosciences, Inc. | PLATE IMAGE PRODUCER |
| CA3207097A1 (en) * | 2020-12-31 | 2022-07-07 | Q-State Biosciences, Inc. | Optical plate controller and reader |
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| US20220357313A1 (en) * | 2021-05-04 | 2022-11-10 | Q-State Biosciences, Inc. | Drug fingerprinting |
| US12105023B2 (en) | 2021-06-30 | 2024-10-01 | Quelltx, Inc. | Multi-well plate readers and methods of their use |
| AU2023259903A1 (en) * | 2022-04-25 | 2024-11-21 | Jiksak Bioengineering, Inc. | Targeting agent |
| WO2025084395A1 (ja) * | 2023-10-19 | 2025-04-24 | 株式会社Jiksak Bioengineering | 抗シナプトタグミン２抗体 |
| WO2025089346A1 (ja) * | 2023-10-25 | 2025-05-01 | 株式会社Jiksak Bioengineering | 抗シナプトフィジン抗体 |
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| ATE255727T1 (de) | 1998-07-17 | 2003-12-15 | Vertex Pharma San Diego Llc | Detektor und siebvorrichtung für ionenkanäle |
| US7615356B2 (en) * | 2000-07-10 | 2009-11-10 | Vertex Pharmaceuticals (San Diego) Llc | Ion channel assay methods |
| US7312043B2 (en) * | 2000-07-10 | 2007-12-25 | Vertex Pharmaceuticals (San Diego) Llc | Ion channel assay methods |
| EP1425065A4 (en) * | 2001-07-12 | 2004-12-15 | Merck & Co Inc | ELECTRIC FIELD STIMULATION WITH EUKARYONTIC CELLS |
| US7221981B2 (en) * | 2002-03-28 | 2007-05-22 | Northstar Neuroscience, Inc. | Electrode geometries for efficient neural stimulation |
| US20070274923A1 (en) | 2005-01-11 | 2007-11-29 | Philippe Brulet | Non-invasive real-time in vivo bioluminescence imaging of local Ca2+ dynamics in living organisms |
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| JP2016019736A (ja) | 2016-02-04 |
| CN102203622A (zh) | 2011-09-28 |
| KR20110073494A (ko) | 2011-06-29 |
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| US20180136198A1 (en) | 2018-05-17 |
| WO2010027446A3 (en) | 2010-05-20 |
| AU2016202387A1 (en) | 2016-05-05 |
| EP2329275A2 (en) | 2011-06-08 |
| WO2010027446A4 (en) | 2010-08-05 |
| AU2009288657A1 (en) | 2010-03-11 |
| US20120053084A1 (en) | 2012-03-01 |
| CA2744804A1 (en) | 2010-03-11 |
| JP6106225B2 (ja) | 2017-03-29 |
| JP2012501646A (ja) | 2012-01-26 |
| WO2010027446A2 (en) | 2010-03-11 |
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