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1. Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Author

James Paul Mason, Alexandra Werth, Colin G. West, Allison Youngblood, Donald L. Woodraska, Courtney L. Peck, Arvind J. Aradhya, Yijian Cai, David Chaparro, James W. Erikson, Koushik Ganesan, T. R. Geerdts, Thi D Hoang, Thomas M. Horning, Yan Jin, Haixin Liu, Noah Lordi, Zheng Luo, Thanmay S. Menon, Josephine C. Meyer, Emma E Nelson, Kristin A. Oliver, Jorge L Ramirez Ortiz, Andrew Osborne, Alyx Patterson, Nick Pellatz, John Pitten, Nanako Shitara, Daniel Steckhahn, Aseem Visal, Hongda Wang, Chaoran Wang, Evan Wickenden, John Wilson, Mengyu Wu, Nikolay Yegovtsev, Ingrid H Zimmermann, James Holland Aaron, Jumana T. Abdullah, Jonathan M. Abrams, Riley Abrashoff, Andres B. Acevedo, Iker Acha, Daniela M. Meza Acosta, Megan M. Adam, Dante Q. Adams, Kalvyn N Adams, Elena R Adams, Zainab A. Akbar, Ushmi H. Akruwala, Adel Al-Ghazwi, Batool H. Alabbas, Areej A. Alawadhi, Yazeed A. Alharbi, Mohammed S. Alahmed, Mohammed A. Albakr, Yusef J. Albalushi, Jonathan Albaum, Ahmed Aldhamen, Nolan Ales, Mohammad Alesmail, Abdulelah Alhabeeb, Dania Alhamli, Isehaq Alhuseini, Suhail Alkaabi, Tameem Alkhezzi, Mohamed Alkubaisi, Nasser Allanqawi, Martin Allsbrook, Yousef A. Almohsen, Justin Thomas Almquist, Teeb Alnaji, Yousef A Alnasrallah, Nicholas Alonzi, Meshal Alosaimi, Emeen Alqabani, Mohammad Alrubaie, Reema A. Alsinan, Ava L. Altenbern, Abdullah Altokhais, Saleh A. Alyami, Federico Ameijenda, Hamzi Amer, Meggan Amos, Hunter J. Anderson, Carter Andrew, Jesse C Andringa, Abigail Angwin, Gabreece Van Anne, Andrew Aramians, Camila Villamil Arango, Jack. W. Archibald, Brian A. Arias-Robles, Maryam Aryan, Kevin Ash, Justin Astalos, N. S. Atchley-Rivers, Dakota N. Augenstein, Bryce W. Austin, Abhinav Avula, Matthew C. Aycock, Abdulrahman A. Baflah, Sahana Balaji, Brian Balajonda, Leo M Balcer, James O. Baldwin, David J Banda, Titus Bard, Abby Barmore, Grant M. Barnes, Logan D. W. Barnhart, Kevin M. Barone, Jessica L. Bartman, Claire Bassel, Catalina S Bastias, Batchimeg Bat-Ulzii, Jasleen Batra, Lexi Battist, Joshua Bay, Simone Beach, Sara Beard, Quinn I Beato, Ryan Beattie, Thomas Beatty, Tristan De La Beaujardiere, Jacob N. Beauprez, M. G. Beck, Lily Beck, Simone E. Becker, Braden Behr, Timothy A. Behrer, Joshua Beijer, Brennan J. Belei, Annelene L. Belknap, Aislyn Bell, Caden Bence, Evan Benke, Naomi Berhanu, Zachary D. Berriman-Rozen, Chrisanna Bertuccio, Owen A. Berv, Blaine B. Biediger, Samuel J Biehle, Brennen Billig, Jacob Billingsley, Jayce A. Billman, Connor J. Biron, Gabrielle E. Bisacca, Cassidy A. Blake, Guillermo Blandon, Olivia Blevins, Ethan Blouin, Michal Bodzianowski, Taylor A. Boeyink, Matthew Bondar, Lauren Bone, Alberto Espinosa De Los Monteros Bonilla, William T Borelli, Luke R. Borgerding, Troy Bowen, Christine Boyer, Aidan Boyer, Aidan P. Boyle, Tom Boyne, Donovan Branch, Ariana E. Brecl, David J. Brennan, Alexander J Brimhall, Jennifer L. Brockman, Sarah Brookins, Gabriel T. Brown, Cameron L. Brown, Ryan Brown, Jordi Brownlow, Grant Brumage-Heller, Preston J. Brumley, Samuel Bryan, A. Brzostowicz, Maryam Buhamad, Gigi Bullard-Connor, J. R. Ramirez Bunsow, Annemarie C. Burns, John J. Burritt, Nicholas David Burton, Taylor Burton, Celeste Busch, Dylan R. Butler, B. W. Buxton, Malena C. Toups, Carter C. Cabbage, Breonna Cage, Jackson R. Cahn, Andrew J Campbell, Braden P. Canales, Alejandro R. Cancio, Luke Carey, Emma L. Carillion, Michael Andrew Carpender, Emily Carpenter, Shivank Chadda, Paige Chambers, Jasey Chanders, Olivia M. Chandler, Ethan C. Chang, Mitchell G. Chapman, Logan T. Chapman, S. Chavali, Luis Chavez, Kevin Chen, Lily Chen, Sam Chen, Judy Chen, Jenisha Chhetri, Bradyn Chiles, Kayla M. Chizmar, Katherine E Christiansen, Nicholas A. Cisne, Alexis Cisneros, David B. Clark, Evelyn Clarke, Peter C Clarkson, Alexis R. Clausi, Brooke Cochran, Ryan W. Coe, Aislinn Coleman-Plante, Jake R. Colleran, Zachary Colleran, Curran Collier, Nathaniel A. Collins, Sarah Collins, Jack C. Collins, Michael Colozzi, Aurora Colter, Rebecca A. Cone, Thomas C. Conroy, Reese Conti, Charles J. Contizano, Destiny J. Cool, Nicholas M. Cooper, Jessica S Corbitt, Jonas Courtney, Olivia Courtney, Corben L. Cox, Wilmsen B. Craig, Joshua B. Creany, Anastasia Crews, K. A. Crocker, A. J. Croteau, Christian J. Crow, Zoe Cruse, Avril Cruz, Tyler L. Curnow, Hayden Current, Riley T. Curry, Libby Cutler, Aidan St. Cyr, Frederick M. Dabberdt, Johnston Daboub, Olivia Damgaard, Swagatam Das, Emma A. B. Davis, Elyse Debarros, Sean Deel, Megan E. Delasantos, Tianyue Deng, Zachary Derwin, Om Desai, Kai Dewey, John S. Dias, Kenzie A. Dice, R. Dick, Cyrus A. Dicken, Henry Dietrick, Alexis M. Dinser, Alyssa M. Dixon, Thomas J. Dixon, Helen C. Do, Chris H Doan, Connor Doane, Joshua Dodrill, Timothy Doermer, Lizbeth Montoya Dominguez, J. Dominguez, Emerson N. Domke, Caroline R. Doran, Jackson A. Dorr, Philip Dorricott, Danielle C. Dresdner, Michael Driscoll, Kailer H. Driscoll, Sheridan J. Duncan, Christian Dunlap, Gabrielle M. Dunn, Tien Q. Duong, Tomi Oshima Dupeyron, Peter Dvorak, Andrew East, Andrew N. East, Bree Edwards, Lauren Ehrlich, Sara I. Elbashir, Rasce Engelhardt, Jacob Engelstad, Colin England, Andrew Enrich, Abbey Erickson, Benjamin Erickson, Nathan Evans, Calvin A Ewing, Elizabeth A. Eyeson, Ian Faber, Avery M. Fails, John T Fauntleroy, Kevin Fell, Zitian Feng, Logan D. Fenwick, Nikita Feoktistov, Ryann Fife, John Alfred D. Figueirinhas, Jean-Paul Fisch, Emmalee Fischer, Jules Fischer-White, Aidan F. Fitton, Alexander Fix, Lydia Flackett, Fernando Flores, Aidan Floyd, Leonardo Del Foco, Adeduni Folarin, Aidan E. Forbes, Elise Fortino, Benjamin L. Fougere, Alexandra A. Fowler, Margaret Fox, James M. French, Katherine V. French, Florian G. Frick, Calvin R. Fuchs, Bethany E. S. Fuhrman, Sebastian Furney, Moutamen Gabir, Gabriela Galarraga, Skylar Gale, Keala C. Gapin, A. J. Garscadden, Rachel Gasser, Lily Gayou, Emily E. Gearhart, Jane Geisman, Julianne R. Geneser, Sl Genne, Julia G Gentile, Eleanor Gentry, Jacob D. George, Nathaniel James Georgiades, Phillip Gerhardstein, Clint Gersabeck, Bandar Abu Ghaith, Dorsa Ghiassi, B. C. Giebner, Dalton Gilmartin, Connor B. Gilpatrick, Michael Gjini, Olivia Golden, Nathan T. Golding, C. A. Goldsberry, Angel R. Gomez, Angel A. Gomez, Sean Gopalakrishnan, Mariam Gopalani, Nicholas Gotlib, Alaina S. Graham, Michael J Gray, Alannah H. Gregory, Joshua A. Gregory, Kristyn Grell, Justus Griego, Nicholas F. Griffin, Kyle J. Griffin, Matt Guerrero, Nicole Gunderson, Mutian Guo, E. R. Gustavsson, Grace K. Hach, L. N. Haile, Jessica Haines, Jack J. Mc Hale, Ryder Buchanan Hales, Mark S. Haley, Jacqueline L. Hall, Sean R. Hamilton, Soonhee Han, Tyler Hand, Luke C. Hanley, Connor M Hansen, Joshua A. Hansen, Jonathan Hansson, Tony Yunfei Hao, Nicholas Haratsaris, Isabelle Hardie, Dillon F. Hardwick, Cameron T. Hares, Logan Swous Harris, Coyle M. Harris, Omer Hart, Kyle Hashiro, Elsie Hattendorf, Calder Haubrich, Elijah Hawat, Griffin A. Hayrynen, Danielle A. Heintz, Tim Hellweg, Angel Hernandez, Emanuel Herrera, Robert N. Herrington, Tim Herwig, Troy M. Hesse, Quinn Hiatt, Lea Pearl Hibbard, Imari R. Hicks, Andrew J. Hicks, Nigel Highhouse, Annalise K. Hildebrand, Paula Hill, Hallie Hill, Evan Hintsa, Anna E. Hirschmann, Travis Hitt, Ella Ho, Isabelle J. Hoff, Alex Hoffman, Blake A. Hogen, Linda Horne, Timothy J Houck, Noah H. Howell, E. M. Hrudka, J. Hu, Jianyang Huang, Chenqi Huang, Shancheng Huang, Zachary A. Hudson, Nathan C. Hudson, Tyler J. Huebsch, Owen Hull, Samuel C Hunter, Troy Husted, Abigail P. Hutabarat, Leslie Huynh, Antonio E. Samour Ii, Yolande Idoine, Julia A. Ingram, Taro Iovan, Samuel A. Isert, Antonio Salcido-Alcontar, Thomas Jacobsen, Alan A Jaimes, Connor Jameson, J. R. Jarriel, Sam Jarvis, Josh Jenkins, Alexander V. Jensen, Jacob Jeong, Luke A. Jeseritz, Trevor Jesse, Soo Yeun Ji, Yufan Jiang, Owen Johnson, Matthew Johnson, Sawyer Johnson, Julia Johnston, Braedon Y. Johnston, Olivia M. Jones, M. R. Jones, Tara Jourabchi, Tony A. House, Parker Juels, Sabrina J. H. T. Kainz, Emily Kaiser, Nicolas Ian Kallemeyn, Madison H. Kalmus, Etash Kalra, Margaret Kamenetskiy, Jeerakit Kanokthippayakun, Shaun D. Kapla, Brennan J. Karsh, Caden J. Keating, Morgan A. Kelley, Michael P. Kelley, Nicholas Kelly, James Kelly, Teagan Kelly, Christopher M Kelly, Kellen Kennedy, Cayla J. Kennedy, Forrest Kennedy, Abigail Kennedy, Liana Kerr-Layton, Marilyn Ketterer, Ibraheem A. Khan, Usman Khan, Sapriya Khanal, Jack L. Kiechlin, Dominic Killian, Kevin Kim, Brian T. Kim, Matthew M. Kim, Jake Kim, Aspen Kimlicko, Isabel M Kipp, Hunter B. Kirkpatrick, Natalie Kissner, Emily R. Kite, Olivia R. Kleinhaus, Philip Whiting Knott, Will Koch, Greta Koenig, Emily Koke, Thomas Kokes, Yash S. Kothamdi, Zack Krajnak, Zoe M. Kresek, Dylan Kriegman, Jake E. Kritzberg, Davis J. Krueger, Bartlomiej Kubiak, Kirsten Kuehl, Chrisanne Kuester, Nicolas A. Kuiper, Aman Priyadarshi Kumar, Connor Kuybus, Daniel Kwiatkowski, Quintin Y. Lafemina, Kevin Lacjak, Kyle Lahmers, Antonia Lam, Kalin Landrey, Maxwell B. Lantz, Zachary Larter, Benjamin P. Lau, Megan Lauzon, Rian Lawlor, Tyler Learned, E. C. Lee, Junwon Lee, Adrianna J. Lee, Justin Lee, Alexis Ying-Shan Lee, Christian J Lee, Nathaniel F. Lee, Linzhi Leiker, Dylan Lengerich, Cecilia Leoni, Adrienne R. Lezak, David Y. Li, Isaac Li, Ryan Z. Liao, Bridget Linders, Morgan I Linger, Katherine B. Linnane, Sam Lippincott, Barrett Lister, Shelby D Litton, Nianzi Liu, Steven Y. Liu, Timothy W. Logan, Nathan Londres, Mia C. Lonergan, Emily Lookhoff, N. E. Loomis, Christian Lopez, Justin Loring, Jeffrey Lucca, Dax Lukianow, Nathan M. Cheang, William Macdonald, Claire A. Madonna, Kasey O. Madsen, Tiffany E. Maksimuk, Macguire Mallory, Ryan A. Malone, Blake Maly, Xander R. Manzanares, Aimee S. Maravi, Serafima M. Marcus, Nasreen Marikar, Josie A. Marquez, Mathew J. Marquez, Lauren Marsh, Toni Marsh, Logan S. Martin, Alexa M. Martinez, Jose R. Martinez, Hazelia K. Martinez, Cara Martyr, Mirna Masri, Giorgio Matessi, Adam Izz Khan Mohd Reduan Mathavan, Randi M. Mathieson, Kabir P. Mathur, Graham Mauer, Victoria A. Mayer, Liam Mazzotta, Glen S. Mccammon, Rowan Mcconvey, Tyler Mccormick, Andrew Mccoy, Kelleen Mcentee, Meaghan V. Mcgarvey, Riley M. Mcgill, James K. Mcintyre, Finbar K. Mckemey, Zane Mcmorris, Jesse J. Mcmullan, Ella Mcquaid, Caden Mcvey, Kyle Mccurry, Mateo M. Medellin, Melissa Medialdea, Amar Mehidic, Stella Meillon, Jonah B. Meiselman-Ashen, Sarah Mellett, Dominic Menassa, Citlali Mendez, Patricia Mendoza-Anselmi, Riley Menke, Sarah Mesgina, William J. Mewhirter, Ethan Meyer, Aya M. Miften, Ethan J. Miles, Andrew Miller, Joshua B. Miller, Emily B. Millican, Sarah J. Millican, Dylan P. Mills, Josh Minimo, Jay H. Misener, Alexander J. Mitchell, Alexander Z. Mizzi, Luis Molina-Saenz, Tyler S Moll, Hayden Moll, Maximus Montano, Michael Montoya, Eli Monyek, Jacqueline Rodriguez Mora, Gavin Morales, Genaro Morales, Annalise M. Morelock, Cora Morency, Angel J. Moreno, Remy Morgan, Alexander P. Moss, Brandon A. Muckenthaler, Alexander Mueller, Owen T. Mulcahy, Aria T. Mundy, Alexis A. Muniz, Maxwell J. Murphy, Madalyn C. Murphy, Ryan C. Murphy, Tyler Murrel, Andrew J. Musgrave, Michael S. Myer, Kshmya Nandu, Elena R. Napoletano, Abdulaziz Naqi, Anoothi Narayan, Liebe Nasser, Brenna K Neeland, Molly Nehring, Maya Li Nelson, Lena P. Nguyen, Lena Nguyen, Leonardo Nguyen, Valerie A. Nguyen, Khoa D Nguyen, Kelso Norden, Cooper Norris, Dario Nunes-Valdes, Rosemary O. Nussbaum, Cian O’Sullivan, Ian O’Neill, S. H. Oakes, Anand Odbayar, Caleb Ogle, Sean Oishi-Holder, Nicholas Olguin, Nathaniel P. Olson, Jason Ong, Elena N. Opp, Dan Orbidan, Ryan Oros, Althea E. Ort, Matthew Osborn, Austin Osogwin, Grant Otto, Jessica Oudakker, Igor Overchuk, Hannah M. Padgette, Jacqueline Padilla, Mallory Palizzi, Madeleine L. Palmgren, Adler Palos, Luke J. Pan, Nathan L. Parker, Sasha R. Parker, Evan J. Parkinson, Anish Parulekar, Paige J. Pastor, Kajal Patel, Akhil Patel, Neil S. Patel, Samuel Patti, Catherine Patton, Genevieve K. Payne, Matthew P. Payne, Harrison M. Pearl, Charles B. Beck Von Peccoz, Alexander J. Pedersen, Lily M. Pelster, Munisettha E. Peou, J. S. Perez, Freddy Perez, Anneliese Pesce, Audrey J. Petersen, B. Peterson, Romeo S. L. Petric, Joshua Pettine, Ethan J. Phalen, Alexander V. Pham, Denise M. Phan, Callie C Pherigo, Lance Phillips, Justin Phillips, Krista Phommatha, Alex Pietras, Tawanchai P. Pine, Sedique Pitsuean-Meier, Andrew M. Pixley, Will Plantz, William C. Plummer, Kaitlyn E. Plutt, Audrey E. Plzak, Kyle Pohle, Hyden Polikoff, Matthew Pollard, Madelyn Polly, Trevor J. Porter, David Price, Nicholas K. Price, Gale H. Prinster, Henry Austin Propper, Josh Quarderer, Megan S. Quinn, Oliver Quinonez, Devon Quispe, Cameron Ragsdale, Anna L. Rahn, M. Rakhmonova, Anoush K Ralapanawe, Nidhi Ramachandra, Nathaniel Ramirez, Ariana C. Ramirez, Sacha Ramirez, Parker Randolph, Anurag Ranjan, Frederick C Rankin, Sarah Grace Rapaport, Nicholas O Ratajczyk, Mia G. V. Ray, Brian D. Reagan, John C. Recchia, Brooklyn J. Reddy, Joseph Reed, Charlie Reed, Justin Reeves, Eileen N. Reh, Ferin J. Von Reich, Andrea B. Reyna, Alexander Reynolds, Hope Reynolds, Matthew Rippel, Guillermo A. Rivas, Anna Linnea Rives, Amanda M. Robert, Samuel M. Robertson, Maeve Rodgers, Stewart Rojec, Andres C. Romero, Ryan Rosasco, Beth Rossman, Michael Rotter, Tyndall Rounsefell, Charlotte Rouse, Allie C. Routledge, Marc G. Roy, Zoe A. Roy, Ryan Ruger, Kendall Ruggles-Delgado, Ian C. Rule, Madigan Rumley, Brenton M. Runyon, Collin Ruprecht, Bowman Russell, Sloan Russell, Diana Ryder, David Saeb, J. Salazar, Violeta Salazar, Maxwell Saldi, Jose A. Salgado, Adam D. Salindeho, Ethan S. Sanchez, Gustavo Sanchez-Sanchez, Darian Sarfaraz, Sucheta Sarkar, Ginn A. Sato, Carl Savage, Marcus T. Schaller, Benjamin T. Scheck, Jared A. W. Schlenker, Matthew J Schofer, Stephanie H. Schubert, Courtney Schultze, Grace K Schumacher, Kasper Seglem, Lauren Serio, Octave Seux, Hannan Shahba, Callie D. Shannahan, Shajesh Sharma, Nathan Shaver, Timothy Shaw, Arlee K. Shelby, Emma Shelby, Grace Shelchuk, Tucker Sheldrake, Daniel P. Sherry, Kyle Z. Shi, Amanda M. Shields, Kyungeun Shin, Michael C. Shockley, Dominick Shoha, Jadon Shortman, Mitchell Shuttleworth, Lisa Sibrell, Molly G. Sickler, Nathan Siles, H. K. Silvester, Conor Simmons, Dylan M. Simone, Anna Simone, Savi Singh, Maya A. Singh, Madeline Sinkovic, Leo Sipowicz, Chris Sjoroos, Ryan Slocum, Colin Slyne, Korben Smart, Alexandra N. Smith, Kelly Smith, Corey Smith, Elena K. Smith, Samantha M. Smith, Percy Smith, Trevor J Smith, G. L. Snyder, Daniel A. Soby, Arman S. Sohail, William J. Solorio, Lincoln Solt, Caitlin Soon, Ava A Spangler, Benjamin C. Spicer, Ashish Srivastava, Emily Stamos, Peter Starbuck, Ethan K. Stark, Travis Starling, Caitlyn Staudenmier, Sheen L. Steinbarth, Christopher H. Steinsberger, Tyler Stepaniak, Ellie N. Steward, Trey Stewart, T. C. Stewart, Cooper N. Stratmeyer, Grant L. Stratton, Jordin L. Stribling, S. A Sulaiman, Brandon J Sullivan, M. E. Sundell, Sohan N. Sur, Rohan Suri, Jason R. Swartz, Joshua D. Sweeney, Konner Syed, Emi Szabo, Philip Szeremeta, Michael-Tan D. Ta, Nolan C. Tanguma, Kyle Taulman, Nicole Taylor, Eleanor Taylor, Liam C. Taylor, K. E. Tayman, Yesica Tellez, Richard Terrile, Corey D Tesdahl, Quinn N. Thielmann, Gerig Thoman, Daniel Thomas, Jeffrey J. Thomas, William N. Thompson, Noah R. Thornally, Darien P. Tobin, Kelly Ton, Nathaniel J. Toon, Kevin Tran, Bryn Tran, Maedee Trank-Greene, Emily D. Trautwein, Robert B. Traxler, Judah Tressler, Tyson R. Trofino, Thomas Troisi, Benjamin L. Trunko, Joshua K. Truong, Julia Tucker, Thomas D Umbricht, C. H. Uphoff, Zachary T. Upthegrove, Shreenija Vadayar, Whitney Valencia, Mia M. Vallery, Eleanor Vanetten, John D. Vann, Ilian Varela, Alexandr Vassilyev, Nicholas J. Vaver, Anjali A. Velamala, Evan Vendetti, Nancy Ortiz Venegas, Aditya V. Vepa, Marcus T. Vess, Jenna S. Veta, Andrew Victory, Jessica Vinson, Connor Maklain Vogel, Michaela Wagoner, Steven P. Wallace, Logan Wallace, Caroline Waller, Jiawei Wang, Keenan Warble, N. R. D. Ward-Chene, James Adam Watson, Robert J. Weber, Aidan B. Wegner, Anthony A Weigand, Amanda M. Weiner, Ayana West, Ethan Benjamin Wexler, Nicola H. Wheeler, Jamison R. White, Zachary White, Oliver S. White, Lloyd C. Whittall, Isaac Wilcove, Blake C. Wilkinson, John S. Willard, Abigail K. Williams, Sajan Williams, Orion K. Wilson, Evan M. Wilson, Timothy R. Wilson, Connor B. Wilson, Briahn Witkoff, Aubrey M. Wolfe, Jackson R. Wolle, Travis M. Wood, Aiden L. Woodard, Katelynn Wootten, Catherine Xiao, Jianing Yang, Zhanchao Yang, Trenton J. Young, Isabel Young, Thomas Zenner, Jiaqi Zhang, Tianwei Zhao, Tiannie Zhao, Noah Y. Zhao, Chongrui Zhou, Josh J Ziebold, Lucas J. Ziegler, James C. Zygmunt, Jinhua Zhang, and H. J. Lewandowski

Subjects
Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, FOS: Physical sciences, Astronomy and Astrophysics, Solar and Stellar Astrophysics (astro-ph.SR)
Abstract

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating., Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 71

Published
2023
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3. ESA Habitat Conservation Plans document db

Author

Carter, Andrew, Malcom, Jacob, and Harl, Heather

Subjects
U.S. Fish and Wildlife Service, Endangered Species Act, HCP, Habitat Conservation Plans, ESA
Abstract

A corpus of documents related to over 600 Habitat Conservation Plans created under the US Endangered Species Act.

Published
2022
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4. ESA 4(b)(2) exclusions

Author

Malcom, Jacob, Evans, Michael, and Carter, Andrew

Subjects
Endangered Species Act, critical habitat, ESA
Abstract

A brief memo of critical habitat exclusions under section 4(b)(2) of the ESA.

Published
2022
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5. Cretaceous Granitic Magmatism in South-Central Vietnam: Constraints from Zircon U–Pb Geochronology

Author

Huu Hiep NGUYEN, Nhu Sang PHAM, Van Long HOANG, Carter ANDREW, Vinh Hau BUI, Hoang Bac BUI, Thanh Trung TRINH, and Lam Anh NGUYEN

Subjects
Geochemistry and Petrology, Geotechnical Engineering and Engineering Geology
Abstract

South-central Vietnam abundantly presents magmatic rocks with larger volumes ofCretaceous granitic rocks. In this study, zircon U–Pb geochronology of granite samples from the Deoca,Ankroet, and Dinhquan complexes in south-central Vietnam are utilized to investigate Cretaceousgranitic magmatism. According to U–Pb analysis results, zircon ages of granitic rocks display the Deocaat ~113–92 Ma, the Ankroet at ~103–98 Ma, and the Dinhquan at ~97–113 Ma. The range of ages isnarrow from 113 to 92 Ma, with most common ages date at ~100 Ma. Published data and our resultsdisplay that Cretaceous granitic magmatism was active between ~87–118 Ma and most active at ~100Ma in south-central Vietnam. Additionally, the Deoca and Dinhquan complexes show inherited ages inTriassic followed by Proterozoic and Carboniferous to Ordovician. The obtained ages indicate that Itypegranitic rocks could be derived from melting of basement rocks. Our study suggests that I-typegranitic rocks in south-central Vietnam were significantly intruded around 100 Ma.

Published
2021
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6. Philosophical Foundations of Environmental Policy Analysis: Can Critical Realism Bridge the Neopositivist/Interpretivist Divide?

Author

Carter, Andrew

Subjects
bepress|Arts and Humanities|Philosophy|Epistemology, bepress|Arts and Humanities|Philosophy, bepress|Arts and Humanities|Philosophy|Philosophy of Science, SocArXiv|Arts and Humanities, SocArXiv|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration|Environmental Policy, SocArXiv|Arts and Humanities|Philosophy, SocArXiv|Arts and Humanities|Philosophy|Philosophy of Science, SocArXiv|Social and Behavioral Sciences|Environmental Studies, SocArXiv|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration, bepress|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration|Environmental Policy, bepress|Social and Behavioral Sciences, bepress|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration, bepress|Social and Behavioral Sciences|Environmental Studies, SocArXiv|Social and Behavioral Sciences, SocArXiv|Arts and Humanities|Philosophy|Epistemology, bepress|Arts and Humanities
Abstract

Traditional environmental policy analysis has followed a neopositivist epistemological frame, using the natural sciences as a template as to how social-ecological problems can be analyzed. Such approaches to policy analysis have been caught up in the same crisis as the social sciences have in general: an overarching failure to create a predictive science of society or to consistently provide solutions to social problems. This has led some policy researchers to align with the interpretivist turn, which has had its own drawbacks. In this review I summarize the historical development and main tenets of both approaches, examining their advantages and disadvantages. I then review an alternative epistemological approach to social science, critical realism, which combines an ontological realism with an epistemological relativism, a focus on elucidating causal mechanisms in the social-ecological systems studied, an approach that may be particularly suited for analyzing the complex social-ecological systems studied in environmental policy analysis.

Published
2021
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7. A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude

Author

Marschalek, J.W., Zurli, L., Talarico, F., van de Flierdt, T., Vermeesch, P., Carter, Andrew, Beny, F., Bout-Roumazeilles, V., Sangiorgi, F., Hemming, S.R., Pérez, L.F., Colleoni, F., Prebble, J.G., van Peer, T.E., Perotti, M., Shevenell, A.E., Browne, I., Kulhanek, D.K., Levy, R., Harwood, D., Sullivan, N.B., Meyers, S.R., Griffith, E.M., Hillenbrand, C.-D., Gasson, E., Siegert, M. J., Keisling, B., Licht, K. J., Kuhn, G., Dodd, J. P., Boshuis, C., De Santis, L., McKay, R. M., Ash, J., Browne, I.M., Cortese, G., Dodd, J.P., Esper, O.M., Gales, J.A., Harwood, D.M., Ishino, S., Keisling, B.A., Kim, S., Laberg, J.S., Leckie, R.M., McKay, R.M., Müller, J., Patterson, M.O., Romans, B.W., Romero, O.E., Seki, O., Singh, S.M., Cordeiro de Sousa, I.M., Sugisaki, S.T., Xiao, W., Xiong, Z., Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), White, M, and Natural Environment Research Council (NERC)

Subjects
LARGE IGNEOUS PROVINCE, Paleoclimate, General Science & Technology, [SDV]Life Sciences [q-bio], West Antarctic Ice Sheet, Early Miocene, Ross Sea, Antarctica, Paleoclimate, Antarctic Regions, Climate Models, WALLED DINOFLAGELLATE CYSTS, Sea Level Rise, CONTINENTAL-SHELF, MARIE-BYRD-LAND, Ross Sea, SOUTHERN VICTORIA LAND, MAGNETIZATION LOCK-IN, IODP Expedition 374, DETRITAL ZIRCONS, Ice Cover, Seawater, History, Ancient, [PHYS]Physics [physics], Early Miocene, Science & Technology, Multidisciplinary, West Antarctic Ice Sheet, Multidisciplinary Sciences, U-PB GEOCHRONOLOGY, es, [SDU]Sciences of the Universe [physics], [SDE]Environmental Sciences, Science & Technology - Other Topics, CENTRAL TRANSANTARCTIC MOUNTAINS, Antarctica
Abstract

This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at https://doi.org/10.1038/s41586-021-04148-0. Early to Middle Miocene sea-level oscillations of approximately 40–60 m estimated from far-field records1,2,3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72–17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution

Published
2021
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8. Bimodal Endocytic Probe for Three-Dimensional Correlative Light and Electron Microscopy

Author

Fermie, Job, de Jager, Leanne, Foster, Helen E, Veenendaal, Tineke, de Heus, Cecilia, van Dijk, Suzanne, Ten Brink, Corlinda, Oorschot, Viola, Yang, Lin, Li, Wei, Müller, Wally H, Howes, Stuart, Carter, Andrew P, Förster, Friedrich, Posthuma, George, Gerritsen, Hans C, Klumperman, Judith, Liv, Nalan, Structural Biochemistry, Soft Condensed Matter and Biophysics, Sub Algemeen Biologie, Sub Molecular Biophysics, Sub Structural Biochemistry, Afd Biologie Algemeen, Structural Biochemistry, Soft Condensed Matter and Biophysics, Sub Algemeen Biologie, Sub Molecular Biophysics, Sub Structural Biochemistry, and Afd Biologie Algemeen

Subjects
Materials science, Endosome, Endocytic cycle, cryoelectron microscopy, electron tomography, Genetics and Molecular Biology (miscellaneous), Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, law.invention, volume-electron microscopy, law, Genetics, Fluorescence microscope, nanogold fiducials, Radiology, Nuclear Medicine and imaging, correlative light and electron microscopy, Fluorescence, Computer Science Applications, Radiology Nuclear Medicine and imaging, Colloidal gold, endolysosomal system, Biophysics, Ultrastructure, Electron microscope, Fiducial marker, Biotechnology
Abstract

Correlative light and electron microscopy (CLEM) can infer molecular, functional and dynamic information to ultrastructure by linking information of different imaging modalities. One of the main challenges, especially in 3D-CLEM, is the accurate registration of fluorescent signals to electron microscopy (EM). Here, we present fluorescent BSA-gold (fBSA-Au), a bimodal endocytic tracer as fiducial marker for 2D and 3D CLEM applications. fBSA-Au consists of colloidal gold (Au) particles stabilized with fluorescent bovine serum albumin (BSA). The conjugate is efficiently endocytosed and distributed throughout the 3D endo-lysosomal network of the cells, and has an excellent visibility both in fluorescence microscopy (FM) and EM. We demonstrate the use of fBSA-Au in several 2D and 3D CLEM applications using Tokuyasu cryosections, resin-embedded material, and cryo-EM. As a fiducial marker, fBSA-Au facilitates rapid registration of regions of interest between FM and EM modalities and enables accurate (50-150 nm) correlation of fluorescence to EM data. Endocytosed fBSA-Au benefits from a homogenous 3D distribution throughout the endosomal system within the cell, and does not obscure any cellular ultrastructure. The broad applicability and visibility in both modalities makes fBSA-Au an excellent endocytic fiducial marker for 2D and 3D (cryo-)CLEM applications.

Published
2021
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9. A thermostable, closed SARS-CoV-2 spike protein trimer

Author

Xiong, Xiaoli, Qu, Kun, Ciazynska, Katarzyna A., Hosmillo, Myra, Carter, Andrew P., Ebrahimi, Soraya, Ke, Zunlong, Scheres, Sjors H. W., Bergamaschi, Laura, Grice, Guinevere L., Zhang, Ying, Bradley, John, Lyons, Paul A., Smith, Kenneth G. C., Toshner, Mark, Elmer, Anne, Ribeiro, Carla, Kourampa, Jenny, Jose, Sherly, Kennet, Jane, Rowlands, Jane, Meadows, Anne, O’Brien, Criona, Rastall, Rebecca, Crucusio, Cherry, Hewitt, Sarah, Price, Jane, Calder, Jo, Canna, Laura, Bucke, Ashlea, Tordesillas, Hugo, Harris, Julie, Ruffolo, Valentina, Domingo, Jason, Graves, Barbara, Butcher, Helen, Caputo, Daniela, Le Gresley, Emma, Dunmore, Benjamin J., Martin, Jennifer, Legchenko, Ekaterina, Treacy, Carmen, Huang, Christopher, Wood, Jennifer, Sutcliffe, Rachel, Hodgson, Josh, Shih, Joy, Graf, Stefan, Tong, Zhen, Mescia, Federica, Tilly, Tobias, O’Donnell, Ciara, Hunter, Kelvin, Pointon, Linda, Pond, Nicole, Wylot, Marta, Jones, Emma, Fawke, Stuart, Bullman, Ben, Turner, Lori, Jarvis, Isobel, Omarjee, Ommar, De Sa, Aloka, Marsden, Joe, Betancourt, Ariana, Perera, Marianne, Epping, Maddie, Richoz, Nathan, Bower, Georgie, Sharma, Rahul, Nice, Francesca, Huhn, Oisin, Stark, Hannah, Walker, Neil, Stirrups, Kathy, Ovington, Nigel, Dewhust, Eleanor, Li, Emily, Papadia, Sofia, Nathan, James A., Baker, Stephen, James, Leo C., Baxendale, Helen E., Goodfellow, Ian, Doffinger, Rainer, Briggs, John A. G., Hosmillo, Myra [0000-0002-3514-7681], Nathan, James [0000-0002-0248-1632], Baker, Stephen [0000-0003-1308-5755], Goodfellow, Ian [0000-0002-9483-510X], and Apollo - University of Cambridge Repository

Subjects
Models, Molecular, Immunogen, Protein Conformation, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Trimer, Enzyme-Linked Immunosorbent Assay, Receptor binding site, medicine.disease_cause, Protein Engineering, Article, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Protein structure, COVID-19 Testing, Models, Structural Biology, medicine, Humans, Disulfides, Molecular Biology, 030304 developmental biology, Cell entry, 0303 health sciences, Mutation, Clinical Laboratory Techniques, Protein Stability, SARS-CoV-2, Cryoelectron Microscopy, Temperature, Spike Protein, Molecular, Coronavirus Infections, Flow Cytometry, Immunoglobulin G, Protein Multimerization, Spike Glycoprotein, Coronavirus, Spike Glycoprotein, 3. Good health, Coronavirus, Membrane, Biophysics, 030217 neurology & neurosurgery
Abstract

The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. S exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor binding site, and subsequently from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S which allow production of thermostable, crosslinked, S protein trimers that are trapped in the closed, pre-fusion, state. We have determined the structures of crosslinked and non-crosslinked proteins, identifying two distinct closed conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.

Published
2020
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10. Supplemental_Material_Dynein_Screen_Vincent_et_al - A High-Throughput Cellular Screening Assay for Small-Molecule Inhibitors and Activators of Cytoplasmic Dynein-1-Based Cargo Transport

Author

Vincent, John, Preston, Marian, Mouchet, Elizabeth, Laugier, Nicolas, Corrigan, Adam, Boulanger, Jérôme, Brown, Dean G., Clark, Roger, Wigglesworth, Mark, Carter, Andrew P., and Bullock, Simon L.

Subjects
FOS: Clinical medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental_Material_Dynein_Screen_Vincent_et_al for A High-Throughput Cellular Screening Assay for Small-Molecule Inhibitors and Activators of Cytoplasmic Dynein-1-Based Cargo Transport by John Vincent, Marian Preston, Elizabeth Mouchet, Nicolas Laugier, Adam Corrigan, Jérôme Boulanger, Dean G. Brown, Roger Clark, Mark Wigglesworth, Andrew P. Carter and Simon L. Bullock in SLAS Discovery

Published
2020
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11. The Case for Plagiarism

Author

Carter, Andrew M

Subjects
Law and Society, Law, Legal Ethics and Professional Responsibility
Published
2019

16. Controls on Erosion in the Western Tarin Basin: Implications for the Uplift of Northwest Tibet and the Parmir

Author

Clift, Peter D., Zheng, Hongbo, Carter, Andrew, Böning, Philipp, Jonell, Tara N., Schorr, Hannah, Shan, Xin, Pahnke, Katharina, Wei, Xiaochun, Rittenour, Tammy M., and Geological Society of America

Subjects
Asia, Cenozoic, apatite, Earth Sciences, Physical Sciences and Mathematics, exhumation, Geology, absolute age
Abstract

We present here bulk sediment major element chemistry, Nd and Sr isotope ratios, and detrital apatite fission-track (AFT) and U-Pb zircon ages to characterize the provenance of the southwestern Taklimakan Desert (northwest China) and the three major rivers draining this region. We establish the spatial and temporal controls on erosion and sediment transport in the modern Tibetan rain shadow. The Hotan River drains the North Kunlun block and is characterized by zircon populations at 160–230 Ma and 370–520 Ma. The Yarkand River shares these grains with the Hotan, but also has a very prominent zircon population at 40–160 Ma, which is common in Karakoram basement, indicating heavy sediment flux from these ranges to that drainage. This implies a strong control on erosion by topographic steepness and precipitation mediated through glaciation. Our zircon data confirm earlier studies that indicated that the Taklimakan sand is derived from both the Kunlun and Pamir Mountains. AFT ages are younger in the Hotan River than in the Kashgar River, which drains the Pamir, and in both are younger than in the Transhimalaya and parts of the western edge of the Tibetan Plateau. Exhumation is estimated at ∼1000 m/m.y. in the North Kunlun and ∼500 m/m.y. in the eastern Pamir, which have been exhuming more slowly than the western ranges in the recent past. Holocene aggradation terracing was dated using quartz optically stimulated luminescence methods and is mostly associated with times of fluctuating climate after 4 ka, with phases of valley filling dated at 2.6, 1.4, and 0.4 ka. The heights and volumes of the terraces show that sediment storage in the mountains is not a significant buffer to sediment transport, in contrast to the more monsoonal Indus system directly to the south. South of the Mazatag Ridge a significant eolian deposit accumulated ∼500 yr ago, but this has been deflated in more recent times. Comparison of the modern river data with those previously measured from Cenozoic foreland sedimentary rocks shows that no sediment similar to that of the modern Yarkand River is seen in the geologic record, which is inferred to be younger than 11 Ma, and probably much less. Uplift of the North Kunlun had started by ca. 17 Ma, somewhat after that of the Pamir and Songpan Garze of northwestern Tibet, dated to before 24 Ma. Sediment from the Kunlun reached the foreland basin between 14 and 11 Ma. North Kunlun exhumation accelerated before 3.7 Ma, likely linked to faster rock uplift.

Published
2017

17. Bright Lights and White Nights

Author

Carter, Andrew and Carter, Andrew

Abstract

At first, moving east appears an inspired decision for Troy. But things take a disastrous turn. He inadvertently becomes embroiled in a debauched adventure, involving the players and oddballs of Hong Kong's cocaine underworld … and a police informant against his will.

Published
2015

18. Tactile-channel interactions in the somatosensory system

Author

Carter, Andrew

Subjects
Rapidly adapting, Channel convergence, Modality convergence, Tactile channel convergence, Tactile submodality convergence
Abstract

The sense of touch is mediated by several separate tactile ‘channels’ defined by the classes of peripheral tactile receptors in the skin. How the information arising in these channels interacts during cortical processing is currently debated. This thesis explores the topic of tactile cross-channel interaction with a specific focus on the stimulus property of intensity in fast-adapting receptors. This is done using both neurophysiological and psychophysical methodologies: electrophysiological recordings using large multielectrode arrays in primary and secondary somatosensory cortices of the anaesthetised cat (Chapters 3 and 4); and psychophysical studies using human subjects (Chapter 5). Chapter 3 shows that some neurons in primary and secondary somatosensory cortex of the cat receive input from both fast-adapting channels of the glabrous skin, contrary to the prevailing model that argues for no cross-channel convergence. Chapter 4 describes the spatial extent of the region of primary and secondary somatosensory cortex activated by a vibrotactile stimulus of varying stimulus intensity. The results suggest that the area of activated cortex increases with increasing stimulus intensity, but that this is mostly due to a ‘filling in’ of a mosaic-like active region of cortex. Chapter 5 shows that cross-channel interaction between both fast-adapting glabrous tactile channels affects the detection threshold of a low-frequency vibrotactile stimulus. A high-frequency sinusoidal masking stimulus presented to the same location as a low-frequency sinusoidal stimulus resulted in an increased detection threshold of the low-frequency stimulus, whereas a high-frequency masker presented at a proximal location from the low-frequency stimulus does not produce an increase in detection threshold. The results obtained from all these studies support the claim for cross-channel interaction among the tactile channels, even for the processing of basic perceptual properties such as detection threshold that likely occur as early as primary and secondary somatosensory cortical regions.

Published
2015
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19. Observation and Modeling of Extrasolar Planets

Author

Carter, Andrew James

Subjects
Astrophysics::Earth and Planetary Astrophysics
Abstract

The field of exoplanet research has currently yielded the discovery of 552 planets. This figure includes 132 transiting planets which can be studied in greater detail and have formed the cornerstone of research to characterise the exoplanet population. In particular, such studies seek to analyse the planetary atmospheres, but research has thus far yielded more questions than answers. \ud \ud Exoplanetary atmospheric studies have typically focussed on one planet apiece - complicating any comparative analysis as every result employs different methods and instruments. For a comprehensive, comparative study, a robust and reliable means of reducing and analysing such observations is required, along with a body of data from a single instrument. \ud \ud One such instrument is the Bubble Space Telescope (BST) whose NICMOS (Near Infrared Camera and Multi-Object Spectrometer) instrument has observed the transits of nine extrasolar planets across multiple wavelengths in the near-infrared. A robust pipeline has been developed to reduce all such observations using the fame techniques. \ud \ud This pipeline reduces grism images of an exoplanet host star across a transit event. These exposures are checked for bad pixels, flat fielded and background-subtracted before robust extraction of a transit light curve. This light curve is then detrended to remove systematic noise by application of a new technique developed in this study. Following detrending, the light curve is modelled using a be- spoke MCMC (Markov-Chain Monte-Carlo) algorithm to determine the planetary parameters. A continuum of wavelength-dependent transit light curves is also extracted, detrended and modelled to de- termine the variation in transit depth with wavelength; and .hereby infer the transmission spectrum of the planet's atmosphere. \ud \ud The finished pipeline has been applied to three sets of HST NIC- MOS observations covering the transits of WASP-2b, HD189733b and GJ436b. For each data set, a new set of planetary parameters has been derived and for WASP-2b and HD189733b an atmospheric transmission spectrum extracted. Both spectra show signs of atmospheric haze and molecular absorption, but also evidence of residual systematic noise, complicating analysis.

Published
2012
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20. A thermostable, closed SARS-CoV-2 spike protein trimer

Author

Xiong, Xiaoli, Qu, Kun, Ciazynska, Katarzyna A, Hosmillo, Myra, Carter, Andrew P, Ebrahimi, Soraya, Ke, Zunlong, Scheres, Sjors HW, Bergamaschi, Laura, Grice, Guinevere L, Zhang, Ying, CITIID-NIHR COVID-19 BioResource Collaboration, Nathan, James A, Baker, Stephen, James, Leo C, Baxendale, Helen E, Goodfellow, Ian, Doffinger, Rainer, and Briggs, John AG

Subjects
Models, Molecular, Clinical Laboratory Techniques, Protein Conformation, Protein Stability, SARS-CoV-2, Cryoelectron Microscopy, Temperature, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Protein Engineering, 3. Good health, Betacoronavirus, COVID-19 Testing, Immunoglobulin G, Mutation, Spike Glycoprotein, Coronavirus, Humans, Disulfides, Protein Multimerization, Coronavirus Infections
Abstract

The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S that allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, prefusion state. Structures of the disulfide-stabilized and non-disulfide-stabilized proteins reveal distinct closed and locked conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.

21. Cryo-EM reveals the complex architecture of dynactin's shoulder region and pointed end

Author

Clinton K. Lau, Francis J. O’Reilly, Balaji Santhanam, Andrew P. Carter, Samuel E Lacey, Juri Rappsilber, Lau, Clinton K [0000-0003-1083-2989], O'Reilly, Francis J [0000-0001-9258-0150], Santhanam, Balaji [0000-0001-8523-4145], Lacey, Samuel E [0000-0002-3807-8888], Rappsilber, Juri [0000-0001-5999-1310], Carter, Andrew P [0000-0001-7292-5430], and Apollo - University of Cambridge Repository

Subjects
cryo‐electron microscopy, Cryo-electron microscopy, Protein subunit, Dynein, cryo-electron microscopy, macromolecular substances, Biology, Molecular Dynamics Simulation, Topology, Article, General Biochemistry, Genetics and Molecular Biology, Protein filament, 03 medical and health sciences, 0302 clinical medicine, cargo adaptors, Protein Domains, Structural Biology, Microtubule, dynactin, Molecular motor, Humans, Molecular Biology, 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, protein complex, Cryoelectron Microscopy, conservation, Articles, Dynactin Complex, Protein Subunits, Shoulder region, Dynactin, Cell Adhesion, Polarity & Cytoskeleton, Protein Multimerization, 030217 neurology & neurosurgery
Abstract

Dynactin is a 1.1 MDa complex that activates the molecular motor dynein for ultra‐processive transport along microtubules. In order to do this, it forms a tripartite complex with dynein and a coiled‐coil adaptor. Dynactin consists of an actin‐related filament whose length is defined by its flexible shoulder domain. Despite previous cryo‐EM structures, the molecular architecture of the shoulder and pointed end of the filament is still poorly understood due to the lack of high‐resolution information in these regions. Here we combine multiple cryo‐EM datasets and define precise masking strategies for particle signal subtraction and 3D classification. This overcomes domain flexibility and results in high‐resolution maps into which we can build the shoulder and pointed end. The unique architecture of the shoulder securely houses the p150 subunit and positions the four identical p50 subunits in different conformations to bind dynactin’s filament. The pointed end map allows us to build the first structure of p62 and reveals the molecular basis for cargo adaptor binding to different sites at the pointed end., Refinement of dynactin cryo‐EM structures offers insights into dynactin subunit organization in the shoulder region and adaptor binding to its pointed end.

Published
2021
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22. Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma

Author

Amanda J. Russell, Giovanni Perini, Stefania Purgato, André Oberthuer, Bing Liu, Federico M. Giorgi, Georgina L. Eden, Denise M. T. Yu, Sara Sarraf, Murray D. Norris, Michelle Haber, Emanuele Valli, Giorgio Milazzo, Claudia Flemming, Belamy B. Cheung, Simone Di Giacomo, Laura D. Gamble, Jamie I. Fletcher, David S. Ziegler, Toby Trahair, Sophie Allan, Glenn M. Marshall, Lin Xiao, Wendy B. London, Matthias Fischer, Michael D. Hogarty, Andrew J. Gifford, Jayne Murray, Daniel R. Carter, Alvin Kamili, Kimberley M. Hanssen, Chelsea Mayoh, Mark R. Burns, and Laura D. Gamble, Stefania Purgato, Jayne Murray, Lin Xiao, Denise M. T. Yu, Kimberley M. Hanssen, Federico M. Giorgi, Daniel R. Carter, Andrew J. Gifford, Emanuele Valli, Giorgio Milazzo, Alvin Kamili, Chelsea Mayoh, Bing Liu, Georgina Eden, Sara Sarraf, Sophie Allan, Simone Di Giacomo, Claudia L. Flemming, Amanda J. Russell, Belamy B. Cheung, Andre Oberthuer, Wendy B. London, Matthias Fischer, Toby N. Trahair, Jamie I. Fletcher, Glenn M. Marshall, David S. Ziegler, Michael D. Hogarty, Mark R. Burns, Giovanni Perini, Murray D. Norris, and Michelle Haber

Subjects
MYCN Neuroblastoma Polyamine ODC1 Cancer Pediatric Therapy Oncology Tumor Microenvironment, Ornithine decarboxylase, Cohort Studies, chemistry.chemical_compound, Mice, Neuroblastoma, Cell Line, Tumor, medicine, Polyamines, Animals, neoplasms, Proportional Hazards Models, Gene knockdown, N-Myc Proto-Oncogene Protein, Chemistry, Gene Amplification, Membrane Transport Proteins, General Medicine, medicine.disease, Prognosis, Survival Analysis, Biosynthetic Pathways, Spermidine, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Treatment Outcome, Gene Expression Regulation, Tumor progression, Cancer cell, Multivariate Analysis, Cancer research, Disease Progression, Childhood Neuroblastoma, Polyamine
Abstract

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Amplification of the MYCN oncogene is associated with an aggressive phenotype and poor outcome in childhood neuroblastoma. Polyamines are highly regulated essential cations that are frequently elevated in cancer cells, and the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase 1 (ODC1), is a direct transcriptional target of MYCN. Treatment of neuroblastoma cells with the ODC1 inhibitor difluoromethylornithine (DFMO), although a promising therapeutic strategy, is only partially effective at impeding neuroblastoma cell growth due to activation of compensatory mechanisms resulting in increased polyamine uptake from the surrounding microenvironment. In this study, we identified solute carrier family 3 member 2 (SLC3A2) as the key transporter involved in polyamine uptake in neuroblastoma. Knockdown of SLC3A2 in neuroblastoma cells reduced the uptake of the radiolabeled polyamine spermidine, and DFMO treatment increased SLC3A2 protein. In addition, MYCN directly increased polyamine synthesis and promoted neuroblastoma cell proliferation by regulating SLC3A2 and other regulatory components of the polyamine pathway. Inhibiting polyamine uptake with the small-molecule drug AMXT 1501, in combination with DFMO, prevented or delayed tumor development in neuroblastoma-prone mice and extended survival in rodent models of established tumors. Our findings suggest that combining AMXT 1501 and DFMO with standard chemotherapy might be an effective strategy for treating neuroblastoma.

Published
2019

23. Localised dynactin protects growing microtubules to deliver oskar mRNA to the posterior cortex of the Drosophila oocyte

Author

Andrew P. Carter, Ross Nieuwburg, Daniel St Johnston, Raymond E. Goldstein, Philipp Khuc Trong, Maximilian Ah Jakobs, Dmitry Nashchekin, Nashchekin, Dmitry [0000-0001-7372-0752], Jakobs, Maximilian [0000-0002-0879-7937], Carter, Andrew P [0000-0001-7292-5430], Goldstein, Raymond [0000-0003-2645-0598], St Johnston, Robert [0000-0001-5582-3301], Apollo - University of Cambridge Repository, Goldstein, Raymond E [0000-0003-2645-0598], and St Johnston, Daniel [0000-0001-5582-3301]

Subjects
QH301-705.5, Science, RNA localisation, Kinesins, macromolecular substances, Biology, oskar, Microtubules, 03 medical and health sciences, developmental biology, Microtubule, stem cells, Cortex (anatomy), cell biology, medicine, MRNA transport, Animals, Drosophila Proteins, RNA, Messenger, Biology (General), 030304 developmental biology, 0303 health sciences, D. melanogaster, urogenital system, motor proteins, 030302 biochemistry & molecular biology, Anatomy, Kinesin, Oocyte, Actins, Cell biology, cell polarity, Cytoskeletal Proteins, medicine.anatomical_structure, Drosophila melanogaster, Cytoplasm, Dynactin, Oocytes, Medicine
Abstract

The localisation ofoskarmRNA to the posterior of theDrosophilaoocyte defines where the abdomen and germ cells form in the embryo. Kinesin 1 transportsoskarmRNA to the oocyte posterior along a polarised microtubule cytoskeleton that grows from non-centrosomal microtubule organising centres (ncMTOCs) along the anterior/lateral cortex. Here we show that the formation of this polarised microtubule network also requires the posterior regulation of microtubule growth. A mutation in the Dynactin Arp1 subunit causes mostoskarmRNA to localise in the posterior cytoplasm rather than cortically.oskarmRNA transport and anchoring are normal in this mutant, but the microtubules fail to reach the posterior pole. Thus, Dynactin acts as an anti-catastrophe factor that extends microtubule growth posteriorly. Kinesin 1 transports Dynactin to the oocyte posterior, creating a positive feedback loop that increases the length and persistence of the posterior microtubules that deliveroskarmRNA to the cortex.

Published
2018
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