Search

Your search keyword '"Myers, Richard"' showing total 3,720 results
Start Over Author "Myers, Richard"
3,720 results on '"Myers, Richard"'

1. Carrollian Partition Functions and the Flat Limit of AdS

Author

Kraus, Per and Myers, Richard M.

Subjects
High Energy Physics - Theory
Abstract

The formulation of the S-matrix as a path integral with specified asymptotic boundary conditions naturally leads to the realization of a Carrollian partition function defined on the boundary of Minkowski space. This partition function, specified at past and future null infinity in the case of massless particles, generates Carrollian correlation functions that encode the S-matrix. We explore this connection, including the realization of symmetries, soft theorems arising from large gauge transformations, and the correspondence with standard momentum space amplitudes. This framework is also well-suited for embedding the Minkowski space S-matrix into the AdS/CFT duality in the large radius limit. In particular, we identify the AdS and Carrollian partition functions through a simple map between their respective asymptotic data, establishing a direct correspondence between the actions of symmetries on both sides. Our approach thus provides a coherent framework that ties together various topics extensively studied in recent and past literature., Comment: 59 pages; v2 corrected typos, added discussion of flat space Witten diagrams in section 3

Published
2024

3. S-Matrix Path Integral Approach to Symmetries and Soft Theorems

Author

Kim, Seolhwa, Kraus, Per, Monten, Ruben, and Myers, Richard M.

Subjects
High Energy Physics - Theory
Abstract

We explore a formulation of the S-matrix in terms of the path integral with specified asymptotic data, as originally proposed by Arefeva, Faddeev, and Slavnov. In the tree approximation the S-matrix is equal to the exponential of the classical action evaluated on-shell. This formulation is well-suited to questions involving asymptotic symmetries, as it avoids reference to non-gauge/diffeomorphism invariant bulk correlators or sources at intermediate stages. We show that the soft photon theorem, originally derived by Weinberg and more recently connected to asymptotic symmetries by Strominger and collaborators, follows rather simply from invariance of the action under large gauge transformations applied to the asymptotic data. We also show that this formalism allows for efficient computation of the S-matrix in curved spacetime, including particle production due to a time dependent metric., Comment: 38 pages

Published
2023

4. APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016.

Author

OToole, Áine, Neher, Richard, Ndodo, Nnaemeka, Borges, Vitor, Gannon, Ben, Gomes, João, Groves, Natalie, King, David, Maloney, Daniel, Lemey, Philippe, Lewandowski, Kuiama, Loman, Nicholas, Myers, Richard, Omah, Ifeanyi, Worobey, Michael, Chand, Meera, Ihekweazu, Chikwe, Ulaeto, David, Adetifa, Ifedayo, Rambaut, Andrew, and Suchard, Marc

Subjects
Animals, Humans, Africa, Central, Africa, Western, APOBEC Deaminases, Disease Outbreaks, Mpox (monkeypox), Monkeypox virus, Mutation, Phylogeny, Viral Zoonoses, RNA Editing
Abstract

Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control.

Published
2023

5. The James Webb Space Telescope Mission

Author

Gardner, Jonathan P., Mather, John C., Abbott, Randy, Abell, James S., Abernathy, Mark, Abney, Faith E., Abraham, John G., Abraham, Roberto, Abul-Huda, Yasin M., Acton, Scott, Adams, Cynthia K., Adams, Evan, Adler, David S., Adriaensen, Maarten, Aguilar, Jonathan Albert, Ahmed, Mansoor, Ahmed, Nasif S., Ahmed, Tanjira, Albat, Rüdeger, Albert, Loïc, Alberts, Stacey, Aldridge, David, Allen, Mary Marsha, Allen, Shaune S., Altenburg, Martin, Altunc, Serhat, Alvarez, Jose Lorenzo, Álvarez-Márquez, Javier, de Oliveira, Catarina Alves, Ambrose, Leslie L., Anandakrishnan, Satya M., Andersen, Gregory C., Anderson, Harry James, Anderson, Jay, Anderson, Kristen, Anderson, Sara M., Aprea, Julio, Archer, Benita J., Arenberg, Jonathan W., Argyriou, Ioannis, Arribas, Santiago, Artigau, Étienne, Arvai, Amanda Rose, Atcheson, Paul, Atkinson, Charles B., Averbukh, Jesse, Aymergen, Cagatay, Bacinski, John J., Baggett, Wayne E., Bagnasco, Giorgio, Baker, Lynn L., Balzano, Vicki Ann, Banks, Kimberly A., Baran, David A., Barker, Elizabeth A., Barrett, Larry K., Barringer, Bruce O., Barto, Allison, Bast, William, Baudoz, Pierre, Baum, Stefi, Beatty, Thomas G., Beaulieu, Mathilde, Bechtold, Kathryn, Beck, Tracy, Beddard, Megan M., Beichman, Charles, Bellagama, Larry, Bely, Pierre, Berger, Timothy W., Bergeron, Louis E., Darveau-Bernier, Antoine, Bertch, Maria D., Beskow, Charlotte, Betz, Laura E., Biagetti, Carl P., Birkmann, Stephan, Bjorklund, Kurt F., Blackwood, James D., Blazek, Ronald Paul, Blossfeld, Stephen, Bluth, Marcel, Boccaletti, Anthony, Boegner Jr., Martin E., Bohlin, Ralph C., Boia, John Joseph, Böker, Torsten, Bonaventura, N., Bond, Nicholas A., Bosley, Kari Ann, Boucarut, Rene A., Bouchet, Patrice, Bouwman, Jeroen, Bower, Gary, Bowers, Ariel S., Bowers, Charles W., Boyce, Leslye A., Boyer, Christine T., Boyer, Martha L., Boyer, Michael, Boyer, Robert, Bradley, Larry D., Brady, Gregory R., Brandl, Bernhard R., Brannen, Judith L., Breda, David, Bremmer, Harold G., Brennan, David, Bresnahan, Pamela A., Bright, Stacey N., Broiles, Brian J., Bromenschenkel, Asa, Brooks, Brian H., Brooks, Keira J., Brown, Bob, Brown, Bruce, Brown, Thomas M., Bruce, Barry W., Bryson, Jonathan G., Bujanda, Edwin D., Bullock, Blake M., Bunker, A. J., Bureo, Rafael, Burt, Irving J., Bush, James Aaron, Bushouse, Howard A., Bussman, Marie C., Cabaud, Olivier, Cale, Steven, Calhoon, Charles D., Calvani, Humberto, Canipe, Alicia M., Caputo, Francis M., Cara, Mihai, Carey, Larkin, Case, Michael Eli, Cesari, Thaddeus, Cetorelli, Lee D., Chance, Don R., Chandler, Lynn, Chaney, Dave, Chapman, George N., Charlot, S., Chayer, Pierre, Cheezum, Jeffrey I., Chen, Bin, Chen, Christine H., Cherinka, Brian, Chichester, Sarah C., Chilton, Zachary S., Chittiraibalan, Dharini, Clampin, Mark, Clark, Charles R., Clark, Kerry W., Clark, Stephanie M., Claybrooks, Edward E., Cleveland, Keith A., Cohen, Andrew L., Cohen, Lester M., Colón, Knicole D., Coleman, Benee L., Colina, Luis, Comber, Brian J., Comeau, Thomas M., Comer, Thomas, Reis, Alain Conde, Connolly, Dennis C., Conroy, Kyle E., Contos, Adam R., Contreras, James, Cook, Neil J., Cooper, James L., Cooper, Rachel Aviva, Correia, Michael F., Correnti, Matteo, Cossou, Christophe, Costanza, Brian F., Coulais, Alain, Cox, Colin R., Coyle, Ray T., Cracraft, Misty M., Noriega-Crespo, Alberto, Crew, Keith A., Curtis, Gary J., Cusveller, Bianca, Maciel, Cleyciane Da Costa, Dailey, Christopher T., Daugeron, Frédéric, Davidson, Greg S., Davies, James E., Davis, Katherine Anne, Davis, Michael S., Day, Ratna, de Chambure, Daniel, de Jong, Pauline, De Marchi, Guido, Dean, Bruce H., Decker, John E., Delisa, Amy S., Dell, Lawrence C., Dellagatta, Gail, Dembinska, Franciszka, Demosthenes, Sandor, Dencheva, Nadezhda M., Deneu, Philippe, DePriest, William W., Deschenes, Jeremy, Dethienne, Nathalie, Detre, Örs Hunor, Diaz, Rosa Izela, Dicken, Daniel, DiFelice, Audrey S., Dillman, Matthew, Disharoon, Maureen O., van Dishoeck, Ewine F., Dixon, William V., Doggett, Jesse B., Dominguez, Keisha L., Donaldson, Thomas S., Doria-Warner, Cristina M., Santos, Tony Dos, Doty, Heather, Douglas Jr., Robert E., Doyon, René, Dressler, Alan, Driggers, Jennifer, Driggers, Phillip A., Dunn, Jamie L., DuPrie, Kimberly C., Dupuis, Jean, Durning, John, Dutta, Sanghamitra B., Earl, Nicholas M., Eccleston, Paul, Ecobichon, Pascal, Egami, Eiichi, Ehrenwinkler, Ralf, Eisenhamer, Jonathan D., Eisenhower, Michael, Eisenstein, Daniel J., Hamel, Zaky El, Elie, Michelle L., Elliott, James, Elliott, Kyle Wesley, Engesser, Michael, Espinoza, Néstor, Etienne, Odessa, Etxaluze, Mireya, Evans, Leah, Fabreguettes, Luce, Falcolini, Massimo, Falini, Patrick R., Fatig, Curtis, Feeney, Matthew, Feinberg, Lee D., Fels, Raymond, Ferdous, Nazma, Ferguson, Henry C., Ferrarese, Laura, Ferreira, Marie-Héléne, Ferruit, Pierre, Ferry, Malcolm, Filippazzo, Joseph Charles, Firre, Daniel, Fix, Mees, Flagey, Nicolas, Flanagan, Kathryn A., Fleming, Scott W., Florian, Michael, Flynn, James R., Foiadelli, Luca, Fontaine, Mark R., Fontanella, Erin Marie, Forshay, Peter Randolph, Fortner, Elizabeth A., Fox, Ori D., Framarini, Alexandro P., Francisco, John I., Franck, Randy, Franx, Marijn, Franz, David E., Friedman, Scott D., Friend, Katheryn E., Frost, James R., Fu, Henry, Fullerton, Alexander W., Gaillard, Lionel, Galkin, Sergey, Gallagher, Ben, Galyer, Anthony D., Marín, Macarena García, Gardner, Lisa E., Garland, Dennis, Garrett, Bruce Albert, Gasman, Danny, Gáspár, András, Gastaud, René, Gaudreau, Daniel, Gauthier, Peter Timothy, Geers, Vincent, Geithner, Paul H., Gennaro, Mario, Gerber, John, Gereau, John C., Giampaoli, Robert, Giardino, Giovanna, Gibbons, Paul C., Gilbert, Karolina, Gilman, Larry, Girard, Julien H., Giuliano, Mark E., Gkountis, Konstantinos, Glasse, Alistair, Glassmire, Kirk Zachary, Glauser, Adrian Michael, Glazer, Stuart D., Goldberg, Joshua, Golimowski, David A., Gonzaga, Shireen P., Gordon, Karl D., Gordon, Shawn J., Goudfrooij, Paul, Gough, Michael J., Graham, Adrian J., Grau, Christopher M., Green, Joel David, Greene, Gretchen R., Greene, Thomas P., Greenfield, Perry E., Greenhouse, Matthew A., Greve, Thomas R., Greville, Edgar M., Grimaldi, Stefano, Groe, Frank E., Groebner, Andrew, Grumm, David M., Grundy, Timothy, Güdel, Manuel, Guillard, Pierre, Guldalian, John, Gunn, Christopher A., Gurule, Anthony, Gutman, Irvin Meyer, Guy, Paul D., Guyot, Benjamin, Hack, Warren J., Haderlein, Peter, Hagan, James B., Hagedorn, Andria, Hainline, Kevin, Haley, Craig, Hami, Maryam, Hamilton, Forrest Clifford, Hammann, Jeffrey, Hammel, Heidi B., Hanley, Christopher J., Hansen, Carl August, Hardy, Bruce, Harnisch, Bernd, Harr, Michael Hunter, Harris, Pamela, Hart, Jessica Ann, Hartig, George F., Hasan, Hashima, Hashim, Kathleen Marie, Hashimoto, Ryan, Haskins, Sujee J., Hawkins, Robert Edward, Hayden, Brian, Hayden, William L., Healy, Mike, Hecht, Karen, Heeg, Vince J., Hejal, Reem, Helm, Kristopher A., Hengemihle, Nicholas J., Henning, Thomas, Henry, Alaina, Henry, Ronald L., Henshaw, Katherine, Hernandez, Scarlin, Herrington, Donald C., Heske, Astrid, Hesman, Brigette Emily, Hickey, David L., Hilbert, Bryan N., Hines, Dean C., Hinz, Michael R., Hirsch, Michael, Hitcho, Robert S., Hodapp, Klaus, Hodge, Philip E., Hoffman, Melissa, Holfeltz, Sherie T., Holler, Bryan Jason, Hoppa, Jennifer Rose, Horner, Scott, Howard, Joseph M., Howard, Richard J., Huber, Jean M., Hunkeler, Joseph S., Hunter, Alexander, Hunter, David Gavin, Hurd, Spencer W., Hurst, Brendan J., Hutchings, John B., Hylan, Jason E., Ignat, Luminita Ilinca, Illingworth, Garth, Irish, Sandra M., Isaacs III, John C., Jackson Jr., Wallace C., Jaffe, Daniel T., Jahic, Jasmin, Jahromi, Amir, Jakobsen, Peter, James, Bryan, James, John C., James, LeAndrea Rae, Jamieson, William Brian, Jandra, Raymond D., Jayawardhana, Ray, Jedrzejewski, Robert, Jeffers, Basil S., Jensen, Peter, Joanne, Egges, Johns, Alan T., Johnson, Carl A., Johnson, Eric L., Johnson, Patricia, Johnson, Phillip Stephen, Johnson, Thomas K., Johnson, Timothy W., Johnstone, Doug, Jollet, Delphine, Jones, Danny P., Jones, Gregory S., Jones, Olivia C., Jones, Ronald A., Jones, Vicki, Jordan, Ian J., Jordan, Margaret E., Jue, Reginald, Jurkowski, Mark H., Justis, Grant, Justtanont, Kay, Kaleida, Catherine C., Kalirai, Jason S., Kalmanson, Phillip Cabrales, Kaltenegger, Lisa, Kammerer, Jens, Kan, Samuel K., Kanarek, Graham Childs, Kao, Shaw-Hong, Karakla, Diane M., Karl, Hermann, Kassin, Susan A., Kauffman, David D., Kavanagh, Patrick, Kelley, Leigh L., Kelly, Douglas M., Kendrew, Sarah, Kennedy, Herbert V., Kenny, Deborah A., Keski-Kuha, Ritva A., Keyes, Charles D., Khan, Ali, Kidwell, Richard C., Kimble, Randy A., King, James S., King, Richard C., Kinzel, Wayne M., Kirk, Jeffrey R., Kirkpatrick, Marc E., Klaassen, Pamela, Klingemann, Lana, Klintworth, Paul U., Knapp, Bryan Adam, Knight, Scott, Knollenberg, Perry J., Knutsen, Daniel Mark, Koehler, Robert, Koekemoer, Anton M., Kofler, Earl T., Kontson, Vicki L., Kovacs, Aiden Rose, Kozhurina-Platais, Vera, Krause, Oliver, Kriss, Gerard A., Krist, John, Kristoffersen, Monica R., Krogel, Claudia, Krueger, Anthony P., Kulp, Bernard A., Kumari, Nimisha, Kwan, Sandy W., Kyprianou, Mark, Labador, Aurora Gadiano, Labiano, Álvaro, Lafrenière, David, Lagage, Pierre-Olivier, Laidler, Victoria G., Laine, Benoit, Laird, Simon, Lajoie, Charles-Philippe, Lallo, Matthew D., Lam, May Yen, LaMassa, Stephanie Marie, Lambros, Scott D., Lampenfield, Richard Joseph, Lander, Matthew Ed, Langston, James Hutton, Larson, Kirsten, Larson, Melora, LaVerghetta, Robert Joseph, Law, David R., Lawrence, Jon F., Lee, David W., Lee, Janice, Lee, Yat-Ning Paul, Leisenring, Jarron, Leveille, Michael Dunlap, Levenson, Nancy A., Levi, Joshua S., Levine, Marie B., Lewis, Dan, Lewis, Jake, Lewis, Nikole, Libralato, Mattia, Lidon, Norbert, Liebrecht, Paula Louisa, Lightsey, Paul, Lilly, Simon, Lim, Frederick C., Lim, Pey Lian, Ling, Sai-Kwong, Link, Lisa J., Link, Miranda Nicole, Lipinski, Jamie L., Liu, XiaoLi, Lo, Amy S., Lobmeyer, Lynette, Logue, Ryan M., Long, Chris A., Long, Douglas R., Long, Ilana D., Long, Knox S., López-Caniego, Marcos, Lotz, Jennifer M., Love-Pruitt, Jennifer M., Lubskiy, Michael, Luers, Edward B., Luetgens, Robert A., Luevano, Annetta J., Lui, Sarah Marie G. Flores, Lund III, James M., Lundquist, Ray A., Lunine, Jonathan, Lützgendorf, Nora, Lynch, Richard J., MacDonald, Alex J., MacDonald, Kenneth, Macias, Matthew J., Macklis, Keith I., Maghami, Peiman, Maharaja, Rishabh Y., Maiolino, Roberto, Makrygiannis, Konstantinos G., Malla, Sunita Giri, Malumuth, Eliot M., Manjavacas, Elena, Marini, Andrea, Marrione, Amanda, Marston, Anthony, Martel, André R, Martin, Didier, Martin, Peter G., Martinez, Kristin L., Maschmann, Marc, Masci, Gregory L., Masetti, Margaret E., Maszkiewicz, Michael, Matthews, Gary, Matuskey, Jacob E., McBrayer, Glen A., McCarthy, Donald W., McCaughrean, Mark J., McClare, Leslie A., McClare, Michael D., McCloskey, John C., McClurg, Taylore D., McCoy, Martin, McElwain, Michael W., McGregor, Roy D., McGuffey, Douglas B., McKay, Andrew G., McKenzie, William K., McLean, Brian, McMaster, Matthew, McNeil, Warren, De Meester, Wim, Mehalick, Kimberly L., Meixner, Margaret, Meléndez, Marcio, Menzel, Michael P., Menzel, Michael T., Merz, Matthew, Mesterharm, David D., Meyer, Michael R., Meyett, Michele L., Meza, Luis E., Midwinter, Calvin, Milam, Stefanie N., Miller, Jay Todd, Miller, William C., Miskey, Cherie L., Misselt, Karl, Mitchell, Eileen P., Mohan, Martin, Montoya, Emily E., Moran, Michael J., Morishita, Takahiro, Moro-Martín, Amaya, Morrison, Debra L., Morrison, Jane, Morse, Ernie C., Moschos, Michael, Moseley, S. H., Mosier, Gary E., Mosner, Peter, Mountain, Matt, Muckenthaler, Jason S., Mueller, Donald G., Mueller, Migo, Muhiem, Daniella, Mühlmann, Prisca, Mullally, Susan Elizabeth, Mullen, Stephanie M., Munger, Alan J, Murphy, Jess, Murray, Katherine T., Muzerolle, James C., Mycroft, Matthew, Myers, Andrew, Myers, Carey R., Myers, Fred Richard R., Myers, Richard, Myrick, Kaila, Nagle IV, Adrian F., Nayak, Omnarayani, Naylor, Bret, Neff, Susan G., Nelan, Edmund P., Nella, John, Nguyen, Duy Tuong, Nguyen, Michael N., Nickson, Bryony, Nidhiry, John Joseph, Niedner, Malcolm B., Nieto-Santisteban, Maria, Nikolov, Nikolay K., Nishisaka, Mary Ann, Nota, Antonella, O'Mara, Robyn C., Oboryshko, Michael, O'Brien, Marcus B., Ochs, William R., Offenberg, Joel D., Ogle, Patrick Michael, Ohl, Raymond G., Olmsted, Joseph Hamden, Osborne, Shannon Barbara, O'Shaughnessy, Brian Patrick, Östlin, Göran, O'Sullivan, Brian, Otor, O. Justin, Ottens, Richard, Ouellette, Nathalie N. -Q., Outlaw, Daria J., Owens, Beverly A., Pacifici, Camilla, Page, James Christophe, Paranilam, James G., Park, Sang, Parrish, Keith A., Paschal, Laura, Patapis, Polychronis, Patel, Jignasha, Patrick, Keith, Pattishall Jr., Robert A., Paul, Douglas William, Paul, Shirley J., Pauly, Tyler Andrew, Pavlovsky, Cheryl M., Peña-Guerrero, Maria, Pedder, Andrew H., Peek, Matthew Weldon, Pelham, Patricia A., Penanen, Konstantin, Perriello, Beth A., Perrin, Marshall D., Perrine, Richard F., Perrygo, Chuck, Peslier, Muriel, Petach, Michael, Peterson, Karla A., Pfarr, Tom, Pierson, James M., Pietraszkiewicz, Martin, Pilchen, Guy, Pipher, Judy L., Pirzkal, Norbert, Pitman, Joseph T., Player, Danielle M., Plesha, Rachel, Plitzke, Anja, Pohner, John A., Poletis, Karyn Konstantin, Pollizzi, Joseph A., Polster, Ethan, Pontius, James T., Pontoppidan, Klaus, Porges, Susana C., Potter, Gregg D., Prescott, Stephen, Proffitt, Charles R., Pueyo, Laurent, Neira, Irma Aracely Quispe, Radich, Armando, Rager, Reiko T., Rameau, Julien, Ramey, Deborah D., Alarcon, Rafael Ramos, Rampini, Riccardo, Rapp, Robert, Rashford, Robert A., Rauscher, Bernard J., Ravindranath, Swara, Rawle, Timothy, Rawlings, Tynika N., Ray, Tom, Regan, Michael W., Rehm, Brian, Rehm, Kenneth D., Reid, Neill, Reis, Carl A., Renk, Florian, Reoch, Tom B., Ressler, Michael, Rest, Armin W., Reynolds, Paul J., Richon, Joel G., Richon, Karen V., Ridgaway, Michael, Riedel, Adric Richard, Rieke, George H., Rieke, Marcia, Rifelli, Richard E., Rigby, Jane R., Riggs, Catherine S., Ringel, Nancy J., Ritchie, Christine E., Rix, Hans-Walter, Robberto, Massimo, Robinson, Michael S., Robinson, Orion, Rock, Frank W., Rodriguez, David R., del Pino, Bruno Rodríguez, Roellig, Thomas, Rohrbach, Scott O., Roman, Anthony J., Romelfanger, Frederick J., Romo Jr., Felipe P., Rosales, Jose J., Rose, Perry, Roteliuk, Anthony F., Roth, Marc N., Rothwell, Braden Quinn, Rouzaud, Sylvain, Rowe, Jason, Rowlands, Neil, Roy, Arpita, Royer, Pierre, Rui, Chunlei, Rumler, Peter, Rumpl, William, Russ, Melissa L., Ryan, Michael B., Ryan, Richard M., Saad, Karl, Sabata, Modhumita, Sabatino, Rick, Sabbi, Elena, Sabelhaus, Phillip A., Sabia, Stephen, Sahu, Kailash C., Saif, Babak N., Salvignol, Jean-Christophe, Samara-Ratna, Piyal, Samuelson, Bridget S., Sanders, Felicia A., Sappington, Bradley, Sargent, B. A., Sauer, Arne, Savadkin, Bruce J., Sawicki, Marcin, Schappell, Tina M., Scheffer, Caroline, Scheithauer, Silvia, Scherer, Ron, Schiff, Conrad, Schlawin, Everett, Schmeitzky, Olivier, Schmitz, Tyler S., Schmude, Donald J., Schneider, Analyn, Schreiber, Jürgen, Schroeven-Deceuninck, Hilde, Schultz, John J., Schwab, Ryan, Schwartz, Curtis H., Scoccimarro, Dario, Scott, John F., Scott, Michelle B., Seaton, Bonita L., Seely, Bruce S., Seery, Bernard, Seidleck, Mark, Sembach, Kenneth, Shanahan, Clare Elizabeth, Shaughnessy, Bryan, Shaw, Richard A., Shay, Christopher Michael, Sheehan, Even, Sheth, Kartik, Shih, Hsin-Yi, Shivaei, Irene, Siegel, Noah, Sienkiewicz, Matthew G., Simmons, Debra D., Simon, Bernard P., Sirianni, Marco, Sivaramakrishnan, Anand, Slade, Jeffrey E., Sloan, G. C., Slocum, Christine E., Slowinski, Steven E., Smith, Corbett T., Smith, Eric P., Smith, Erin C., Smith, Koby, Smith, Robert, Smith, Stephanie J., Smolik, John L., Soderblom, David R., Sohn, Sangmo Tony, Sokol, Jeff, Sonneborn, George, Sontag, Christopher D., Sooy, Peter R., Soummer, Remi, Southwood, Dana M., Spain, Kay, Sparmo, Joseph, Speer, David T., Spencer, Richard, Sprofera, Joseph D., Stallcup, Scott S., Stanley, Marcia K., Stansberry, John A., Stark, Christopher C., Starr, Carl W., Stassi, Diane Y., Steck, Jane A., Steeley, Christine D., Stephens, Matthew A., Stephenson, Ralph J., Stewart, Alphonso C., Stiavelli, Massimo, Stockman Jr., Hervey, Strada, Paolo, Straughn, Amber N., Streetman, Scott, Strickland, David Kendal, Strobele, Jingping F., Stuhlinger, Martin, Stys, Jeffrey Edward, Such, Miguel, Sukhatme, Kalyani, Sullivan, Joseph F., Sullivan, Pamela C., Sumner, Sandra M., Sun, Fengwu, Sunnquist, Benjamin Dale, Swade, Daryl Allen, Swam, Michael S., Swenton, Diane F., Swoish, Robby A., Litten, Oi In Tam, Tamas, Laszlo, Tao, Andrew, Taylor, David K., Taylor, Joanna M., Plate, Maurice te, Van Tea, Mason, Teague, Kelly K., Telfer, Randal C., Temim, Tea, Texter, Scott C., Thatte, Deepashri G., Thompson, Christopher Lee, Thompson, Linda M., Thomson, Shaun R., Thronson, Harley, Tierney, C. M., Tikkanen, Tuomo, Tinnin, Lee, Tippet, William Thomas, Todd, Connor William, Tran, Hien D., Trauger, John, Trejo, Edwin Gregorio, Truong, Justin Hoang Vinh, Tsukamoto, Christine L., Tufail, Yasir, Tumlinson, Jason, Tustain, Samuel, Tyra, Harrison, Ubeda, Leonardo, Underwood, Kelli, Uzzo, Michael A., Vaclavik, Steven, Valenduc, Frida, Valenti, Jeff A., Van Campen, Julie, van de Wetering, Inge, Van Der Marel, Roeland P., van Haarlem, Remy, Vandenbussche, Bart, Vanterpool, Dona D., Vernoy, Michael R., Costas, Maria Begoña Vila, Volk, Kevin, Voorzaat, Piet, Voyton, Mark F., Vydra, Ekaterina, Waddy, Darryl J., Waelkens, Christoffel, Wahlgren, Glenn Michael, Walker Jr., Frederick E., Wander, Michel, Warfield, Christine K., Warner, Gerald, Wasiak, Francis C., Wasiak, Matthew F., Wehner, James, Weiler, Kevin R., Weilert, Mark, Weiss, Stanley B., Wells, Martyn, Welty, Alan D., Wheate, Lauren, Wheeler, Thomas P., White, Christy L., Whitehouse, Paul, Whiteleather, Jennifer Margaret, Whitman, William Russell, Williams, Christina C., Willmer, Christopher N. A., Willott, Chris J., Willoughby, Scott P., Wilson, Andrew, Wilson, Debra, Wilson, Donna V., Windhorst, Rogier, Wislowski, Emily Christine, Wolfe, David J., Wolfe, Michael A., Wolff, Schuyler, Wondel, Amancio, Woo, Cindy, Woods, Robert T., Worden, Elaine, Workman, William, Wright, Gillian S., Wu, Carl, Wu, Chi-Rai, Wun, Dakin D., Wymer, Kristen B., Yadetie, Thomas, Yan, Isabelle C., Yang, Keith C., Yates, Kayla L., Yeager, Christopher R., Yerger, Ethan John, Young, Erick T., Young, Gary, Yu, Gene, Yu, Susan, Zak, Dean S., Zeidler, Peter, Zepp, Robert, Zhou, Julia, Zincke, Christian A., Zonak, Stephanie, and Zondag, Elisabeth

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit., Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figures

Published
2023
Full Text
View/download PDF

6. Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.

Author

Hotta, Ryo, Rahman, Ahmed, Bhave, Sukhada, Stavely, Rhian, Pan, Weikang, Srinivasan, Shriya, de Couto, Geoffrey, Rodriguez-Borlado, Luis, Myers, Richard, Burns, Alan, and Goldstein, Allan

Subjects
Cell therapy, Enteric neuropathies, Gastrointestinal motility, Nitric oxide synthase, Optogenetics, Animals, Mice, Neurons, Muscle, Smooth, Cell- and Tissue-Based Therapy, Colon, Electric Stimulation
Abstract

BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function. METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS-/- mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1-2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility. RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS-/- recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS. CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.

Published
2023

7. Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes

Author

Aterido, Adrià, López-Lasanta, María, Blanco, Francisco, Juan-Mas, Antonio, García-Vivar, María Luz, Erra, Alba, Pérez-García, Carolina, Sánchez-Fernández, Simón Ángel, Sanmartí, Raimon, Fernández-Nebro, Antonio, Alperi-López, Mercedes, Tornero, Jesús, Ortiz, Ana María, Fernández-Cid, Carlos Marras, Palau, Núria, Pan, Wenjing, Byrne-Steele, Miranda, Starenki, Dmytro, Weber, Daniel, Rodriguez-Nunez, Ivan, Han, Jian, Myers, Richard M., Marsal, Sara, and Julià, Antonio

Published
2024
Full Text
View/download PDF

8. Systematics of Boundary Actions in Gauge Theory and Gravity

Author

Kim, Seolhwa, Kraus, Per, and Myers, Richard M.

Subjects
High Energy Physics - Theory, General Relativity and Quantum Cosmology
Abstract

We undertake a general study of the boundary (or edge) modes that arise in gauge and gravitational theories defined on a space with boundary, either asymptotic or at finite distance, focusing on efficient techniques for computing the corresponding boundary action. Such actions capture all the dynamics of the system that are implied by its asymptotic symmetry group, such as correlation functions of the corresponding conserved currents. Working in the covariant phase space formalism, we develop a collection of approaches for isolating the boundary modes and their dynamics, and illustrate with various examples, notably AdS$_3$ gravity (with and without a gravitational Chern-Simons terms) subject to assorted boundary conditions., Comment: 67 pages. v2: references added, typos corrected

Published
2023
Full Text
View/download PDF

9. Competitive Wrestling-related Injuries in School Aged Athletes in U.S. Emergency Departments

Author

Myers, Richard J, Linakis, Seth W, Mello, Michael J, and Linakis, James G

Subjects
injury prevention, wrestling, child, adolescent, sports, Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Objective: To describe the characteristics of wrestling injuries occurring in male athletes aged 7-17 treated in United States (U.S.) emergency departments (ED) from 2000-2006, and to compare injury patterns between younger & older youth wrestlers.Methods: A stratified probability sample of U.S. hospitals providing emergency services in the National Electronic Injury Surveillance System was used for 2000-2006. ED visits for injuries sustained in organized wrestling were analyzed for male patients ages 7-17 years old (subdivided into 7-11 years old [youth group] and 12-17 years old [scholastic group]).Results: During the study period, there were an estimated 167,606 ED visits for wrestling injuries in 7-17 years old U.S. males, with 152,710 (91.1%) occurring in the older (12-17 years old) group. The annual injury incidence was 6.49 injuries/1,000 wrestlers in the youth group and 29.57 injuries/1,000 wrestlers in the scholastic group. The distribution of diagnoses was similar in both age groups, with sprain/strain as the most common diagnosis, followed by fracture and contusion/abrasion. Distributions of injury by location were significantly different between groups (p=0.02), although both groups exhibited approximately 75% of all injuries from the waist up. Overexertion and struck by/against were the most common precipitating and direct mechanisms in both groups, respectively. Over 97% of all injured wrestlers were treated and released.Conclusion: The types of injury in youth (7-11 years old) wrestlers are similar to those of scholastic (12-17 years old) wrestlers, although the distribution of body parts injured differs between the age groups. The majority of injuries occurs above the waist and may be a target for prevention strategies. [West J Emerg Med. 2010; 11(5):442-449.]

Published
2010

10. The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Author

Rozowsky, Joel, Gao, Jiahao, Borsari, Beatrice, Yang, Yucheng, Galeev, Timur, Gürsoy, Gamze, Epstein, Charles, Xiong, Kun, Xu, Jinrui, Li, Tianxiao, Liu, Jason, Yu, Keyang, Berthel, Ana, Chen, Zhanlin, Navarro, Fabio, Sun, Maxwell, Wright, James, Chang, Justin, Cameron, Christopher, Shoresh, Noam, Gaskell, Elizabeth, Drenkow, Jorg, Adrian, Jessika, Aganezov, Sergey, Aguet, François, Balderrama-Gutierrez, Gabriela, Banskota, Samridhi, Corona, Guillermo, Chee, Sora, Chhetri, Surya, Cortez Martins, Gabriel, Danyko, Cassidy, Davis, Carrie, Farid, Daniel, Farrell, Nina, Gabdank, Idan, Gofin, Yoel, Gorkin, David, Gu, Mengting, Hecht, Vivian, Hitz, Benjamin, Issner, Robbyn, Jiang, Yunzhe, Kirsche, Melanie, Kong, Xiangmeng, Lam, Bonita, Li, Shantao, Li, Bian, Li, Xiqi, Lin, Khine, Luo, Ruibang, Mackiewicz, Mark, Meng, Ran, Moore, Jill, Mudge, Jonathan, Nelson, Nicholas, Nusbaum, Chad, Popov, Ioann, Pratt, Henry, Qiu, Yunjiang, Ramakrishnan, Srividya, Raymond, Joe, Salichos, Leonidas, Scavelli, Alexandra, Schreiber, Jacob, Sedlazeck, Fritz, See, Lei, Sherman, Rachel, Shi, Xu, Shi, Minyi, Sloan, Cricket, Strattan, J, Tan, Zhen, Tanaka, Forrest, Vlasova, Anna, Wang, Jun, Werner, Jonathan, Williams, Brian, Xu, Min, Yan, Chengfei, Yu, Lu, Zaleski, Christopher, Zhang, Jing, Ardlie, Kristin, Cherry, J, Mendenhall, Eric, Noble, William, Weng, Zhiping, Levine, Morgan, Dobin, Alexander, Wold, Barbara, Mortazavi, Ali, Ren, Bing, Gillis, Jesse, Myers, Richard, Choudhary, Jyoti, Milosavljevic, Aleksandar, Schatz, Michael, Bernstein, Bradley, and Guigó, Roderic

Subjects
ENCODE, GTEx, allele-specific activity, eQTLs, functional epigenomes, functional genomics, genome annotations, personal genome, predictive models, structural variants, tissue specificity, transformer model, Epigenome, Quantitative Trait Loci, Genome-Wide Association Study, Genomics, Phenotype, Polymorphism, Single Nucleotide
Abstract

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

Published
2023

11. Isolation, Expansion, and Endoscopic Delivery of Autologous Enteric Neuronal Stem Cells in Swine.

Author

Hotta, Ryo, Pan, Weikang, Bhave, Sukhada, Nagy, Nandor, Stavely, Rhian, Ohkura, Takahiro, Krishnan, Kumar, de Couto, Geoffrey, Myers, Richard, Rodriguez-Borlado, Luis, Burns, Alan, and Goldstein, Allan

Subjects
autologous, cell therapy, endoscopic ultrasound, enteric neuropathies, swine, Humans, Animals, Swine, Infant, Neurons, Neural Stem Cells, Enteric Nervous System, Intestine, Small, Neuroglia
Abstract

The enteric nervous system (ENS) is an extensive network of neurons and glia within the wall of the gastrointestinal (GI) tract that regulates many essential GI functions. Consequently, disorders of the ENS due to developmental defects, inflammation, infection, or age-associated neurodegeneration lead to serious neurointestinal diseases. Despite the prevalence and severity of these diseases, effective treatments are lacking as they fail to directly address the underlying pathology. Neuronal stem cell therapy represents a promising approach to treating diseases of the ENS by replacing the absent or injured neurons, and an autologous source of stem cells would be optimal by obviating the need for immunosuppression. We utilized the swine model to address key questions concerning cell isolation, delivery, engraftment, and fate in a large animal relevant to human therapy. We successfully isolated neural stem cells from a segment of small intestine resected from 1-month-old swine. Enteric neuronal stem cells (ENSCs) were expanded as neurospheres that grew optimally in low-oxygen (5%) culture conditions. Enteric neuronal stem cells were labeled by lentiviral green fluorescent protein (GFP) transduction, then transplanted into the same swine from which they had been harvested. Endoscopic ultrasound was then utilized to deliver the ENSCs (10,000-30,000 neurospheres per animal) into the rectal wall. At 10 and 28 days following injection, autologously derived ENSCs were found to have engrafted within rectal wall, with neuroglial differentiation and no evidence of ectopic spreading. These findings strongly support the feasibility of autologous cell isolation and delivery using a clinically useful and minimally invasive technique, bringing us closer to first-in-human ENSC therapy for neurointestinal diseases.

Published
2023

12. Neurotransmission-related gene expression in the frontal pole is altered in subjects with bipolar disorder and schizophrenia

Author

Medina, Adriana M, Hagenauer, Megan Hastings, Krolewski, David M, Hughes, Evan, Forrester, Liam Cannon Thew, Walsh, David M, Waselus, Maria, Richardson, Evelyn, Turner, Cortney A, Sequeira, P Adolfo, Cartagena, Preston M, Thompson, Robert C, Vawter, Marquis P, Bunney, Blynn G, Myers, Richard M, Barchas, Jack D, Lee, Francis S, Schatzberg, Alan F, Bunney, William E, Akil, Huda, and Watson, Stanley J

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Mental Health, Genetics, Serious Mental Illness, Brain Disorders, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Humans, Adolescent, Bipolar Disorder, Schizophrenia, Frontal Lobe, Gene Expression, Synaptic Transmission, Clinical Sciences, Public Health and Health Services, Clinical sciences, Biological psychology
Abstract

The frontal pole (Brodmann area 10, BA10) is the largest cytoarchitectonic region of the human cortex, performing complex integrative functions. BA10 undergoes intensive adolescent grey matter pruning prior to the age of onset for bipolar disorder (BP) and schizophrenia (SCHIZ), and its dysfunction is likely to underly aspects of their shared symptomology. In this study, we investigated the role of BA10 neurotransmission-related gene expression in BP and SCHIZ. We performed qPCR to measure the expression of 115 neurotransmission-related targets in control, BP, and SCHIZ postmortem samples (n = 72). We chose this method for its high sensitivity to detect low-level expression. We then strengthened our findings by performing a meta-analysis of publicly released BA10 microarray data (n = 101) and identified sources of convergence with our qPCR results. To improve interpretation, we leveraged the unusually large database of clinical metadata accompanying our samples to explore the relationship between BA10 gene expression, therapeutics, substances of abuse, and symptom profiles, and validated these findings with publicly available datasets. Using these convergent sources of evidence, we identified 20 neurotransmission-related genes that were differentially expressed in BP and SCHIZ in BA10. These results included a large diagnosis-related decrease in two important therapeutic targets with low levels of expression, HTR2B and DRD4, as well as other findings related to dopaminergic, GABAergic and astrocytic function. We also observed that therapeutics may produce a differential expression that opposes diagnosis effects. In contrast, substances of abuse showed similar effects on BA10 gene expression as BP and SCHIZ, potentially amplifying diagnosis-related dysregulation.

Published
2023

13. The Science Performance of JWST as Characterized in Commissioning

Author

Rigby, Jane, Perrin, Marshall, McElwain, Michael, Kimble, Randy, Friedman, Scott, Lallo, Matt, Doyon, René, Feinberg, Lee, Ferruit, Pierre, Glasse, Alistair, Rieke, Marcia, Rieke, George, Wright, Gillian, Willott, Chris, Colon, Knicole, Milam, Stefanie, Neff, Susan, Stark, Christopher, Valenti, Jeff, Abell, Jim, Abney, Faith, Abul-Huda, Yasin, Acton, D. Scott, Adams, Evan, Adler, David, Aguilar, Jonathan, Ahmed, Nasif, Albert, Loïc, Alberts, Stacey, Aldridge, David, Allen, Marsha, Altenburg, Martin, Marquez, Javier Alvarez, de Oliveira, Catarina Alves, Andersen, Greg, Anderson, Harry, Anderson, Sara, Argyriou, Ioannis, Armstrong, Amber, Arribas, Santiago, Artigau, Etienne, Arvai, Amanda, Atkinson, Charles, Bacon, Gregory, Bair, Thomas, Banks, Kimberly, Barrientes, Jaclyn, Barringer, Bruce, Bartosik, Peter, Bast, William, Baudoz, Pierre, Beatty, Thomas, Bechtold, Katie, Beck, Tracy, Bergeron, Eddie, Bergkoetter, Matthew, Bhatawdekar, Rachana, Birkmann, Stephan, Blazek, Ronald, Blome, Claire, Boccaletti, Anthony, Boeker, Torsten, Boia, John, Bonaventura, Nina, Bond, Nicholas, Bosley, Kari, Boucarut, Ray, Bourque, Matthew, Bouwman, Jeroen, Bower, Gary, Bowers, Charles, Boyer, Martha, Bradley, Larry, Brady, Greg, Braun, Hannah, Breda, David, Bresnahan, Pamela, Bright, Stacey, Britt, Christopher, Bromenschenkel, Asa, Brooks, Brian, Brooks, Keira, Brown, Bob, Brown, Matthew, Brown, Patricia, Bunker, Andy, Burger, Matthew, Bushouse, Howard, Cale, Steven, Cameron, Alex, Cameron, Peter, Canipe, Alicia, Caplinger, James, Caputo, Francis, Cara, Mihai, Carey, Larkin, Carniani, Stefano, Carrasquilla, Maria, Carruthers, Margaret, Case, Michael, Catherine, Riggs, Chance, Don, Chapman, George, Charlot, Stéphane, Charlow, Brian, Chayer, Pierre, Chen, Bin, Cherinka, Brian, Chichester, Sarah, Chilton, Zack, Chonis, Taylor, Clampin, Mark, Clark, Charles, Clark, Kerry, Coe, Dan, Coleman, Benee, Comber, Brian, Comeau, Tom, Connolly, Dennis, Cooper, James, Cooper, Rachel, Coppock, Eric, Correnti, Matteo, Cossou, Christophe, Coulais, Alain, Coyle, Laura, Cracraft, Misty, Curti, Mirko, Cuturic, Steven, Davis, Katherine, Davis, Michael, Dean, Bruce, DeLisa, Amy, deMeester, Wim, Dencheva, Nadia, Dencheva, Nadezhda, DePasquale, Joseph, Deschenes, Jeremy, Detre, Örs Hunor, Diaz, Rosa, Dicken, Dan, DiFelice, Audrey, Dillman, Matthew, Dixon, William, Doggett, Jesse, Donaldson, Tom, Douglas, Rob, DuPrie, Kimberly, Dupuis, Jean, Durning, John, Easmin, Nilufar, Eck, Weston, Edeani, Chinwe, Egami, Eiichi, Ehrenwinkler, Ralf, Eisenhamer, Jonathan, Eisenhower, Michael, Elie, Michelle, Elliott, James, Elliott, Kyle, Ellis, Tracy, Engesser, Michael, Espinoza, Nestor, Etienne, Odessa, Etxaluze, Mireya, Falini, Patrick, Feeney, Matthew, Ferry, Malcolm, Filippazzo, Joseph, Fincham, Brian, Fix, Mees, Flagey, Nicolas, Florian, Michael, Flynn, Jim, Fontanella, Erin, Ford, Terrance, Forshay, Peter, Fox, Ori, Franz, David, Fu, Henry, Fullerton, Alexander, Galkin, Sergey, Galyer, Anthony, Marin, Macarena Garcia, Gardner, Jonathan, Gardner, Lisa, Garland, Dennis, Garrett, Bruce, Gasman, Danny, Gaspar, Andras, Gaudreau, Daniel, Gauthier, Peter, Geers, Vincent, Geithner, Paul, Gennaro, Mario, Giardino, Giovanna, Girard, Julien, Giuliano, Mark, Glassmire, Kirk, Glauser, Adrian, Glazer, Stuart, Godfrey, John, Golimowski, David, Gollnitz, David, Gong, Fan, Gonzaga, Shireen, Gordon, Michael, Gordon, Karl, Goudfrooij, Paul, Greene, Thomas, Greenhouse, Matthew, Grimaldi, Stefano, Groebner, Andrew, Grundy, Timothy, Guillard, Pierre, Gutman, Irvin, Ha, Kong Q., Haderlein, Peter, Hagedorn, Andria, Hainline, Kevin, Haley, Craig, Hami, Maryam, Hamilton, Forrest, Hammel, Heidi, Hansen, Carl, Harkins, Tom, Harr, Michael, Hart, Jessica, Hart, Quyen, Hartig, George, Hashimoto, Ryan, Haskins, Sujee, Hathaway, William, Havey, Keith, Hayden, Brian, Hecht, Karen, Heller-Boyer, Chris, Henriques, Caroline, Henry, Alaina, Hermann, Karl, Hernandez, Scarlin, Hesman, Brigette, Hicks, Brian, Hilbert, Bryan, Hines, Dean, Hoffman, Melissa, Holfeltz, Sherie, Holler, Bryan J., Hoppa, Jennifer, Hott, Kyle, Howard, Joseph, Howard, Rick, Hunter, Alexander, Hunter, David, Hurst, Brendan, Husemann, Bernd, Hustak, Leah, Ignat, Luminita Ilinca, Illingworth, Garth, Irish, Sandra, Jackson, Wallace, Jahromi, Amir, Jakobsen, Peter, James, LeAndrea, James, Bryan, Januszewski, William, Jenkins, Ann, Jirdeh, Hussein, Johnson, Phillip, Johnson, Timothy, Jones, Vicki, Jones, Ron, Jones, Danny, Jones, Olivia, Jordan, Ian, Jordan, Margaret, Jurczyk, Sarah, Jurling, Alden, Kaleida, Catherine, Kalmanson, Phillip, Kammerer, Jens, Kang, Huijo, Kao, Shaw-Hong, Karakla, Diane, Kavanagh, Patrick, Kelly, Doug, Kendrew, Sarah, Kennedy, Herbert, Kenny, Deborah, Keski-kuha, Ritva, Keyes, Charles, Kidwell, Richard, Kinzel, Wayne, Kirk, Jeff, Kirkpatrick, Mark, Kirshenblat, Danielle, Klaassen, Pamela, Knapp, Bryan, Knight, J. Scott, Knollenberg, Perry, Koehler, Robert, Koekemoer, Anton, Kovacs, Aiden, Kulp, Trey, Kumari, Nimisha, Kyprianou, Mark, La Massa, Stephanie, Labador, Aurora, Ortega, Alvaro Labiano, Lagage, Pierre-Olivier, Lajoie, Charles-Phillipe, Lallo, Matthew, Lam, May, Lamb, Tracy, Lambros, Scott, Lampenfield, Richard, Langston, James, Larson, Kirsten, Law, David, Lawrence, Jon, Lee, David, Leisenring, Jarron, Lepo, Kelly, Leveille, Michael, Levenson, Nancy, Levine, Marie, Levy, Zena, Lewis, Dan, Lewis, Hannah, Libralato, Mattia, Lightsey, Paul, Link, Miranda, Liu, Lily, Lo, Amy, Lockwood, Alexandra, Logue, Ryan, Long, Chris, Long, Douglas, Loomis, Charles, Lopez-Caniego, Marcos, Alvarez, Jose Lorenzo, Love-Pruitt, Jennifer, Lucy, Adrian, Luetzgendorf, Nora, Maghami, Peiman, Maiolino, Roberto, Major, Melissa, Malla, Sunita, Malumuth, Eliot, Manjavacas, Elena, Mannfolk, Crystal, Marrione, Amanda, Marston, Anthony, Martel, André, Maschmann, Marc, Masci, Gregory, Masciarelli, Michaela, Maszkiewicz, Michael, Mather, John, McKenzie, Kenny, McLean, Brian, McMaster, Matthew, Melbourne, Katie, Meléndez, Marcio, Menzel, Michael, Merz, Kaiya, Meyett, Michele, Meza, Luis, Miskey, Cherie, Misselt, Karl, Moller, Christopher, Morrison, Jane, Morse, Ernie, Moseley, Harvey, Mosier, Gary, Mountain, Matt, Mueckay, Julio, Mueller, Michael, Mullally, Susan, Murphy, Jess, Murray, Katherine, Murray, Claire, Mustelier, David, Muzerolle, James, Mycroft, Matthew, Myers, Richard, Myrick, Kaila, Nanavati, Shashvat, Nance, Elizabeth, Nayak, Omnarayani, Naylor, Bret, Nelan, Edmund, Nickson, Bryony, Nielson, Alethea, Nieto-Santisteban, Maria, Nikolov, Nikolay, Noriega-Crespo, Alberto, O'Shaughnessy, Brian, O'Sullivan, Brian, Ochs, William, Ogle, Patrick, Oleszczuk, Brenda, Olmsted, Joseph, Osborne, Shannon, Ottens, Richard, Owens, Beverly, Pacifici, Camilla, Pagan, Alyssa, Page, James, Park, Sang, Parrish, Keith, Patapis, Polychronis, Paul, Lee, Pauly, Tyler, Pavlovsky, Cheryl, Pedder, Andrew, Peek, Matthew, Pena-Guerrero, Maria, Pennanen, Konstantin, Perez, Yesenia, Perna, Michele, Perriello, Beth, Phillips, Kevin, Pietraszkiewicz, Martin, Pinaud, Jean-Paul, Pirzkal, Norbert, Pitman, Joseph, Piwowar, Aidan, Platais, Vera, Player, Danielle, Plesha, Rachel, Pollizi, Joe, Polster, Ethan, Pontoppidan, Klaus, Porterfield, Blair, Proffitt, Charles, Pueyo, Laurent, Pulliam, Christine, Quirt, Brian, Neira, Irma Quispe, Alarcon, Rafael Ramos, Ramsay, Leah, Rapp, Greg, Rapp, Robert, Rauscher, Bernard, Ravindranath, Swara, Rawle, Timothy, Regan, Michael, Reichard, Timothy A., Reis, Carl, Ressler, Michael E., Rest, Armin, Reynolds, Paul, Rhue, Timothy, Richon, Karen, Rickman, Emily, Ridgaway, Michael, Ritchie, Christine, Rix, Hans-Walter, Robberto, Massimo, Robinson, Gregory, Robinson, Michael, Robinson, Orion, Rock, Frank, Rodriguez, David, Del Pino, Bruno Rodriguez, Roellig, Thomas, Rohrbach, Scott, Roman, Anthony, Romelfanger, Fred, Rose, Perry, Roteliuk, Anthony, Roth, Marc, Rothwell, Braden, Rowlands, Neil, Roy, Arpita, Royer, Pierre, Royle, Patricia, Rui, Chunlei, Rumler, Peter, Runnels, Joel, Russ, Melissa, Rustamkulov, Zafar, Ryden, Grant, Ryer, Holly, Sabata, Modhumita, Sabatke, Derek, Sabbi, Elena, Samuelson, Bridget, Sapp, Benjamin, Sappington, Bradley, Sargent, B., Sauer, Arne, Scheithauer, Silvia, Schlawin, Everett, Schlitz, Joseph, Schmitz, Tyler, Schneider, Analyn, Schreiber, Jürgen, Schulze, Vonessa, Schwab, Ryan, Scott, John, Sembach, Kenneth, Shanahan, Clare, Shaughnessy, Bryan, Shaw, Richard, Shawger, Nanci, Shay, Christopher, Sheehan, Evan, Shen, Sharon, Sherman, Allan, Shiao, Bernard, Shih, Hsin-Yi, Shivaei, Irene, Sienkiewicz, Matthew, Sing, David, Sirianni, Marco, Sivaramakrishnan, Anand, Skipper, Joy, Sloan, Gregory, Slocum, Christine, Slowinski, Steven, Smith, Erin, Smith, Eric, Smith, Denise, Smith, Corbett, Snyder, Gregory, Soh, Warren, Sohn, Tony, Soto, Christian, Spencer, Richard, Stallcup, Scott, Stansberry, John, Starr, Carl, Starr, Elysia, Stewart, Alphonso, Stiavelli, Massimo, Straughn, Amber, Strickland, David, Stys, Jeff, Summers, Francis, Sun, Fengwu, Sunnquist, Ben, Swade, Daryl, Swam, Michael, Swaters, Robert, Swoish, Robby, Taylor, Joanna M., Taylor, Rolanda, Plate, Maurice Te, Tea, Mason, Teague, Kelly, Telfer, Randal, Temim, Tea, Thatte, Deepashri, Thompson, Christopher, Thompson, Linda, Thomson, Shaun, Tikkanen, Tuomo, Tippet, William, Todd, Connor, Toolan, Sharon, Tran, Hien, Trejo, Edwin, Truong, Justin, Tsukamoto, Chris, Tustain, Samuel, Tyra, Harrison, Ubeda, Leonardo, Underwood, Kelli, Uzzo, Michael, Van Campen, Julie, Vandal, Thomas, Vandenbussche, Bart, Vila, Begoña, Volk, Kevin, Wahlgren, Glenn, Waldman, Mark, Walker, Chanda, Wander, Michel, Warfield, Christine, Warner, Gerald, Wasiak, Matthew, Watkins, Mitchell, Weaver, Andrew, Weilert, Mark, Weiser, Nick, Weiss, Ben, Weissman, Sarah, Welty, Alan, West, Garrett, Wheate, Lauren, Wheatley, Elizabeth, Wheeler, Thomas, White, Rick, Whiteaker, Kevin, Whitehouse, Paul, Whiteleather, Jennifer, Whitman, William, Williams, Christina, Willmer, Christopher, Willoughby, Scott, Wilson, Andrew, Wirth, Gregory, Wislowski, Emily, Wolf, Erin, Wolfe, David, Wolff, Schuyler, Workman, Bill, Wright, Ray, Wu, Carl, Wu, Rai, Wymer, Kristen, Yates, Kayla, Yeager, Christopher, Yeates, Jared, Yerger, Ethan, Yoon, Jinmi, Young, Alice, Yu, Susan, Zak, Dean, Zeidler, Peter, Zhou, Julia, Zielinski, Thomas, Zincke, Cristian, and Zonak, Stephanie

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies., Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb293

Published
2022
Full Text
View/download PDF

14. Concept validation of a high dynamic range point-diffraction interferometer for wavefront sensing in adaptive optics

Author

Dubost, Nicolas, Bharmal, Nazim Ali, Dubbeldam, Marc, and Myers, Richard M.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The direct detection and imaging of exoplanets requires the use of high-contrast adaptive optics (AO). In these systems quasi-static aberrations need to be highly corrected and calibrated. In order to achieve this, the pupil-modulated point-diffraction interferometer (m-PDI), was presented in an earlier paper. This present paper focuses on m-PDI concept validation through three experiments. First, the instrument's accuracy and dynamic range are characterised by measuring the spatial transfer function at all spatial frequencies and at different amplitudes. Then, using visible monochromatic light, an adaptive optics control loop is closed on the system's systematic bias to test for precision and completeness. In a central section of the pupil with 72% of the total radius the residual error is 7.7nm-rms. Finally, the control loop is run using polychromatic light with a spectral FWHM of 77nm around the R-band. The control loop shows no drop in performance with respect to the monochromatic case, reaching a final Strehl ratio larger than 0.7.

Published
2022
Full Text
View/download PDF

15. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

16. Context-specific emergence and growth of the SARS-CoV-2 Delta variant

Author

McCrone, John T, Hill, Verity, Bajaj, Sumali, Pena, Rosario Evans, Lambert, Ben C, Inward, Rhys, Bhatt, Samir, Volz, Erik, Ruis, Christopher, Dellicour, Simon, Baele, Guy, Zarebski, Alexander E, Sadilek, Adam, Wu, Neo, Schneider, Aaron, Ji, Xiang, Raghwani, Jayna, Jackson, Ben, Colquhoun, Rachel, O’Toole, Áine, Peacock, Thomas P, Twohig, Kate, Thelwall, Simon, Dabrera, Gavin, Myers, Richard, Faria, Nuno R, Huber, Carmen, Bogoch, Isaac I, Khan, Kamran, du Plessis, Louis, Barrett, Jeffrey C, Aanensen, David M, Barclay, Wendy S, Chand, Meera, Connor, Thomas, Loman, Nicholas J, Suchard, Marc A, Pybus, Oliver G, Rambaut, Andrew, and Kraemer, Moritz UG

Subjects
Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, COVID-19, Cities, Contact Tracing, England, Genome, Viral, Humans, Quarantine, SARS-CoV-2, Travel, COVID-19 Genomics UK (COG-UK) Consortium, General Science & Technology
Abstract

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).

Published
2022

17. Field Theory of Interacting Boundary Gravitons

Author

Ebert, Stephen, Hijano, Eliot, Kraus, Per, Monten, Ruben, and Myers, Richard M.

Subjects
High Energy Physics - Theory, General Relativity and Quantum Cosmology
Abstract

Pure three-dimensional gravity is a renormalizable theory with two free parameters labelled by $G$ and $\Lambda$. As a consequence, correlation functions of the boundary stress tensor in AdS$_3$ are uniquely fixed in terms of one dimensionless parameter, which is the central charge of the Virasoro algebra. The same argument implies that AdS$_3$ gravity at a finite radial cutoff is a renormalizable theory, but now with one additional parameter corresponding to the cutoff location. This theory is conjecturally dual to a $T\overline{T}$-deformed CFT, assuming that such theories actually exist. To elucidate this, we study the quantum theory of boundary gravitons living on a cutoff planar boundary and the associated correlation functions of the boundary stress tensor. We compute stress tensor correlation functions to two-loop order ($G$ being the loop counting parameter), extending existing tree level results. This is made feasible by the fact that the boundary graviton action simplifies greatly upon making a judicious field redefinition, turning into the Nambu-Goto action. After imposing Lorentz invariance, the correlators at this order are found to be unambiguous up to a single undetermined renormalization parameter., Comment: 71 pages, 1 figure, typos corrected and clarifications added in response to the referees' questions

Published
2022
Full Text
View/download PDF

19. Transforming for the war on terrorism

Author

Myers, Richard B., Gen

Subjects
WAR ON TERRORISM, 2001-, ARMED FORCES - United States - Organization
Abstract

illus por

Published
2004

20. Understanding transformation

Author

Myers, Richard B., Gen

Subjects
JOINT FORCES - United States, ARMED FORCES - United States, DEFENSES - United States
Abstract

illus

Published
2003

22. Author Correction: Perspectives on ENCODE

Author

Snyder, Michael P, Gingeras, Thomas R, Moore, Jill E, Weng, Zhiping, Gerstein, Mark B, Ren, Bing, Hardison, Ross C, Stamatoyannopoulos, John A, Graveley, Brenton R, Feingold, Elise A, Pazin, Michael J, Pagan, Michael, Gilchrist, Daniel A, Hitz, Benjamin C, Cherry, J Michael, Bernstein, Bradley E, Mendenhall, Eric M, Zerbino, Daniel R, Frankish, Adam, Flicek, Paul, and Myers, Richard M

Subjects
ENCODE Project Consortium, General Science & Technology
Abstract

In this Article, the authors Rizi Ai (Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA) and Shantao Li (Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA) were mistakenly omitted from the ENCODE Project Consortium author list. The original Article has been corrected online.

Published
2022

23. Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes

Author

Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping

Subjects
ENCODE Project Consortium, General Science & Technology
Abstract

In the version of this article initially published, two members of the ENCODE Project Consortium were missing from the author list. Rizi Ai (Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA) and Shantao Li (Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA) are now included in the author list. These errors have been corrected in the online version of the article.

Published
2022

24. SARS-CoV-2 Testing in the Community: Testing Positive Samples with the TaqMan SARS-CoV-2 Mutation Panel To Find Variants in Real Time

Author

Ashford, Fiona, Best, Angus, Dunn, Steven J, Ahmed, Zahra, Siddiqui, Henna, Melville, Jordan, Wilkinson, Samuel, Mirza, Jeremy, Cumley, Nicola, Stockton, Joanne, Ferguson, Jack, Wheatley, Lucy, Ratcliffe, Elizabeth, Casey, Anna, Plant, Tim, Aggarwal, Dinesh, Blane, Beth, Brooks, Ellena, Carabelli, Alessandro M, Churcher, Carol M, Galai, Katerina, Girgis, Sophia T, Gupta, Ravi K, Hadjirin, Nazreen F, Leek, Danielle, Ludden, Catherine, McManus, Georgina M, Palmer, Sophie, Peacock, Sharon J, Smith, Kim S, Allara, Elias, Bibby, David, Bishop, Chloe, Bosworth, Andrew, Bradshaw, Daniel, Chalker, Vicki, Chand, Meera, Dabrera, Gavin, Ellaby, Nicholas, Gallagher, Eileen, Groves, Natalie, Harrison, Ian, Hartman, Hassan, Hopes, Richard, Hubb, Jonathan, Hutchings, Stephanie, Lackenby, Angie, Ledesma, Juan, Lee, David, Manesis, Nikos, Manso, Carmen, Mbisa, Tamyo, Miah, Shahjahan, Muir, Peter, Myers, Richard, Osman, Husam, Patel, Vineet, Pearson, Clare, Platt, Steven, Pymont, Hannah M, Ramsay, Mary, Robinson, Esther, Schaefer, Ulf, Thornton, Alicia, Twohig, Katherine A, Vipond, Ian B, Williams, David, Hamilton, William L, Warne, Ben, Aigrain, Louise, Alderton, Alex, Amato, Roberto, Ariani, Cristina V, Barrett, Jeff, Bassett, Andrew R, Beale, Mathew A, Beaver, Charlotte, Bellis, Katherine L, Betteridge, Emma, Bonfield, James, Bronner, Iraad F, Chapman, Michael HS, Danesh, John, Davies, Robert, Dorman, Matthew J, Drury, Eleanor, Durham, Jillian, Farr, Ben W, Foulser, Luke, Goncalves, Sonia, Goodwin, Scott, Gourtovaia, Marina, Harrison, Ewan M, Jackson, David K, James, Keith, Jamrozy, Dorota, Johnston, Ian, Kane, Leanne, Kay, Sally, and Keatley, Jon-Paul

Subjects
Human Genome, Prevention, Biodefense, Genetics, Lung, Vaccine Related, Emerging Infectious Diseases, Good Health and Well Being, COVID-19, COVID-19 Testing, Humans, Mutation, SARS-CoV-2, COVID-19 Genomics UK (COG-UK) Consortium, PCR, SNPs, genome sequencing, genotyping, real time, variants of concern, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract

Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, is an excellent complement to genome sequencing, and has real clinical health value potential, allowing laboratories to report and take action on variants of concern much more quickly.

Published
2022

25. Rare coding variants in ten genes confer substantial risk for schizophrenia.

Author

Singh, Tarjinder, Poterba, Timothy, Curtis, David, Akil, Huda, Al Eissa, Mariam, Barchas, Jack D, Bass, Nicholas, Bigdeli, Tim B, Breen, Gerome, Bromet, Evelyn J, Buckley, Peter F, Bunney, William E, Bybjerg-Grauholm, Jonas, Byerley, William F, Chapman, Sinéad B, Chen, Wei J, Churchhouse, Claire, Craddock, Nicholas, Cusick, Caroline M, DeLisi, Lynn, Dodge, Sheila, Escamilla, Michael A, Eskelinen, Saana, Fanous, Ayman H, Faraone, Stephen V, Fiorentino, Alessia, Francioli, Laurent, Gabriel, Stacey B, Gage, Diane, Gagliano Taliun, Sarah A, Ganna, Andrea, Genovese, Giulio, Glahn, David C, Grove, Jakob, Hall, Mei-Hua, Hämäläinen, Eija, Heyne, Henrike O, Holi, Matti, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Hwu, Hai-Gwo, Kahn, René S, Kang, Hyun Min, Karczewski, Konrad J, Kirov, George, Knowles, James A, Lee, Francis S, Lehrer, Douglas S, Lescai, Francesco, Malaspina, Dolores, Marder, Stephen R, McCarroll, Steven A, McIntosh, Andrew M, Medeiros, Helena, Milani, Lili, Morley, Christopher P, Morris, Derek W, Mortensen, Preben Bo, Myers, Richard M, Nordentoft, Merete, O'Brien, Niamh L, Olivares, Ana Maria, Ongur, Dost, Ouwehand, Willem H, Palmer, Duncan S, Paunio, Tiina, Quested, Digby, Rapaport, Mark H, Rees, Elliott, Rollins, Brandi, Satterstrom, F Kyle, Schatzberg, Alan, Scolnick, Edward, Scott, Laura J, Sharp, Sally I, Sklar, Pamela, Smoller, Jordan W, Sobell, Janet L, Solomonson, Matthew, Stahl, Eli A, Stevens, Christine R, Suvisaari, Jaana, Tiao, Grace, Watson, Stanley J, Watts, Nicholas A, Blackwood, Douglas H, Børglum, Anders D, Cohen, Bruce M, Corvin, Aiden P, Esko, Tõnu, Freimer, Nelson B, Glatt, Stephen J, Hultman, Christina M, McQuillin, Andrew, Palotie, Aarno, Pato, Carlos N, Pato, Michele T, Pulver, Ann E, and St Clair, David

Subjects
Humans, Genetic Predisposition to Disease, Receptors, N-Methyl-D-Aspartate, Case-Control Studies, Schizophrenia, Mutation, Exome, Neurodevelopmental Disorders, Human Genome, Biotechnology, Mental Health, Neurosciences, Brain Disorders, Genetics, Serious Mental Illness, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, General Science & Technology
Abstract

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P

Published
2022

27. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

Author

Mullins, Niamh, Kang, JooEun, Campos, Adrian I, Coleman, Jonathan RI, Edwards, Alexis C, Galfalvy, Hanga, Levey, Daniel F, Lori, Adriana, Shabalin, Andrey, Starnawska, Anna, Su, Mei-Hsin, Watson, Hunna J, Adams, Mark, Awasthi, Swapnil, Gandal, Michael, Hafferty, Jonathan D, Hishimoto, Akitoyo, Kim, Minsoo, Okazaki, Satoshi, Otsuka, Ikuo, Ripke, Stephan, Ware, Erin B, Bergen, Andrew W, Berrettini, Wade H, Bohus, Martin, Brandt, Harry, Chang, Xiao, Chen, Wei J, Chen, Hsi-Chung, Crawford, Steven, Crow, Scott, DiBlasi, Emily, Duriez, Philibert, Fernández-Aranda, Fernando, Fichter, Manfred M, Gallinger, Steven, Glatt, Stephen J, Gorwood, Philip, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A, Hwu, Hai-Gwo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Keel, Pamela K, Kennedy, James L, Klump, Kelly L, Li, Dong, Liao, Shih-Cheng, Lieb, Klaus, Lilenfeld, Lisa, Liu, Chih-Min, Magistretti, Pierre J, Marshall, Christian R, Mitchell, James E, Monson, Eric T, Myers, Richard M, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W, Schmahl, Christian, Sokolowski, Marcus, Strober, Michael, Thornton, Laura M, Treasure, Janet, Tsuang, Ming T, Witt, Stephanie H, Woodside, D Blake, Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Air, Tracy M, Alda, Martin, Alfredsson, Lars, Andreassen, Ole A, Anjorin, Adebayo, Appadurai, Vivek, Soler Artigas, María, Van der Auwera, Sandra, Azevedo, M Helena, Bass, Nicholas, Bau, Claiton HD, Baune, Bernhard T, Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M, Bigdeli, Tim B, Binder, Elisabeth B, Boehnke, Michael, Boks, Marco P, Bosch, Rosa, and Braff, David L

Subjects
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, German Borderline Genomics Consortium, MVP Suicide Exemplar Workgroup, VA Million Veteran Program, Humans, Risk Factors, Suicide, Attempted, Mental Disorders, Depressive Disorder, Major, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt, Human Genome, Behavioral and Social Science, Mental Health, Prevention, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundSuicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.MethodsWe conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.ResultsTwo loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.ConclusionsOur results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Published
2022

28. Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

Author

Das, Sujan C, Hjelm, Brooke E, Rollins, Brandi L, Sequeira, Adolfo, Morgan, Ling, Omidsalar, Audrey A, Schatzberg, Alan F, Barchas, Jack D, Lee, Francis S, Myers, Richard M, Watson, Stanley J, Akil, Huda, Bunney, William E, and Vawter, Marquis P

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Serious Mental Illness, Mental Health, Neurosciences, Eye Disease and Disorders of Vision, Schizophrenia, Mental health, Bipolar Disorder, DNA Copy Number Variations, DNA, Mitochondrial, Female, Humans, Mitochondria, Synapses, Clinical Sciences, Public Health and Health Services, Clinical sciences, Biological psychology
Abstract

Mitochondrial dysfunction is a neurobiological phenomenon implicated in the pathophysiology of schizophrenia and bipolar disorder that can synergistically affect synaptic neurotransmission. We hypothesized that schizophrenia and bipolar disorder share molecular alterations at the mitochondrial and synaptic levels. Mitochondria DNA (mtDNA) copy number (CN), mtDNA common deletion (CD), mtDNA total deletion, complex I activity, synapse number, and synaptic mitochondria number were studied in the postmortem human dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), primary visual cortex (V1), and nucleus accumbens (NAc) of controls (CON), and subjects with schizophrenia (SZ), and bipolar disorder (BD). The results showed (i) the mtDNA CN is significantly higher in DLPFC of both SZ and BD, decreased in the STG of BD, and unaltered in V1 and NAc of both SZ and BD; (ii) the mtDNA CD is significantly higher in DLPFC of BD while unaltered in STG, V1, and NAc of both SZ and BD; (iii) The total deletion burden is significantly higher in DLPFC in both SZ and BD while unaltered in STG, V1, and NAc of SZ and BD; (iv) Complex I activity is significantly lower in DLPFC of both SZ and BD, which is driven by the presence of medications, with no alteration in STG, V1, and NAc. In addition, complex I protein concentration, by ELISA, was decreased across three cortical regions of SZ and BD subjects; (v) The number of synapses is decreased in DLPFC of both SZ and BD, while the synaptic mitochondria number was significantly lower in female SZ and female BD compared to female controls. Overall, these findings will pave the way to understand better the pathophysiology of schizophrenia and bipolar disorder for therapeutic interventions.

Published
2022

32. Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements

Author

Rogers, Brianne B., Anderson, Ashlyn G., Lauzon, Shelby N., Davis, M. Natalie, Hauser, Rebecca M., Roberts, Sydney C., Rodriguez-Nunez, Ivan, Trausch-Lowther, Katie, Barinaga, Erin A., Hall, Paige I., Knuesel, Matthew T., Taylor, Jared W., Mackiewicz, Mark, Roberts, Brian S., Cooper, Sara J., Rizzardi, Lindsay F., Myers, Richard M., and Cochran, J. Nicholas

Published
2024
Full Text
View/download PDF

34. 3D Gravity in a Box

Author

Kraus, Per, Monten, Ruben, and Myers, Richard M.

Subjects
High Energy Physics - Theory
Abstract

The quantization of pure 3D gravity with Dirichlet boundary conditions on a finite boundary is of interest both as a model of quantum gravity in which one can compute quantities which are "more local" than S-matrices or asymptotic boundary correlators, and for its proposed holographic duality to $T \overline{T}$-deformed CFTs. In this work we apply covariant phase space methods to deduce the Poisson bracket algebra of boundary observables. The result is a one-parameter nonlinear deformation of the usual Virasoro algebra of asymptotically AdS$_3$ gravity. This algebra should be obeyed by the stress tensor in any $T\overline{T}$-deformed holographic CFT. We next initiate quantization of this system within the general framework of coadjoint orbits, obtaining - in perturbation theory - a deformed version of the Alekseev-Shatashvili symplectic form and its associated geometric action. The resulting energy spectrum is consistent with the expected spectrum of $T\overline{T}$-deformed theories, although we only carry out the explicit comparison to $\mathcal{O}(1/\sqrt{c})$ in the $1/c$ expansion., Comment: 59 pages, corrected typos and minus signs. This is the published version

Published
2021
Full Text
View/download PDF

36. Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

Author

Jia, Xiaoming, Goes, Fernando S, Locke, Adam E, Palmer, Duncan, Wang, Weiqing, Cohen-Woods, Sarah, Genovese, Giulio, Jackson, Anne U, Jiang, Chen, Kvale, Mark, Mullins, Niamh, Nguyen, Hoang, Pirooznia, Mehdi, Rivera, Margarita, Ruderfer, Douglas M, Shen, Ling, Thai, Khanh, Zawistowski, Matthew, Zhuang, Yongwen, Abecasis, Gonçalo, Akil, Huda, Bergen, Sarah, Burmeister, Margit, Chapman, Sinéad, DelaBastide, Melissa, Juréus, Anders, Kang, Hyun Min, Kwok, Pui-Yan, Li, Jun Z, Levy, Shawn E, Monson, Eric T, Moran, Jennifer, Sobell, Janet, Watson, Stanley, Willour, Virginia, Zöllner, Sebastian, Adolfsson, Rolf, Blackwood, Douglas, Boehnke, Michael, Breen, Gerome, Corvin, Aiden, Craddock, Nick, DiFlorio, Arianna, Hultman, Christina M, Landen, Mikael, Lewis, Cathryn, McCarroll, Steven A, Richard McCombie, W, McGuffin, Peter, McIntosh, Andrew, McQuillin, Andrew, Morris, Derek, Myers, Richard M, O'Donovan, Michael, Ophoff, Roel, Boks, Marco, Kahn, Rene, Ouwehand, Willem, Owen, Michael, Pato, Carlos, Pato, Michele, Posthuma, Danielle, Potash, James B, Reif, Andreas, Sklar, Pamela, Smoller, Jordan, Sullivan, Patrick F, Vincent, John, Walters, James, Neale, Benjamin, Purcell, Shaun, Risch, Neil, Schaefer, Catherine, Stahl, Eli A, Zandi, Peter P, and Scott, Laura J

Subjects
Humans, Genetic Predisposition to Disease, Bipolar Disorder, Schizophrenia, Polymorphism, Single Nucleotide, Genetic Variation, Genome-Wide Association Study, Exome, Brain Disorders, Prevention, Clinical Research, Human Genome, Serious Mental Illness, Genetics, Mental Health, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.

Published
2021

37. Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease

Author

Lai, Dongbing, Alipanahi, Babak, Fontanillas, Pierre, Schwantes‐An, Tae‐Hwi, Aasly, Jan, Alcalay, Roy N, Beecham, Gary W, Berg, Daniela, Bressman, Susan, Brice, Alexis, Brockman, Kathrin, Clark, Lorraine, Cookson, Mark, Das, Sayantan, Van Deerlin, Vivianna, Follett, Jordan, Farrer, Matthew J, Trinh, Joanne, Gasser, Thomas, Goldwurm, Stefano, Gustavsson, Emil, Klein, Christine, Lang, Anthony E, Langston, J William, Latourelle, Jeanne, Lynch, Timothy, Marder, Karen, Marras, Connie, Martin, Eden R, McLean, Cory Y, Mejia‐Santana, Helen, Molho, Eric, Myers, Richard H, Nuytemans, Karen, Ozelius, Laurie, Payami, Haydeh, Raymond, Deborah, Rogaeva, Ekaterina, Rogers, Michael P, Ross, Owen A, Samii, Ali, Saunders‐Pullman, Rachel, Schüle, Birgitt, Schulte, Claudia, Scott, William K, Tanner, Caroline, Tolosa, Eduardo, Tomkins, James E, Vilas, Dolores, Trojanowski, John Q, Team, The 23andMe Research, Uitti, Ryan, Vance, Jeffery M, Visanji, Naomi P, Wszolek, Zbigniew K, Zabetian, Cyrus P, Mirelman, Anat, Giladi, Nir, Urtreger, Avi Orr, Cannon, Paul, Fiske, Brian, and Foroud, Tatiana

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Genetics, Brain Disorders, Prevention, Parkinson's Disease, Neurodegenerative, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Mutation, Parkinson Disease, Penetrance, 23andMe Research Team, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveThe aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease.MethodsWe performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers.ResultsA variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset.InterpretationThis study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94.

Published
2021

38. A word from the chairman

Author

Myers, Richard B., Gen

Subjects
MILITARY POLICY - United States - Testing
Abstract

illus

Published
2004

40. Blocking of the CD80/86 axis as a therapeutic approach to prevent progression to more severe forms of COVID-19

Author

Julià, Antonio, Bonafonte, Irene, Gómez, Antonio, López-Lasanta, María, López-Corbeto, Mireia, Martínez-Mateu, Sergio H., Lladós, Jordi, Rodríguez-Nunez, Iván, Myers, Richard M., and Marsal, Sara

Subjects
Quantitative Biology - Tissues and Organs, Quantitative Biology - Genomics
Abstract

In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -- a CD80/86 co-stimulation inhibitor -- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoV-infected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs., Comment: 23 pages, 8 figures, 1 Table, Supplementary data (3 supplementary figures and 3 supplementary Tables)

Published
2020

45. The New American Way of War

Author

Myers, Richard B., Gen

Subjects
DOCTRINE - Air Force - United States, DOCTRINE - Air Force - United States - History
Abstract

illus por

Published
2003

46. Shift to a global perspective

Author

Myers, Richard B., Gen

Subjects
DOCTRINE - Armed Forces - United States, ARMED FORCES - United States - Organization, ARMED FORCES - United States - Lessons Learned
Abstract

bibliog

Published
2003

48. A medley of books

Author

Myers, Richard B., Gen

Subjects
TERRORISM - Bibliography, BOOKS AND READING
Abstract

illus

Published
2002

Catalog

Books, media, physical & digital resources
See catalog results