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2. The Initial Mass Function Based on the Full-sky 20-pc Census of $\sim$3,600 Stars and Brown Dwarfs

Author

Kirkpatrick, J. Davy, Marocco, Federico, Gelino, Christopher R., Raghu, Yadukrishna, Faherty, Jacqueline K., Gagliuffi, Daniella C. Bardalez, Schurr, Steven D., Apps, Kevin, Schneider, Adam C., Meisner, Aaron M., Kuchner, Marc J., Caselden, Dan, Smart, R. L., Casewell, S. L., Raddi, Roberto, Kesseli, Aurora, Andersen, Nikolaj Stevnbak, Antonini, Edoardo, Beaulieu, Paul, Bickle, Thomas P., Bilsing, Martin, Chieng, Raymond, Colin, Guillaume, Deen, Sam, Dereveanco, Alexandru, Doll, Katharina, Luca, Hugo A. Durantini, Frazer, Anya, Gantier, Jean Marc, Gramaize, Léopold, Grant, Kristin, Hamlet, Leslie K., Higashimura, Hiro, Hyogo, Michiharu, Jałowiczor, Peter A., Jonkeren, Alexander, Kabatnik, Martin, Kiwy, Frank, Martin, David W., Michaels, Marianne N., Pendrill, William, Machado, Celso Pessanha, Pumphrey, Benjamin, Rothermich, Austin, Russwurm, Rebekah, Sainio, Arttu, Sanchez, John, Sapelkin-Tambling, Fyodor Theo, Schümann, Jörg, Selg-Mann, Karl, Singh, Harshdeep, Stenner, Andres, Sun, Guoyou, Tanner, Christopher, Thévenot, Melina, Ventura, Maurizio, Voloshin, Nikita V., Walla, Jim, Wedracki, Zbigniew, Adorno, Jose I., Aganze, Christian, Allers, Katelyn N., Brooks, Hunter, Burgasser, Adam J., Calamari, Emily, Connor, Thomas, Costa, Edgardo, Eisenhardt, Peter R., Gagné, Jonathan, Gerasimov, Roman, Gonzales, Eileen C., Hsu, Chih-Chun, Kiman, Rocio, Li, Guodong, Low, Ryan, Mamajek, Eric, Pantoja, Blake M., Popinchalk, Mark, Rees, Jon M., Stern, Daniel, Suárez, Genaro, Theissen, Christopher, Tsai, Chao-Wei, Vos, Johanna M., Zurek, David, Worlds, The Backyard, and Collaboration, Planet 9

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

A complete accounting of nearby objects -- from the highest-mass white dwarf progenitors down to low-mass brown dwarfs -- is now possible, thanks to an almost complete set of trigonometric parallax determinations from Gaia, ground-based surveys, and Spitzer follow-up. We create a census of objects within a Sun-centered sphere of 20-pc radius and check published literature to decompose each binary or higher-order system into its separate components. The result is a volume-limited census of $\sim$3,600 individual star formation products useful in measuring the initial mass function across the stellar ($<8 M_\odot$) and substellar ($\gtrsim 5 M_{Jup}$) regimes. Comparing our resulting initial mass function to previous measurements shows good agreement above 0.8$M_\odot$ and a divergence at lower masses. Our 20-pc space densities are best fit with a quadripartite power law, $\xi(M) = dN/dM \propto M^{-\alpha}$ with long-established values of $\alpha = 2.3$ at high masses ($0.55 < M < 8.00 M_\odot$) and $\alpha = 1.3$ at intermediate masses ($0.22 < M < 0.55 M_\odot$), but at lower masses we find $\alpha = 0.25$ for $0.05 < M <0.22 M_\odot$ and $\alpha = 0.6$ for $0.01 < M < 0.05 M_\odot$. This implies that the rate of production as a function of decreasing mass diminishes in the low-mass star/high-mass brown dwarf regime before increasing again in the low-mass brown dwarf regime. Correcting for completeness, we find a star to brown dwarf number ratio of, currently, 4:1, and an average mass per object of 0.41 $M_\odot$., Comment: Accepted for publication in The Astrophysical Journal Supplement Series. 123 pages with four ancillary files

Published
2023

7. 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
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8. Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease

Author

Peter D. Burbelo, Julio A. Huapaya, Zohreh Khavandgar, Margaret Beach, Iago Pinal-Fernandez, Andrew L. Mammen, John A. Chiorini, Payam Noroozi Farhadi, Frederick W. Miller, Adam Schiffenbauer, Kakali Sarkar, Blake M. Warner, and Lisa G. Rider

Subjects
interstitial lung disease, myositis-specific autoantibody, myositis-associated autoantibody, idiopathic inflammatory myopathies, Sjögren’s disease, Immunologic diseases. Allergy, RC581-607
Abstract

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren’s disease (SjD), and 10 healthy volunteers. LIPS detected a broad dynamic range of autoantibodies, to MDA5, Jo-1, PL12, KS, U1-70K, and Ro52, and matched seropositivity status with established immunoassays. Robust anti-MDA5 autoantibodies in four IIM-ILD patients had a median value of 1,134,000 LU (IQR 473,000-2,317,000), which was 500 times higher than in 21 seronegative IIM patients. Markedly elevated anti-Jo-1 autoantibodies in five IIM-ILD patients demonstrated a median value of 1,177,000 LU (IQR: 604,000-2,520,000), which was 1000-fold higher than in seronegative patients. Robust anti-Ro52 and other anti-tRNA-synthetase autoantibodies were detected in a subset of IIM-ILD subjects. In SjD, only anti-U1-70K and KS autoantibodies were identified in ILD patients with a prevalence of 30% and 20%, respectively. In longitudinal samples of five IIM-ILD patients, anti-Jo-1 autoantibody levels paralleled clinical improvement of lung function. LIPS can accurately quantify autoantibody levels as biomarkers for treatment response in patients with autoimmune ILD.

Published
2024
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11. Structure-based network analysis predicts pathogenic variants in human proteins associated with inherited retinal disease

Author

Blake M. Hauser, Yuyang Luo, Anusha Nathan, Ahmad Al-Moujahed, Demetrios G. Vavvas, Jason Comander, Eric A. Pierce, Emily M. Place, Kinga M. Bujakowska, Gaurav D. Gaiha, and Elizabeth J. Rossin

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Advances in gene sequencing technologies have accelerated the identification of genetic variants, but better tools are needed to understand which are causal of disease. This would be particularly useful in fields where gene therapy is a potential therapeutic modality for a disease-causing variant such as inherited retinal disease (IRD). Here, we apply structure-based network analysis (SBNA), which has been successfully utilized to identify variant-constrained amino acid residues in viral proteins, to identify residues that may cause IRD if subject to missense mutation. SBNA is based entirely on structural first principles and is not fit to specific outcome data, which makes it distinct from other contemporary missense prediction tools. In 4 well-studied human disease-associated proteins (BRCA1, HRAS, PTEN, and ERK2) with high-quality structural data, we find that SBNA scores correlate strongly with deep mutagenesis data. When applied to 47 IRD genes with available high-quality crystal structure data, SBNA scores reliably identified disease-causing variants according to phenotype definitions from the ClinVar database. Finally, we applied this approach to 63 patients at Massachusetts Eye and Ear (MEE) with IRD but for whom no genetic cause had been identified. Untrained models built using SBNA scores and BLOSUM62 scores for IRD-associated genes successfully predicted the pathogenicity of novel variants (AUC = 0.851), allowing us to identify likely causative disease variants in 40 IRD patients. Model performance was further augmented by incorporating orthogonal data from EVE scores (AUC = 0.927), which are based on evolutionary multiple sequence alignments. In conclusion, SBNA can used to successfully identify variants as causal of disease in human proteins and may help predict variants causative of IRD in an unbiased fashion.

Published
2024
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12. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus

Author

Kincer, Laura P, Joseph, Sarah Beth, Gilleece, Maria M, Hauser, Blake M, Sizemore, Sabrina, Zhou, Shuntai, Di Germanio, Clara, Zetterberg, Henrik, Fuchs, Dietmar, Deeks, Steven G, Spudich, Serena, Gisslen, Magnus, Price, Richard W, and Swanstrom, Ronald

Subjects
Microbiology, Biological Sciences, Neurosciences, Infectious Diseases, HIV/AIDS, Pediatric AIDS, Pediatric, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Humans, T-Lymphocytes, HIV-1, HIV Infections, Central Nervous System, Antiviral Agents, Medical Microbiology
Abstract

HIV-1 persists as a latent reservoir in people receiving suppressive antiretroviral therapy (ART). When ART is interrupted (treatment interruption/TI), rebound virus re-initiates systemic infection in the lymphoid system. During TI, HIV-1 is also detected in cerebrospinal fluid (CSF), although the source of this rebound virus is unknown. To investigate whether there is a distinct HIV-1 reservoir in the central nervous system (CNS), we compared rebound virus after TI in the blood and CSF of 11 participants. Peak rebound CSF viral loads vary and we show that high viral loads and the appearance of clonally amplified viral lineages in the CSF are correlated with the transient influx of white blood cells. We found no evidence of rebound macrophage-tropic virus in the CSF, even in one individual who had macrophage-tropic HIV-1 in the CSF pre-therapy. We propose a model in which R5 T cell-tropic virus is released from infected T cells that enter the CNS from the blood (or are resident in the CNS during therapy), with clonal amplification of infected T cells and virus replication occurring in the CNS during TI.

Published
2023

14. Clinical Outcomes of Non–Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry

Author

Sayfo, Sameh, Rosol, Zachary P., Vazquez, David Fernandez, Mamawala, Mufaddal, Bruneman, Blake M., Weideman, Sarah G., Adelman, Kennedy S., Jeong, Minseob, Ramanan, Bala, Tsai, Shirling, Shammas, Nicolas W., Monteleone, Peter P., Nanjundappa, Aravinda, Chu, Hung B., Smith, Bertram L., Grimsley, Bradley R., Hohmann, Stephen E., Vasquez, Javier, Jr, Metzger, Chris, Das, Tony S., Gable, Dennis R., Eidt, John F., and Banerjee, Subhash

Published
2024
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16. Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds

Author

Eike-Christian Wamhoff, Larance Ronsard, Jared Feldman, Grant A. Knappe, Blake M. Hauser, Anna Romanov, James Brett Case, Shilpa Sanapala, Evan C. Lam, Kerri J. St. Denis, Julie Boucau, Amy K. Barczak, Alejandro B. Balazs, Michael S. Diamond, Aaron G. Schmidt, Daniel Lingwood, and Mark Bathe

Subjects
Science
Abstract

Abstract Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

Published
2024
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25. Introduction

Author

Alderink, Gordon J., Ashby, Blake M., Alderink, Gordon J., and Ashby, Blake M.

Published
2023
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30. Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG

Author

Gao, Yaqi, Kim, Kyoungmin, Vitrac, Heidi, Salazar, Rebecca L., Gould, Benjamin D., Soedkamp, Daniel, Spivia, Weston, Raedschelders, Koen, Dinh, An Q., Guzman, Anna G., Tan, Lin, Azinas, Stavros, Taylor, David J.R., Schiffer, Walter, McNavish, Daniel, Burks, Helen B., Gottlieb, Roberta A., Lorenzi, Philip L., Hanson, Blake M., Van Eyk, Jennifer E., Taegtmeyer, Heinrich, and Karlstaedt, Anja

Published
2024
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34. Publisher Correction: Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

Author

Nanishi, Etsuro, Borriello, Francesco, Seo, Hyuk-Soo, O’Meara, Timothy R., McGrath, Marisa E., Saito, Yoshine, Chen, Jing, Diray-Arce, Joann, Song, Kijun, Xu, Andrew Z., Barman, Soumik, Menon, Manisha, Dong, Danica, Caradonna, Timothy M., Feldman, Jared, Hauser, Blake M., Schmidt, Aaron G., Baden, Lindsey R., Ernst, Robert K., Dillen, Carly, Yu, Jingyou, Chang, Aiquan, Hilgers, Luuk, Platenburg, Peter Paul, Dhe-Paganon, Sirano, Barouch, Dan H., Ozonoff, Al, Zanoni, Ivan, Frieman, Matthew B., Dowling, David J., and Levy, Ofer

Published
2023
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36. Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

Author

Nanishi, Etsuro, Borriello, Francesco, Seo, Hyuk-Soo, O’Meara, Timothy R., McGrath, Marisa E., Saito, Yoshine, Chen, Jing, Diray-Arce, Joann, Song, Kijun, Xu, Andrew Z., Barman, Soumik, Menon, Manisha, Dong, Danica, Caradonna, Timothy M., Feldman, Jared, Hauser, Blake M., Schmidt, Aaron G., Baden, Lindsey R., Ernst, Robert K., Dillen, Carly, Yu, Jingyou, Chang, Aiquan, Hilgers, Luuk, Platenburg, Peter Paul, Dhe-Paganon, Sirano, Barouch, Dan H., Ozonoff, Al, Zanoni, Ivan, Frieman, Matthew B., Dowling, David J., and Levy, Ofer

Published
2023
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37. Salivary excretion of systemically injected [18F]DCFPyL in prostate cancer patients undergoing PSMA scans

Author

Bruna Fernandes, Jyoti Roy, Falguni Basuli, Blake M. Warner, Liza Lindenberg, Esther Mena, Steven S. Adler, Gary L. Griffiths, Peter L. Choyke, and Frank I. Lin

Subjects
PSMA, [18F]-DCFPyL, salivary excretion, PET imaging, xerostomia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

IntroductionProstate-specific membrane antigen (PSMA) is present in high amounts in salivary glands, but it is unclear whether labeled binders of PSMA are excreted in the saliva.MethodsTen patients with prostate cancer underwent whole-body [18F]DCFPyL PET/CT (NCT03181867), and saliva samples were collected between 0-120 minutes post-injection. [18F]DCFPyL salivary excretion was measured over 120 minutes and expressed as %ID/g. Protein-associated binding was estimated by the percentage of [18F]DCFPyL versus parent radiotracer.ResultsAll PET scans of 10 patients (69 ± 8 years) with histologically confirmed prostate cancer (PSA= 2.4 ± 2.4, and Gleason Grade = 6-9) showed high uptake of [18F]-DCFPyL in salivary glands while 8 patients demonstrated high uptake in the saliva at 45 minutes. The intact [18F]-DCFPyL (98%) was also confirmed in the saliva samples at 120 min with increasing salivary radioactivity between 30-120 min.ConclusionSystemically injected [18F]DCFPyL shows salivary gland uptake, an increasing amount of which is secreted in saliva over time and is not maximized by 120 minutes post-injection. Although probably insignificant for diagnostic studies, patients undergoing PSMA-targeted therapies should be aware of radioactivity in saliva.

Published
2024
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38. Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study

Author

Wang, Minggui, Earley, Michelle, Chen, Liang, Hanson, Blake M, Yu, Yunsong, Liu, Zhengyin, Salcedo, Soraya, Cober, Eric, Li, Lanjuan, Kanj, Souha S, Gao, Hainv, Munita, Jose M, Ordoñez, Karen, Weston, Greg, Satlin, Michael J, Valderrama-Beltrán, Sandra L, Marimuthu, Kalisvar, Stryjewski, Martin E, Komarow, Lauren, Luterbach, Courtney, Marshall, Steve H, Rudin, Susan D, Manca, Claudia, Paterson, David L, Reyes, Jinnethe, Villegas, Maria V, Evans, Scott, Hill, Carol, Arias, Rebekka, Baum, Keri, Fries, Bettina C, Doi, Yohei, Patel, Robin, Kreiswirth, Barry N, Bonomo, Robert A, Chambers, Henry F, Fowler, Vance G, Arias, Cesar A, van Duin, David, Investigators, Multi-Drug Resistant Organism Network, Abbo, Lilian M, Anderson, Deverick J, Chew, Kean Lee, Cross, Heather R, De, Partha Pratim, Desai, Samit, Dhar, Sorabh, Di Castelnuovo, Valentina, Diaz, Lorena, Dinh, AN Q, Eilertson, Brandon, Evans, Beth, Garcia-Diaz, Julia, Garner, Omai B, Greenwood-Quaintance, Kerryl, Hanson, Blake, Herc, Erica, Jacob, Jesse T, Jiang, Jianping, Kalayjian, Robert C, Kaye, Keith S, Kim, Angela, Lauterbach, Courtney, Marshall, Steven H, McCarty, Todd, Munita, Jose, Ng, Oon Tek, Gutierrez, Jose Millan Oñate, Peleg, Anton, Salata, Robert A, Schmidt-Malan, Suzannah, and Smitasin, Nares

Subjects
Pneumonia & Influenza, Lung, Clinical Research, Pneumonia, Infectious Diseases, Infection, Good Health and Well Being, Anti-Bacterial Agents, Bacteremia, Carbapenem-Resistant Enterobacteriaceae, Carbapenems, Cohort Studies, Humans, Klebsiella Infections, Klebsiella pneumoniae, Prospective Studies, Respiratory Sounds, Multi-Drug Resistant Organism Network Investigators, Clinical Sciences, Medical Microbiology, Public Health and Health Services, Microbiology
Abstract

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.MethodsIn this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete.FindingsBetween June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96).InterpretationGlobal CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions.FundingThe National Institutes of Health.

Published
2022

39. The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George AW, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria-Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S, and Seror, Raphaele

Published
2024
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40. Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C

Author

Burbelo, Peter D, Castagnoli, Riccardo, Shimizu, Chisato, Delmonte, Ottavia M, Dobbs, Kerry, Discepolo, Valentina, Vecchio, Andrea Lo, Guarino, Alfredo, Licciardi, Francesco, Ramenghi, Ugo, Rey-Jurado, Emma, Vial, Cecilia, Marseglia, Gian Luigi, Licari, Amelia, Montagna, Daniela, Rossi, Camillo, Sanchez, Gina A Montealegre, Barron, Karyl, Warner, Blake M, Chiorini, John A, Espinosa, Yazmin, Noguera, Loreani, Dropulic, Lesia, Truong, Meng, Gerstbacher, Dana, Mató, Sayonara, Kanegaye, John, Tremoulet, Adriana H, Group, Pediatric Emergency Medicine Kawasaki, Eisenstein, Eli M, Su, Helen C, Imberti, Luisa, Poli, Maria Cecilia, Burns, Jane C, Notarangelo, Luigi D, Cohen, Jeffrey I, Abe, Naomi, Bryl, Amy, Donofrio-Odmann, J Joelle, Ekpenyong, Atim, Gardiner, Michael, Gutglass, David J, Nguyen, Margaret B, and Ulrich, Stacey

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunization, Pediatric, Coronaviruses, Emerging Infectious Diseases, Coronaviruses Disparities and At-Risk Populations, Clinical Research, Autoimmune Disease, Infectious Diseases, Health Disparities, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adaptor Proteins, Signal Transducing, Adenosine Triphosphatases, Adult, Autoantibodies, Autoantigens, Autoimmune Diseases, Autoimmunity, COVID-19, Child, Humans, Immunoglobulins, Intravenous, Lupus Erythematosus, Systemic, Ribonucleoproteins, Systemic Inflammatory Response Syndrome, autoantibodies, MIS-C multisystem inflammatory syndrome in children, IVIG, autoimmunity, Pediatric Emergency Medicine Kawasaki Group, Immunology, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Published
2022

41. Osteotomies for Knee Arthritis

Author

Douoguih, Wiemi A., Bodendorfer, Blake M., Shu, Henry Tout, Deshmukh, Ajit J., editor, Shabani, Bujar H., editor, Waldstein, Wenzel, editor, Oni, Julius K., editor, and Thakkar, Savyasachi C., Editor-in-Chief

Published
2023
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43. Rapid generation of potent antibodies by autonomous hypermutation in yeast

Author

Wellner, Alon, McMahon, Conor, Gilman, Morgan SA, Clements, Jonathan R, Clark, Sarah, Nguyen, Kianna M, Ho, Ming H, Hu, Vincent J, Shin, Jung-Eun, Feldman, Jared, Hauser, Blake M, Caradonna, Timothy M, Wingler, Laura M, Schmidt, Aaron G, Marks, Debora S, Abraham, Jonathan, Kruse, Andrew C, and Liu, Chang C

Subjects
Prevention, Biotechnology, Vaccine Related, Immunization, Generic health relevance, Antibodies, Antibody Formation, Antigens, COVID-19, Humans, Peptide Library, Protein Engineering, Recombinant Proteins, SARS-CoV-2, Saccharomyces cerevisiae, Single-Domain Antibodies, Spike Glycoprotein, Coronavirus, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Biochemistry & Molecular Biology
Abstract

The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, not always accessible and poorly compatible with many antigens. Here, we describe 'autonomous hypermutation yeast surface display' (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. By encoding antibody fragments on an error-prone orthogonal DNA replication system, surface-displayed antibody repertoires continuously mutate through simple cycles of yeast culturing and enrichment for antigen binding to produce high-affinity clones in as little as two weeks. We applied AHEAD to generate potent nanobodies against the SARS-CoV-2 S glycoprotein, a G-protein-coupled receptor and other targets, offering a template for streamlined antibody generation at large.

Published
2021

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