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1. Proceedings from the 9th annual conference on the science of dissemination and implementation: Washington, DC, USA. 14-15 December 2016

Author

Chambers, David, Simpson, Lisa, Neta, Gila, Schwarz, Ulrica von Thiele, Percy-Laurry, Antoinette, Aarons, Gregory A., Brownson, Ross, Vogel, Amanda, Stirman, Shannon Wiltsey, Sherr, Kenneth, Sturke, Rachel, Norton, Wynne E., Varley, Allyson, Vinson, Cynthia, Klesges, Lisa, Heurtin-Roberts, Suzanne, Massoud, M. Rashad, Kimble, Leighann, Beck, Arne, Neely, Claire, Boggs, Jennifer, Nichols, Carmel, Wan, Wen, Staab, Erin, Laiteerapong, Neda, Moise, Nathalie, Shah, Ravi, Essock, Susan, Handley, Margaret, Jones, Amy, Carruthers, Jay, Davidson, Karina, Peccoralo, Lauren, Sederer, Lloyd, Molfenter, Todd, Scudder, Ashley, Taber-Thomas, Sarah, Schaffner, Kristen, Herschell, Amy, Woodward, Eva, Pitcock, Jeffery, Ritchie, Mona, Kirchner, JoAnn, Moore, Julia E., Khan, Sobia, Rashid, Shusmita, Park, Jamie, Courvoisier, Melissa, Straus, Sharon, Blonigen, Daniel, Rodriguez, Allison, Manfredi, Luisa, Nevedal, Andrea, Rosenthal, Joel, Smelson, David, Timko, Christine, Stadnick, Nicole, Regan, Jennifer, Barnett, Miya, Lau, Anna, Brookman-Frazee, Lauren, Guerrero, Erick, Fenwick, Karissa, Kong, Yinfei, Aarons, Gregory, Lengnick-Hall, Rebecca, Henwood, Benjamin, Sayer, Nina, Rosen, Craig, Orazem, Robert, Smith, Brandy, Zimmerman, Lindsey, Lounsbury, David, Kimerling, Rachel, Trafton, Jodie A., Lindley, Steven, Bhargava, Rahul, Roberts, Hal, Gibson, Laura, Escobar, Gabriel J., Liu, Vincent, Turk, Benjamin, Ragins, Arona, Kipnis, Patricia, Gruszkowski, Ashley Ketterer, Kennedy, Michael W., Drobek, Emily Rentschler, Turgeman, Lior, Milicevic, Aleksandra Sasha, Hubert, Terrence L., Myaskovsky, Larissa, Tjader, Youxu C., Monte, Robert J., Sapnas, Kathryn G., Ramly, Edmond, Lauver, Diane R, Bartels, Christie M, Elnahal, Shereef, Ippolito, Andrea, Peabody, Hillary, Clancy, Carolyn, Cebul, Randall, Love, Thomas, Einstadter, Douglas, Bolen, Shari, Watts, Brook, Yakovchenko, Vera, Park, Angela, Lukesh, William, Miller, Donald R., Thornton, David, Drainoni, Mari-Lynn, Gifford, Allen L., Smith, Shawna, Kyle, Julia, Bauer, Mark S, Eisenberg, Daniel, Liebrecht, Celeste, Barbaresso, Michelle, Kilbourne, Amy, Park, Elyse, Perez, Giselle, Ostroff, Jamie, Greene, Sarah, Parchman, Michael, Austin, Brian, Larson, Eric, Ferreri, Stefanie, Shea, Chris, Smith, Megan, Turner, Kea, Bacci, Jennifer, Bigham, Kyle, Curran, Geoffrey, Frail, Caity, Hamata, Cory, Jankowski, Terry, Lantaff, Wendy, McGivney, Melissa Somma, Snyder, Margie, McCullough, Megan, Gillespie, Chris, Petrakis, Beth Ann, Jones, Ellen, Lukas, Carol VanDeusen, Rose, Adam, Shoemaker, Sarah J., Thomas, Jeremy, Teeter, Benjamin, Swan, Holly, Balamurugan, Appathurai, Lane-Fall, Meghan, Beidas, Rinad, Di Taranti, Laura, Buddai, Sruthi, Hernandez, Enrique Torres, Watts, Jerome, Fleisher, Lee, Barg, Frances, Miake-Lye, Isomi, Olmos, Tanya, Chuang, Emmeline, Rodriguez, Hector, Kominski, Gerald, Yano, Becky, Shortell, Stephen, Hook, Mary, Fleisher, Linda, Fiks, Alexander, Halkyard, Katie, Gruver, Rachel, Sykes, Emily, Vesco, Kimberly, Beadle, Kate, Bulkley, Joanna, Stoneburner, Ashley, Leo, Michael, Clark, Amanda, Smith, Joan, Smyser, Christopher, Wolf, Maggie, Trivedi, Shamik, Hackett, Brian, Rao, Rakesh, Cole, F. Sessions, McGonigle, Rose, Donze, Ann, Proctor, Enola, Mathur, Amit, Gakidou, Emmanuela, Gloyd, Stephen, Audet, Carolyn, Salato, Jose, Vermund, Sten, Amico, Rivet, Smith, Stephanie, Nyirandagijimana, Beatha, Mukasakindi, Hildegarde, Rusangwa, Christian, Franke, Molly, Raviola, Giuseppe, Cummings, Matthew, Goldberg, Elijah, Mwaka, Savio, Kabajaasi, Olive, Cattamanchi, Adithya, Katamba, Achilles, Jacob, Shevin, Kenya-Mugisha, Nathan, Davis, J. Lucian, Reed, Julie, Ramaswamy, Rohit, Parry, Gareth, Sax, Sylvia, Kaplan, Heather, Huang, Keng-yen, Cheng, Sabrina, Yee, Susan, Hoagwood, Kimberly, McKay, Mary, Shelley, Donna, Ogedegbe, Gbenga, Brotman, Laurie Miller, Kislov, Roman, Humphreys, John, Harvey, Gill, Wilson, Paul, Lieberthal, Robert, Payton, Colleen, Sarfaty, Mona, Valko, George, Bolton, Rendelle, Hartmann, Christine, Mueller, Nora, Holmes, Sally K., Bokhour, Barbara, Ono, Sarah, Crabtree, Benjamin, Gordon, Leah, Miller, William, Balasubramanian, Bijal, Solberg, Leif, Cohen, Deborah, McGraw, Kate, Blatt, Andrew, Pittman, Demietrice, Kales, Helen, Berlowitz, Dan, Hudson, Teresa, Helfrich, Christian, Finley, Erin, Garcia, Ashley, Rosen, Kristen, Tami, Claudina, McGeary, Don, Pugh, Mary Jo, Potter, Jennifer Sharpe, Stryczek, Krysttel, Au, David, Zeliadt, Steven, Sayre, George, Leeman, Jennifer, Myers, Allison, Grant, Jennifer, Wangen, Mary, Queen, Tara, Morshed, Alexandra, Dodson, Elizabeth, Tabak, Rachel, Brownson, Ross C., Sheldrick, R. Chris, Mackie, Thomas, Hyde, Justeen, Leslie, Laurel, Yanovitzky, Itzhak, Weber, Matthew, Gesualdo, Nicole, Kristensen, Teis, Stanick, Cameo, Halko, Heather, Dorsey, Caitlin, Powell, Byron, Weiner, Bryan, Lewis, Cara, Carreno, Patricia, Mallard, Kera, Masina, Tasoula, Monson, Candice, Swindle, Taren, Patterson, Zachary, Whiteside-Mansell, Leanne, Hanson, Rochelle, Saunders, Benjamin, Schoenwald, Sonja, Moreland, Angela, Birken, Sarah, Presseau, Justin, Ganz, David, Mittman, Brian, Delevan, Deborah, Hill, Jennifer N., Locatelli, Sara, Fix, Gemmae, Solomon, Jeffrey, Lavela, Sherri L., Scott, Victoria, Scaccia, Jonathan, Alia, Kassy, Skiles, Brittany, Wandersman, Abraham, Sales, Anne, Roberts, Megan, Kennedy, Amy, Khoury, Muin J., Sperber, Nina, Orlando, Lori, Carpenter, Janet, Cavallari, Larisa, Denny, Joshua, Elsey, Amanda, Fitzhenry, Fern, Guan, Yue, Horowitz, Carol, Johnson, Julie, Madden, Ebony, Pollin, Toni, Pratt, Victoria, Rakhra-Burris, Tejinder, Rosenman, Marc, Voils, Corrine, Weitzel, Kristin, Wu, Ryanne, Damschroder, Laura, Lu, Christine, Ceccarelli, Rachel, Mazor, Kathleen M., Wu, Ann, Rahm, Alanna Kulchak, Buchanan, Adam H., Schwartz, Marci, McCormick, Cara, Manickam, Kandamurugu, Williams, Marc S., Murray, Michael F., Escoffery, Ngoc-Cam, Lebow-Skelley, Erin, Udelson, Hallie, Böing, Elaine, Fernandez, Maria E., Wood, Richard J., Mullen, Patricia Dolan, Parekh, Jenita, Caldas, Valerie, Stuart, Elizabeth A., Howard, Shalynn, Thomas, Gilo, Jennings, Jacky M., Torres, Jennifer, Markham, Christine, Shegog, Ross, Peskin, Melissa, Rushing, Stephanie Craig, Gaston, Amanda, Gorman, Gwenda, Jessen, Cornelia, Williamson, Jennifer, Ward, Dianne, Vaughn, Amber, Morris, Ellie, Mazzucca, Stephanie, Burney, Regan, Ramanadhan, Shoba, Minsky, Sara, Martinez-Dominguez, Vilma, Viswanath, Kasisomayajula, Barker, Megan, Fahim, Myra, Ebnahmady, Arezoo, Dragonetti, Rosa, Selby, Peter, Farrell, Margaret, Tompkins, Jordan, Norton, Wynne, Rapport, Kaelin, Hargreaves, Margaret, Lee, Rebekka, Kruse, Gina, Deutsch, Charles, Lanier, Emily, Gray, Ashley, Leppin, Aaron, Christiansen, Lori, Schaepe, Karen, Egginton, Jason, Branda, Megan, Gaw, Charlene, Dick, Sara, Montori, Victor, Shah, Nilay, Korn, Ariella, Hovmand, Peter, Fullerton, Karen, Zoellner, Nancy, Hennessy, Erin, Tovar, Alison, Hammond, Ross, Economos, Christina, Kay, Christi, Gazmararian, Julie, Vall, Emily, Cheung, Patricia, Franks, Padra, Barrett-Williams, Shannon, Weiss, Paul, Hamilton, Erica, Marques, Luana, Dixon, Louise, Ahles, Emily, Valentine, Sarah, Shtasel, Derri, Parra-Cardona, Ruben, Northridge, Mary, Kavathe, Rucha, Zanowiak, Jennifer, Wyatt, Laura, Singh, Hardayal, Islam, Nadia, Monteban, Madalena, Freedman, Darcy, Bess, Kimberly, Walsh, Colleen, Matlack, Kristen, Flocke, Susan, Baily, Heather, Harden, Samantha, Ramalingam, NithyaPriya, Gold, Rachel, Cottrell, Erika, Hollombe, Celine, Dambrun, Katie, Bunce, Arwen, Middendorf, Mary, Dearing, Marla, Cowburn, Stuart, Mossman, Ned, Melgar, Gerry, Hopfer, Suellen, Hecht, Michael, Ray, Anne, Miller-Day, Michelle, BeLue, Rhonda, Zimet, Greg, Nelson, Eve-Lynn, Kuhlman, Sandy, Doolittle, Gary, Krebill, Hope, Spaulding, Ashley, Levin, Theodore, Sanchez, Michael, Landau, Molly, Escobar, Patricia, Minian, Nadia, Noormohamed, Aliya, Zawertailo, Laurie, Baliunas, Dolly, Giesbrecht, Norman, Le Foll, Bernard, Samokhvalov, Andriy, Meisel, Zachary, Polsky, Daniel, Schackman, Bruce, Mitchell, Julia, Sevarino, Kaitlyn, Gimbel, Sarah, Mwanza, Moses, Nisingizwe, Marie Paul, Michel, Catherine, Hirschhorn, Lisa, Choudhary, Mahrukh, Thonduparambil, Della, Meissner, Paul, Pinnock, Hilary, Barwick, Melanie, Carpenter, Christopher, Eldridge, Sandra, Grandes-Odriozola, Gonzalo, Griffiths, Chris, Rycroft-Malone, Jo, Murray, Elizabeth, Patel, Anita, Sheikh, Aziz, Taylor, Stephanie J. C., Guilliford, Martin, Pearce, Gemma, Korngiebel, Diane, West, Kathleen, Burke, Wylie, Hannon, Peggy, Harris, Jeffrey, Hammerback, Kristen, Kohn, Marlana, Chan, Gary K. C., Mafune, Riki, Parrish, Amanda, Beresford, Shirley, Pike, K. Joanne, Shelton, Rachel, Jandorf, Lina, Erwin, Deborah, Charles, Thana-Ashley, Baldwin, Laura-Mae, Ike, Brooke, Fickel, Jacqueline, Lind, Jason, Cowper, Diane, Fleming, Marguerite, Sadler, Amy, Dye, Melinda, Katzburg, Judith, Ong, Michael, Tubbesing, Sarah, Simmons, Molly, Harnish, Autumn, Gabrielian, Sonya, McInnes, Keith, Smith, Jeffrey, Ferrand, John, Torres, Elisa, Green, Amy, Bradbury, Angela R., Patrick-Miller, Linda J., Egleston, Brian L., Domchek, Susan M., Olopade, Olufunmilayo I., Hall, Michael J., Daly, Mary B., Grana, Generosa, Ganschow, Pamela, Fetzer, Dominique, Brandt, Amanda, Chambers, Rachelle, Clark, Dana F., Forman, Andrea, Gaber, Rikki S., Gulden, Cassandra, Horte, Janice, Long, Jessica, Lucas, Terra, Madaan, Shreshtha, Mattie, Kristin, McKenna, Danielle, Montgomery, Susan, Nielsen, Sarah, Powers, Jacquelyn, Rainey, Kim, Rybak, Christina, Seelaus, Christina, Stoll, Jessica, Stopfer, Jill, Yao, Xinxin Shirley, Savage, Michelle, Miech, Edward, Damush, Teresa, Rattray, Nicholas, Myers, Jennifer, Homoya, Barbara, Winseck, Kate, Klabunde, Carrie, Langer, Deb, Aggarwal, Avi, Neilson, Elizabeth, Gunderson, Lara, Gardner, Marla, O’Sulleabhain, Liam, and Kroenke, Candyce

Published
2017
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2. THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites

Author

Chang, Hsiao-Han, Worby, Colin J., Yeka, Adoke, Nankabirwa, Joaniter, Kamya, Moses R., Staedke, Sarah G., Dorsey, Grant, Murphy, Maxwell, Neafsey, Daniel E., Jeffreys, Anna E., Hubbart, Christina, Rockett, Kirk A., Amato, Roberto, Kwiatkowski, Dominic P., Buckee, Caroline O., and Greenhouse, Bryan

Subjects
Social Sciences, Economics, Health Economics, Medicine and Health Sciences, Health Care, Parasitic Diseases, Biology and Life Sciences, Evolutionary Biology, Population Genetics, Genetics, Population Biology, Genetic Loci, Alleles, Molecular Biology, Molecular Biology Techniques, Genotyping, Malaria, Tropical Diseases, Organisms, Protozoans, Parasitic Protozoans, Malarial Parasites, Simulation and Modeling
Abstract

As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings.

Published
2017
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3. An Exploration of Youth Talk Around Representations of Individual Difference in the American Television Show Glee

Author

Dorsey, Jennifer M. and Haste, Helen

Subjects
Mass Communications, Education, General, Language
Abstract

In this study I investigate the ways in which youth talk about difference and fictional television characters in order to better understand youth's relationship with the media and diverse others. I use the theoretical framework of constructivism and the analytic framework of Foucauldian Discourse Analysis in order to answer the following research questions: 1) What discourses and positionings do youth use when talking about fictional characters? 2) What discourses and positionings do youth use when talking about difference in the context of a television program that presents diverse characters, specifically in the areas of (a) ability, (b) sexuality, and (c) ethnicity? 3) What do these ways of talking about characters and difference make possible for youth in the world? I chose to study these questions by investigating the meanings that youth were making of characters on the television show Glee. I conducted a qualitative interview study, recruiting participants in accordance with purposive sampling for maximum variation. Data gathering consisted of qualitative interviews, both with individuals and pairs. Interviews included both photo and video elicitation. Following data collection and interview transcription, I conducted data analysis using positioning theory, discourse theory, and Foucauldian Discourse Analysis. In my first analytic chapter I identified two main discourses that youth use when talking about characters: Character as Person and Character as Creation. In my second analytic chapter I analyze youth speech and discuss the discourses and positionings that they use when talking about difference, identifying three main discourses: Being Different, Having Difference, and Enacting Difference. In my final analytic chapter I look more closely at the parasocial relationships that youth describe having with characters, investigating when youth do and do not describe identifying with the characters on Glee. I note that when youth describe relating strongly with a character because of a shared difference, they most often use the discourses of Character as Person and Being Different. Through the lens of Foucauldian Discourse Analysis, I am able to explore not only the patterns apparent in youth talk about characters and difference, but also what this talk makes possible in the world.

Published
2016

4. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two: National Harbor, MD, USA. 9-13 November 2016

Author

Ager, Casey, Reilley, Matthew, Nicholas, Courtney, Bartkowiak, Todd, Jaiswal, Ashvin, Curran, Michael, Albershardt, Tina C., Bajaj, Anshika, Archer, Jacob F., Reeves, Rebecca S., Ngo, Lisa Y., Berglund, Peter, ter Meulen, Jan, Denis, Caroline, Ghadially, Hormas, Arnoux, Thomas, Chanuc, Fabien, Fuseri, Nicolas, Wilkinson, Robert W., Wagtmann, Nicolai, Morel, Yannis, Andre, Pascale, Atkins, Michael B., Carlino, Matteo S., Ribas, Antoni, Thompson, John A., Choueiri, Toni K., Hodi, F. Stephen, Hwu, Wen-Jen, McDermott, David F., Atkinson, Victoria, Cebon, Jonathan S., Fitzharris, Bernie, Jameson, Michael B., McNeil, Catriona, Hill, Andrew G., Mangin, Eric, Ahamadi, Malidi, van Vugt, Marianne, van Zutphen, Mariëlle, Ibrahim, Nageatte, Long, Georgina V., Gartrell, Robyn, Blake, Zoe, Simoes, Ines, Fu, Yichun, Saito, Takuro, Qian, Yingzhi, Lu, Yan, Saenger, Yvonne M., Budhu, Sadna, De Henau, Olivier, Zappasodi, Roberta, Schlunegger, Kyle, Freimark, Bruce, Hutchins, Jeff, Barker, Christopher A., Wolchok, Jedd D., Merghoub, Taha, Burova, Elena, Allbritton, Omaira, Hong, Peter, Dai, Jie, Pei, Jerry, Liu, Matt, Kantrowitz, Joel, Lai, Venus, Poueymirou, William, MacDonald, Douglas, Ioffe, Ella, Mohrs, Markus, Olson, William, Thurston, Gavin, Capasso, Cristian, Frascaro, Federica, Carpi, Sara, Tähtinen, Siri, Feola, Sara, Fusciello, Manlio, Peltonen, Karita, Martins, Beatriz, Sjöberg, Madeleine, Pesonen, Sari, Ranki, Tuuli, Kyruk, Lukasz, Ylösmäki, Erkko, Cerullo, Vincenzo, Cerignoli, Fabio, Xi, Biao, Guenther, Garret, Yu, Naichen, Muir, Lincoln, Zhao, Leyna, Abassi, Yama, Cervera-Carrascón, Víctor, Siurala, Mikko, Santos, João, Havunen, Riikka, Parviainen, Suvi, Hemminki, Akseli, Dalgleish, Angus, Mudan, Satvinder, DeBenedette, Mark, Plachco, Ana, Gamble, Alicia, Grogan, Elizabeth W., Krisko, John, Tcherepanova, Irina, Nicolette, Charles, Dhupkar, Pooja, Yu, Ling, Kleinerman, Eugenie S., Gordon, Nancy, Grenga, Italia, Lepone, Lauren, Gameiro, Sofia, Knudson, Karin M., Fantini, Massimo, Tsang, Kwong, Hodge, James, Donahue, Renee, Schlom, Jeffrey, Evans, Elizabeth, Bussler, Holm, Mallow, Crystal, Reilly, Christine, Torno, Sebold, Scrivens, Maria, Foster, Cathie, Howell, Alan, Balch, Leslie, Knapp, Alyssa, Leonard, John E., Paris, Mark, Fisher, Terry, Hu-Lieskovan, Siwen, Smith, Ernest, Zauderer, Maurice, Fogler, William, Franklin, Marilyn, Thayer, Matt, Saims, Dan, Magnani, John L., Gong, Jian, Gray, Michael, Fromm, George, de Silva, Suresh, Giffin, Louise, Xu, Xin, Rose, Jason, Schreiber, Taylor H., Gameiro, Sofia R., Clavijo, Paul E., Allen, Clint T., Hodge, James W., Tsang, Kwong Y., Grogan, Jane, Manieri, Nicholas, Chiang, Eugene, Caplazi, Patrick, Yadav, Mahesh, Hagner, Patrick, Chiu, Hsiling, Waldman, Michelle, Klippel, Anke, Thakurta, Anjan, Pourdehnad, Michael, Gandhi, Anita, Henrich, Ian, Quick, Laura, Young, Rob, Chou, Margaret, Hotson, Andrew, Willingham, Stephen, Ho, Po, Choy, Carmen, Laport, Ginna, McCaffery, Ian, Miller, Richard, Tipton, Kimberly A., Wong, Kenneth R., Singson, Victoria, Wong, Chihunt, Chan, Chanty, Huang, Yuanhiu, Liu, Shouchun, Richardson, Jennifer H., Kavanaugh, W. Michael, West, James, Irving, Bryan A., Jaini, Ritika, Loya, Matthew, Eng, Charis, Johnson, Melissa L., Adjei, Alex A., Opyrchal, Mateusz, Ramalingam, Suresh, Janne, Pasi A., Dominguez, George, Gabrilovich, Dmitry, de Leon, Laura, Hasapidis, Jeannette, Diede, Scott J., Ordentlich, Peter, Cruickshank, Scott, Meyers, Michael L., Hellmann, Matthew D., Kalinski, Pawel, Zureikat, Amer, Edwards, Robert, Muthuswamy, Ravi, Obermajer, Nataša, Urban, Julie, Butterfield, Lisa H., Gooding, William, Zeh, Herbert, Bartlett, David, Zubkova, Olga, Agapova, Larissa, Kapralova, Marina, Krasovskaia, Liudmila, Ovsepyan, Armen, Lykov, Maxim, Eremeev, Artem, Bokovanov, Vladimir, Grigoryeva, Olga, Karpov, Andrey, Ruchko, Sergey, Shuster, Alexandr, Khalil, Danny N., Campesato, Luis Felipe, Li, Yanyun, Lazorchak, Adam S., Patterson, Troy D., Ding, Yueyun, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Gowda, Nagaraj, Ramachandra, Raghuveer, Samiulla, Dodheri, Giri, Sanjeev, Eswarappa, Rajesh, Ramachandra, Murali, Tuck, David, Wyant, Timothy, Leshem, Jasmin, Liu, Xiu-fen, Bera, Tapan, Terabe, Masaki, Bossenmaier, Birgit, Niederfellner, Gerhard, Reiter, Yoram, Pastan, Ira, Xia, Leiming, Xia, Yang, Hu, Yangyang, Wang, Yi, Bao, Yangyi, Dai, Fu, Huang, Shiang, Hurt, Elaine, Hollingsworth, Robert E., Lum, Lawrence G., Chang, Alfred E., Wicha, Max S., Li, Qiao, Mace, Thomas, Makhijani, Neil, Talbert, Erin, Young, Gregory, Guttridge, Denis, Conwell, Darwin, Lesinski, Gregory B., Gonzales, Rodney JM Macedo, Huffman, Austin P., Wang, Ximi K., Reshef, Ran, MacKinnon, Andy, Chen, Jason, Gross, Matt, Marguier, Gisele, Shwonek, Peter, Sotirovska, Natalija, Steggerda, Susanne, Parlati, Francesco, Makkouk, Amani, Bennett, Mark K., Emberley, Ethan, Huang, Tony, Li, Weiqun, Neou, Silinda, Pan, Alison, Zhang, Jing, Zhang, Winter, Marshall, Netonia, Marron, Thomas U., Agudo, Judith, Brown, Brian, Brody, Joshua, McQuinn, Christopher, Farren, Matthew, Komar, Hannah, Shakya, Reena, Ludwug, Thomas, Morillon, Y. Maurice, Hammond, Scott A., Greiner, John W., Nath, Pulak R., Schwartz, Anthony L., Maric, Dragan, Roberts, David D., Naing, Aung, Papadopoulos, Kyriakos P., Autio, Karen A., Wong, Deborah J., Patel, Manish, Falchook, Gerald, Pant, Shubham, Ott, Patrick A., Whiteside, Melinda, Patnaik, Amita, Mumm, John, Janku, Filip, Chan, Ivan, Bauer, Todd, Colen, Rivka, VanVlasselaer, Peter, Brown, Gail L., Tannir, Nizar M., Oft, Martin, Infante, Jeffrey, Lipson, Evan, Gopal, Ajay, Neelapu, Sattva S., Armand, Philippe, Spurgeon, Stephen, Leonard, John P., Sanborn, Rachel E., Melero, Ignacio, Gajewski, Thomas F., Maurer, Matthew, Perna, Serena, Gutierrez, Andres A., Clynes, Raphael, Mitra, Priyam, Suryawanshi, Satyendra, Gladstone, Douglas, Callahan, Margaret K., Crooks, James, Brown, Sheila, Gauthier, Audrey, de Boisferon, Marc Hillairet, MacDonald, Andrew, Brunet, Laura Rosa, Rothwell, William T., Bell, Peter, Wilson, James M., Sato-Kaneko, Fumi, Yao, Shiyin, Zhang, Shannon S., Carson, Dennis A., Guiducci, Cristina, Coffman, Robert L., Kitaura, Kazutaka, Matsutani, Takaji, Suzuki, Ryuji, Hayashi, Tomoko, Cohen, Ezra E. W., Schaer, David, Li, Yanxia, Dobkin, Julie, Amatulli, Michael, Hall, Gerald, Doman, Thompson, Manro, Jason, Dorsey, Frank Charles, Sams, Lillian, Holmgaard, Rikke, Persaud, Krishnadatt, Ludwig, Dale, Surguladze, David, Kauh, John S., Novosiadly, Ruslan, Kalos, Michael, Driscoll, Kyla, Pandha, Hardev, Ralph, Christy, Harrington, Kevin, Curti, Brendan, Akerley, Wallace, Gupta, Sumati, Melcher, Alan, Mansfield, David, Kaufman, David R., Schmidt, Emmett, Grose, Mark, Davies, Bronwyn, Karpathy, Roberta, Shafren, Darren, Shamalov, Katerina, Cohen, Cyrille, Sharma, Naveen, Allison, James, Shekarian, Tala, Valsesia-Wittmann, Sandrine, Caux, Christophe, Marabelle, Aurelien, Slomovitz, Brian M., Moore, Kathleen M., Youssoufian, Hagop, Posner, Marshall, Tewary, Poonam, Brooks, Alan D., Xu, Ya-Ming, Wijeratne, Kithsiri, Gunatilaka, Leslie A. 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Kenneth R., Diab, Adi, Sharma, Padmanee, Hong, David, Welsh, James, Parsons, Andrea J., Leleux, Jardin, Ascarateil, Stephane, Koziol, Marie Eve, Bai, Dina, Dai, Peihong, Wang, Weiyi, Yang, Ning, Shuman, Stewart, Deng, Liang, Dillon, Patrick, Petroni, Gina, Brenin, David, Bullock, Kim, Olson, Walter, Smolkin, Mark E., Smith, Kelly, Nail, Carmel, Slingluff, Craig L., Sharma, Meenu, Fa’ak, Faisal, Janssen, Louise, Khong, Hiep, Xiao, Zhilan, Hailemichael, Yared, Singh, Manisha, Vianden, Christina, Overwijk, Willem W., Facciabene, Andrea, Stefano, Pierini, Chongyung, Fang, Rafail, Stavros, Nielsen, Michael, Vanderslice, Peter, Woodside, Darren G., Market, Robert V., Biediger, Ronald J., Marathi, Upendra K., Hollevoet, Kevin, Geukens, Nick, Declerck, Paul, Joly, Nathalie, McIntosh, Laura, Paramithiotis, Eustache, Rizell, Magnus, Sternby, Malin, Andersson, Bengt, Karlsson-Parra, Alex, Kuai, Rui, Ochyl, Lukasz, Schwendeman, Anna, Moon, James, Deng, Weiwen, Hudson, Thomas E., Hanson, Bill, Rae, Chris S., Burrill, Joel, Skoble, Justin, Katibah, George, deVries, Michele, Lauer, Peter, Dubensky, Thomas W., Chen, Xin, Zhou, Li, Ren, Xiubao, Aggarwal, Charu, Mangrolia, Drishty, Cohen, Roger, Weinstein, Gregory, Morrow, Matthew, Bauml, Joshua, Kraynyak, Kim, Boyer, Jean, Yan, Jian, Lee, Jessica, Humeau, Laurent, Oyola, Sandra, Duff, Susan, Weiner, David, Yang, Zane, Bagarazzi, Mark, McNeel, Douglas G., Eickhoff, Jens, Jeraj, Robert, Staab, Mary Jane, Straus, Jane, Rekoske, Brian, Liu, Glenn, Melssen, Marit, Grosh, William, Varhegyi, Nikole, Galeassi, Nadejda, Deacon, Donna H., Gaughan, Elizabeth, Ghisoli, Maurizio, Barve, Minal, Mennel, Robert, Wallraven, Gladice, Manning, Luisa, Senzer, Neil, Nemunaitis, John, Ogasawara, Masahiro, Ota, Shuichi, Peace, Kaitlin M., Hale, Diane F., Vreeland, Timothy J., Jackson, Doreen O., Berry, John S., Trappey, Alfred F., Herbert, Garth S., Clifton, Guy T., Hardin, Mark O., Toms, Anne, Qiao, Na, Litton, Jennifer, Peoples, George E., Mittendorf, 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H., Qiu, Xiaohong, Fraser, Kathryn, Jonas, Adria, Ottoson, Nadine, Gordon, Keith, Kangas, Takashi O., Leonardo, Steven, Ertelt, Kathleen, Walsh, Richard, Uhlik, Mark, Graff, Jeremy, Bose, Nandita, Gupta, Ravi, Mandloi, Nitin, Paul, Kiran, Patil, Ashwini, Sathian, Rekha, Mohan, Aparna, Manoharan, Malini, Chaudhuri, Amitabha, Chen, Yu, Lin, Jing, Ye, Yun-bin, Xu, Chun-wei, Chen, Gang, Guo, Zeng-qing, Komarov, Andrey, Chenchik, Alex, Makhanov, Michael, Frangou, Costa, Zheng, Yi, Coltharp, Carla, Unfricht, Darryn, Dilworth, Ryan, Fridman, Leticia, Liu, Linying, Rajopadhye, Milind, Miller, Peter, Concha-Benavente, Fernando, Bauman, Julie, Trivedi, Sumita, Srivastava, Raghvendra, Ohr, James, Heron, Dwight, Duvvuri, Uma, Kim, Seungwon, Torrey, Heather, Mera, Toshi, Okubo, Yoshiaki, Vanamee, Eva, Foster, Rosemary, Faustman, Denise, Stack, Edward, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Marks, Douglas, Taback, Bret, Horst, Basil, Glickman, Laura Hix, Kanne, David B., Gauthier, Kelsey S., Desbien, Anthony L., Francica, Brian, Leong, Justin L., Sung, Leonard, Metchette, Ken, Kasibhatla, Shailaja, Pferdekamper, Anne Marie, Zheng, Lianxing, Cho, Charles, Feng, Yan, McKenna, Jeffery M., Tallarico, John, Bender, Steven, Ndubaku, Chudi, McWhirter, Sarah M., Gugel, Elena Gonzalez, Bell, Charles J. 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L., Rapisuwon, Suthee, Radfar, Arash, Gardner, Kellie, Gibney, Geoffrey, Atkins, Michael, Rennier, Keith R., Crowder, Robert, Wang, Ping, Pachynski, Russell K., Carrero, Rosa M. Santana, Rivas, Sarai, Beceren-Braun, Figen, Anthony, Scott, Schluns, Kimberly S., Sawant, Deepali, Chikina, Maria, Yano, Hiroshi, Workman, Creg, Salerno, Elise, Mauldin, Ileana, Deacon, Donna, Shea, Sofia, Pinczewski, Joel, Gajewski, Thomas, Spranger, Stefani, Horton, Brendan, Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Puri, Raj K., Sweis, Randy F., Bao, Riyue, Luke, Jason, Theodoraki, Marie-Nicole, Mogundo, Frances-Mary, Won, Haejung, Moreira, Dayson, Gao, Chan, Zhao, Xingli, Duttagupta, Priyanka, Jones, Jeremy, D’Apuzzo, Massimo, and Pal, Sumanta

Published
2016
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5. A preliminary survey of the non-biting midges (Diptera: Chironomidae) of the Dominican Republic

Author

Silva, Fabio Laurindo da, Wiedenbrug, Sofia, and Farrell, Brian Dorsey

Abstract

Chironomidae (Diptera) are among the most diverse and widespread aquatic insects, with roughly 5,500 described species. However, prior to the present work, no species of Chironomidae had been documented from the island of Hispaniola. Collections of non-biting midges, with emphasis on the lotic fauna, were made in the Dominican Republic during July of 2015. In total, 578 specimens belonging to 27 genera and at least 44 species within the subfamilies Chironominae (20 taxa), Orthocladiinae (16 taxa) and Tanypodinae (8 taxa) were found. The subfamilies Chironominae and Orthocladiinae predominated. Polypedilum was the most widespread and diverse genus of Chironominae. Metriocnemus were collected in bromeliad tanks. The chironomid fauna in Dominican Republic includes multiple genera with worldwide distributions, including Holarctic and Neotropical components., Organismic and Evolutionary Biology

Published
2015
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7. Laboulbeniales (Ascomycota) of the Boston Harbor Islands I: Species Parasitizing Coccinellidae and Staphylinidae, with Comments on Typification

Author

Haelewaters, Danny, Zhao, Serena Y., Kesel, André De, Handlin, Rebecca E., Royer, Isabel R., Farrell, Brian Dorsey, and Pfister, Donald H.

Abstract

This paper, based on a recent comprehensive sampling of insects, is the first report of Laboulbeniales from the New England region since the 1930s. We present 7 new records of laboulbenialean parasites on Staphylinidae (rove beetles) and Coccinellidae (lady beetles) from the Boston Harbor Islands National Recreation Area. These are Clonophoromyces nipponicus Terada & I.I. Tav., Hesperomyces virescens Thaxt., Ilyomyces cf. mairei F. Picard, Laboulbenia philonthi Thaxt., Peyritschiella protea Thaxt., Stichomyces conosomatis Thaxt., and Teratomyces actobii Thaxt. One of these parasite species, C. nipponicus, has not been found previously outside of its type locality in Japan. Examination of Roland Thaxter's 1891–1932 slides led to the designation of lectotypes for L. philonthi, P. protea, S. conosomatis, and T. actobii. The following synonymy is established: Teratomyces brevicaulis Thaxt. = T. actobii. In addition, we discovered new localities for H. virescens (from Canada, Cuba, Guatemala, and Japan) and L. philonthi (from Canada, Grenada, Panama, Trinidad, and Venezuela)., Organismic and Evolutionary Biology

Published
2015
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8. Cyclin D1 Represses Gluconeogenesis via Inhibition of the Transcriptional Coactivator PGC1α

Author

Bhalla, Kavita, Liu, Wan-Ju, Thompson, Keyata, Anders, Lars, Devarakonda, Srikripa, Dewi, Ruby, Buckley, Stephanie, Hwang, Bor-Jang, Polster, Brian, Dorsey, Susan G., Sun, Yezhou, Sicinski, Piotr, and Girnun, Geoffrey D.

Abstract

Hepatic gluconeogenesis is crucial to maintain normal blood glucose during periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels by a variety of signal transduction and transcriptional pathways. However, dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While the effects of various signaling pathways on gluconeogenesis are well established, the downstream signaling events repressing gluconeogenic gene expression are not as well understood. The cell-cycle regulator cyclin D1 is expressed in the liver, despite the liver being a quiescent tissue. The most well-studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression of the cell cycle. We show here a novel role for cyclin D1 as a regulator of gluconeogenic and oxidative phosphorylation (OxPhos) gene expression. In mice, fasting decreases liver cyclin D1 expression, while refeeding induces cyclin D1 expression. Inhibition of CDK4 enhances the gluconeogenic gene expression, whereas cyclin D1–mediated activation of CDK4 represses the gluconeogenic gene-expression program in vitro and in vivo. Importantly, we show that cyclin D1 represses gluconeogenesis and OxPhos in part via inhibition of peroxisome proliferator–activated receptor γ coactivator-1α (PGC1α) activity in a CDK4-dependent manner. Indeed, we demonstrate that PGC1α is novel cyclin D1/CDK4 substrate. These studies reveal a novel role for cyclin D1 on metabolism via PGC1α and reveal a potential link between cell-cycle regulation and metabolic control of glucose homeostasis.

Published
2014
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9. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

Author

Trksak, George H., Bracken, Bethany K., Jensen, J. Eric, Plante, David T., Penetar, David M., Tartarini, Wendy L., Maywalt, Melissa A., Dorsey, Cynthia M., Renshaw, Perry F., and Lukas, Scott E.

Abstract

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

Published
2013
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10. Improving practice in community-based settings: a randomized trial of supervision – study protocol

Author

Dorsey, Shannon, Pullmann, Michael D, Deblinger, Esther, Berliner, Lucy, Kerns, Suzanne E, Thompson, Kelly, Unützer, Jürgen, Weisz, John R, and Garland, Ann F

Subjects
Evidence-based treatment, EBT, Supervision, Training, Implementation, Fidelity, Behavioral rehearsal, Symptom monitoring, Role-play, Trauma-focused cognitive behavioral therapy
Abstract

Background: Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. Trial registration ClinicalTrials.gov NCT01800266

Published
2013
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11. Trends in Attention Deficit Hyperactivity Disorder Ambulatory Diagnosis and Medical Treatment in the United States, 2000–2010

Author

Garfield, Craig F., Dorsey, E. Ray, Zhu, Shu, Huskamp, Haiden Ashby, Conti, Rena, Dusetzina, Stacie B., Higashi, Ashley, Perrin, James Marc, Kornfield, Rachel, and Alexander, G. Caleb

Subjects
attention deficit and hyperactivity disorder, pediatrics, pediatric workforce, mental health
Abstract

Objectives: Because of several recent clinical and regulatory changes regarding Attention Deficit Hyperactivity Disorder (ADHD) in the United States, we quantified changes in ADHD diagnosis and medication management from 2000 through 2010. Methods: We used the IMS Health National Disease and Therapeutic Index™, a nationally representative audit of office-based providers, to examine aggregate trends among children and adolescents under 18. We also quantified how diagnosis and treatment patterns have evolved based on patient and physician characteristics and the therapeutic classes used. Results: From 2000 to 2010, the number of physician outpatient visits where ADHD was diagnosed increased 66% from 6.2 million [M] (95% confidence intervals [CI] 5.5- 6.9M) to 10.4M visits (CI 9.3-11.6M). Of these visits, psychostimulants have remained the dominant treatment, used in 96% of treatment visits in 2000 and 87% of treatment visits in 2010. Atomoxetine use declined from 15% of treatment visits upon product launch in 2003 to 6% of treatment visits by 2010. The use of potential substitute therapies – clonidine, guanfacine, and bupropion – remained relatively constant (between 5-9% of treatment visits) during most of the period examined. Over this period, the ADHD management shifted towards psychiatrists (from 24% to 36% of all visits) without large changes in illness severity or the proportion of ADHD treatment visits accounted for by males (73%-77%). Conclusions: In ten years, the ambulatory diagnosis of ADHD increased by two-thirds and is increasingly managed by psychiatrists. The effects of these changing treatment patterns on children's health outcomes and their families are unknown.

Published
2012
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12. The Effects of Biogeography on Ant Diversity and Activity on the Boston Harbor Islands, Massachusetts, U.S.A.

Author

Clark, Adam T., Rykken, Jessica J., and Farrell, Brian Dorsey

Subjects
ants, Boston Harbor Islands, island biogeography, Myrmica scabrinodis, phenology, urban parks
Abstract

Many studies have examined how island biogeography affects diversity on the scale of island systems. In this study, we address how diversity varies over very short periods of time on individual islands. To do this, we compile an inventory of the ants living in the Boston Harbor Islands National Recreation Area, Boston, Massachusetts, USA using data from a five-year All Taxa Biodiversity Inventory of the region's arthropods. Consistent with the classical theory of island biogeography, species richness increased with island size, decreased with island isolation, and remained relatively constant over time. Additionally, our inventory finds that almost half of the known Massachusetts ant fauna can be collected in the BHI, and identifies four new species records for Massachusetts, including one new to the United States, Myrmica scabrinodis. We find that the number of species actually active on islands depended greatly on the timescale under consideration. The species that could be detected during any given week of sampling could by no means account for total island species richness, even when correcting for sampling effort. Though we consistently collected the same number of species over any given week of sampling, the identities of those species varied greatly between weeks. This variation does not result from local immigration and extinction of species, nor from seasonally-driven changes in the abundance of individual species, but rather from weekly changes in the distribution and activity of foraging ants. This variation can be upwards of 50% of ant species per week. This suggests that numerous ant species on the BHI share the same physical space at different times. This temporal partitioning could well explain such unexpectedly high ant diversity in an isolated, urban site., Organismic and Evolutionary Biology

Published
2011
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13. Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Author

Mordukhovich, Irina, Rossner, Pavel, Terry, Mary Beth, Santella, Regina, Zhang, Yu-Jing, Hibshoosh, Hanina, Memeo, Lorenzo, Mansukhani, Mahesh, Long, Chang-Min, Garbowski, Gail, Agrawal, Meenakshi, Gaudet, Mia M., Steck, Susan E., Eng, Sybil M., Teitelbaum, Susan L., Neugut, Alfred I., Conway-Dorsey, Kathleen, Gammon, Marilie D., and Sagiv, Sharon Karnit

Subjects
breast cancer, p53 mutation, p53 overexpression, PAH, polycylic aromatic hydrocarbons
Abstract

Background: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology. Objectives: We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number. Methods: We examined this possibility in a population-based case–control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing. Results: We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH–DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation–negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11–2.15] but not p53 mutation–positive (OR = 0.77; 95% CI, 0.43–1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C→A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects. Conclusions: These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation.

Published
2010
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14. The mTOR Kinase Inhibitor Everolimus Decreases S6 Kinase Phosphorylation But Fails to Reduce Mutant Huntingtin Levels in Brain and is not Neuroprotective in the R6/2 Mouse Model of Huntington's Disease

Author

Fox, Jonathan H, Connor, Teal, Dorsey, Kate, Kama, Jibrin A, Bleckmann, Dorothee, Betschart, Claudia, Hoyer, Daniel, Frentzel, Stefan, Paganetti, Paolo, Chopra, Vanita, DiFiglia, Marian, and Hersch, Steven M.

Abstract

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD). In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results: Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions: Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

Published
2010
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15. 9-Genes Reinforce the Phylogeny of Holometabola and Yield Alternate Views on the Phylogenetic Placement of Strepsiptera

Author

McKenna, Duane D and Farrell, Brian Dorsey

Subjects
evolutionary biology, bioinformatics, evolutionary ecology
Abstract

Background: The extraordinary morphology, reproductive and developmental biology, and behavioral ecology of twisted wing parasites (order Strepsiptera) have puzzled biologists for centuries. Even today, the phylogenetic position of these enigmatic “insects from outer space” [1] remains uncertain and contentious. Recent authors have argued for the placement of Strepsiptera within or as a close relative of beetles (order Coleoptera), as sister group of flies (order Diptera), or even outside of Holometabola.Methodology/Principal Findings Here, we combine data from several recent studies with new data (for a total of 9 nuclear genes and ∼13 kb of aligned data for 34 taxa), to help clarify the phylogenetic placement of Strepsiptera. Our results unequivocally support the monophyly of Neuropteroidea ( = Neuropterida + Coleoptera) + Strepsiptera, but recover Strepsiptera either derived from within polyphagan beetles (order Coleoptera), or in a position sister to Neuropterida. All other supra-ordinal- and ordinal-level relationships recovered with strong nodal support were consistent with most other recent studies. Conclusions/Significance: These results, coupled with the recent proposed placement of Strepsiptera sister to Coleoptera, suggest that while the phylogenetic neighborhood of Strepsiptera has been identified, unequivocal placement to a specific branch within Neuropteroidea will require additional study., Organismic and Evolutionary Biology

Published
2010
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16. Temporal lags and overlap in the diversification of weevils and flowering plants

Author

McKenna, Duane D, Sequeira, Andrea, Marvaldi, A. E., and Farrell, Brian Dorsey

Subjects
coevolution, Coleoptera, Curculionoidea, herbivory, phylogeny
Abstract

The extraordinary diversity of herbivorous beetles is usually attributed to coevolution with angiosperms. However, the degree and nature of contemporaneity in beetle and angiosperm diversification remain unclear. Here we present a large-scale molecular phylogeny for weevils (herbivorous beetles in the superfamily Curculionoidea), one of the most diverse lineages of insects, based on ≈8 kilobases of DNA sequence data from a worldwide sample including all families and subfamilies. Estimated divergence times derived from the combined molecular and fossil data indicate diversification into most families occurred on gymnosperms in the Jurassic, beginning ≈166 Ma. Subsequent colonization of early crown-group angiosperms occurred during the Early Cretaceous, but this alone evidently did not lead to an immediate and major diversification event in weevils. Comparative trends in weevil diversification and angiosperm dominance reveal that massive diversification began in the mid-Cretaceous (ca. 112.0 to 93.5 Ma), when angiosperms first rose to widespread floristic dominance. These and other evidence suggest a deep and complex history of coevolution between weevils and angiosperms, including codiversification, resource tracking, and sequential evolution., Organismic and Evolutionary Biology

Published
2009
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17. Mechanisms of Copper Ion Mediated Huntington's Disease Progression

Author

Fox, Jonathan H., Kama, Jibrin A., Lieberman, Gregory, Chopra, Raman, Dorsey, Kate, Volitakis, Irene, Cherny, Robert A., Chopra, Vanita, Bush, Ashley Ian, and Hersch, Steven M.

Abstract

Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could contribute to pro-oxidant activities and neurodegeneration. We focused on two proteins: huntingtin, because of its centrality to HD, and lactate dehydrogenase (LDH), because of its documented sensitivity to copper, necessity for normoxic brain energy metabolism and evidence for altered lactate metabolism in HD brain. The first 171 amino acids of wild-type huntingtin, and its glutamine expanded mutant form, interacted with copper, but not iron. N171 reduced Cu2+ in vitro in a 1∶1 copper∶protein stoichiometry indicating that this fragment is very redox active. Further, copper promoted and metal chelation inhibited aggregation of cell-free huntingtin. We found decreased LDH activity, but not protein, and increased lactate levels in HD transgenic mouse brain. The LDH inhibitor oxamate resulted in neurodegeneration when delivered intra-striatially to healthy mice, indicating that LDH inhibition is relevant to neurodegeneration in HD. Our findings support a role of pro-oxidant copper-protein interactions in HD progression and offer a novel target for pharmacotherapeutics.

Published
2007
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18. Feature-based cellular texturing for architectural models

Author

Gortler, Steven, Dorsey, Julie, and Legakis, Julie

Abstract

Cellular patterns are all around us, in masonry, tiling, shingles, and many other materials. Such patterns, especially in architectural settings, are influenced by geometric features of the underlying shape. Bricks turn corners, stones frame windows and doorways, and patterns on disconnected portions of a building align to achieve a particular aesthetic goal. We present a strategy for feature-based cellular texturing, where the resulting texture is derived from both patterns of cells and the geometry to which they are applied. As part of this strategy, we perform texturing operations on features in a well-defined order that simplifies the interdependence between cells of adjacent patterns. Occupancy maps are used to indicate which regions of a feature are already occupied by cells of its neighbors, and which regions remain to be textured. We also introduce the notion of a pattern generator — the cellular texturing analogy of a shader used in local illumination — and show how several can be used together to build complex textures. We present results obtained with an implementation of this strategy and discuss details of some example pattern generators., Engineering and Applied Sciences

Published
2001
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