25 results on '"Catherine E. Smith"'
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2. Expert Report of Catherine Smith in Juliana v. United States (D.Or. April 13, 2018)
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Catherine E. Smith
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
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3. Two-Alternative Forced-Choice Paradigm, The
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Maddie Sparks, Catherine E. Smith, and David A. Washburn
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- 2022
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4. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.
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Catherine E Smith, Marc L Mendillo, Nikki Bowen, Hans Hombauer, Christopher S Campbell, Arshad Desai, Christopher D Putnam, and Richard D Kolodner
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Genetics ,QH426-470 - Abstract
Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.
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- 2013
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5. The Two-Alternative Forced-Choice Paradigm
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Maddie Sparks, Catherine E. Smith, and David A. Washburn
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- 2021
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6. CHAPTER 10 The Master’s Tools Will Not Dismantle the Master’s House: Hip Hop, Young M.A., and Gender Norms
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Catherine E. Smith and Zoe Smith-Holladay
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History ,Polymers and Plastics ,Legal doctrine ,media_common.quotation_subject ,Gender studies ,Racism ,Economic Justice ,Industrial and Manufacturing Engineering ,Supreme court ,Queer ,Creative writing ,Sociology ,Practice of law ,Business and International Management ,Transphobia ,media_common - Abstract
Immediately electrifying the rap game, Young M.A. entered the hip hop scene in 2016 and quickly became one of a few openly gay artists to make it big in hip hop. For many LGBT youth, Young M.A. invokes adoration and respect as a long-awaited depiction of the historically excluded queer rapper. For others, she brings controversy. Some critics call out what they perceive to be Young M.A.’s own disdain for women, while dedicated fans interpret it as turning gender on its head by a woman “doing what the men do.” For other listeners, she sparks derision and outright hostility as a reaction to her failure to adhere to expected gender norms. The reaction to Young M.A.’s groundbreaking entry into the hip hop scene represents an important crossroad for a music genre and culture that rebukes racism on one hand, yet often fails to pivot to embrace a progressive vision of gender equality on another. In this chapter, a Black teen and creative writer inspired by Young M.A. and a Black civil rights scholar offer their collective insights on the artist’s lyrics and rise to fame in the hip hop industry. They contend that as long as hip-hop culture shuns those who fail to conform to expected gender norms – norms that are the vestiges of White American culture and perpetuated through legal doctrine – it will fall short of its revolutionary potential to vocalize a radical social justice vision. A hundred years before the hip hop movement began, the United States Supreme Court relied on gross gender norms and stereotypes to exclude women from the practice of law, invoking what one Justice characterized as an “axiomatic truth” that “God designed the sexes to occupy different spheres of action and that it belonged to men to make, apply, and execute laws.” The legal enforcement of this type of patriarchal structure is the root of multiple forms of gender discrimination still present today, including misogyny, homophobia, and transphobia. Hip Hop’s current embrace of these gender norms is simply “serving the master” by partaking in the subordination of Black girls, Black women, and Black LGBT people. As Audre Lorde brilliantly put it, “the master’s tools will never dismantle the master’s house.”
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- 2021
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7. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System*
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Eva M. Goellner, Anjana Srivatsan, Nikki Bowen, William J. Graham, Richard D. Kolodner, and Catherine E. Smith
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Divalent ,Medical and Health Sciences ,Biochemistry ,DNA Mismatch Repair ,proliferating cell nuclear antigen (PCNA) ,yeast genetics ,replication factor C ,Genes, Dominant ,DNA clamp ,biology ,Adaptor Proteins ,Biological Sciences ,exonuclease 1 ,DNA mismatch repair ,MutL Protein Homolog 1 ,mutagenesis ,Biochemistry & Molecular Biology ,congenital, hereditary, and neonatal diseases and abnormalities ,Saccharomyces cerevisiae Proteins ,DNA repair ,DNA recombination ,Cations, Divalent ,replication factor C (RFC) ,Saccharomyces cerevisiae ,DNA and Chromosomes ,DNA replication ,complex mixtures ,Exonuclease 1 ,Replication factor C ,Cations ,Dominant ,neoplasms ,Molecular Biology ,Replication protein A ,Adaptor Proteins, Signal Transducing ,Msh2-Msh6 ,Signal Transducing ,nutritional and metabolic diseases ,Cell Biology ,proliferating cell nuclear antigen ,Molecular biology ,digestive system diseases ,genome instability ,Proliferating cell nuclear antigen ,Enzyme Activation ,MutL Proteins ,Genes ,Chemical Sciences ,Mutation ,biology.protein ,Biocatalysis ,Mutant Proteins ,Carrier Proteins - Abstract
Background: Biochemical analysis of S. cerevisiae MMR mutants has been limited by a lack of reconstituted MMR reactions. Results: 3′ nick-directed Mlh1-Pms1-dependent endonuclease and reconstituted MMR reactions were developed. Conclusion: 3′ nick-directed MMR required the Mlh1-Pms1 endonuclease and was eliminated by mutations inactivating Exo1-independent MMR. Significance: The reconstituted MMR reactions facilitated analysis of uncharacterized MMR mutants and the mechanism of Exo1-independent MMR., Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5′ nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3′ nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg2+ and Mn2+ for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR.
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- 2015
8. Brief of Amici Curiae Scholars of The Constitutional Rights and Interests Of Children in Support of Respondents in Masterpiece Cakeshop LTD, et al v. Colorado Civil Rights Commission
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Catherine E. Smith, Tanya Washington, Barbara Bennett Woodhouse, Angela Onwuachi-Willig, and Laura Fontana
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Harm ,Sexual orientation discrimination ,Law ,Political science ,Sexual orientation ,Public sphere ,Windsor ,Commission ,Sister ,Lesbian - Abstract
Masterpiece Cakeshop LTD, et al v. Colorado Civil Rights Commission is about much more than a wedding cake. It is about the rightful place of LGBT people and their families in the commercial and public sphere. In fact, children are already bearing the brunt of exclusionary practices in the public marketplace because of their relationship to or association with their LGBT parents. In Michigan, a pediatrician refused to treat an infant based solely on the fact that the child had lesbian mothers. In Kentucky, a judge refused to hear adoption cases of children involving LGBT adoptive-parents-to-be. In Tennessee, a nondenominational private school rejected enrollment for a pre-kindergartener and his 8-month-old sister after discovering that the children had two dads. In this brief, we argue that an expressive or religious exemption to sexual orientation discrimination prohibitions will deny children of LGBT parents equal access to the public sphere, inflict upon them psychological harm, and interfere with the “integrity and closeness” of their families — contrary to the aims of public accommodation and anti-discrimination law, and LGBT equality principles advanced in United States v. Windsor and Obergefell v. Hodges.
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- 2017
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9. A Study of the Feasibility of FDG-PET/CT to Systematically Detect and Quantify Differential Metabolic Effects of Chronic Tobacco Use in Organs of the Whole Body-A Prospective Pilot Study
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Mateen Moghbel, Thomas Werner, Natalie Spaccarelli, Judith Green-McKenzie, Jayaram K. Udupa, Marcus D. Goncalves, Drew A. Torigian, Frances S. Shofer, Clementina Mesaros, Saied Gholami, Xianling Liu, Grace Choi, Abass Alavi, Yubing Tong, Prithvi Shiva Kumar, Andrew A. Strasser, Ami H. Parekh, and Catherine E. Smith
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Adult ,Male ,medicine.medical_specialty ,Thyroid Gland ,Adipose tissue ,Standardized uptake value ,Pilot Projects ,Intra-Abdominal Fat ,Gastroenterology ,Article ,030218 nuclear medicine & medical imaging ,Cigarette Smoking ,03 medical and health sciences ,0302 clinical medicine ,Lumbar ,Bone Marrow ,Fluorodeoxyglucose F18 ,medicine.artery ,Internal medicine ,Positron Emission Tomography Computed Tomography ,Testis ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Muscle, Skeletal ,Lung ,Aorta ,Subclinical infection ,Skin ,business.industry ,Myocardium ,Thyroid ,Brain ,Heart ,Middle Aged ,medicine.anatomical_structure ,Liver ,Case-Control Studies ,Feasibility Studies ,Bone marrow ,Radiopharmaceuticals ,business ,Nuclear medicine ,030217 neurology & neurosurgery ,Spleen - Abstract
Rationale and Objectives The aim of this study was to assess the feasibility of 18 F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) to systematically detect and quantify differential effects of chronic tobacco use in organs of the whole body. Materials and Methods Twenty healthy male subjects (10 nonsmokers and 10 chronic heavy smokers) were enrolled. Subjects underwent whole-body FDG-PET/CT, diagnostic unenhanced chest CT, mini-mental state examination, urine testing for oxidative stress, and serum testing. The organs of interest (thyroid, skin, skeletal muscle, aorta, heart, lung, adipose tissue, liver, spleen, brain, lumbar spinal bone marrow, and testis) were analyzed on FDG-PET/CT images to determine their metabolic activities using standardized uptake value (SUV) or metabolic volumetric product (MVP). Measurements were compared between subject groups using two-sample t tests or Wilcoxon rank-sum tests as determined by tests for normality. Correlational analyses were also performed. Results FDG-PET/CT revealed significantly decreased metabolic activity of lumbar spinal bone marrow (MVPmean: 29.8 ± 9.7 cc vs 40.8 ± 11.6 cc, P = 0.03) and liver (SUVmean: 1.8 ± 0.2 vs 2.0 ± 0.2, P = 0.049) and increased metabolic activity of visceral adipose tissue (SUVmean: 0.35 ± 0.10 vs 0.26 ± 0.06, P = 0.02) in chronic smokers compared to nonsmokers. Normalized visceral adipose tissue volume was also significantly decreased ( P = 0.04) in chronic smokers. There were no statistically significant differences in the metabolic activity of other assessed organs. Conclusions Subclinical organ effects of chronic tobacco use are detectable and quantifiable on FDG-PET/CT. FDG-PET/CT may, therefore, play a major role in the study of systemic toxic effects of tobacco use in organs of the whole body for clinical or research purposes.
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- 2016
10. The National Lung Screening Trial: Overview and Study Design
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Natalie Cunningham, Michael Khalili, John Waltz, Ralph Weiben, Deb Gurtner, Linda DeAlmeida, Sanjay Gupta, Sharon Maxfield, Crissy Kibic, Kathleen DeWitt, David DeMets, Walter Allen Bowman, Robert Epstein, Mia Burkhard, Stephen J. Swensen, Hattie Cromwell, Kianoush Rezai, Steadman Sankey, Lisa Scott Wasson, Rita Musanti, Tamim Malbari, Joy Ferola, Qimei He, Patty Trapnell, Melba Francis, Sam Quattlebaum, Joanice Thompson, Ana Birofka, Robin Griggs, Elizabeth Johnson, Margaret R. Spitz, Nicole Richardson, Yuting Liang, Lawrence G. Hutchins, Mirjana Tecmire, Lila Camara, James J. Navin, Eileen Frost, Diane Romano, Carrie Petkus, Eric J. Berns, Pei Jan P Lin, Steve D. Uttecht, Marian Acerra, Lawrence R. Ragard, Leo P. Lawler, Christopher M. Rogers, Alan Lee Goodwin, L. Ellen Martinusen, Melissa Ford, Michael T. Fisher, Beverly Powell, Cindy Lin, Jamie Downs, Brent Fodera, Bonita Wohlers, Michael Brangan, Peggy Bradley, Todd B. Burt, Susan Allen, Shiva Borgheian, Mingying Zeng, Thomas Riley, Danielle Gherardini, Steven Shiff, Olivia Campa, Wahied Gendi, Fang F. Xu, Ivana K. Kazda, Anne Chung, Briar Doi, Helen Price, Maria Vlachou, Alan Morgan, Simone Vuong, Pierre P. Massion, Darcy Watson, Debbie William, Esther Nakano, Karen Broski, David Creed, Melanie Bvorak, Lakisha Hawkins, Gladys Hino, Raymond Dauphinais, Michele Sallas, Helene Shiratori, Venus Brown, Denise Brooks, Heather Porter, Ilana F. Gareen, Tracy Lee, Melissa Cates, Kyle Turner, Tiffanie Hammond, Margaret Paquette, Lorraine Kerchum, Barbara Lewis, Douglas J. Reding, Thomas E. Hartman, Cathy Longden, Melissa Laron, Reza Abaya, Beborah Robertson, J W Semenkovich, Christine Holland, Hugh McGinley, Chani Montalbo, Karen Zubena, Vanessa Ralda, Adam C. Stein, Jennifer Ott, Lawrence M. Kotner, Jing Lee, Arnold Ssali, Michael Young, Quinn A. DeMordaunt, Linda V. White, Steve Dubinett, Pearl Chan, Roxana Phillips, Mallory Kolich, Brent B. Nelson, Phi Do, Jill Spivak, Angele LaFleur, Kesha Smith, Elayne Weslowsky, Patricia Nieters, Maurice LeBlanc, Satinder Singh, Lonna Matthews, Quentin McMullen, Karen Lappe, Sharon Longacre, Cindy Cobb, Jane A. Zehner, Michael Teepe, Pamela M. Marcus, Kathleen Bow, Wendy Francis, Mary Gemmel, Robert S. Fontana, Linda Jurjans, Barbara Ginther, Jonathan B. Clapp, Monica Richel, Scott F. Pickering, Brenda Edwards, Kendrick Looney, Randy Marshall, Roni Atkins, Danielle Wicks, Julie Peterson, Dcanna Cape, Albert J. Cook, Jerry Brekke, Louisa Turner, Larry Stoller, Mark B. Salerno, Bavid E. Midthun, Mark Delano, Minnetta Belyea, Deborah Greene, Jonathan Goldin, Terry Lewis, Virginia Fischer, Andrea Chapman, Shari Jordan, Deb Warren, Demetria Johnson, Rekha Khatri, Lisa Sirianni, Guillermo Geisse, Michael A. Fuchs, Kanya Kumbalasiri, Jeremy J. Erasmus, Vicki Shambaugh, Denise Boyles, Sarah Hallsky, Anna Nanovski, Jill Heinz, Mollie King, Kay Vydareny, Olga Soukhanova, Patricia Rueweler, Perry G. Pernicano, Regina Rendas-Baum, Phyllis Pirotte, Russell Harris, Neil Argyle, Miyoung Kim, June Krebsbach, Audrey Gallego, Sheila Wein, Mukesh F. Karwat, Karla Myra-Bloom, Pamela Byrnes, Mitchell D. Schnall, Hector Ahumada, Eric Sanchez, Donna DesMarais, Julie Maderitz, Cindy Lavergne, Lori Kirchoff, Patricia C. Sanders, Elizabeth Thielke, Michael Sullivan, Jennifer Gaegler, Janet Manual, Jennifer R. Heinz, Ray Zisumbo, Diane C. Strollo, Candace Mueller, Irene Mahon, Brenda Delfosse, Carolyn M. Johnson, William E. Grizzle, Merideth Stanley, Sylvan Green, Pamela Harvey, Lindsay Richardson, Brenda K. Brewer, Philip Costello, Deanna Zapolski, John Worrell, Jeffrey G. Schragin, David S. Alberts, Edward L. Korn, Tamara Owens, Hank Brastater, Kay Mathiesen-Viergutz, Mark Broschinsky, Paul W. Spirn, Grace Isaacs, John S. Waltz, Mitch Goodsitt, Christi Newton-Foster, Sharlene Snowden, Barbara Voight, Gail Bizer, Kathy McDonough, William Huynh, Eduard Van Stam, Robert A. Carlson, Mike Florzyk, Paula M. Jacobs, Joan Fuller, Mauren Grunenwald, Ann Bangerter, Jacksonville, Adriane Andersen, Tess Thompson, Kenneth Nowers, Stephanie Helwi, Martin J. Edelman, Emmanuel Omoba, Rubenia Flores, Kevin T. White, Patrick W. Wolfe, Michael Milacek, Sharon Gard, Brandon B. Bigby, Cynthia H. McCollough, Andrew Burnside, Sheryl L. Ogden, Maisha Pollard, Thomas K. Pilgram, Sydney Laster, Claudia J. Kasales, Bruce W. Turnbull, Cheri Haselhuhn, Laura N. Myers, Jean Jacobsen, Melissa Love, Gavin D. Watt, Cheryl Love, Gerald F. Abbott, Susanne Kozakowski, Jerry L. Montague, Cynthia Hill, Neil F. O'Donnell, Anna Sear, Thomas M. Beck, Jean Wegner, Chrispina Wray, Edward M. Brown, Louise Ledbetter, Karen Bellware, Julie Moody, Noel Bahr, Matthew T. Freedman, Thomas Hensley, John E. Madewell, Leanne Hadfield, David R. Maffitt, Lisa Cottrell, John J. Warner, Deborah Graham, Krystal Arnold, Alejandra Reyes, Kristin Lieberman, Derek Omori, Donna Garland, Mike Burek, Mel Johnson, Judith Harkins, Martha Fronheiser, M. Y. M. Chen, Dawn Simmons, Kathleen Voight, Aaron O. Bungum, Marianne Rice, Lakeshia Murray, Tami Krpata, Donna Sammons, Leslie Kmetty, Catherine Duda, Carissa Krzeczkowski, Anne Nguyen, Richard H. Lane, Cynthia Mack, Loren C. Macey, Eddy Wicklander, Kelly McDaniel, Sue Zahradka, Hassan Bourija, Cristina Farkas, Jincy George, Renae Kiffmeyer, Wendell Christie, Catherine Engartner, John Crump, Mimi Kim, Carol Steinberg, Reginald F. Munden, Deb Kirby, Jo Ann Stetz, Barbara O'Brien, Sally Tenorio, Laura Multerer, Carlotta McCalister-Cross, Jessica Silva-Gietzen, Tamara Saunders, Harvey Glazer, Cam Vashel, Maria Oh, Rodkise Estell, Steven M. Moore, Tara Riley, Grant Izmirlian, D. Claire Anderson, James Burner, Steven Peace, Phil Hoffman, Angela Del Pino, Brian Irons, Carlos Jamis-Dow, John K. Lawlor, Edward F. Patz, Jay Afiat, Amber Barrow, Bawn M. Beno, Melissa S. Fritz, Lynn Coppage, Scott J. Sheltra, Tim Swan, Jerry Bergen, Charlie Fenton, Eric Deaton, Marilyn J. Siegel, Korinna Vigeant, Kerry Engber, Sarah Merrill, Buddy Williams, Kimberly Stryker, Bradley S. Snyder, Christina Romo, Andrea Hugill, Michael J. O'Shea, Linda White, Gail Fellows, Yasmeen Hafeez, Joe Woodside, Shauna Dave Scholl, Philip C. Prorok, Sharon Carmen, Kelly Hatton, Steven V. Marx, Sooah Kim, Robert Kobistek, Dawn Thomas, Lea Momongan, Chris Steward, Kari Bohman, Holly Bradford, Bradley S. Sabloff, Phillip Peterson, William C. Black, Lisa Pineda, James G. Ravenel, Karen Taylor, Beverly Trombley, Mona N. Fouad, Amber McDonald, Lauren J. Ramsay, Lisa Harmon, Jeffrey Geiger, David L. Spizarny, Jeffrey S. Klein, Xizeng Wu, Heather Tumberlinson, Joy Espiritu, Gina Varner, Dawn Fuehrer, Eric A. Hoffman, Sheila Moesinger, Nina Wadhwa, Steve King, Patricia Lavernick, Paola Spicker, Timothy R. Church, Cheryl Whistle, Sheila Greenup, Patricia Fantuz, Stephanie Levi, Peter Balkin, Mary E. Johnson, Johanna Ziegler, Susan Hoffman, Kathy L. Clingan, Craig Kuhlka, Maria Marchese, Lawrence F Cohen, Cylen Javidan-Nejad, Wilbur A. Franklin, Kevin J. Leonard, Tim A. Parritt, Jade Quijano, Kathleen Poler, Jennifer Rosenbaum, Xiuli Zhang, Christine Brown, Terri David-Schlegel, Susan M. Peterson, James R. Jett, Kenneth W. Clark, Edward P. Gelmann, Arthur Migo, Patricia Fox, Lori Hamm, Janie McMahon, Darlene Guillette, Robert C. Young, Patty Beckmann, Jerome Jones, Nikki Jablonsky, Roberta Yoffie, Heather L. Bradley, Darlene Higgins, Francine L. Jacobson, Christine B. Berg, Mark Bramwitt, Constantine N. Petrochko, Karen Stokes, Jennifer Rowe, Kathy McKeeta-Frobeck, Brenda Sleasman, Courtney Bell, Dave Tripp, Saundra S. Buys, Susan Walsh, Jo Rean D. Sicks, Richard G. Barr, Kirk Midkiff, Tom Caldwell, Elisabeth A. Grady, Subbarao Inampudi, Marilyn Calulot, Paul A. Kvale, Alice DuChateau, Kathy Berreth, Ruth Holdener, Katie Kuenhold, Thomas E. Warfel, David P. Naidich, Mandie Leming, Fraser Wilton, Leanne Franceshelli, Kathleen McMurtrie, Elaine Bowman, Donald F. Bittner, Helen Kaemmerer, Merri Mullennix, Adelheid Lowery, Andrew Karellas, Jenny Hirschy, Kate Naughton, Ashley B. Long, Kristin M. Gerndt, Kathleen Young, Richard M. Schwartzstein, Wendy Smith, Joseph Aisner, Shane Ball, Kathleen Krach, Cathy Mueller, Virginia May, Christopher Blue, Marsha Lawrence, Ronald S. Kuzo, Colleen McGuire, Alisha Moore, Sara Cantrell, Christie Leary, Pamela Allen, Maryann Trotta, Clifford Caughman, Peggy J. Gocala, Brian Mullen, Janan Alkilidar, Maryann Duggan, Lin Mueller, Alesis Nieves, Fenghai Duan, Frederick Olson, Edwin G. Williams, Jo Ann Hall Sky, Grant Izmirilian, Peggy Joyce, Judy Preston, Cristine Juul, Julianne Falcone, Bruce Neilson, Fla Lisa Beagle, Beth Evans, Jamie Mood, Janet Bishop, Jean Tsukamoto, Vivien Gardner, Gillian Devereux, Minesh Patel, Sally Fraki, Celia Stolin, Ami Lyn Taplin, Stephenie Johnson, Saeed Matinkhah, Jenna Bradford, Sanjeev Bhalla, Charles Jackson, Julie Haglage, Darlene R. Fleming, Allie M. Bell, Paul A. Bunn, Gail Orvis, Andrew J. Bierhals, Julie Ngo, Belores K. Prudoehl, Elaine N. Daniel, Peggy Olson, Paul F. Pinsky, Glenna M. Fehrmann, Aras Acemgil, Andrea Hamilton-Foss, Leeta Grayson, Smita Patel, Scott Emerson, Carl J. Zylak, James R. Maxwell, Jennifer Fleischer, Suzanne Smith, Jacqueline R. Sheeran, Alan Williams, Scott Gaerte, John Fletcher, Sonya Clark, Nancy Gankiewicz, Stuart S. Sagel, Jason Spaulding, Nancy E. Hanson, Nicole Fields, Richard D. Nawfel, Dinakar Gopalakrishnan, Margaret Oechsli, Susan Wenmoth, Isabelle Forter, Elizabeth Morrell, Jessica Rider, Letitia Clark, Michael Woo, Cynthia A. Brown, Camille Mueller, Mark T. Dransfield, Lois M. Roberts, Anne Randall, Eduard J. Gamito, Carrie O'Brien, Carolyn Palazzolo, Julie Schach, Robert Falk, Melissa Hudson, Jennifer Garcia Livingston, Cynthia L. Andrist, Tammy Fox, Elliott Drake, Tanya Zeiger, Renee Metz, Kevin Thomas, Neha Kumar, Elizabeth Couch, Beborah Bay, Mei Hsiu Chen, Jason Bronfman, Philip Dennis, Deb Engelhard, Pamela McBride, Daniel Kimball, Amy Haas, Pamela M. Mazuerk, Marlea Osterhout, Venetia Cooke, Tina Taylor, Amy St.Claire, Joe Hughes, Becky McElsain, Beverly Brittain, Michele Adkinson, Paige Beck, Martha Maineiro, Paula R. Beerman, Jackie Seivert, Mary M. Pollock, Donald Corle, Tina Herron, Marcella Petruzzi, Natalie F. Scully, Kenneth A. Coleman, Jennifer Yang, Debra Loria, Wendy Moss, Alan Brisendine, Cheryl M. Lewis, Dalphany Blalock, Lonni Schultz, Douglas Bashford, Nora Szabo, David Shea, Amanda Devore, Karen Schleip, Judy Netzer, Barry Clot, Gerald M. Mulligan, Nancy E. Krieger Black, David Schultz, Jim Pool, Craig E. Leymaster, Kathryn Rabanal, Kay Bohn, Tara Berg, Marisol Furlong, Stacey Mitchell, Donna Biracree, Laura Jones, Cassie Olson, Robin Stewart, Jeremy Pierce, Marilyn Bruger, Valene Kennedy, Stephanie Davis, Colin O'Donnell, Glenn A. Tung, Shannon Wright, William Lake, Sharon Jones, Vincent Girardi, Brad Benjamin, Veenu Harjani, Drew A. Torigian, Kevin Edelman, Sue Frederickson, Paul E. Smart, Michelle Wann Haynes, D S Gierada, Glenn Fletcher, Rosalie Ronan, Patricia Ann Street, Eleace Eldridge-Smith, Lynly Wilcox, Cindy Lewis-Burke, La Tonja Davis, Rachel Black Thomas, Dawn Shone, Evangeline Griesemer, Tim Budd, Lindsey Dymond, Marlene Semansky, Amy Rueth, Constantine Gatsonis, Kay H. Vydareny, Usha Singh, Amy Lita Evangelista, Angelica C. Barrett, Bethany Pitino, Shirley Wachholz, Angela M. Williams, Sandra Fiarman, Karen Luttrop, David Chellini, Michael Bradley, Helen Fink, Aaron Zirbes, Roger Inatomi, Joon K. Lee, Heather Bishop Blake, Lisa Woodard, Craig Hritz, Sarah Neff, Aine Marie Kelly, Deborah Harbison, Baigalmaa Yondonsambuu, Amy Lloyd, Christine Gjertson, Erin Cunningham, Angelee Mean, June Morfit, Ping Hu, William Thomas, Jazman Brooke, Paul Marcus, Jeremy Gorelick, Erin Lange, William Stanford, Denise R. Aberle, Lena Glick, Annabelle Lee, Ian Malcomb, Deanna L. Miller, Mary Mesnard, Jacqueline Jackson, Jhenny Hernandez, Desiree E. Morgan, Howard I. Jolies, Jacquie Marietta, Teresa Lanning, Debra Rempinski, Amanda C. Davis, Karen Mathews Batton, Mahadevappa Mahesh, Erik Wilson, Deana Nelson, Sharan L. Campleman, William Manor, Julie Sears, Howard Mann, E. David Crawford, Carl Krinopol, Greg Gambill, Margo Cousins, Rex C. Yung, Sangeeta Tekchandani, Thomas Vahey, Ann D. McGinnis, Kimberly Nolan, Kaylene Crawford, Kelli P. Rockwell, Dana Roeshe, Fred W. Prior, Kari Ranae Kramer, Heidi Nordstrom, Frank Stahan, Shawn Sams, Cherie Baiton, Joy Tani, Thomas J. Watson, Angela Cosas, Diane Kowalik, Pritha Dalal, Ann Jolly, Jeanine Wade, Laura Bailey, Julie Varner, Glen K. Nyborg, Christopher Toyn, David Gemmel, Susanna N. Dyer, Laurie Amendolare, Mary Ellen Frebes, Judy Ho, Adele Perryman, John Keller, D. Sullivan, George Mahoney, Scott Cupp, Linda L. Welch, Peter Greenwald, Robert Sole, Marcello Grigolo, Caroline Chiles, Patricia Sheridan, Deborah M. Chewar, Vijayasri Narayanaswami, Susan Blackwell, Suzanne B. Lenz, Alphonso Dial, Melvin Tockman, Carolyn Hill, John Stubblefield, Catherine E. Smith, Judith Lobaugh, Rosa M. Medina, Jackie Meier, Nandita Bhattacharjee, Robert Tokarz, Lisa Clement, Nancy Caird, Cindy Masiejczyk, Patricia Shwarts, Laura Springhetti, Sandra Schornak-Curtis, Edwin F. Donnelly, Patricia Tesch, Laurie Rathmell, Pamela K. Woodard, Edward A. Sausville, David R. Pickens, Kylee Hansen, Paulette Williams, Barbara Ferris, Rachel L. McCall, Nicole M. Carmichael, Dawn Whistler, Ramachandra Chanapatna, Glynis Marsh, Mary Wiseman, Tony DeAngelis, L. Heather, Vicki Prayer, Robin Laura, Priscilla Bland, Gregory W. Gladish, Amy Garrett, Kelly McNulty, Daniel J. Pluta, Mylene T. Truong, Serelda Young, Crista Cimis, Gordon Jacob Sen, Rhonda Rosario, Anthony B. Miller, Edward Hunt, Juanita Helms, Jill K. Bronson, Jeff Yates, Ginette D. Turgeon, Bo Lu, Nancy Fredericks, Pam Senn, Ryan Pena, Hakan Sahin, Mary Lynn Steele, Jill E. Cordes, Noel Maddy, R. Adam DeBaugh, Hope Hooks, Zipporah Lewis, Robert L. Berger, Shani Harris, Natalie Gray, Jennifer Kasecamp, Elizabeth King, Jacinta Mattingly, Hrudaya Nath, Kathy Torrence, Christine Cole Johnson, Sara Mc Clellan, Kalin Albertsen, Kim Sprenger, Ryan Norton, Jody Wietharn Kristopher, Linda Warren, Byung Choi, Casey O'Quinn, Mark K. Haron, Chris J. Jennings, Karen Robinson, Joan Molton, Dorothy Hastings, Robert I. Garver, Christopher J. Cangelosi, Jeannette Lynch, Peter Ohan, Angela Campbell, Dawn Mead, Miriam Galbraith, Divine Hartwell, Natalya Portnov, Gene L. Colice, Andetta R. Hunsaker, Analisa Somoza, Todd Risa, Daniel C. Sullivan, Karthikeyan Meganathan, Tammy DeCoste, Peter Zamora, Richard M. Fagerstrom, Iiana Gareen, Phyllis J. Walters, Barbara L. Carter, Alem Mulugeta, Rob Bowman, Kavita Garg, Andrea Franco, Mary Adams Zafar Awan, Edward Reed Smith, Rachel Phillips, Michelle Aganon-Acheta, Fred R. Hirsch, Peter Jenkins, Pamela Taybus, Joy Knowles, Karen M. Horton, Cheryl Spoutz-Ryan, Sarah Landes, William G. Hocking, Laura B. Schroeder, Erini Makariou, Jered Sieren, Kaylene Evans, Erin Nekervis, Brenda Polding, Tonda Robinson, Joel L. Weissfeld, Terry J. Sackett, Michael F. McNitt-Gray, Leslie Dobson, Raymond Weatherby, Randell Kruger, Revathy B. Iyer, Mary Krisk, Anthony Levering, Susan Collins, Alison Schmidt, William M. Hanson, Patricia Schuler, Karen Glanz, Morgan Ford, Beatrice Trotman-Bickenson, Richard Guzman, Paul Koppel, Judith K. Amorosa, Meredith Slear, Dayna Love, Carol Vaughn, Kellyn Adams, Celeste Monje, Garry Morrison, Sherri Mesquita, Paul Cronin, Tony Blake, Constance Elbon-Copp, Robert A. Clark, Felix Mestas, Erich Allman, Armen Markarian, Cheryl Souza, Karen O’Toole, Elliot K. Fishman, Karen Augustine, Jane Hill, Bonnie Kwit, Ralph Drosten, Susan Foley, Stacy E. Smith, Angie Bailey, Jennifer Bishop Kaufmann, Shelly Meese, Phillip M. Boiselle, Howard Morrow, Thomas D. Hinke, Barry Edelstein, Erin Schuler, William C. Bailey, Donna Letizia, David S. Gierada, Frederick J. Larke, Robin Haverman, Sarah Baum, Sally Hurst, Richard L. Morin, Ben Dickstein, William Russell, J. Anthony Seibert, Sophia Sabina, Mary Alyce Riley, Michael A. Taylor, Katherine BeAngelis, Robert A. Hawkins, Fernando R. Gutierrez, Amie Welch, Heather Lancor, George Armah, James Blaine, Eric Henricks, Joel Dunnington, Carole Walker, Laura Motley, Melody Kolich, Bruce J. Hillman, David W. Sturges, Mindy Lofthouse, Amy Warren, Michael Black, Mark Kolich, Lisa A. Holloway, Shannon M. Pretzel, Susan Shannon, Yassminda Harts, Dallas Sorrel, Lance A. Yokochi, Diana Wisler, Arthur Sandy, Roberta Clune, Shirley Terrian, Shalonda Manning, Bradley Willcox, Thomas J. Payne, James L. Tatum, Dale Brawner, Sandy Morales, Rodolfo C. Morice, Amy Vieth, Emily Jewitt, Chelsea O'Carroll, Theresa C. McLoud, John E. Langenfeld, Chris H. Cagnon, Lisa B. Hinshaw, Gena Kucera, Helena R. Richter, Drew Torigian, June McSwain, Courtney Eysmans, Vinis Salazar, David Spizarny, Mary Kelly-Truran, Mark Whitty, Henry Albano, Connie L. Sathre, William R. Geiser, Barnett S. Kramer, Marianna Gustitis, Gordon C. Jones, Neil E. Caporaso, Timothy Welsh, Roger Tischner, Ana Maria Mendez, Dominick A. Antico, Cathy L. Bornhorst, Carla Chadwell, Stephanie Pawlak, Kelli M. West, Joe V. Selby, Randall Kruger, Jodi Hildestad, Elaine Freesmeier, Nicole Rivas, Andrew Goodman, Naima Vera-Gonzalez, Stuart Lutzker, Eric M. Hart, Melanie Yeh, Shane Sorrell, Deb Multerer, Sharon Jacoby, Debbie Gembala, Elizabeth Fleming, Myrle Johnson, Michael J. Flynn, Frank Tabrah, Martin L. Schwartz, Deanna Mandley, Brad Siga, Guillermo Marquez, Jeffrey Koford, Victoria Jenkins, Janice Pitts, Constantine A. Gatsonis, Natalie Baptiste, Edith M. Marom, Gina Sammons, Anne Burrough, Martha Ramirez, Jack Cahill, Carl Jaffe, Linda Heinrichs, Aura Cole, Paul Rust, Alon Coppens, Gregg Hamm, Lisa Conklin, Kathleen A. Robbins, Carleaner Williams, Gwen Chalom, Winston Sterling, Colleen Hudak, Lea Matous, Ella A. Kazerooni, Denise Kriescher, David A. Lynch, Liz Bolan, Jacob Wolf, Jonathan G. Goldin, Roberta Quinn, L. A. Schneider, Kathleen A. Murray, Erica Sturgeon, Jennifer Avrin, Michelle T. Biringer, Mark Hinson, Cynthia Reiners, Brian Chin, Amy Brunst, Ann M. Lambrecht, Katherine Lohmann, Jennifer Bacon, Ulander Giles, Diane Shepherd, William T. Corey, Timothy Cosgrove, Lana C. Walters, Nancy Kadish, Hilary C. Nosker, Christine D. Berg, Thomas Payne, Jackie Becker, Kanistha Sookpisal, Lyn Seguin, Todd R. Hazelton, Roy Adaniya, James Fisher, Annmarie Walsh, Shirleen Hyun, Laura Stark, Kenneth Hansen, Carolyn Nelson, Martin Tammemagi, Mary A. Wolfsberger, Barry H. Gross, Valentina Ortico, Marge Watry, Jeff Childs, Gabe Herron, Loretta Thorpe, Lisa Damon, Evanthia Papadopoulos, Denise Moline, Voula E. Christopoulos, John D. Minna, Tony Jones, Mitchell Machtay, Michael Plunkett, Melissa Laughren, Luis Zagarra, Adam Leming, Eda Ordonez, Chris Howell, Marissa Peters, Wendy Mosiman, Joanne Gerber, Alfonso Lorenzo, Barbara L. McComb, Laura Hill, Gale Christensen, Hanna Comer, Carmen Guzman, Kathy Taylor, Misty Oviatt, Malcolm King, Lily Stone, Rex Welsh, Bernadette Pennetta, Cristina Raver, Jan E. Hyder, Stephanie Clabo, Peggy Lau, Jacqueline Fearon, Patricia Pangburn, Pamela Dow, William K. Evans, Victor De Caravalho, Mike Wirth, Brooke Johnson, Meridith Blevins, Lisa H. Gren, Sharon L. Kurjan, James P. Evans, Kirk E. Smith, Donna King, John A. Worrell, Mindy S. Geisser, Philip F. Judy, Richard Barr, Sue Misko, Stanley R. Phillips, Jillian Nickel, Christine M. McKey, Joe Austin, Donna Hartfeil, Laura Young, Shovonna White, Alexis K. Potemkin, Anthony Boulos, Tawny Martin, Karen Kofka, Heather McLaughlin, Matthew K. Siemionko, Melissa Houston, Angela Lee Rowley, Adys Fernandez, Murray Backer, Jagdish Singh, Mary Weston, Nancy Payte, Charles Apgar, John K. Gohagan, Jeff Fairbanks, Wylie Burke, David Chi, Michael Nahill, Kevin DeMarco, Karen Patella, Beverly Rozanok, Carol M. Moser, Nicole Matetic Mac, Karen Boyle, Dinah Lorenzo, Elanor Adkins, Phyllis Olsson, Amanda M. Adams, Sujaya Rao, K.E. Jones, Polly Kay, D. Lynn Werner, John B. Weaver, Sally Anne Kopesec, Jennifer Frye, Victoria Chun, Cathy Francow, Cheri Whiton, Jo Ann Nevilles, Andrew Bodd, Barbara Galen, Sabrina Chen, Cindy Cyphert, Stephen M. Moore, Petra J. Lewis, Shanna Nichols, Mareie Walters, Thea Palmer Zimmerman, Warren B. Gefter, Peter Dubbs, Ann Reinert, Holly Washburn, Renee MacDonald, Boleyn R. Andrist, Dianalyn M. Evans, Marvin Flores, Tricia Adrales-Bentz, Claudine Isaacs, Regina C. MacDougall, Greg M. Silverman, Nichoie Cadez, Lynne Bradford, Rochelle Williams, Angela M. McLaughlin, Ellen Sandberg, Cheryl Crozier, Robert Mayer, Richard P. Remitz, Sheron Bube, Leroy Riley, Vish Iyer, Sophie Breer, Stephen Baylin, Anna Boyle, Shannon Williams, Kristen Keating, Martin M. Oken, Gerald L. Andriole, Bruce E. Hubler, Eric T. Goodman, David Engelhart, Bonna Au, Brianne Whittaker, Tricia Hoffa, Eng Brown, Tammy Wolfsohn, Denise L. Foster, Barry H. Cohen, Linda Galocy, Matthew T. Bee, Jacqueline Matuza, Leslie Henry, Katherine Meagher, Mona Fouad, Beth McLellan, Troy Cook, John Sheflin, Lilian Villaruz, Marcella Moore, Brandy Mack-Pipkin, Vanessa Graves, Ryan Weyls, William T. Herbick, Geoffrey McLennan, Lynn Hoese, Janise Webb, Terrie Kitchner, Michele Lee, Robert T. Greenlee, Charles C. Matthews, Nicole Spiese, Jeffrey Heffernon, Dianna D. Cody, Patricia Blair, Kathy Garrett, Michael A. Sullivan, and Loretta Granger
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Oncology ,medicine.medical_specialty ,business.industry ,Mortality rate ,medicine.disease ,law.invention ,Quality-adjusted life year ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,National Lung Screening Trial ,Radiology ,Overdiagnosis ,business ,Lung cancer ,Lung cancer screening ,Mass screening - Abstract
The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.
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- 2011
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11. Aberrant Double-Strand Break Repair Resulting in Half Crossovers in Mutants Defective for Rad51 or the DNA Polymerase δ Complex
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Alicia F. Lam, Lorraine S. Symington, and Catherine E. Smith
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DNA Replication ,Saccharomyces cerevisiae Proteins ,DNA Repair ,DNA polymerase ,DNA repair ,DNA polymerase II ,Saccharomyces cerevisiae ,DNA polymerase delta ,Gene Expression Regulation, Fungal ,DNA Breaks, Double-Stranded ,Strand invasion ,Molecular Biology ,DNA Polymerase III ,Recombination, Genetic ,biology ,DNA replication ,Chromosome Breakage ,Articles ,Cell Biology ,Base excision repair ,Processivity ,Molecular biology ,Mutation ,biology.protein ,Rad51 Recombinase ,Chromosomes, Fungal - Abstract
DNA double-strand breaks (DSBs) are potentially lethal lesions that can occur spontaneously during normal cell metabolism, by treatment of cells with DNA-damaging agents, or during programmed recombination processes (54). There are two major pathways to repair DSBs: nonhomologous end joining (NHEJ) and homologous recombination (HR). NHEJ involves the religation of the two ends of the broken chromosome and can occur with high fidelity or be accompanied by a gain or loss of nucleotides at the junction (9). Repair of two-ended DSBs by HR generally occurs by gene conversion resulting from a transfer of information from the intact donor duplex to the broken chromosome (Fig. (Fig.1).1). HR occurs preferentially during S and G2 when a sister chromatid is available to template repair (2, 19, 22). Sister-chromatid recombination events are genetically silent, whereas gene conversion between nonsister chromatids associated with an exchange of flanking markers can result in extensive loss of heterozygosity (LOH) or chromosome rearrangements (3, 21). One-ended DSBs that arise by replication fork collapse or by erosion of uncapped telomeres are thought to repair by strand invasion into homologous duplex DNA followed by replication to the end of the chromosome, a process referred to as break-induced replication (BIR) (35). BIR appears to be suppressed at two-ended breaks, presumably because it can lead to extensive LOH if it occurs between homologues or to chromosome translocations when strand invasion initiates within dispersed repeated sequences (5, 28, 31, 50, 52, 55). FIG. 1. Models for gene conversion and BIR. After formation of a DSB, the ends are resected to generate 3′ single-strand DNA tails. One end undergoes Rad51-dependent strand invasion to prime DNA synthesis from the invading 3′ end templated by ... The strand invasion step of BIR is assumed to be the same as that for gene conversion based on the requirement for the same HR proteins: Rad51, Rad52, Rad54, Rad55, and Rad57 (10). However, subsequent steps in BIR are less well defined. Recent studies of the fate of the invading end during BIR in diploid strains with polymorphic chromosome III homologues using a plasmid-based assay have shown that following strand invasion, the invading end is capable of dissociating from the initial homologous template. Following dissociation, the displaced end subsequently reinvades into the same or a different chromosome III homologue by a process termed template switching (52). One of the interesting features of the template switching events is that they occur over a region of about 10 kb downstream of the site of strand invasion and do not extend over the entire left arm of chromosome III. There are a number of possible mechanisms that could account for this apparent change in the processivity of BIR. First, it is possible that the strand invasion intermediate is cleaved by a structure-specific nuclease and once the invading strand is covalently joined to one of the template strands, the strand invasion process is irreversible. Recent studies of Schizosaccharomyces pombe have shown an essential role for Mus81, a structure-specific nuclease, in resolution of sister chromatid recombination intermediates during repair of collapsed replication forks (48). Another possibility is that there could be a switch between a translesion DNA polymerase and a highly processive DNA polymerase during BIR. The translesion polymerases in budding yeast, polymerase ζ (Pol ζ) and Pol η, are encoded by REV3-REV7 and RAD30, respectively (34, 40, 43). Deletion of REV3 has been shown to increase the fidelity of DNA synthesis associated with HR but has no effect on the overall frequency of DSB-induced HR (16). Deletion of POLη in chicken DT40 cells reduces the frequency of DSB-induced gene conversion, and human POL η has been shown to extend the invading 3′ end of D-loop intermediates in vitro (23, 36). However, this same preference for Pol η is not found for Saccharomyces cerevisiae. Instead, DNA synthesis during meiotic and mitotic recombination appears to be carried out by Pol δ, one of the three nuclear replicative polymerases, which normally functions with Pol α in Okazaki fragment synthesis (13, 32, 33, 44). Pol ɛ is thought to be the primary leading-strand polymerase (47), but in the absence of the Pol ɛ catalytic domain, Pol δ is presumed to carry out leading-strand synthesis (24). Recent studies by Lydeard et al. (30) have shown a requirement for the lagging-strand polymerases, Pol δ and Pol α, to form the initial primer extension product during BIR, and Pol ɛ is required to complete replication to the end of the chromosome. In contrast, repair of DSBs by gene conversion does not require Pol α, and there appears to be functional redundancy between Pol δ and Pol ɛ (56). To address the roles of Mus81, Pol δ, and Pol η in BIR and in particular template switching, we used the transformation-based BIR assay with diploids with polymorphic chromosome III homologues. Because the transformation assay can only be used with strains with viable mutations of replication factors, we used a null allele of POL32, encoding a nonessential subunit of the Pol δ complex (14), and a point mutation in the gene encoding the essential catalytic subunit, POL3. The pol3-ct allele results in a truncation removing the last four amino acids of the Pol3 protein; the C-terminal region of Pol3 is implicated in interaction with the other essential subunit of the Pol δ complex, Pol31 (15, 49). The interesting feature of the pol3-ct allele is that it decreases the length of gene conversion tracts during mitotic and meiotic recombination, presumably by affecting the processivity of Pol δ, but confers no apparent defect in normal DNA synthesis (32, 33). Because BIR requires more-extensive tracts of DNA synthesis than gene conversion, we expected the pol3-ct mutant to exhibit a BIR defect. We found that in the absence of a fully functional Pol δ complex, chromosome fragment (CF) formation proceeds by a half-crossover mechanism associated with loss of the template chromosome, an event with potentially catastrophic consequences (6, 57). This was also found to occur in rad51 mutants, suggesting nonreciprocal translocations arise by failure to undergo strand invasion or because replication following strand invasion is inefficient. In contrast to rad51 mutants, the Pol δ complex mutants are proficient for repair of a 238-bp gap by gene conversion and fully resistant to ionizing radiation, suggesting there is a unique requirement for Pol δ to complete BIR. Consistent with studies of gene conversion in S. cerevisiae (33), we found no role for Pol η in BIR or the process of template switching.
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- 2009
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12. Explosive Pleistocene diversification and hemispheric expansion of a 'great speciator'
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Jared M. Diamond, Christopher E. Filardi, Robert G. Moyle, and Catherine E. Smith
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Multidisciplinary ,Old World ,Geography ,Genetic Speciation ,Ecology ,Molecular Sequence Data ,Biodiversity ,Biological Sciences ,Diversification (marketing strategy) ,Biology ,biology.organism_classification ,Biological Evolution ,Time ,Zosterops ,Birds ,Animals ,Biological dispersal ,White-eye ,Clade ,Phylogeny - Abstract
Factors that influence speciation rates among groups of organisms are integral to deciphering macroevolutionary processes; however, they remain poorly understood. Here, we use molecular phylogenetic data and divergence time estimates to reconstruct the pattern and tempo of speciation within a widespread and homogeneous bird family (white-eyes, Zosteropidae) that contains an archetypal “great speciator.” Our analyses show that the majority of this species-rich family constitutes a clade that arose within the last 2 million years, yielding a per-lineage diversification rate among the highest reported for vertebrates (1.95–2.63 species per million years). However, unlike most rapid radiations reported to date, this burst of diversification was not limited in geographic scope, but instead spanned the entire Old World tropics, parts of temperate Asia, and numerous Atlantic, Pacific, and Indian Ocean archipelagos. The tempo and geographic breadth of this rapid radiation defy any single diversification paradigm, but implicate a prominent role for lineage-specific life-history traits (such as rapid evolutionary shifts in dispersal ability) that enabled white-eyes to respond rapidly and persistently to the geographic drivers of diversification.
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- 2009
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13. Break-induced replication: What is it and what is it for?
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Lorraine S. Symington, Catherine E. Smith, and Bertrand Llorente
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DNA Replication ,DNA Repair ,Models, Genetic ,DNA repair ,RAD51 ,Cell Biology ,Biology ,Molecular biology ,Rad52 DNA Repair and Recombination Protein ,Homology directed repair ,Control of chromosome duplication ,Postreplication repair ,Humans ,DNA Breaks, Double-Stranded ,Rad51 Recombinase ,Strand invasion ,Homologous recombination ,Molecular Biology ,Replication protein A ,Developmental Biology - Abstract
Homologous recombination (HR) is considered to be an error-free mechanism for the repair of DNA double-strand breaks (DSBs). Indeed, most DSB repair events occur by a non-crossover mechanism limiting loss of heterozygosity (LOH) for markers downstream of the site of repair and preventing chromosome rearrangements. However, DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). As BIR from one of the two ends of a DSB would result in a long tract of LOH it suggests BIR is suppressed when DSBs have two ends in order for repair to occur by a more conservative HR mechanism. Recent studies showed that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation resulting in chromosome rearrangements when dissociation and reinvasion occur within dispersed repeated sequences. Thus template switching BIR can be highly mutagenic and this process could be important for genome evolution and disease development.
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- 2008
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14. Brief of Amici Curiae Scholars of the Constitutional Rights of Children in Support of Petitioners in Obergefell v. Hodges
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Tanya Washington, Lauren Fontana, Susannah William Pollvogt, and Catherine E. Smith
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Government ,Harm ,Jurisprudence ,Law ,Political science ,Caste ,Control (management) ,Social benefits ,Moral responsibility ,health care economics and organizations ,humanities ,Supreme court - Abstract
Supreme Court precedent establishes that the government may not punish children for matters beyond their control. Same-sex marriage bans and non-recognition laws (“marriage bans”) do precisely this. The states argue that marriage is good for children, yet marriage bans categorically exclude an entire class of children – children of same-sex couples – from the legal, economic and social benefits of marriage. This amicus brief recounts a powerful body of equal protection jurisprudence that prohibits punishing children to reflect moral disapproval of parental conduct or to incentivize adult behavior. We then explain that marriage bans punish children of same-sex couples because they: 1) foreclose their central legal route to family formation; 2) categorically void their existing legal parent-child relationships incident to out-of-state marriages; 3) deny them economic rights and benefits; and 4) inflict psychological and stigmatic harm. States cannot justify marriage bans as good for children and then exclude children of same-sex couples based on moral disapproval of their same-sex parents’ relationships or to incentivize opposite-sex couples to “procreate” within the bounds of marriage. To do so, severs the connection between legal burdens and individual responsibility and creates a permanent class or caste distinction.
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- 2015
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15. Brief for Amici Curiae Scholars of the Constitutional Rights of Children in Support of Respondent Edith Windsor Addressing the Merits and Supporting Affirmance
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Kyle C. Velte, Catherine E. Smith, J. Robert Brown, Tanya Washington, and Susannah William Pollvogt
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Law ,Respondent ,Section (typography) ,Windsor ,Sociology ,humanities - Abstract
This amicus brief filed by Scholars of the Constitutional Rights of Children turns the spotlight on children in same-sex families. The brief enumerates the ways Section 3 of DOMA impairs children's interests by denying federal recognition of their parents' marriages.
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- 2015
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16. New Behavioral, Ecological, and Biogeographic Data On the Montane Avifauna of Kolombangara, Solomon Islands
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Christopher E. Filardi, Catherine E. Smith, Paul R. Sweet, Gerald W. Scoville, Jared M. Diamond, Teu Zinghite, and Brian C. Weeks
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0106 biological sciences ,0301 basic medicine ,Ecology ,biology ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,030104 developmental biology ,Peregrinus ,Geography ,Habitat ,Montane ecology ,Animal Science and Zoology ,Parrotfinch ,Endemism ,Ecology, Evolution, Behavior and Systematics ,Erythrura trichroa - Abstract
— We report new observational and specimen data on the avifauna of Kolombangara, Western Province, Solomon Islands. These data, collected from 3–9 October 1974 and 13–21 May 2004, and supplemented with more recent observations, represent the first comprehensive survey of this globally significant island since 1927. All encounters of montane species are reported along with select species accounts for notable lower-elevation species. Numerous observations presented here suggest avifauna even more unique than previously reported. For example, we confirm a probable resident form of Peregrine Falcon (Falco peregrinus) and report the first observations and collected materials for a Blue-faced Parrotfinch (Erythrura trichroa) from Kolombangara. We observed all of the island's high-elevation endemics and found their relative abundances and patterns of occurrence to be consistent with those of an intact montane avifauna. Our findings suggest that despite large-scale modification of lowland habitat, montan...
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- 2017
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17. Avifauna of a Lowland Forest Site on Isabel, Solomon Islands
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Andrew W. Kratter, David W. Steadman, Catherine E. Smith, Christopher E. Filardi, and Horace P. Webb
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Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics - Abstract
We provide the first comprehensive description of a bird community from a lowland rainforest site on a major island in the Solomon Islands. During two dry season visits (July 1997, June 1998) to the lower Garanga River valley on the island of Isabel, we recorded 65 resident and 6 migrant species of birds. We document relative abundances, habitat preferences, and foraging guilds for the members of the bird community. The Garanga River site sustains all but 11 of the 76 species of landbirds known from Isabel. Of those 11 species, four are small-island or beach specialists, three are montane, and four are of unknown status. Habitat heterogeneity, maintained largely by river dynamics, is a major contributor to avian diversity at the site. The avifauna is dominated by nonpasserines, especially parrots, pigeons, kingfishers, and hawks. The flightless rail Nesoclopeus woodfordi, previously regarded as rare and threatened with extinction, was common. We recorded Ixobrychus flavicollis, Falco severus, and Eudynamys scolopacea for the first time on Isabel. We also documented occurrence in the lowlands of Micropsitta finschii, Collocalia spodiopygia, Coracina caledonica, and Pachycephala pectoralis, four species previously thought to be confined to upper elevations on Isabel. The depauperate understory avifauna of the Garanga River site may be anthropogenic and could belie what otherwise seems to be an intact avifauna.
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- 2001
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18. A Phenotypic Test of Haldane's Rule in an Avian Hybrid Zone
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Catherine E. Smith and Sievert Rohwer
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Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics - Abstract
We introduce a phenotypic method to test for excess mortality in hybrids of the heterogametic sex, as expected from Haldane's rule, and apply this method to the unusually narrow hybrid zones between Hermit Warblers (Dendroica occidentalis) and Townsend's Warblers (D. townsendi) in the Pacific Northwest. Our test requires establishing comparable hybrid indices for male and female warblers. The hybrid index that we developed for females produced age-corrected distributions for phenotypically pure reference samples that closely matched those used by Rohwer and Wood (1998) for males. The similarity in these distributions enabled us to compare the relative frequency of males and females in hybrids and parentals. We detected no deficiency of hybrid females and thus no inviability in the heterogametic sex. Our failure to find evidence of the inviability component of Haldane's rule is not unexpected given the close relationship between these taxa; nonetheless, our methods should be generally useful for studies of hybrid zones.
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- 2000
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19. Reconstitution of long and short patch mismatch repair reactions using Saccharomyces cerevisiae proteins
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Jack D. Griffith, Anjana Srivatsan, Catherine E. Smith, Nikki Bowen, Richard D. Kolodner, and Smaranda Willcox
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congenital, hereditary, and neonatal diseases and abnormalities ,Saccharomyces cerevisiae Proteins ,DNA polymerase ,Eukaryotic DNA replication ,complex mixtures ,DNA Mismatch Repair ,Polymerase Chain Reaction ,Catalysis ,Genomic Instability ,Exonuclease 1 ,Microscopy, Electron, Transmission ,Proliferating Cell Nuclear Antigen ,Replication Protein A ,DNA, Fungal ,Replication protein A ,DNA Polymerase III ,DNA Primers ,MutS Homolog 2 Protein ,Multidisciplinary ,biology ,Biological Sciences ,Molecular biology ,digestive system diseases ,Cell biology ,Proliferating cell nuclear antigen ,Exodeoxyribonucleases ,MSH2 ,Multiprotein Complexes ,biology.protein ,DNA mismatch repair - Abstract
A problem in understanding eukaryotic DNA mismatch repair (MMR) mechanisms is linking insights into MMR mechanisms from genetics and cell-biology studies with those from biochemical studies of MMR proteins and reconstituted MMR reactions. This type of analysis has proven difficult because reconstitution approaches have been most successful for human MMR whereas analysis of MMR in vivo has been most advanced in the yeast Saccharomyces cerevisiae. Here, we describe the reconstitution of MMR reactions using purified S. cerevisiae proteins and mispair-containing DNA substrates. A mixture of MutS homolog 2 (Msh2)–MutS homolog 6, Exonuclease 1, replication protein A, replication factor C-Δ1N, proliferating cell nuclear antigen and DNA polymerase δ was found to repair substrates containing TG, CC, +1 (+T), +2 (+GC), and +4 (+ACGA) mispairs and either a 5′ or 3′ strand interruption with different efficiencies. The Msh2–MutS homolog 3 mispair recognition protein could substitute for the Msh2–Msh6 mispair recognition protein and showed a different specificity of repair of the different mispairs whereas addition of MutL homolog 1–postmeiotic segregation 1 had no affect on MMR. Repair was catalytic, with as many as 11 substrates repaired per molecule of Exo1. Repair of the substrates containing either a 5′ or 3′ strand interruption occurred by mispair binding-dependent 5′ excision and subsequent resynthesis with excision tracts of up to ∼2.9 kb occurring during the repair of the substrate with a 3′ strand interruption. The availability of this reconstituted MMR reaction now makes possible detailed biochemical studies of the wealth of mutations identified that affect S. cerevisiae MMR.
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- 2013
20. Template switching during break-induced replication
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Bertrand Llorente, Catherine E. Smith, and Lorraine S. Symington
- Subjects
Genetics ,DNA Replication ,Recombination, Genetic ,Multidisciplinary ,Models, Genetic ,Fungal genetics ,Chromosome Breakage ,Saccharomyces cerevisiae ,Templates, Genetic ,Biology ,Translocation, Genetic ,Cell biology ,Telomere ,chemistry.chemical_compound ,chemistry ,Homologous chromosome ,DNA Breaks, Double-Stranded ,Gene conversion ,Strand invasion ,Chromosome breakage ,Chromosomes, Fungal ,Homologous recombination ,DNA - Abstract
DNA double-strand breaks (DSBs) are potentially lethal lesions that arise spontaneously during normal cellular metabolism, as a consequence of environmental genotoxins or radiation, or during programmed recombination processes. Repair of DSBs by homologous recombination generally occurs by gene conversion resulting from transfer of information from an intact donor duplex to both ends of the break site of the broken chromosome. In mitotic cells, gene conversion is rarely associated with reciprocal exchange and thus limits loss of heterozygosity for markers downstream of the site of repair and restricts potentially deleterious chromosome rearrangements. DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). BIR from one of the two ends of a DSB would result in loss of heterozygosity, suggesting that BIR is suppressed when DSBs have two ends so that repair occurs by the more conservative gene conversion mechanism. Here we show that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation. We further show that chromosome rearrangements can occur during BIR if dissociation and reinvasion occur within dispersed repeated sequences. This dynamic process could function to promote gene conversion by capture of the displaced invading strand at two-ended DSBs to prevent BIR.
- Published
- 2007
21. Molecular phylogenetics of monarch flycatchers (genus Monarcha) with emphasis on Solomon Island endemics
- Author
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Christopher E. Filardi and Catherine E. Smith
- Subjects
Paraphyly ,Molecular Sequence Data ,Zoology ,Biology ,DNA, Mitochondrial ,Monophyly ,Genus ,Polyphyly ,Genetics ,Animals ,Passeriformes ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,DNA Primers ,Demography ,Likelihood Functions ,Base Sequence ,Models, Genetic ,Island monarch ,Sequence Analysis, DNA ,Monarcha ,biology.organism_classification ,Taxon ,Molecular phylogenetics ,Melanesia - Abstract
Systematic relationships among monarch flycatchers (genus Monarcha) are poorly understood despite dramatic patterns of morphological differentiation that have long attracted the attention of evolutionary biologists. With sequence data from the mitochondrial ND2 gene and Control Region, we produced a phylogenetic hypothesis for evolutionary relationships within Monarcha and among the biogeographically complex Solomon Island endemics. Outgroup analyses contradicted monophyly of the genus by imbedding a representative of the genus Clytorhynchus within one of two major clades recovered within Monarcha. These two monarch clades generally correspond with ecological and morphological distinctions, suggesting the genus may warrant revision pending the inclusion of taxa currently allied with Clytorhynchus (e.g., Neolalage spp.). Maximum likelihood reconstructions support monophyletic groupings of the two endemic Solomon Island monarch radiations, however, two currently recognized superspecies (Monarcha manadensis and M. melanopsis) were polyphyletic and paraphyletic, respectively. Interestingly, molecular and morphological differentiation were strikingly decoupled among several Solomon Island endemics and between migratory and non-migratory forms of Monarcha trivirgatus in eastern Australia, suggesting morphological evolution has masked the true history of speciation in these groups. This initial phylogeny provides a novel platform for ongoing exploration of the history underlying dramatic patterns of geographic variation among tropical Pacific flycatchers.
- Published
- 2005
22. Polarized bidirectional reflectance from leaves in the visible and infrared
- Author
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David L. Jordan, Catherine E. Smith, and Peter N. Raven
- Subjects
Brewster's angle ,Materials science ,business.industry ,Scattering ,Infrared ,Polarimetry ,Gloss (optics) ,symbols.namesake ,Optics ,symbols ,Stokes parameters ,Diffuse reflection ,Bidirectional reflectance distribution function ,business ,Remote sensing - Abstract
The incorporation of polarisation sensitive optics offers considerable potential for improving the utility of remote sensing imaging systems operating within the visible or infrared wavebands. Systems now exist allowing measurement of the four components of Stokes vector arising from each pixel in the image. In order to develop the interpretation of polarimetric images, knowledge is required of the polarised directional reflectance properties of the materials in the scene, which determine the radiation reaching the sensor. Natural vegetation forms a significant element of many scenes observed with remote sensing systems. Although the size of a leaf may be below the spatial resolution of a system, the reflectance properties of individual leaves will affect the polarimetric data observed. This paper will report the results of measurements of the linear polarised bidirectional reflectance distribution function (BRDF) from two examples of leaves. The polarimetric properties of the directional reflectance from an individual leaf will depend on the surface and volume scattering properties. We report data on two leaves representing extreme cases of the leaf structure. Laurel (prunus laurecatious) has a nacreous surface creating a gloss finish to the leaf. Mullein (verbascum thapsus) has a highly pubescent surface, creating a highly diffuse surface reflectance. Measurements of the linear polarisation BRDF are reported at 632.8nm, 1064nm, 3.39pm and 10.6µm as a function of the polar scatter angles. These wavelengths characterise the polarised reflectance from the leaves under different conditions of absorption and scattering. In both cases the body of the leaf acts a highly diffuse reflector through multiple scattering, but this mechanism is only important when the absorption by the leaf constituents is low. In the spectral regions of moderate and high absorption the surface reflectance dominates. In the case of laurel the surface is relatively smooth, with an associated Brewster angle, whereas the data suggests the layer of hair covering a mullein leaf acts as an array of scattering sources.
- Published
- 2000
- Full Text
- View/download PDF
23. Need for an international legislation on space debris
- Author
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Catherine E. Smith
- Subjects
education.field_of_study ,media_common.quotation_subject ,Liability ,Population ,Outer space ,Legislation ,Space (commercial competition) ,Convention ,Geography ,Law ,education ,Outer Space Treaty ,media_common ,Space debris - Abstract
Since the launch of the first Sputnik in 1957, the number of space debris in orbit is progressively increasing, up to a point that is today considered serious. Scientists quickly became aware of this phenomena and started studying the evolution, mitigation, and characterization of space debris. But jurists are today confronted with a situation that the United Nations Outer Space Treaties did not foresee. The purpose of the presentation is to look at the existing international public law and examine how it may help to characterize and/or mitigate the space debris population. After having briefly described the problem caused by space debris, the first part will study the United Nations Space Treaties and in particular the principles of responsibility and liability as laid down in the 1967 Outer Space Treaty and the 1972 Liability Convention, which should allow us to conclude that there is an urgent need for a new international convention of space debris. The second part will then focus on the several proposals made concerning space debris and will lay down a set of general principles of the legislation on space debris.
- Published
- 1995
- Full Text
- View/download PDF
24. Polarized directional reflectance from laurel and mullein leaves
- Author
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David L. Jordan, Peter N. Raven, and Catherine E. Smith
- Subjects
Physics ,Tree canopy ,biology ,business.industry ,General Engineering ,Polarimetry ,biology.organism_classification ,Gloss (optics) ,Atomic and Molecular Physics, and Optics ,symbols.namesake ,Optics ,Verbascum thapsus ,Leaf angle distribution ,symbols ,Emissivity ,Stokes parameters ,Bidirectional reflectance distribution function ,business ,Remote sensing - Abstract
The ability to perform polarimetric imaging throughout the vis- ible and infrared (IR) wavebands has improved considerably in the past decade. Systems now exist that enable measurements to be made of all four Stokes parameters arising from each pixel in the image. The ques- tion of whether polarimetric imaging offers an advantage over conven- tional imaging methods for discrimination of plant type in scenes of natu- ral vegetation remains to be answered. Although the size of a leaf may be below the spatial resolution of an imaging system, the polarimetric properties of individual leaves may affect the data observed from a tree or forest canopy. We report the results of measurements of the polarized hemispherical directional reflectance (HDR), which is related to the di- rectional emissivity, and bidirectional reflectance distribution function (BRDF) from two examples of leaves. To completely characterize the polarimetric properties of a leaf, and ultimately a leaf canopy, an exten- sive measurement of the polarized BRDF and HDR of individual leaves is required. This is necessary because of the large range of possible relative orientations of the illumination, leaf and observer, and the range of polarization states of incident radiation. We report a limited set of laboratory measurements designed to investigate whether any gross po- larimetric difference exist between two dissimilar types of plant leaves in the visible, near IR (NIR), and IR spectral wavebands. Laurel (prunus laurecatious) has a wax surface creating a gloss or glabrous appearance to the leaf. The surface of mullein (verbascum thapsus) is highly pubes- cent with a dense layer of hair over the adaxial surface, creating a highly diffuse surface reflectance. Significant differences are found between the two species of leaf in the measured polarized directional reflectance and emissivity. © 2002 Society of Photo-Optical Instrumentation Engineers.
- Published
- 2002
- Full Text
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25. Visualization of Eukaryotic DNA Mismatch Repair Reveals Distinct Recognition and Repair Intermediates
- Author
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Arshad Desai, Hans Hombauer, Richard D. Kolodner, Christopher S. Campbell, and Catherine E. Smith
- Subjects
DNA Replication ,congenital, hereditary, and neonatal diseases and abnormalities ,Eukaryotic DNA replication ,Saccharomyces cerevisiae ,Biology ,DNA Mismatch Repair ,DNA polymerase delta ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Replication factor C ,Control of chromosome duplication ,Proliferating Cell Nuclear Antigen ,MutS-1 ,Animals ,Humans ,Replication protein A ,neoplasms ,030304 developmental biology ,0303 health sciences ,Biochemistry, Genetics and Molecular Biology(all) ,nutritional and metabolic diseases ,Molecular biology ,digestive system diseases ,DNA-Binding Proteins ,DNA Repair Enzymes ,Exodeoxyribonucleases ,MutS Homolog 2 Protein ,030220 oncology & carcinogenesis ,Origin recognition complex ,DNA mismatch repair - Abstract
SummaryDNA mismatch repair (MMR) increases replication fidelity by eliminating mispaired bases resulting from replication errors. In Saccharomyces cerevisiae, mispairs are primarily detected by the Msh2-Msh6 complex and corrected following recruitment of the Mlh1-Pms1 complex. Here, we visualized functional fluorescent versions of Msh2-Msh6 and Mlh1-Pms1 in living cells. We found that the Msh2-Msh6 complex is an S phase component of replication centers independent of mispaired bases; this localized pool accounted for 10%–15% of MMR in wild-type cells but was essential for MMR in the absence of Exo1. Unexpectedly, Mlh1-Pms1 formed nuclear foci that, although dependent on Msh2-Msh6 for formation, rarely colocalized with Msh2-Msh6 replication-associated foci. Mlh1-Pms1 foci increased when the number of mispaired bases was increased; in contrast, Msh2-Msh6 foci were unaffected. These findings suggest the presence of replication machinery-coupled and -independent pathways for mispair recognition by Msh2-Msh6, which direct formation of superstoichiometric Mlh1-Pms1 foci that represent sites of active MMR.
- Full Text
- View/download PDF
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