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380 The kinesin-like protein Kif11 is essential for the survival of TP53 mutant triple-negative breast cancer cells
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- Amanda Lanier, William Tahaney, Abhijit Mazumdar, Powel Brown
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 112-113
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OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.
Influence of environmental conditions and facility on faecal glucocorticoid concentrations in captive pygmy rabbits (Brachylagus idahoensis)
- CD Scarlata, BA Elias, JR Godwin, RA Powell, D Shepherdson, LA Shipley, JL Brown
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- Animal Welfare / Volume 22 / Issue 3 / August 2013
- Published online by Cambridge University Press:
- 01 January 2023, pp. 357-368
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The objective of this study was to determine if housing conditions, specifically pen size and soil enrichment, had an effect on faecal glucocorticoid concentrations in the endangered pygmy rabbit (Brachylagus idahoensis). The success of the captive breeding programme has been limited, so one hypothesis is that chronic stress due to sub-optimal housing conditions may be responsible for poor fecundity. Faecal glucocorticoid concentrations were assessed in 50 females housed among several pen types at two breeding facilities. The highest glucocorticoid concentrations were found in females housed in 0.37 m2 crates as compared to enclosures ranging from 0.96 to 75 m2 in size. Results also indicated that enrichment of enclosures with soil had a significant influence on adrenal activity, based on a reduction in glucocorticoid excretion for females moved from non-soil pens to those with soil. Last, a significant facility effect on glucocorticoid concentrations was observed, suggesting that factors other than housing influenced adrenal activity in these rabbits. In conclusion, based on measurements of faecal glucocorticoids, pygmy rabbits are best managed in enclosures that contain soil for digging burrows. Pen size had little effect on stress hormones, except for crates where limited space and/or absence of soil was associated with higher glucocorticoid concentrations. These results underline the importance of monitoring glucocorticoid concentrations in captive breeding programmes to identify optimal husbandry and management practices.
Neutron Star Extreme Matter Observatory: A kilohertz-band gravitational-wave detector in the global network
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- K. Ackley, V. B. Adya, P. Agrawal, P. Altin, G. Ashton, M. Bailes, E. Baltinas, A. Barbuio, D. Beniwal, C. Blair, D. Blair, G. N. Bolingbroke, V. Bossilkov, S. Shachar Boublil, D. D. Brown, B. J. Burridge, J. Calderon Bustillo, J. Cameron, H. Tuong Cao, J. B. Carlin, S. Chang, P. Charlton, C. Chatterjee, D. Chattopadhyay, X. Chen, J. Chi, J. Chow, Q. Chu, A. Ciobanu, T. Clarke, P. Clearwater, J. Cooke, D. Coward, H. Crisp, R. J. Dattatri, A. T. Deller, D. A. Dobie, L. Dunn, P. J. Easter, J. Eichholz, R. Evans, C. Flynn, G. Foran, P. Forsyth, Y. Gai, S. Galaudage, D. K. Galloway, B. Gendre, B. Goncharov, S. Goode, D. Gozzard, B. Grace, A. W. Graham, A. Heger, F. Hernandez Vivanco, R. Hirai, N. A. Holland, Z. J. Holmes, E. Howard, E. Howell, G. Howitt, M. T. Hübner, J. Hurley, C. Ingram, V. Jaberian Hamedan, K. Jenner, L. Ju, D. P. Kapasi, T. Kaur, N. Kijbunchoo, M. Kovalam, R. Kumar Choudhary, P. D. Lasky, M. Y. M. Lau, J. Leung, J. Liu, K. Loh, A. Mailvagan, I. Mandel, J. J. McCann, D. E. McClelland, K. McKenzie, D. McManus, T. McRae, A. Melatos, P. Meyers, H. Middleton, M. T. Miles, M. Millhouse, Y. Lun Mong, B. Mueller, J. Munch, J. Musiov, S. Muusse, R. S. Nathan, Y. Naveh, C. Neijssel, B. Neil, S. W. S. Ng, V. Oloworaran, D. J. Ottaway, M. Page, J. Pan, M. Pathak, E. Payne, J. Powell, J. Pritchard, E. Puckridge, A. Raidani, V. Rallabhandi, D. Reardon, J. A. Riley, L. Roberts, I. M. Romero-Shaw, T. J. Roocke, G. Rowell, N. Sahu, N. Sarin, L. Sarre, H. Sattari, M. Schiworski, S. M. Scott, R. Sengar, D. Shaddock, R. Shannon, J. SHI, P. Sibley, B. J. J. Slagmolen, T. Slaven-Blair, R. J. E. Smith, J. Spollard, L. Steed, L. Strang, H. Sun, A. Sunderland, S. Suvorova, C. Talbot, E. Thrane, D. Töyrä, P. Trahanas, A. Vajpeyi, J. V. van Heijningen, A. F. Vargas, P. J. Veitch, A. Vigna-Gomez, A. Wade, K. Walker, Z. Wang, R. L. Ward, K. Ward, S. Webb, L. Wen, K. Wette, R. Wilcox, J. Winterflood, C. Wolf, B. Wu, M. Jet Yap, Z. You, H. Yu, J. Zhang, J. Zhang, C. Zhao, X. Zhu
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- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 05 November 2020, e047
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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Septic Shock: A Genomewide Association Study and Polygenic Risk Score Analysis
- Shannon D’Urso, Dorrilyn Rajbhandari, Elizabeth Peach, Erika de Guzman, Qiang Li, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, CHARGE Inflammation Working Group, Symen Ligthart, Matthew A. Brown, Joseph Powell, Colin McArthur, Andrew Rhodes, Jason Meyer, Simon Finfer, John Myburgh, Antje Blumenthal, Jeremy Cohen, Balasubramanian Venkatesh, Gabriel Cuellar-Partida, David M. Evans
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- Journal:
- Twin Research and Human Genetics / Volume 23 / Issue 4 / August 2020
- Published online by Cambridge University Press:
- 05 August 2020, pp. 204-213
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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Development of materials to support parents whose babies cry excessively: findings and health service implications
- Jaqui Long, Charlotte Powell, Deborah Bamber, Rosemary Garratt, Jayne Brown, Sue Dyson, Ian St James-Roberts
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- Journal:
- Primary Health Care Research & Development / Volume 19 / Issue 4 / July 2018
- Published online by Cambridge University Press:
- 10 January 2018, pp. 320-332
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Aim
To develop evidence-based materials which provide information and support for parents who are concerned about their baby’s excessive crying. As well as meeting these parents’ needs, the aim was to develop a package of materials suitable for use by the UK National Health Service (NHS).
BackgroundParents report that around 20% of infants in Western countries cry excessively without an apparent reason during the first four months of age. Traditionally, research has focused on the crying and its causes. However, evidence is growing that how parents evaluate and respond to the crying needs to receive equal attention. This focus encompasses parental resources, vulnerabilities, well-being and mental health. At present, the UK NHS lacks a set of routine provisions to support parents who are concerned about their baby’s excessive crying. The rationales, methods and findings from a study developing materials for this purpose are reported.
MethodFollowing a literature review, 20 parents whose babies previously cried excessively took part in focus groups or interviews. They provided reports on their experiences and the supports they would have liked when their baby was crying excessively. In addition, they identified their preferred delivery methods and devices for accessing information and rated four example support packages identified by the literature review.
FindingsDuring the period their baby cried excessively, most parents visited a health service professional and most considered these direct contacts to have provided helpful information and support. Websites were similarly popular. Telephones and tablets were the preferred means of accessing online information. Groups to meet other parents were considered an important additional resource by all the parents. Three package elements – a Surviving Crying website, a printed version of the website and a programme of Cognitive Behaviour Therapy-based support sessions delivered to parents by a qualified practitioner, were developed for further evaluation.
DNA evidence for multiple introductions of barley into Europe following dispersed domestications in Western Asia
- G. Jones, M.P. Charles, M.K. Jones, S. Colledge, F.J. Leigh, D.A. Lister, L.M.J. Smith, W. Powell, T.A. Brown, H. Jones
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It has long been recognised that the Neolithic spread across Europe via two separate routes, one along the Mediterranean coasts, the other following the axis of the major rivers. But did these two streams have a common point of origin in south-west Asia, at least with regard to the principal plant and animals species that were involved? This study of barley DNA shows that the domesticated barley grown in Neolithic Europe falls into three separate types (groups A, B and C), each of which may have had a separate centre of origin in south-west Asia. Barley was relatively rarely cultivated by the early Linearbandkeramik farmers of Central and Northern Europe, but became more common during the fifth and fourth millennia BC. The analysis reported here indicates that a genetic variety of barley more suitable for northern growing conditions was introduced from south-west Asia at this period. It also suggests that the barley grown in south-eastern Europe at the very beginning of the Neolithic may have arrived there by different routes from two separate centres of domestication in south-west Asia. The multiple domestications that this pattern reveals imply that domestication may have been more a co-evolutionary process between plants and people than an intentional human action.
Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
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- By Joanne R. Adler, David A. Alexander, Laurence Alison, Catherine C. Ayoub, Peter Banister, Anthony R. Beech, Amanda Biggs, Julian Boon, Adrian Bowers, Neil Brewer, Eric Broekaert, Paula Brough, Jennifer M. Brown, Kevin Browne, Elizabeth A. Campbell, David Canter, Michael Carlin, Shihning Chou, Martin A. Conway, Claire Cooke, David Cooke, Ilse Derluyn, Robert J. Edelmann, Vincent Egan, Tom Ellis, Marie Eyre, David P. Farrington, Seena Fazel, Daniel B. Fishman, Victoria Follette, Katarina Fritzon, Elizabeth Gilchrist, Nathan D. Gillard, Renée Gobeil, Agnieszka Golec de Zavala, Jane Goodman-Delahunty, Lynsey Gozna, Don Grubin, Gisli H. Gudjonsson, Helinä Häkkänen-Nyholm, Guy Hall, Nathan Hall, Roisin Hall, Sean Hammond, Leigh Harkins, Grant T. Harris, Camilla Herbert, Robert D. Hoge, Todd E. Hogue, Clive R. Hollin, Lorraine Hope, Miranda A. H. Horvath, Kevin Howells, Carol A. Ireland, Jane L. Ireland, Mark Kebbell, Michael King, Bruce D. Kirkcaldy, Heidi La Bash, Cara Laney, William R. Lindsay, Elizabeth F. Loftus, L. E. Marshall, W. L. Marshall, James McGuire, Neil McKeganey, T. M. McMillan, Mary McMurran, Joav Merrick, Becky Milne, Joanne M. Nadkarni, Claire Nee, M. D. O’Brien, William O’Donohue, Darragh O’Neill, Jane Palmer, Adria Pearson, Derek Perkins, Devon L. L. Polaschek, Louise E. Porter, Charlotte C. Powell, Graham E. Powell, Martine Powell, Christine Puckering, Ethel Quayle, Vernon L. Quinsey, Marnie E. Rice, Randall Richardson-Vejlgaard, Richard Rogers, Louis B Schlesinger, Carolyn Semmler, G. A. Serran, Ralph C. Serin, John L. Taylor, Max Taylor, Brian Thomas-Peter, Paul A. Tiffin, Graham Towl, Rosie Travers, Arlene Vetere, Graham Wagstaff, Helen Wakeling, Fiona Warren, Brandon C. Welsh, David Wexler, Margaret Wilson, Dan Yarmey, Susan Young
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2 - The rice blast story: from genome sequence to function
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- By R. A. Dean, Center for Integrated Fungal Research Department of Plant Pathology 1200 Partners Building II Box 7251 North Carolina State University Raleigh NC 27695 USA, T. Mitchell, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, R. Kulkarni, RTI 3040 Cornwallis Road Research Triangle Park NC 27709 USA, N. Donofrio, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, A. Powell, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, Y. Y. Oh, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, S. Diener, North Carolina State University Department of Plant Pathology Campus Box 7253 Raleigh NC 27695–7253 USA, H. Pan, RTI 3040 Cornwallis Road Research Triangle Park NC 27709 USA, D. Brown, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, J. Deng, North Carolina State University Department of Plant Pathology Campus Box 7251 Raleigh NC 27695–7251 USA, I. Carbone, North Carolina State University Department of Plant Pathology Campus Box 7244 Raleigh NC 27695–7244 USA, D. J. Ebbole, Department of Plant Pathology and Microbiology Peterson Building Rm 120 MS# 2132 Texas A&M University College Station TX 77843–2132 USA, M. Thon, Department of Computer Science 320C Peterson Building MS# 2132 Texas A&M University College Station TX 77843–2132 USA, M. L. Farman, Department of Plant Pathology University of Kentucky 1405 Veterans Drive Lexington KY 40546–0312 USA, M. J. Orbach, Department of Plant Pathology University of Arizona Forbes Room 105 PO Box 210036 Tucson AZ 85721–0036 USA, C. Soderlund, Director of Bioinformatics Department of Plant Science 303 Forbes Building Tucson AZ 85721 USA, J-R. Xu, Department of Botany and Plant Pathology 915 West State Street Purdue University West Lafayette IN 47906 USA, Y-H. Lee, Seoul National University School of Agricultural Biotechnology Suwon 441–744 Korea, N. J. Talbot, Department of Biological Sciences University of Exeter Hatherly Laboratories Prince of Wales Road Exeter EX4 4PS UK, S. Coughlan, Agilent Technologies Inc. Little Falls Site 2850 Centerville Road Wilmington DE 19808 USA, J. E. Galagan, The Broad Institute Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139–4307 USA, B. W. Birren, The Broad Institute Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139–4307 USA
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Summary
Introduction
Rice blast disease, caused by the filamentous fungus Magnaporthe grisea, is a serious and recurrent problem in all rice-growing regions of the world (Talbot, 2003; Valent & Chumley, 1991). It is estimated that each year enough rice is destroyed by rice blast disease to feed 60 million people. Control of this disease is difficult; new host-specific forms develop quickly to overcome host resistance and chemical control is typically not cost effective (Ou, 1987). Infections occur when fungal spores land and attach themselves to leaves using a special adhesive released from the tip of each spore (Hamer et al., 1988). The germinating spore develops an appressorium, a specialized infection cell, which generates enormous turgor pressure – up to 8 MPa – that ruptures the leaf cuticle allowing invasion of the underlying leaf tissue (de Jong et al., 1997; Dean, 1997). Subsequent colonization of the leaf produces disease lesions from which the fungus sporulates and spreads to new plants. When rice blast infects young rice seedlings, whole plants often die, while spread of the disease to the stems, nodes or panicle of older plants results in nearly total loss of the rice grain. Recent reports have further shown that the fungus has the capacity to infect plant roots (Sesma & Osbourn, 2004). Different host-limited forms of Magnaporthe also infect a broad range of grass species including wheat, barley and millet.
TEM and STEM Studies of the Atomic Structure and Chemistry of Ferritin in Human Liver Biopsies
- Y Pan, A Brown, R Brydson, A Warley, A Li, J Powell, A Bleloch, U Falke, M Falke
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Extended abstract of a paper presented at Microscopy and Microanalysis 2005 in Honolulu, Hawaii, USA, July 31--August 4, 2005
2 - The regulatory environment
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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- Serious Money
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- 27 August 2009
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- 29 September 1995, pp 14-29
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Summary
The strategic calculations of political campaigns logically begin with the rules of play. In the case of presidential nomination campaigns, those rules are set by national parties, state legislatures, Congress, and the Supreme Court. These four noncoordinated rule-making bodies have produced a complex and evolving strategic environment characterized in recent election cycles by many primary contests, ever-changing regulations for selecting delegates, and an increasingly front-loaded event calendar. An important and relatively stable part of this strategic environment has been the congressionally and judicially mandated set of rules governing nomination campaign finance.
These finance rules have been in place since 1976 and fully implemented in four election cycles, starting in 1980. They limit the amount of money individuals can give to candidates and the amount candidates can spend nationally and in each state. They also provide matching funds for individual contributions, which enhances the ability of candidates to raise large sums from many small donations. This legal framework thus creates a regulatory structure within which the strategic calculations of nomination campaigns must be made. It also creates the environment in which individual decisions to contribute are taken. In doing so, it strongly influences the interactions between the campaigns and those individuals who may wish to participate. This chapter explores the impact of these rules on presidential nomination finance.
The regulation of contributions: FECA
In 1971 Congress passed the Federal Election Campaign Act (FECA), which provided for the disclosure of contributions and expenditures in the quest for national office.
Acknowledgments
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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3 - The contributor pool
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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Summary
Most donors of serious money to presidential nomination candidates come from an established pool of habitual givers, not from a body of mostly first-time contributors assembled on an ad hoc basis by different candidates each election cycle. As we saw in the preceding chapter, the size of the pool has generally grown election by election since the inception of the FECA rules. Yet even though there is defection from and especially recruitment to this pool, at any point in time the great majority of those who give serious money have contributed before and will do so again, though not necessarily in every election. In 1988, for example, 83% reported that they had contributed previously to a presidential candidate; 95% said they had previously made a political contribution of some kind.
This should not be surprising, since those who are motivated to contribute in one election will probably be motivated to do so the next time. All potential contributors must weigh the opportunity costs of making a cash contribution against an array of political, social, or material benefits that such a contribution might produce. Those who decided in the past that the benefits of contributing outweighed the costs are more likely to make a similar decision in the future than those who decided not to contribute in the past, or those who simply never considered doing so. Thus those who have a propensity to contribute in one election will probably have a propensity to do so next time.
Furthermore, such people are given every opportunity to act on their propensities and remain in the pool.
List of figures and tables
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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Index
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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- Serious Money
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- 29 September 1995, pp 181-184
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6 - Recruiting contributors and solicitors: Candidate and individual decisions
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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Summary
We have shown that there exists a relatively constant pool of campaign contributors with a heterogeneous set of motives that are approached by candidates either through personal networks or through mail and telemarketing. Although campaigns often seek to expand the pool of contributors by attracting new members, two of the most basic decisions by campaign strategists are which segments of the existing pool to target and how to target them. Individual contributors must then decide whether or not to respond to a solicitation by a campaign. In addition, when campaigns employ personal networking, they must develop a strategy to identify which of their contributors will be asked to solicit others to give. Those asked to solicit must in turn decide whether or not to invest the time, energy, and social capital to do so.
Our panel study of 1988 and 1992 contributors enables us to examine these series of decisions by campaigns, contributors, and potential solicitors. The 1988 data consisted entirely of people who were asked to give and who gave, so we cannot compare them to those members of the pool who were not asked or who were asked but chose not to give in 1988. Thus, using the 1988 data alone we cannot examine campaign decisions about whom to solicit, or contributor decisions about whether to contribute. The 1992 survey asked the 1988 contributors whether they were asked to give in 1992, whether they gave, whether they were asked to solicit others to give, and whether they did solicit. The panel study therefore allows us to examine the decision calculus of candidates and potential contributors, which cross-sectional studies cannot do.
Bibliography
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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- 29 September 1995, pp 171-180
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1 - Introduction
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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Summary
Robert Farmer, a major fundraiser for both Michael Dukakis and Bill Clinton, offered this blunt assessment of Paul Tsongas's decision to quit the 1992 presidential race: “People don't lose campaigns. They run out of money and can't get their planes in the air. That's the reality” (Congressional Quarterly Weekly Report, 1992). Although Tsongas himself may have had several reasons for dropping out, he highlighted finance as one of them: “If you have no resources to fight back with, you are defenseless in this business. … Michael Dukakis had the most money and could take out Dick Gephardt and everybody else, and Bill Clinton basically did the same thing” (“MacNeil/Lehrer Newshour” 1992).
There can be little doubt that money is important: in seven of the eight major-party presidential nomination contests that took place since the current financial rules of engagement went into effect in 1980, the eventual winner had the largest amount of cash in the bank on January 1 when the process started in earnest. Caution, of course, is warranted in assuming a causal connection here. Those who have the most cash reserves at the start of the process (or who eventually raise the most money) do so for a reason, and the political resources that enable candidates to win the nomination may also be those resources that enable them to raise large amounts of money and raise them early. Attractive, viable candidates tend to receive more money as well as more votes.
It is also wrong to assume that just because a candidate raises a lot of money he or she will do well.
Contents
- Clifford W. Brown, Union College, Rhode Island, Lynda W. Powell, University of Rochester, New York, Clyde Wilcox, Georgetown University, Washington DC
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- Serious Money
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