275 results on '"McDonnell, E."'
Search Results
52. A perfect square root routine.
- Author
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McDonnell, E. E.
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- 1986
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53. A notation for the GCD and LCM functions.
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McDonnell, E. E.
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- 1975
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54. APL\?
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Hui, Roger K. W., primary, Iverson, Kenneth E., additional, McDonnell, E. E., additional, and Whitney, Arthur T., additional
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- 1990
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55. Development and delivery of a nutrition education course with an electronic mail component.
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McDonnell E and Achterberg C
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- 1997
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56. Evaluation of implementation of an interdisciplinary nutrition curriculum in middle schools.
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Probart C, McDonnell E, Achterberg C, and Anger S
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- 1997
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57. Phrasal forms.
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McDonnell, E. E. and Iverson, K. E.
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- 1989
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58. Trees with the same degree sequence and path numbers
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Gordon, G. and McDonnell, E.
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- 1995
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59. Skeletal muscle analysis of wheelchair athletes
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Taylor, A W, McDonnell, E, Royer, D, Loiselle, R, Lush, N, and Steadward, R
- Abstract
The present study reports the results of using the biopsy technique with members of the Canadian Wheelchair International Team. The results demonstrate that these athletes possess muscles with larger fibre areas than seen in Olympic athletes.
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- 1979
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60. 8 ways to prosper in 1992.
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McDonnell, E. and McIver, R.
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PERSONAL finance - Abstract
Details eight steps people can take to build up their family's economic security in the 1990s. Includes cutting credit card spending, calculating annual cost of living, and liquidating loans. Examples; Ways to save.
- Published
- 1992
61. Minnowbrook APL workshop.
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Pesch, R H, McDonnell, E E, Iverson, K E, Bernecky, B, and Allen, D B
- Published
- 1986
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62. An implementation of complex APL.
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McDonnell, E. E.
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- 1981
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63. The socio-technical beginnings of APL.
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McDonnell, E. E.
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- 1979
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64. Soft drink advertising in high schools
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Probart, C., McDonnell, E., and Bailey-Davis, L.
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Soft drink industry -- Target marketing -- Health aspects ,Advertising -- Health aspects ,Children -- Target marketing -- Health aspects ,Food/cooking/nutrition ,Target marketing ,Health aspects - Abstract
Health professionals are concerned about the practice of advertising targeted at children because of children's inability to critically evaluate advertisements. Particular attention and criticism is being focused on exposure of [...]
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- 2007
65. Readers Report.
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Barbee, Scott L., McDonnell, E., Englund, Richard T., McCain, Joseph E., Wetor, Paul J., Hoff, Elizabeth, Bedingfield, Ray, Ehrlich, Everett M., Phillips, John Aristotle, and Fields, Jack
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LETTERS to the editor ,UNITED States economy ,NEW business enterprises - Abstract
Several letters to the editor are presented in response to articles in the January 1996 issue including "How not to measure the U.S. economy" in the January 15 issue, "The press of new business" in The Corporation section of the January 15 issue, and "Arthur Levitt speaks softly and carries a little stick" in the Washington Outlook section of the January 8 issue.
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- 1996
66. RAIN REPELLENT
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SNELL (FOSTER D) INC NEW YORK, Swindell, E., McDonnell, E., Fain, J. Mitchell, SNELL (FOSTER D) INC NEW YORK, Swindell, E., McDonnell, E., and Fain, J. Mitchell
- Abstract
A rain repellent Formula 2911K-394, was developed, and is packaged in aerosol containers. Spraying of the repellent into the windstream hitting the windshield under rain conditions forms a coating which provides visibility. Application of the repellent to a dry panel and treatment with a solution of p- toluene sulfonic acid in alcohol results in a film having good life when subjected to rain spray and resistance to both jet fuel and isopropyl alcohol. The use of 10 centistoke methyl silicone oil, as contained in Formula 2911K-394, produces a film having improved resistance to jet fuel.
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- 1963
67. RAIN REPELLENT.
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SNELL (FOSTER D) INC NEW YORK, Miglas,W., McDonnell,E., Fain,J. Mitchell, SNELL (FOSTER D) INC NEW YORK, Miglas,W., McDonnell,E., and Fain,J. Mitchell
- Abstract
A reaction mechanism is provided for formation and utilization of silicone-titanium copolymer H. The use of heated air on the rain spray apparatus did not result in increased durability of formulations containing silicone-titanium copolymer H. A new rain spray apparatus is under construction which is designed to deliver a more uniform rain spray and allow the use of larger test panels. In the preparation of silicone-zirconium copolymers reaction at a temperature of 138-140 C. results in a clear liquid yielding a dry, waxy film, whereas reaction at 105 C. results in a cloudy liquid giving a soft and tacky film. (Author)
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- 1964
68. RAIN REPELLENT
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SNELL (FOSTER D) INC NEW YORK, FRIEDMAN,M., MCDONNELL,E., FAIN,J. MITCHELL, SNELL (FOSTER D) INC NEW YORK, FRIEDMAN,M., MCDONNELL,E., and FAIN,J. MITCHELL
- Abstract
The rin spray apparatus ws modified to permit evaluation of rain repellent formulations applied during rain conditions. Means were provided to deliver the rain s ray and the spray of the repellent solutions simultaneously. The use of surfactans incorporated in acidified dimethyldiethoxysilane did not improve repellency during rain conditions. The use of Ti in ester form alone and in conjunction with slane and silicones makes possble the formation of coaings on glass under ain conditions which permit visibility, but have shot life. (Author)
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- 1962
69. RAIN REPELLENT
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SNELL (FOSTER D) INC NEW YORK, BLAUFOX,R., MCDONNELL,E., FAIN,J. MITCHELL, SNELL (FOSTER D) INC NEW YORK, BLAUFOX,R., MCDONNELL,E., and FAIN,J. MITCHELL
- Abstract
A high wind speed rain spray tester was constructed to replace the AN-R-24 rain spray test apparatus used in previous work. The durability of a number of rain repellent formulations whose life on the AN-R-24 test apparatus had been determined was evaluated on the new machine. Investigation of the action of colloidal silica and other finely divided powders in combination with silicone oils resulted in formulations which show improved repellency particularly after exposure to heat. (Author)
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- 1960
70. RAIN REPELLENT
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SNELL (FOSTER D) INC NEW YORK, BLAUFOX,R., MCDONNELL,E., FAIN,J. MITCHELL, SNELL (FOSTER D) INC NEW YORK, BLAUFOX,R., MCDONNELL,E., and FAIN,J. MITCHELL
- Abstract
A formulation based on acidified dimethyldiethoxysilane dissolved in n-hexyl ether and combined with silicone oil has good rain repellent properties and an increased flash point. Its proper utilization in an aerosol package requires further investigation. A formulation based on acidified dimethyldiethoxysilane is stable to temperatures of -10 and 160 F. It withstands temper tures of -65 and 500 F after application. Its films are resistant to isopropyl alcohol. (Author)
- Published
- 1961
71. Full-scale shake table test of mass-timber building with resilient post-tensioned rocking walls
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Pei, S., Lindt, J. W., Andre Barbosa, Berman, J., Mcdonnell, E., Dolan, J. D., Zimmerman, R. B., Sause, R., Ricles, J., and Ryan, K.
72. Numerical modeling of CLT diaphragms tested on a shake-table experiment
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Barbosa, A. R., Rodrigues, L., Sinha, A., Higgins, C., Zimmerman, R. B., Breneman, S., Pei, S., Lindt, J., Berman, J., Mcdonnell, E., Branco, J. M., Luis Neves, and Universidade do Minho
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Diaphragms ,Numerical modelling ,Shake table ,CLT ,Seismic response - Abstract
Current standards and existing literature provide very limited information regarding the design of cross-laminated timber (CLT) floor diaphragms. In addition, limited procedures exist to develop analytical models to estimate the deformation response of CLT floor diaphragms. This paper presents a modelling approach that captures the response of CLT timber diaphragms, with a special focus on CLT spline panel-to-panel connections. The modeling approach is validated through the comparison of the results of the computation model with experimental data obtained from a series of shake-tables test performed on a two-story full-scale building tested in the summer of 2017 at UC San Diego Large High Performance Outdoor Shake Table. The two-story building included two diaphragm designs at each floor level. The first solution consists of CLT panels connected with plywood surface splines that are fastened using self-tapping screws, while the second consists of a CLT-concrete composite floor solution. Results from the nonlinear pushover analysis describe accurately the experimental data obtained., (undefined)
73. Pinitol and Other Solutes in Salt-stressed Sesbania aculeata
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Gorham, J., primary, McDonnell, E., additional, and Wyn Jones, R.G., additional
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- 1984
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74. Life: Nasty, brutish, and short
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McDonnell, E. E., primary
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- 1988
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75. Life: Nasty, brutish, and short
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McDonnell, E. E., primary
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- 1987
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76. Membrane Lipids and Phosphatidyl Choline Turnover in Embryos from Germinating Low and High Vigour Wheat (Triticum aestivum)
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McDONNELL, E. M., primary, PULFORD, F. G., additional, MIRBAHAR, R. B., additional, TOMOS, A. D., additional, and LAIDMAN, D. L., additional
- Published
- 1982
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77. Determination of betaines as ultraviolet-absorbing esters
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Gorham, J., primary, McDonnell, E., additional, and Wyn Jones, R.G., additional
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- 1982
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78. Zero divided by zero
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McDonnell, E. E., primary
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- 1976
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79. IN VIVO PROPERTIES OF THE SKIN OF INFANTS
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Philips, Joseph B, primary, Alexander, Harold, additional, Brown, Edwin O, additional, Mcdonnell, E, additional, and Sweet, Avron Y, additional
- Published
- 1977
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80. A perfect square root routine
- Author
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McDonnell, E. E., primary
- Published
- 1986
- Full Text
- View/download PDF
81. Phrasal forms
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McDonnell, E. E., primary and Iverson, K. E., additional
- Published
- 1989
- Full Text
- View/download PDF
82. Salt Tolerance in the Triticeae:Leymus sabulosus
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GORHAM, J., primary, MCDONNELL, E., additional, and JONES, R. G. WYN, additional
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- 1984
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83. Salt Tolerance in the Triticeae: Growth and Solute Accumulation in Leaves ofThinopyrum bessarabicum
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GORHAM, J., primary, MCDONNELL, E., additional, BUDREWICZ, E., additional, and JONES, R. G. WYN, additional
- Published
- 1985
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84. 5. On the Formation of Sugar and Amyloid Substance in the Animal Economy.
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McDonnell, E., primary
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- 1862
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85. Macropyroglobulinemia: Immunochemical Studies in Three Cases
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Stefanini, Mario, primary, Erle Mcdonnell, E., additional, Andracki, Edward G., additional, Swansbro, William J., additional, and Durr, Pearl, additional
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- 1970
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86. Birgittinische Klostergrundungen Des Mittelalters
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McDonnell, E. W., primary and Nyberg, Tore, additional
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- 1968
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87. Educator-Congressmen.
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McDonnell, E. L.
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LETTERS to the editor ,VOTING - Abstract
Presents a letter to the editor related to editorial on study of voting records published in the August 9, 1943 issue of "National Educational Association Journal."
- Published
- 1943
88. Zero divided by zero.
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McDonnell, E. E.
- Published
- 1976
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89. Gem no. 333. School food service 'Computer Exploration Kit'.
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Ledikwe J, McDonnell E, Birkenshaw P, and Probart C
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- 2001
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90. Processing and analysis of foetal phonocardiograms.
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McDonnell, E., Dripps, J.H., and Grant, P.
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- 1989
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91. Some mechanisms of salt tolerance in crop plants
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McDonnell, E., Jones, R. G. Wyn, and Gorham, J.
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BOTANY ,SALINITY - Published
- 1985
92. New faces.
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Wild, D. and McDonnell, E.
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ROCK music - Abstract
Profiles three up-and-coming musical acts. Singer-songwriter Marc Cohn; Rock band King Missile; Rock band V.I.E.W., which features Chicago White Sox pitchers Jack McDowell and Wayne Edwards; Details.
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- 1991
93. New faces.
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McDonnell, E. and Mundy, C.
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MUSICIANS - Abstract
Discusses three new musical acts. New Zealand rock group the Verlaines; Irish rock group called An Emotional Fish; Bluegrass fiddle player Alison Krauss.
- Published
- 1990
94. Recordings.
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McDonnell, E.
- Subjects
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SOUND recordings ,REVIEWS - Abstract
Reviews the albums `Black and Tan Club,' and `Jazzspeak,' two spoken-word compilations produced by Harvey Robert Kubernik.
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- 1992
95. Designing a broad-spectrum integrative approach for cancer prevention and treatment
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Chandra S. Boosani, William K. Decker, Punita Dhawan, Georgia Zhuo Chen, Mark E. Prince, Balakrishna L. Lokeshwar, Nagi B. Kumar, Michelle F. Green, Alan Bilsland, Michael P. Murphy, Dong M. Shin, H.P. Vasantha Rupasinghe, Paul Yaswen, Anupam Bishayee, Christian Frezza, John Stagg, Mahin Khatami, Lynnette R. Ferguson, R. Brooks Robeydf, Kanya Honoki, Alan K. Meeker, A.R.M. Ruhul Amin, Huanjie Yang, Eoin McDonnell, Virginia R. Parslow, Phuoc T. Tran, Patricia Hentosh, Frank Gieseler, Gloria S. Huang, Sulma I. Mohammed, Ho Young Lee, Giovanna Damia, Alexandra Arreola, Wamidh H. Talib, Mark A. Feitelson, Luigi Ricciardiello, Massimo Zollo, Sarallah Rezazadeh, Diana M. Stafforini, Katia Aquilano, Phillip Karpowicz, Markus D. Siegelin, Neetu Singh, Alexandros G. Georgakilas, Domenico Ribatti, Neeraj K. Saxena, Carl Smythe, Beom K. Choi, Mark M. Fuster, Gian Luigi Russo, Amedeo Amedei, Anna Mae Diehl, Terry Lichtor, D. James Morré, Charlotte Gyllenhaal, Vasundara Venkateswaran, Colleen S. Curran, Ramzi M. Mohammad, Jiyue Zhu, Anne Leb, Lizzia Raffaghello, Fabian Benencia, Sid P. Kerkar, Eddy S. Yang, Wen Guo Jiang, Jason W. Locasale, Alla Arzumanyan, W. Nicol Keith, Dorota Halicka, Gunjan Guhal, Xin Yin, Helen Chen, Irfana Muqbil, Gary L. Firestone, Panagiotis J. Vlachostergios, Maria Marino, Meenakshi Malhotra, Stacy W. Blain, Amancio Carnero, Liang Tzung Lin, Dass S. Vinay, Satya Prakash, Hsue-Yin Hsu, María L. Martínez-Chantar, Daniele Generali, Jeffrey C. Rathmell, Karen L. MacKenzie, Valter D. Longo, Dipita Bhakta, Ralph J. DeBerardinis, S. Salman Ashraf, Elena Niccolai, Hendrik Ungefroren, Carmela Fimognari, Mahya Mehrmohamadi, Zongwei Wang, Clement G. Yedjou, Costas A. Lyssiotis, Lasse Jensen, Jörg Reichrath, Sarah K. Thompson, Rita Nahta, David Sidransky, Q. Ping Dou, Brendan Grue, Isidro Sánchez-García, Brad Poore, Helen M. Coley, Bassel F. El-Rayes, Sophie Chen, Randall F. Holcombe, Dipali Sharma, Mrinmay Chakrabarti, Asfar S. Azmi, William G. Helferich, Gregory A. Michelotti, H. M. C. Shantha Kumara, Petr Heneberg, Rodney E. Shackelford, Andrew James Sanders, Daniel Sliva, Swapan K. Ray, Omer Kucuk, Christopher Maxwellx, Abbas Samadi, Leroy Lowe, Sarah Crawford, Daniele Santini, Andrew Collins, Yi Charlie Chen, Santanu Dasgupta, Kathryn E. Wellen, Richard L. Whelan, Janice E. Drewa, Ander Matheu, Sharanya Sivanand, Tetsuro Sasada, Xujuan Yang, Lee W. Jones, Byoung S. Kwon, Amr Amin, Francis Rodierdh, Ganji Purnachandra Nagaraju, Charlotta Dabrosin, Graham Pawelec, Rob J. Kulathinal, Elizabeth P. Ryan, Hiromasa Fujii, Thomas E. Carey, Somaira Nowsheen, Young Hee Ko, Deepak Poudyal, Eyad Elkord, Emanuela Signori, Rupesh Chaturvedi, Peter L. Pedersen, Carmela Spagnuolo, Keith I. Block, Marianeve Carotenuto, Vinayak Muralidharcq, Stephanie C. Casey, Kapil Mehta, Tabetha Sundin, Dean W. Felsheru, Matthew D. Hirschey, Matthew G. Vander Heiden, Lorne J. Hofseth, Francesco Pantano, Maria Rosa Ciriolo, Michael A. Leab, Carolina Panis, Marisa Connell, Gazala Khan, W. Kimryn Rathmell, Malancha Sarkar, Michael Gilbertson, Jack L. Arbiser, Penny B. Block, Pochi R. Subbarayan, Jin-Tang Dong, Frezza, Christian [0000-0002-3293-7397], Murphy, Mike [0000-0003-1115-9618], Apollo - University of Cambridge Repository, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Associazione Italiana per la Ricerca sul Cancro, Avon Foundation for Women, Junta de Castilla y León, Ministerio de Ciencia e Innovación (España), Federal Ministry of Education and Research (Germany), Canadian Institutes of Health Research, Ikerbasque Basque Foundation for Science, American Cancer Society, European Commission, Swedish Research Council, University of Glasgow, Block, Keith I, Gyllenhaal, Charlotte, Lowe, Leroy, Amedei, Amedeo, Amin, A. R. M. Ruhul, Amin, Amr, Aquilano, Katia, Arbiser, Jack, Arreola, Alexandra, Arzumanyan, Alla, Ashraf, S. Salman, Azmi, Asfar S, Benencia, Fabian, Bhakta, Dipita, Bilsland, Alan, Bishayee, Anupam, Blain, Stacy W, Block, Penny B, Boosani, Chandra S, Carey, Thomas E, Carnero, Amancio, Carotenuto, Marianeve, Casey, Stephanie C, Chakrabarti, Mrinmay, Chaturvedi, Rupesh, Chen, Georgia Zhuo, Chen, Helen, Chen, Sophie, Chen, Yi Charlie, Choi, Beom K, Ciriolo, Maria Rosa, Coley, Helen M, Collins, Andrew R, Connell, Marisa, Crawford, Sarah, Curran, Colleen S, Dabrosin, Charlotta, Damia, Giovanna, Dasgupta, Santanu, Deberardinis, Ralph J, Decker, William K, Dhawan, Punita, Diehl, Anna Mae E, Dong, Jin Tang, Dou, Q. Ping, Drew, Janice E, Elkord, Eyad, El Rayes, Bassel, Feitelson, Mark A, Felsher, Dean W, Ferguson, Lynnette R, Fimognari, Carmela, Firestone, Gary L, Frezza, Christian, Fujii, Hiromasa, Fuster, Mark M, Generali, Daniele, Georgakilas, Alexandros G, Gieseler, Frank, Gilbertson, Michael, Green, Michelle F, Grue, Brendan, Guha, Gunjan, Halicka, Dorota, Helferich, William G, Heneberg, Petr, Hentosh, Patricia, Hirschey, Matthew D, Hofseth, Lorne J, Holcombe, Randall F, Honoki, Kanya, Hsu, Hsue Yin, Huang, Gloria S, Jensen, Lasse D, Jiang, Wen G, Jones, Lee W, Karpowicz, Phillip A, Keith, W. Nicol, Kerkar, Sid P, Khan, Gazala N, Khatami, Mahin, Ko, Young H, Kucuk, Omer, Kulathinal, Rob J, Kumar, Nagi B, Kwon, Byoung S, Le, Anne, Lea, Michael A, Lee, Ho Young, Lichtor, Terry, Lin, Liang Tzung, Locasale, Jason W, Lokeshwar, Bal L, Longo, Valter D, Lyssiotis, Costas A, Mackenzie, Karen L, Malhotra, Meenakshi, Marino, Maria, Martinez Chantar, Maria L, Matheu, Ander, Maxwell, Christopher, Mcdonnell, Eoin, Meeker, Alan K, Mehrmohamadi, Mahya, Mehta, Kapil, Michelotti, Gregory A, Mohammad, Ramzi M, Mohammed, Sulma I, Morre, D. Jame, Muralidhar, Vinayak, Muqbil, Irfana, Murphy, Michael P, Nagaraju, Ganji Purnachandra, Nahta, Rita, Niccolai, Elena, Nowsheen, Somaira, Panis, Carolina, Pantano, Francesco, Parslow, Virginia R, Pawelec, Graham, Pedersen, Peter L, Poore, Brad, Poudyal, Deepak, Prakash, Satya, Prince, Mark, Raffaghello, Lizzia, Rathmell, Jeffrey C, Rathmell, W. Kimryn, Ray, Swapan K, Reichrath, Jörg, Rezazadeh, Sarallah, Ribatti, Domenico, Ricciardiello, Luigi, Robey, R. Brook, Rodier, Franci, Rupasinghe, H. P. Vasantha, Russo, Gian Luigi, Ryan, Elizabeth P, Samadi, Abbas K, Sanchez Garcia, Isidro, Sanders, Andrew J, Santini, Daniele, Sarkar, Malancha, Sasada, Tetsuro, Saxena, Neeraj K, Shackelford, Rodney E, Shantha Kumara, H. M. C, Sharma, Dipali, Shin, Dong M, Sidransky, David, Siegelin, Markus David, Signori, Emanuela, Singh, Neetu, Sivanand, Sharanya, Sliva, Daniel, Smythe, Carl, Spagnuolo, Carmela, Stafforini, Diana M, Stagg, John, Subbarayan, Pochi R, Sundin, Tabetha, Talib, Wamidh H, Thompson, Sarah K, Tran, Phuoc T, Ungefroren, Hendrik, Vander Heiden, Matthew G, Venkateswaran, Vasundara, Vinay, Dass S, Vlachostergios, Panagiotis J, Wang, Zongwei, Wellen, Kathryn E, Whelan, Richard L, Yang, Eddy S, Yang, Huanjie, Yang, Xujuan, Yaswen, Paul, Yedjou, Clement, Yin, Xin, Zhu, Jiyue, Zollo, Massimo, Amin, A R M Ruhul, Ashraf, S Salman, Dong, Jin-Tang, Dou, Q Ping, El-Rayes, Bassel, Hsu, Hsue-Yin, Keith, W Nicol, Lee, Ho-Young, Lin, Liang-Tzung, Martinez-Chantar, Maria L, Morre, D Jame, Rathmell, W Kimryn, Robey, R Brook, Rupasinghe, H P Vasantha, Sanchez-Garcia, Isidro, Shantha Kumara, H M C, Block, Ki, Gyllenhaal, C, Lowe, L, Amedei, A, Amin, Ar, Amin, A, Aquilano, K, Arbiser, J, Arreola, A, Arzumanyan, A, Ashraf, S, Azmi, A, Benencia, F, Bhakta, D, Bilsland, A, Bishayee, A, Blain, Sw, Block, Pb, Boosani, C, Carey, Te, Carnero, A, Casey, Sc, Chakrabarti, M, Chaturvedi, R, Chen, Gz, Chen, H, Chen, S, Chen, Yc, Choi, Bk, Ciriolo, Mr, Coley, Hm, Collins, Ar, Connell, M, Crawford, S, Curran, C, Dabrosin, C, Damia, G, Dasgupta, S, Deberardinis, Rj, Decker, Wk, Dhawan, P, Diehl, Am, Dong, Jt, Dou, Qp, Drew, Je, Elkord, E, El Rayes, B, Feitelson, Ma, Felsher, Dw, Ferguson, Lr, Fimognari, C, Firestone, Gl, Frezza, C, Fujii, H, Fuster, Mm, Generali, D, Georgakilas, Ag, Gieseler, F, Gilbertson, M, Green, Mf, Grue, B, Guha, G, Halicka, D, Helferich, Wg, Heneberg, P, Hentosh, P, Hirschey, Md, Hofseth, Lj, Holcombe, Rf, Honoki, K, Hsu, Hy, Huang, G, Jensen, Ld, Jiang, Wg, Jones, Lw, Karpowicz, Pa, Keith, Wn, Kerkar, Sp, Khan, Gn, Khatami, M, Ko, Yh, Kucuk, O, Kulathinal, Rj, Kumar, Nb, Kwon, B, Le, A, Lea, Ma, Lee, Hy, Lichtor, T, Lin, Lt, Locasale, Jw, Lokeshwar, Bl, Longo, Vd, Lyssiotis, Ca, Mackenzie, Kl, Malhotra, M, Marino, M, Martinez Chantar, Ml, Matheu, A, Maxwell, C, Mcdonnell, E, Meeker, Ak, Mehrmohamadi, M, Mehta, K, Michelotti, Ga, Mohammad, Rm, Mohammed, Si, Morre, Dj, Muralidhar, V, Muqbil, I, Murphy, Mp, Nagaraju, Gp, Nahta, R, Niccolai, E, Nowsheen, S, Panis, C, Pantano, F, Parslow, Vr, Pawelec, G, Pedersen, Pl, Poore, B, Poudyal, D, Prakash, S, Prince, M, Raffaghello, L, Rathmell, Jc, Rathmell, Wk, Ray, Sk, Reichrath, J, Rezazadeh, S, Ribatti, D, Ricciardiello, L, Robey, Rb, Rodier, F, Rupasinghe, Hp, Russo, Gl, Ryan, Ep, Samadi, Ak, Sanchez Garcia, I, Sanders, Aj, Santini, D, Sarkar, M, Sasada, T, Saxena, Nk, Shackelford, Re, Shantha Kumara, Hm, Sharma, D, Shin, Dm, Sidransky, D, Siegelin, Md, Signori, E, Singh, N, Sivanand, S, Sliva, D, Smythe, C, Spagnuolo, C, Stafforini, Dm, Stagg, J, Subbarayan, Pr, Sundin, T, Talib, Wh, Thompson, Sk, Tran, Pt, Ungefroren, H, Vander Heiden, Mg, Venkateswaran, V, Vinay, D, Vlachostergios, Pj, Wang, Z, Wellen, Ke, Whelan, Rl, Yang, E, Yang, H, Yang, X, Yaswen, P, Yedjou, C, Yin, X, Zhu, J, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Ruhul Amin, A. R. M., Salman Ashraf, S., Azmi, Asfar S., Blain, Stacy W., Block, Penny B., Boosani, Chandra S., Carey, Thomas E., Casey, Stephanie C., Choi, Beom K., Coley, Helen M., Collins, Andrew R., Curran, Colleen S., Deberardinis, Ralph J., Decker, William K., Diehl, Anna Mae E., Drewa, Janice E., Feitelson, Mark A., Felsheru, Dean W., Ferguson, Lynnette R., Firestone, Gary L., Fuster, Mark M., Georgakilas, Alexandros G., Green, Michelle F., Guhal, Gunjan, Helferich, William G., Hirschey, Matthew D., Hofseth, Lorne J., Holcombe, Randall F., Huang, Gloria S., Jensen, Lasse D., Jiang, Wen G., Jones, Lee W., Karpowicz, Phillip A., Kerkar, Sid P., Khan, Gazala N., Ko, Young H., Kulathinal, Rob J., Kumar, Nagi B., Kwon, Byoung S., Leb, Anne, Leab, Michael A., Locasale, Jason W., Lokeshwar, Bal L., Longo, Valter D., Lyssiotis, Costas A., Maxwellx, Christopher, Meeker, Alan K., Michelotti, Gregory A., Mohammad, Ramzi M., Mohammed, Sulma I., Muralidharcq, Vinayak, Murphy, Michael P., Parslow, Virginia R., Pedersen, Peter L., Rathmell, Jeffrey C., Ray, Swapan K., Robeydf, R. Brook, Rodierdh, Franci, Ryan, Elizabeth P., Samadi, Abbas K., Sanders, Andrew J., Saxena, Neeraj K., Shackelford, Rodney E., Shantha Kumara, H. M. C., Shin, Dong M., Stafforini, Diana M., Subbarayan, Pochi R., Talib, Wamidh H., Thompson, Sarah K., Tran, Phuoc T., Vinay, Dass S., Vlachostergios, Panagiotis J., Wellen, Kathryn E., Whelan, Richard L., and Yang, Eddy S.
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Cancer Research ,medicine.medical_treatment ,Phytochemicals ,ComputingMilieux_LEGALASPECTSOFCOMPUTING ,Pharmacology ,Bioinformatics ,Targeted therapy ,Broad spectrum ,0302 clinical medicine ,Cancer hallmark ,Neoplasms ,Tumor Microenvironment ,Molecular Targeted Therapy ,Precision Medicine ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Cancer hallmarks ,Integrative medicine ,Multi-targeted ,1. No poverty ,Life Sciences ,3. Good health ,030220 oncology & carcinogenesis ,Signal Transduction ,Phytochemical ,Article ,RC0254 ,03 medical and health sciences ,Therapeutic approach ,Genetic Heterogeneity ,medicine ,Humans ,Settore BIO/10 ,Biology ,030304 developmental biology ,Tumor microenvironment ,Cancer och onkologi ,Cancer prevention ,business.industry ,Cancer ,Precision medicine ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Drug Resistance, Neoplasm ,Data_GENERAL ,Cancer and Oncology ,business - Abstract
Under a Creative Commons license.-- Review.-- et al., Targeted therapies and the consequent adoption of >personalized> oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity >broad-spectrum> therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered., Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIHAR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Amancio Carnero was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.), Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant AI076535, Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza “would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant”; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program ‘Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 ‘Biomimetic Radical Chemistry’; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365), Lorne J. Hofseth was supported by NIH grants (1R01CA151304, 1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, Ollie och Elof Ericssons Stiftelse, Linkopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S. Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee., This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant R01 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and AI110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States’ Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5I01-BX001517-02; Valter D. Longo acknowledges support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221), Ander Matheu is funded by Carlos III Health Institute (AM: CP10/00539), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 “IDEAL”); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell’IRPEF–Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K. Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement n°278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007–2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Québec Santé (FR: 22624), and the Terry Fox Research Institute (FR: 1030), Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013–14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro Sanchez-Garcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XWH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U. Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011), Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013.
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- 2015
96. P.453 - Consistency between natural history and clinical trial placebo arms for 48-week changes in six-minute walk distance (6MWD) in patients with Duchenne muscular dystrophy (DMD).
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Mercuri, E., Goemans, N., Sajeev, G., Yao, Z., Mcdonnell, E., Ward, S., and Signorovitch, J.
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DUCHENNE muscular dystrophy , *PHYSIOLOGICAL aspects of walking , *PLACEBOS , *PATIENTS - Published
- 2017
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97. P.454 - Validation of a prognostic score for changes in six-minute walk distance (6MWD) in patients with Duchenne muscular dystrophy (DMD).
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Goemans, N., Hauwe, M. Vanden, Sajeev, G., Yao, Z., Mcdonnell, E., Ward, S., and Signorovitch, J.
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DUCHENNE muscular dystrophy , *PROGNOSTIC tests , *PATIENTS - Published
- 2017
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98. SERPINA3 is a marker of cartilage differentiation and is essential for the expression of extracellular matrix genes during early chondrogenesis.
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Barter MJ, Turner DA, Rice SJ, Hines M, Lin H, Falconer AMD, McDonnell E, Soul J, Arques MDC, Europe-Finner GN, Rowan AD, Young DA, and Wilkinson DJ
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- Humans, Cartilage metabolism, Cartilage growth & development, Cartilage cytology, Gene Expression Regulation, Developmental, Biomarkers metabolism, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins metabolism, Cells, Cultured, Chondrogenesis genetics, Cell Differentiation, Chondrocytes metabolism, Chondrocytes cytology, Extracellular Matrix metabolism, Extracellular Matrix genetics, Serpins genetics, Serpins metabolism, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology
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Serine proteinase inhibitors (serpins) are a family of structurally similar proteins which regulate many diverse biological processes from blood coagulation to extracellular matrix (ECM) remodelling. Chondrogenesis involves the condensation and differentiation of mesenchymal stem cells (MSCs) into chondrocytes which occurs during early development. Here, and for the first time, we demonstrate that one serpin, SERPINA3 (gene name SERPINA3, protein also known as alpha-1 antichymotrypsin), plays a critical role in chondrogenic differentiation. We observed that SERPINA3 expression was markedly induced at early time points during in vitro chondrogenesis. We examined the expression of SERPINA3 in human cartilage development, identifying significant enrichment of SERPINA3 in developing cartilage compared to total limb, which correlated with well-described markers of cartilage differentiation. When SERPINA3 was silenced using siRNA, cartilage pellets were smaller and contained lower proteoglycan as determined by dimethyl methylene blue assay (DMMB) and safranin-O staining. Consistent with this, RNA sequencing revealed significant downregulation of genes associated with cartilage ECM formation perturbing chondrogenesis. Conversely, SERPINA3 silencing had a negligible effect on the gene expression profile during osteogenesis suggesting the role of SERPINA3 is specific to chondrocyte differentiation. The global effect on cartilage formation led us to investigate the effect of SERPINA3 silencing on the master transcriptional regulator of chondrogenesis, SOX9. Indeed, we observed that SOX9 protein levels were markedly reduced at early time points suggesting a role for SERPINA3 in regulating SOX9 expression and activity. In summary, our data support a non-redundant role for SERPINA3 in enabling chondrogenesis via regulation of SOX9 levels., Competing Interests: Declaration of compting interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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99. Epigenetic mechanisms of osteoarthritis risk in human skeletal development.
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McDonnell E, Orr SE, Barter MJ, Rux D, Brumwell A, Wrobel N, Murphy L, Overmann LM, Sorial AK, Young DA, Soul J, and Rice SJ
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The epigenome, including the methylation of cytosine bases at CG dinucleotides, is intrinsically linked to transcriptional regulation. The tight regulation of gene expression during skeletal development is essential, with ~1/500 individuals born with skeletal abnormalities. Furthermore, increasing evidence is emerging to link age-associated complex genetic musculoskeletal diseases, including osteoarthritis (OA), to developmental factors including joint shape. Multiple studies have shown a functional role for DNA methylation in the genetic mechanisms of OA risk using articular cartilage samples taken from aged patients. Despite this, our knowledge of temporal changes to the methylome during human cartilage development has been limited. We quantified DNA methylation at ~700,000 individual CpGs across the epigenome of developing human articular cartilage in 72 samples ranging from 7-21 post-conception weeks, a time period that includes cavitation of the developing knee joint. We identified significant changes in 8% of all CpGs, and >9400 developmental differentially methylated regions (dDMRs). The largest hypermethylated dDMRs mapped to transcriptional regulators of early skeletal patterning including MEIS1 and IRX1 . Conversely, the largest hypomethylated dDMRs mapped to genes encoding extracellular matrix proteins including SPON2 and TNXB and were enriched in chondrocyte enhancers. Significant correlations were identified between the expression of these genes and methylation within the hypomethylated dDMRs. We further identified 811 CpGs at which significant dimorphism was present between the male and female samples, with the majority (68%) being hypermethylated in female samples. Following imputation, we captured the genotype of these samples at >5 million variants and performed epigenome-wide methylation quantitative trait locus (mQTL) analysis. Colocalization analysis identified 26 loci at which genetic variants exhibited shared impacts upon methylation and OA genetic risk. This included loci which have been previously reported to harbour OA-mQTLs (including GDF5 and ALDH1A2 ), yet the majority (73%) were novel (including those mapping to CHST3, FGF1 and TEAD1 ). To our knowledge, this is the first extensive study of DNA methylation across human articular cartilage development. We identify considerable methylomic plasticity within the development of knee cartilage and report active epigenomic mediators of OA risk operating in prenatal joint tissues., Competing Interests: Declaration of Interests LM has received speaker and consultancy fees from Illumina. We have no other conflicting interest to declare.
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- 2024
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100. Prospective 1-year results of atrial fibrillation ablation using the pentaspline pulsed field ablation catheter: The initial French experience.
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Chaumont C, McDonnell E, Boveda S, Savoure A, Rollin A, Combes S, Al Hamoud R, Mandel F, Zeriouh S, Eltchaninoff H, Maury P, and Anselme F
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- Humans, Prospective Studies, Treatment Outcome, Catheters, Recurrence, Atrial Fibrillation diagnosis, Atrial Fibrillation surgery, Atrial Fibrillation complications, Pulmonary Veins, Catheter Ablation adverse effects, Catheter Ablation methods
- Abstract
Background: Pulsed field ablation has recently emerged as an interesting non-thermal energy for atrial fibrillation ablation. At a time of rapid spread of this technology, there is still a lack of prospective real-life data., Aim: To describe multicentre prospective safety and 1-year efficacy data in three of the first French centres to use pulsed field ablation., Methods: All consecutive patients undergoing a first pulsed field ablation were included prospectively. The primary outcome was freedom from documented atrial arrhythmia. The safety endpoint was a composite of major adverse events. Univariate and multivariable analyses, including patient and procedural characteristics, were performed to identify factors predictive of recurrence., Results: Between May 2021 and June 2022, 311 patients were included (paroxysmal atrial fibrillation in 53%, persistent atrial fibrillation in 35% and long-standing persistent atrial fibrillation in 11%). Additional non-pulmonary vein pulsed field ablation applications were performed in 104/311 patients. One-year freedom from arrhythmia recurrence was 77.6% in the overall population and was significantly higher in patients with paroxysmal atrial fibrillation (88.4%) compared with patients with persistent atrial fibrillation (69.7%; P<0.001) and those with long-standing persistent atrial fibrillation (49.0%; P<0.001). The major complication rate was 2.6% (tamponade in four patients, stroke in two patients and coronary spasm in one patient). Besides the usual predictors of recurrences (left atrium size, CHA
2 DS2 -VASc score, type of atrial fibrillation), the presence of atrial fibrillation at procedure start was independently associated with arrhythmia recurrence (hazard ratio: 2.04, 95% confidence interval: 1.10-3.77)., Conclusion: In this prospective multicentre real-world study, pulsed field ablation for atrial fibrillation ablation seems to be associated with a good safety profile and rather favourable acute and 1-year success rates., (Copyright © 2024. Published by Elsevier Masson SAS.)- Published
- 2024
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