43 results on '"Santoso, N"'
Search Results
2. Different perspective on biodiversity: high conservation value or high cultivation value
- Author
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Soedomo, S, primary and Santoso, N, additional
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- 2023
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3. Underground-caves connectedness preview using the geoelectrical profiling method as an effort to revive natural tourism in “Gua Pandan,” East Lampung Regency
- Author
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Antosia, R M, primary, Akbar, H H, additional, Santoso, N A, additional, Putri, I A, additional, Farishi, B A, additional, and Natalia, H C, additional
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- 2023
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4. Sustainability level of Silvofishery ponds on the coast of Semarang City
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Muthoh, R F, primary, Santoso, N, additional, and Mulatsih, S, additional
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- 2022
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5. Habitat Preference and Habitat Suitability of Cuscus in the Work Area of PT Wijaya Sentosa, Teluk Wondama Regency
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Maulana, F A, primary, Santoso, N, additional, and Rahman, D A, additional
- Published
- 2022
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6. Smart Development of Big Data App for Determining the Modelling of Covid-19 Medicinal Compounds Using Deep AI Core Engine System
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Cholissodin, I, primary, Sutrisno, S, additional, Santoso, N, additional, Soebroto, A A, additional, Hidayat, N, additional, and Rochman, N T, additional
- Published
- 2020
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7. Distributing PID controllers applied in water-mixing process
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Rudati, P S, primary, Feriyonika, F, additional, Sudarsa, Y, additional, Ruyadi, F, additional, and Santoso, N W, additional
- Published
- 2020
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8. THE EFFECTIVENESS OF WATER FILTERS WITH ACTIVATED CARBON MEDIA OF BAGASSE SUGARCANE FOR REDUCING IRON LEVELS IN GROUNDWATER
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Maharani, Zulfia, primary, Santoso, N. Budi, primary, Anggraini, Amelia, primary, and Rajiani, Ismi, primary
- Published
- 2019
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9. Optimal design of switchable distribution capacitors by piecewise method
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Santoso, N. I. and Tan, O. T.
- Published
- 1990
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10. Characterization of Volcanic Ash From the 2017 Agung Eruption, Bali, Indonesia
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Devi, S, primary, Bijaksana, S, additional, Fajar, S J, additional, and Santoso, N A, additional
- Published
- 2019
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11. Magnetic characterization of soil to determine the source origin. Case study: soil around Bromo Volcano, Tengger Volcanic Complex
- Author
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Santoso, N A, primary, Syaifullah, K I, additional, Zulaikah, S, additional, and Bijaksana, S, additional
- Published
- 2019
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12. The Effect of Fitosan Supplementation on Methane Production in Cow’s Rumen Liquid by In Vitro Method
- Author
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Sugoro, I, primary, Nuryanthi, N, additional, Ermadevi, D N I, additional, Khoiriyah, M, additional, Santoso, N A, additional, Mangunwardoyo, W, additional, and Darwis, D, additional
- Published
- 2019
- Full Text
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13. Study of pH and Magnetic Susceptibility to Fertility Rate of Agricultural Soil around Institut Teknologi Sumatera, Lampung, Indonesia
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Santoso, N A, primary, Iqbal, M, additional, Ekawati, G, additional, and Firdaus, R, additional
- Published
- 2019
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14. Utilization of waterbirds by Ujungpangkah Community, Gresik Regency, East Java
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Ilmar, R D, primary and Santoso, N, additional
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- 2019
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15. Diversity and spatial use of birds in the Ujung Pangkah coastal area of Gresik Regency, West Java
- Author
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Budiman, MAK, primary, Fahrudin, A, additional, and Santoso, N, additional
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- 2019
- Full Text
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16. Stakeholder Analysis in Community Based Mangrove Management: Case of Forest Management Unit in Region 3 of Aceh Province
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Hasnanda, OK, primary, Nugroho, B, additional, Kartodihardjo, H, additional, and Santoso, N, additional
- Published
- 2018
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17. SYNTHESIS AND CHARACTERIZATION OF Ni-NH2/MESOPOROUS SILICA CATALYST FROM LAPINDO MUD FOR HYDROCRACKING OF WASTE COOKING OIL INTO BIOFUEL.
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Trisunaryanti, W., Triyono, Paramesti, C., Larasati, S., Santoso, N. R., and Fatmawati, D. A.
- Subjects
CATALYSTS ,HYDROCRACKING ,SYNTHESIS gas ,BIOMASS energy ,DIESEL fuels ,MUD - Abstract
The synthesis and characterization of Ni-NH
2 /Mesoporous Silica (MS) catalysts from Lapindo mud for the hydrocracking of waste cooking oil into biofuel has been conducted. The MS was synthesized by the hydrothermal method using CTAB as a template. The functionalization of -NH2 into MS was carried out by the grafting method. The Ni metal was loaded into NH2 /MS by wet impregnation. The catalytic activity test was done for hydrocracking of waste cooking oil by using the MS, NH2 /MS, and Ni-NH2 /MS catalysts. The results of the liquid product of the hydrocracking were analyzed by the gravimetric method and GC-MS. The experimental result showed that the liquid products of the hydrocracking using MS, NH2 /MS, and Ni-NH2 /MS catalysts were 63.95, 70.32, and 66.44 wt.%. The highest selectivity of the gasoline fraction (34.98 wt.%) was produced by the NH2 /MS catalyst and the highest diesel oil fraction (1.52 wt.%) was produced by MS. The NH2 /MS catalyst was successfully used as a catalyst in the hydrocracking of waste cooking oil into the hydrocarbons (biofuel). [ABSTRACT FROM AUTHOR]- Published
- 2020
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18. Trust Arrangements in Relation to the CFC Rule and Anti-Tax Treaty Abuse
- Author
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Karyadi, F., primary and Santoso, N., additional
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- 2018
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19. The Effects of Silicon on The Hardness and Wear of Ferritic Grey Cast Iron on Shoe Brake of Train
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Darmo, S, primary, Setyana, L D, additional, Tarmono, T, additional, and Santoso, N, additional
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- 2018
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20. Ecological Impacts of Oil-Palm Plantation on Butterfly and Bird Species Diversity
- Author
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Kwatrina, R T, primary, Santosa, Y, additional, Bismark, M, additional, and Santoso, N, additional
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- 2018
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21. Comprehensive genomic characterization of head and neck squamous cell carcinomas
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Lawrence, MS, Sougnez, C, Lichtenstein, L, Cibulskis, K, Lander, E, Gabriel, SB, Getz, G, Ally, A, Balasundaram, M, Birol, I, Bowlby, R, Brooks, D, Butterfield, YSN, Carlsen, R, Cheng, D, Chu, A, Dhalla, N, Guin, R, Holt, RA, Jones, SJM, Lee, D, Li, HI, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Robertson, AG, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Protopopov, A, Santoso, N, Lee, S, Parfenov, M, Zhang, J, Mahadeshwar, HS, Tang, J, Ren, X, Seth, S, Haseley, P, Zeng, D, Yang, L, Xu, AW, Song, X, Pantazi, A, Bristow, CA, Hadjipanayis, A, Seidman, J, Chin, L, Park, PJ, Kucherlapati, R, Akbani, R, Casasent, T, Liu, W, Lu, Y, Mills, G, Motter, T, Weinstein, J, Diao, L, Wang, J, Hong Fan, Y, Liu, J, Wang, K, Auman, JT, Balu, S, Bodenheimer, T, Buda, E, Hayes, DN, Hoadley, KA, Hoyle, AP, Jefferys, SR, Jones, CD, Kimes, PK, Liu, Y, Marron, JS, Meng, S, Mieczkowski, PA, Mose, LE, Parker, JS, Perou, CM, Prins, JF, Roach, J, Shi, Y, Simons, JV, Singh, D, Soloway, MG, Tan, D, Veluvolu, U, Walter, V, Waring, S, Wilkerson, MD, and Wu, J
- Abstract
© 2015 Macmillan Publishers Limited. All rights reserved. The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
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- 2015
22. Efficient Reasoning
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GREINER, RUSSELL, DARKEN, CHRISTIAN, and SANTOSO, N. IWAN
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System design ,Company business management ,Company systems management ,Knowledge-based system ,Reasoning -- Information management ,System design -- Management ,Systems analysis -- Management ,Knowledge-based systems -- Management - Abstract
1. INTRODUCTION Many information systems use a corpus of explicitly stored information (a.k.a. a 'knowledge base,' KB) to solve their range of problems. For example, medical diagnostic systems use general […], Many tasks require "reasoning"--i.e., deriving conclusions from a corpus of explicitly stored information--to solve their range of problems. An ideal reasoning system would produce all-and-only the correct answers to every possible query, produce answers that are as specific as possible, be expressive enough to permit any possible fact to be stored and any possible query to be asked, and be (time) efficient. Unfortunately, this is provably impossible: as correct and precise systems become more expressive, they can become increasingly inefficient, or even undecidable. This survey first formalizes these hardness results, in the context of both logic- and probability-based reasoning, then overviews the techniques now used to address, or at least side-step, this dilemma. Categories and Subject Descriptors: I.2.3 [Computing Methodologies]: Artificial Intelligence--Deduction and Theorem Proving--Answer/reason extraction, Inference Engines, Probabilistic Reasoning; 1.2.4 [Computing Methodologies]: .Artificial Intelligence--Knowledge Representation Formalisms and Methods--Bayesian Belief Nets, Rule-based Systems General Terms: Performance, Algorithms Additional Key Words and Phrases: Efficiency trade-offs, soundness/completeness/ expressibility
- Published
- 2001
23. Intelligent Distributed Simulation and Control of Power Plants
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Lee, Kwang Y., Perakis, Mark, Sevcik, Donald R., Santoso, N. Iwan, Lausterer, Gerhard K., and Samad, Tariq
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Power plants -- Technology application ,Real-time systems -- Research ,Intelligent control systems -- Research ,Business ,Electronics ,Electronics and electrical industries - Abstract
This paper presents summaries of five research and development activities in intelligent distributed simulation and control of power plants which were presented in a panel session of the same name at the IEEE Power Engineering Society Winter Meeting on February 6, 1997 in New York City. Each of the panelists discussed methods of how they have incorporated intelligent systems techniques into their research and development efforts in power plant control. The panel was organized by the Working Group on Intelligent Methods in Station Control, Station Control Subcommittee, and the Energy Development and Power Generation Committee of the IEEE Power Engineering Society. Index Terms--Control room evolution, instrumentation and control, intelligent control, power plant automation, real-time monitoring.
- Published
- 2000
24. Characterization of HPV and host genome interactions in primary head and neck cancers
- Author
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Song, X., Mahadeshwar, H., Haddad, R. I., Xu, A. W., Ren, X., Wilkerson, M. D., Jung, J., Gehlenborg, N., Ivanova, E. V., Pantazi, A., Hayes, D. N., Meyerson, M., Zhang, J., Issaeva, N., El-Naggar, A. K., Hadjipanayis, A. G., Tang, J., Parfenov, M., Park, P. J., Pedamallu, C. S., Bristow, C. A., Danilova, L., Protopopov, A., Seth, S., Wheeler, D. A., Yarbrough, W. G., Ojesina, A. I., Santoso, N., Freeman, S. S., Lee, S., Yang, L., and Grandis, J. R.
- Subjects
virus diseases ,female genital diseases and pregnancy complications - Abstract
A significant proportion of head and neck cancer is driven by human papillomavirus (HPV) infection, and the expression of viral oncogenes is involved in the development of these tumors. However, the role of HPV integration in primary tumors beyond increasing the expression of viral oncoproteins is not understood. Here, we describe how HPV integration impacts the host genome by amplification of oncogenes and disruption of tumor suppressors as well as driving inter- and intrachromosomal rearrangements. Tumors that do and do not have HPV integrants display distinct gene expression profiles and DNA methylation patterns, which further support the view that the mechanisms by which tumors with integrated and nonintegrated HPV arise are distinct.
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- 2014
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25. Cost-Constrained Power Factor Optimization with Source Harmonics Using LC Compensators.
- Author
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Richards, Gill G., Tan, Owen T., Klinkhachorn, Powsiri, and Santoso, N. Iwan
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- 1987
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26. Ecoliteracy: Integrating ecology and language education for high school students
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Suwandi, S., Ahmad Yunus, Drajati, N. A., and Santoso, N. P.
27. Comprehensive molecular profiling of lung adenocarcinoma
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Amie Radenbaugh, Noreen Dhalla, Christina Williamson, Charles Saller, James Suh, Ramaswamy Govindan, Travis I. Zack, Paul T. Spellman, Daniel DiCara, Harvey I. Pass, Deepak Srinivasan, William G. Richards, Robert J. Cerfolio, Igor Letovanec, A. Gordon Robertson, Gabriel Sica, Chad J. Creighton, Hendrik Dienemann, Jeffrey A. Borgia, Boris Reva, Bryan F. Meyers, Yiling Lu, Nikolaus Schultz, Christopher I. Amos, Dante Trusty, Carmelo Gaudioso, Michael Meister, James T. Robinson, Lihua Zou, James Shin, Jeremy Parfitt, Darlene Lee, Junyuan Wu, Carl Morrison, Scott L. Carter, Giovanni Ciriello, Nils Weinhold, Elena Nemirovich-Danchenko, Andrew Wei Xu, Christopher G. Maher, Lori Boice, Irina Zaytseva, Dennis A. Wigle, Kenna R. Mills Shaw, Matthew G. Soloway, Matthew Meyerson, Peng Chieh Chen, Frank Schneider, Troy Shelton, Douglas Voet, Steven E. Schumacher, D L Rotin, Saianand Balu, Stuart R. Jefferys, Tom Bodenheimer, Bradley A. Ozenberger, Eric S. Lander, Edward Gabrielson, Konstantin V. Fedosenko, Rehan Akbani, William D. Travis, Ari B. Kahn, Marcin Imielinski, Jacqueline E. Schein, Thomas L. Bauer, Kai Ye, Samuel A. Yousem, Robert C. Onofrio, Thomas Muley, Ayesha S. Bryant, Michael K. Asiedu, Monique Albert, Pei Lin, Corbin D. Jones, Edwina Duhig, Jean C. Zenklusen, Lucinda Fulton, Christina Yau, J. Todd Auman, Leigh B. Thorne, Elena Helman, Richard T. Cheney, William Lee, Patrick K. Kimes, Juok Cho, Alexei Protopopov, Wenbin Liu, Lee Lichtenstein, Jing Wang, Lixing Yang, W. Kimryn Rathmell, Jo Ellen Weaver, David A. Wheeler, Leslie Cope, Mark A. Watson, Heidi J. Sofia, Angeliki Pantazi, Ronglai Shen, Jeffrey Roach, Eric A. Collisson, Patrick Kwok Shing Ng, Angela Hadjipanayis, Peter S. Hammerman, David Van Den Berg, Kwun M. Fong, Nils Gehlenborg, Natasha Rekhtman, William K. Funkhouser, D. Neil Hayes, Harshad S. Mahadeshwar, Semin Lee, Martin Peifer, David Mallery, Piotr A. Mieczkowski, Ranabir Guin, Madhusmita Behera, Philipp A. Schnabel, Jill M. Siegfried, Carmen Gomez-Fernandez, Johanna Gardner, Lynn M. Herbert, Hailei Zhang, Robert S. Fulton, Travis Sullivan, Sahil Seth, Sam Ng, Chandra Sekhar Pedamallu, Barry S. Taylor, Venkatraman E. Seshan, Valerie W. Rusch, Jinze Liu, Daniel P. Raymond, Jianjiong Gao, Nathan A. Pennell, Marco A. Marra, Jan F. Prins, Payal Sipahimalani, Janae V. Simons, Joel S. Parker, Rileen Sinha, Lindy Hunter, Raju Kucherlapati, Dennis T. Maglinte, Fedor Moiseenko, Eric E. Snyder, Roy Tarnuzzer, Beverly Lee, James Stephen Marron, Kristian Cibulskis, Jerome Myers, Haiyan I. Li, Robert Penny, Hartmut Juhl, Richard K. Wilson, Zhining Wang, Eran Hodis, Carrie Sougnez, Jiabin Tang, William Mallard, Bryan Hernandez, Liming Yang, Jennifer Brown, Gad Getz, Farhad Kosari, Catrina Fronick, Juliann Chmielecki, Jianhua Zhang, Suresh S. Ramalingam, Michael Parfenov, Peter J. Park, Tanja Davidsen, Philip H. Lai, Jeff Boyd, Dang Huy Quoc Thinh, Harmanjatinder S. Sekhon, Malcolm V. Brock, Mark Pool, Margi Sheth, Kimberly M. Rieger-Christ, Michael J. Liptay, E. Getz, S. Onur Sumer, Ian A. Yang, B. Arman Aksoy, Douglas B. Flieder, Bradley M. Broom, Carrie Hirst, Solange Peters, Joshua M. Stuart, Khurram Z. Khan, Scott Morris, Donghui Tan, Andrew J. Mungall, Ming-Sound Tsao, Gordon B. Mills, Stephen B. Baylin, Rebecca Carlsen, Sanja Dacic, Julien Baboud, Brenda Rabeno, Richard A. Hajek, Lauren Averett Byers, Yaron S.N. Butterfield, Miruna Balasundaram, Chip Stewart, Katherine Tarvin, Peter B. Illei, James G. Herman, David J. Kwiatkowski, Andy Chu, David Haussler, Natasja Wye, Charles M. Perou, Peter W. Laird, Timothy J. Triche, Yan Shi, Jill P. Mesirov, Angela N. Brooks, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Lixia Diao, Anthony A. Gal, David G. Beer, Angela Tam, Ashley H. Salazar, Mark A. Jensen, Robert A. Holt, Katherine A. Hoadley, John A. Demchok, Sandra McDonald, Chandra Goparaju, David Pot, Belinda E. Clarke, Gordon Robertson, Michael C. Wendl, Helga Thorvaldsdottir, Kristen Rogers, Joshua D. Campbell, Chris Sander, Rayleen V. Bowman, Marc Danie Nazaire, Michael Mayo, Olga Voronina, Ludmila Danilova, Paul Zippile, Netty Santoso, John V. Heymach, Matthew D. Wilkerson, John Eckman, Morgan Windsor, Cureline Oleg Dolzhanskiy, Nina Thiessen, Mara Rosenberg, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Richard Varhol, Elizabeth Buda, Li Ding, Alice H. Berger, Xingzhi Song, John M. S. Bartlett, Michael D. McLellan, Olga Potapova, Joseph Paulauskis, Igor Jurisica, Benjamin Gross, Jaegil Kim, John N. Weinstein, Kevin Lau, Christopher R. Cabanski, Philip Bonomi, Michael S. Noble, Maureen F. Zakowski, George E. Sandusky, Mary Iacocca, Eric J. Burks, Erin Curley, Lynda Chin, Rajiv Dhir, Singer Ma, Sophie C. Egea, Umadevi Veluvolu, Sugy Kodeeswaran, Christopher A. Miller, Moiz S. Bootwalla, Daniel J. Weisenberger, Shaowu Meng, Mei Huang, Elaine R. Mardis, Gordon Saksena, Nicholas J. Petrelli, Yvonne Owusu-Sarpong, Christopher C. Benz, Bernard Kohl, Jingchun Zhu, David I. Heiman, Carol Farver, Scot Waring, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Stacey Gabriel, Christine Czerwinski, Alan P. Hoyle, Cancer Genome Atlas Research Network, Collisson, E. A., Campbell, J.D., Brooks, A.N., Berger, A.H., Lee, W., Chmielecki, J., Beer, D.G., Cope, L., Creighton, C.J., Danilova, L., Ding, L., Getz, G., Hammerman, P.S., Hayes, D.N., Hernandez, B., Herman, J.G., Heymach, J.V., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M.S., Travis, W.D., Weinstein, J.N., Wigle, D.A., Wilkerson, M.D., Chu, A., Cherniack, A.D., Hadjipanayis, A., Rosenberg, M., Weisenberger, D.J., Laird, P.W., Radenbaugh, A., Ma, S., Stuart, J.M., Averett Byers, L., Baylin, S.B., Govindan, R., Meyerson, M., Gabriel, S.B., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E.S., Lawrence, M.S., Kandoth, C., Fulton, R., Fulton, L.L., McLellan, M.D., Wilson, R.K., Ye, K., Fronick, C.C., Maher, C.A., Miller, C.A., Wendl, M.C., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y.S., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H.I., Mayo, M., Moore, R.A., Mungall, A.J., Schein, J.E., Sipahimalani, P., Tam, A., Varhol, R., Robertson, A., Wye, N., Thiessen, N., Holt, R.A., Jones, S.J., Marra, M.A., Imielinski, M., Onofrio, R.C., Hodis, E., Zack, T., Helman, E., Sekhar Pedamallu, C., Mesirov, J., Saksena, G., Schumacher, S.E., Carter, S.L., Garraway, L., Beroukhim, R., Lee, S., Mahadeshwar, H.S., Pantazi, A., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Yang, L., Zhang, J., Chen, P.C., Parfenov, M., Wei Xu, A., Santoso, N., Chin, L., Park, P.J., Hoadley, K.A., Auman, J.T., Meng, S., Shi, Y., Buda, E., Waring, S., Veluvolu, U., Tan, D., Mieczkowski, P.A., Jones, C.D., Simons, J.V., Soloway, M.G., Bodenheimer, T., Jefferys, S.R., Roach, J., Hoyle, A.P., Wu, J., Balu, S., Singh, D., Prins, J.F., Marron, J.S., Parker, J.S., Perou, C.M., Liu, J., Maglinte, D.T., Lai, P.H., Bootwalla, M.S., Van Den Berg, D.J., Triche, T., Cho, J., DiCara, D., Heiman, D., Lin, P., Mallard, W., Voet, D., Zhang, H., Zou, L., Noble, M.S., Gehlenborg, N., Thorvaldsdottir, H., Nazaire, M.D., Robinson, J., Aksoy, B.A., Ciriello, G., Taylor, B.S., Dresdner, G., Gao, J., Gross, B., Seshan, V.E., Reva, B., Sumer, S.O., Weinhold, N., Sander, C., Ng, S., Zhu, J., Benz, C.C., Yau, C., Haussler, D., Spellman, P.T., Kimes, P.K., Broom, B.M., Wang, J., Lu, Y., Kwok Shing Ng, P., Diao, L., Liu, W., Amos, C.I., Akbani, R., Mills, G.B., Curley, E., Paulauskis, J., Lau, K., Morris, S., Shelton, T., Mallery, D., Gardner, J., Penny, R., Saller, C., Tarvin, K., Richards, W.G., Cerfolio, R., Bryant, A., Raymond, D.P., Pennell, N.A., Farver, C., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Brown, J., Bauer, T., Dolzhanskiy, O., Potapova, O., Rotin, D., Voronina, O., Nemirovich-Danchenko, E., Fedosenko, K.V., Gal, A., Behera, M., Ramalingam, S.S., Sica, G., Flieder, D., Boyd, J., Weaver, J., Kohl, B., Huy Quoc Thinh, D., Sandusky, G., Juhl, H., Duhig, E., Illei, P., Gabrielson, E., Shin, J., Lee, B., Rodgers, K., Trusty, D., Brock, M.V., Williamson, C., Burks, E., Rieger-Christ, K., Holway, A., Sullivan, T., Asiedu, M.K., Kosari, F., Rekhtman, N., Zakowski, M., Rusch, V.W., Zippile, P., Suh, J., Pass, H., Goparaju, C., Owusu-Sarpong, Y., Bartlett, J.M., Kodeeswaran, S., Parfitt, J., Sekhon, H., Albert, M., Eckman, J., Myers, J.B., Cheney, R., Morrison, C., Gaudioso, C., Borgia, J.A., Bonomi, P., Pool, M., Liptay, M.J., Moiseenko, F., Zaytseva, I., Dienemann, H., Meister, M., Schnabel, P.A., Muley, T.R., Peifer, M., Gomez-Fernandez, C., Herbert, L., Egea, S., Huang, M., Thorne, L.B., Boice, L., Hill Salazar, A., Funkhouser, W.K., Rathmell, W.K., Dhir, R., Yousem, S.A., Dacic, S., Schneider, F., Siegfried, J.M., Hajek, R., Watson, M.A., McDonald, S., Meyers, B., Clarke, B., Yang, I.A., Fong, K.M., Hunter, L., Windsor, M., Bowman, R.V., Peters, S., Letovanec, I., Khan, K.Z., Jensen, M.A., Snyder, E.E., Srinivasan, D., Kahn, A.B., Baboud, J., Pot, D.A., Mills Shaw, K.R., Sheth, M., Davidsen, T., Demchok, J.A., Wang, Z., Tarnuzzer, R., Zenklusen, J.C., Ozenberger, B.A., Sofia, H.J., Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
- Subjects
Male ,Lung Neoplasms ,Adenocarcinoma/genetics ,Adenocarcinoma/pathology ,Cell Cycle Proteins/genetics ,Female ,Gene Dosage ,Gene Expression Regulation, Neoplastic ,Genomics ,Humans ,Lung Neoplasms/genetics ,Lung Neoplasms/pathology ,Molecular Typing ,Mutation/genetics ,Oncogenes/genetics ,Sex Factors ,Transcriptome/genetics ,Adenocarcinoma of Lung ,Cell Cycle Proteins ,Biology ,Adenocarcinoma ,Exon ,Germline mutation ,microRNA ,Adenocarcinoma of the lung ,medicine ,Gene ,Multidisciplinary ,Oncogene ,Oncogenes ,medicine.disease ,MET Exon 14 Skipping Mutation ,Molecular biology ,3. Good health ,Mutation ,Transcriptome - Abstract
Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
- Published
- 2013
28. The first use of a photogrammetry drone to estimate population abundance and predict age structure of threatened Sumatran elephants.
- Author
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Rahman DA, Herliansyah R, Subhan B, Hutasoit D, Imron MA, Kurniawan DB, Sriyanto T, Wijayanto RD, Fikriansyah MH, Siregar AF, and Santoso N
- Subjects
- Animals, Humans, Unmanned Aerial Devices, Forests, Animals, Wild, Ecosystem, Elephants
- Abstract
Wildlife monitoring in tropical rainforests poses additional challenges due to species often being elusive, cryptic, faintly colored, and preferring concealable, or difficult to access habitats. Unmanned aerial vehicles (UAVs) prove promising for wildlife surveys in different ecosystems in tropical forests and can be crucial in conserving inaccessible biodiverse areas and their associated species. Traditional surveys that involve infiltrating animal habitats could adversely affect the habits and behavior of elusive and cryptic species in response to human presence. Moreover, collecting data through traditional surveys to simultaneously estimate the abundance and demographic rates of communities of species is often prohibitively time-intensive and expensive. This study assesses the scope of drones to non-invasively access the Bukit Tigapuluh Landscape (BTL) in Riau-Jambi, Indonesia, and detect individual elephants of interest. A rotary-wing quadcopter with a vision-based sensor was tested to estimate the elephant population size and age structure. We developed hierarchical modeling and deep learning CNN to estimate elephant abundance and age structure. Drones successfully observed 96 distinct individuals at 8 locations out of 11 sampling areas. We obtained an estimate of the elephant population of 151 individuals (95% CI [124, 179]) within the study area and predicted more adult animals than subadults and juvenile individuals in the population. Our calculations may serve as a vital spark for innovation for future UAV survey designs in large areas with complex topographies while reducing operational effort., (© 2023. The Author(s).)
- Published
- 2023
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29. SARS-CoV-2 Nsp14 protein associates with IMPDH2 and activates NF-κB signaling.
- Author
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Li TW, Kenney AD, Park JG, Fiches GN, Liu H, Zhou D, Biswas A, Zhao W, Que J, Santoso N, Martinez-Sobrido L, Yount JS, and Zhu J
- Subjects
- Bortezomib, Cytokines metabolism, Humans, Inosine, Interleukin-6, Interleukin-8, Mycophenolic Acid, Oxidoreductases, Proteomics, Ribavirin, SARS-CoV-2, COVID-19, Exoribonucleases metabolism, IMP Dehydrogenase metabolism, NF-kappa B metabolism, Viral Nonstructural Proteins metabolism
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), which is known to regulate NF-κB signaling. We confirmed the Nsp14-IMPDH2 protein interaction and identified that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14- mediated NF-κB activation and cytokine induction. Furthermore, IMPDH2 inhibitors (RIB, MPA) or NF-κB inhibitors (bortezomib, BAY 11-7082) restricted SARS-CoV-2 infection, indicating that IMPDH2-mediated activation of NF-κB signaling is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in inducing NF-κB activation through IMPDH2 to promote viral infection., Competing Interests: J-GP and LM-S are listed as inventors on a pending patent application describing the SARS-CoV-2 antibody 1207B4. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Kenney, Park, Fiches, Liu, Zhou, Biswas, Zhao, Que, Santoso, Martinez-Sobrido, Yount and Zhu.)
- Published
- 2022
- Full Text
- View/download PDF
30. SARS-CoV-2 Nsp14 activates NF-κB signaling and induces IL-8 upregulation.
- Author
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Li T, Kenney AD, Liu H, Fiches GN, Zhou D, Biswas A, Que J, Santoso N, Yount JS, and Zhu J
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) protein, which is known to regulate NF-κB signaling. We confirmed the Nsp14-IMPDH2 protein interaction and found that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14-mediated NF-κB activation and cytokine induction. Furthermore, IMDPH2 inhibitors (RIB, MPA) efficiently blocked SARS-CoV-2 infection, indicating that IMDPH2, and possibly NF-κB signaling, is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in causing the activation of NF-κB.
- Published
- 2021
- Full Text
- View/download PDF
31. FACT subunit SUPT16H associates with BRD4 and contributes to silencing of antiviral interferon signaling.
- Author
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Zhou D, Park JG, Wu Z, Huang H, Fiches GN, Biswas A, Li TW, Ma Q, Martinez-Sobrido L, Santoso N, and Zhu J
- Abstract
FACT ( FA cilitates C hromatin T ranscription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated at lysine 674 (K674) of middle domain (MD), which involves TIP60 histone acetyltransferase. Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (EZH2, HDAC1) and affects histone marks (H3K9me3, H3K27me3 and H3ac). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, CBL0137 is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that CBL0137 also causes the remarkable activation of IFN signaling in natural killer (NK) cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of CBL0137 to treat viral infections.
- Published
- 2021
- Full Text
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32. Profiling of immune related genes silenced in EBV-positive gastric carcinoma identified novel restriction factors of human gammaherpesviruses.
- Author
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Fiches GN, Zhou D, Kong W, Biswas A, Ahmed EH, Baiocchi RA, Zhu J, and Santoso N
- Subjects
- Biomarkers analysis, DNA Methylation, Gammaherpesvirinae genetics, HEK293 Cells, Herpesviridae Infections virology, Homeobox A10 Proteins genetics, Humans, Incidence, Metallothionein genetics, Stomach Neoplasms epidemiology, Stomach Neoplasms metabolism, Stomach Neoplasms virology, Virus Activation, Virus Replication, Biomarkers metabolism, Epigenesis, Genetic, Gammaherpesvirinae isolation & purification, Gene Expression Regulation, Viral, Herpesviridae Infections complications, Host-Pathogen Interactions, Stomach Neoplasms genetics
- Abstract
EBV-associated gastric cancer (EBVaGC) is characterized by high frequency of DNA methylation. In this study, we investigated how epigenetic alteration of host genome contributes to pathogenesis of EBVaGC through the analysis of transcriptomic and epigenomic datasets from NIH TCGA (The Cancer Genome Atlas) consortium. We identified that immune related genes (IRGs) is a group of host genes preferentially silenced in EBV-positive gastric cancers through DNA hypermethylation. Further functional characterizations of selected IRGs reveal their novel antiviral activity against not only EBV but also KSHV. In particular, we showed that metallothionein-1 (MT1) and homeobox A (HOXA) gene clusters are down-regulated via EBV-driven DNA hypermethylation. Several MT1 isoforms suppress EBV lytic replication and release of progeny virions as well as KSHV lytic reactivation, suggesting functional redundancy of these genes. In addition, single HOXA10 isoform exerts antiviral activity against both EBV and KSHV. We also confirmed the antiviral effect of other dysregulated IRGs, such as IRAK2 and MAL, in scenario of EBV and KSHV lytic reactivation. Collectively, our results demonstrated that epigenetic silencing of IRGs is a viral strategy to escape immune surveillance and promote viral propagation, which is overall beneficial to viral oncogenesis of human gamma-herpesviruses (EBV and KSHV), considering that these IRGs possess antiviral activities against these oncoviruses., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
33. Inhibition of Polo-like kinase 1 (PLK1) facilitates the elimination of HIV-1 viral reservoirs in CD4 + T cells ex vivo.
- Author
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Zhou D, Hayashi T, Jean M, Kong W, Fiches G, Biswas A, Liu S, Yosief HO, Zhang X, Bradner J, Qi J, Zhang W, Santoso N, and Zhu J
- Subjects
- HIV-1 physiology, Humans, Virus Activation, Virus Latency, Polo-Like Kinase 1, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes virology, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins metabolism, HIV Infections, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins metabolism
- Abstract
Although combination antiretroviral therapy is effective in controlling HIV-1 infection, latent HIV-1 proviruses cannot be eliminated. HIV-1 reactivation induced by the mere use of latency-reversing agents is insufficient to render death of reservoir cells, indicating that certain intrinsic survival mechanisms exist. We report that Polo-like kinase 1 (PLK1) plays a critical role in survival of CD4
+ T cells that undergo HIV-1 reactivation from latency or de novo infection. PLK1 is elevated in both scenarios, which requires HIV-1 Nef. HIV-1 enhances PLK1 SUMOylation, causing its nuclear translocation and protein stabilization. Inhibition or knockdown of PLK1 markedly facilitates death of HIV-1-infected CD4+ T cells. Furthermore, PLK1 inhibitors strikingly reduce the size of HIV-1 latent reservoirs in primary CD4+ T cells. Our findings demonstrate that HIV-1 infection hijacks PLK1 to prevent cell death induced by viral cytopathic effects, and that PLK1 is a promising target for chemical "killing" of HIV-1 reservoir cells., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)- Published
- 2020
- Full Text
- View/download PDF
34. Nucleolar protein NOP2/NSUN1 suppresses HIV-1 transcription and promotes viral latency by competing with Tat for TAR binding and methylation.
- Author
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Kong W, Biswas A, Zhou D, Fiches G, Fujinaga K, Santoso N, and Zhu J
- Subjects
- Humans, Jurkat Cells, DNA Methylation, DNA, Viral metabolism, HIV Long Terminal Repeat, HIV-1 physiology, Nuclear Proteins metabolism, RNA, Viral metabolism, Transcription, Genetic, Virus Latency physiology, tRNA Methyltransferases metabolism, tat Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
Recent efforts have been paid to identify previously unrecognized HIV-1 latency-promoting genes (LPGs) that can potentially be targeted for eradication of HIV-1 latent reservoirs. From our earlier orthologous RNAi screens of host factors regulating HIV-1 replication, we identified that the nucleolar protein NOP2/NSUN1, a m5C RNA methyltransferase (MTase), is an HIV-1 restriction factor. Loss- and gain-of-function analyses confirmed that NOP2 restricts HIV-1 replication. Depletion of NOP2 promotes the reactivation of latently infected HIV-1 proviruses in multiple cell lines as well as primary CD4+ T cells, alone or in combination with latency-reversing agents (LRAs). Mechanistically, NOP2 associates with HIV-1 5' LTR, interacts with HIV-1 TAR RNA by competing with HIV-1 Tat protein, as well as contributes to TAR m5C methylation. RNA MTase catalytic domain (MTD) of NOP2 mediates its competition with Tat and binding with TAR. Overall, these findings verified that NOP2 suppresses HIV-1 transcription and promotes viral latency., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
35. A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG).
- Author
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Huang H, Kong W, Jean M, Fiches G, Zhou D, Hayashi T, Que J, Santoso N, and Zhu J
- Subjects
- Aminopyridines pharmacology, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes virology, Cell Line, Tumor, Cells, Cultured, Demethylation drug effects, Dioxygenases antagonists & inhibitors, Dioxygenases metabolism, Gene Expression Regulation, Viral drug effects, HEK293 Cells, HIV Infections metabolism, HIV Infections virology, HIV-1 drug effects, HIV-1 physiology, Histone Deacetylase Inhibitors pharmacology, Histone Demethylases antagonists & inhibitors, Histone Demethylases metabolism, Histones metabolism, Host-Pathogen Interactions drug effects, Host-Pathogen Interactions genetics, Humans, Hydrazones pharmacology, Methylation drug effects, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins metabolism, RNA Interference, CRISPR-Cas Systems, Dioxygenases genetics, HIV Infections genetics, HIV-1 genetics, Histone Demethylases genetics, Nuclear Proteins genetics, Virus Latency genetics
- Abstract
Although combination antiretroviral therapy is potent to block active replication of HIV-1 in AIDS patients, HIV-1 persists as transcriptionally inactive proviruses in infected cells. These HIV-1 latent reservoirs remain a major obstacle for clearance of HIV-1. Investigation of host factors regulating HIV-1 latency is critical for developing novel antiretroviral reagents to eliminate HIV-1 latent reservoirs. From our recently accomplished CRISPR/Cas9 sgRNA screens, we identified that the histone demethylase, MINA53, is potentially a novel HIV-1 latency-promoting gene (LPG). We next validated MINA53's function in maintenance of HIV-1 latency by depleting MINA53 using the alternative RNAi approach. We further identified that in vitro MINA53 preferentially demethylates the histone substrate, H3K36me3 and that in cells MINA53 depletion by RNAi also increases the local level of H3K36me3 at LTR. The effort to map the downstream effectors unraveled that H3K36me3 has the cross-talk with another epigenetic mark H4K16ac, mediated by KAT8 that recognizes the methylated H3K36 and acetylated H4K16. Removing the MINA53-mediated latency mechanisms could benefit the reversal of post-integrated latent HIV-1 proviruses for purging of reservoir cells. We further demonstrated that a pan jumonji histone demethylase inhibitor, JIB-04, inhibits MINA53-mediated demethylation of H3K36me3, and JIB-04 synergizes with other latency-reversing agents (LRAs) to reactivate latent HIV-1., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2019
- Full Text
- View/download PDF
36. Enhancing the ligand efficiency of anti-HIV compounds targeting frameshift-stimulating RNA.
- Author
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Anokhina VS, McAnany JD, Ciesla JH, Hilimire TA, Santoso N, Miao H, and Miller BL
- Subjects
- Humans, Ligands, Frameshift Mutation genetics, HIV-1 genetics, RNA, Viral metabolism
- Abstract
Ribosomal frameshifting, a process whereby a translating ribosome is diverted from one reading frame to another on a contiguous mRNA, is an important regulatory mechanism in biology and an opportunity for therapeutic intervention in several human diseases. In HIV, ribosomal frameshifting controls the ratio of Gag and Gag-Pol, two polyproteins critical to the HIV life cycle. We have previously reported compounds able to selectively bind an RNA stemloop within the Gag-Pol mRNA; these compounds alter the production of Gag-Pol in a manner consistent with increased frameshifting. Importantly, they also display antiretroviral activity in human T-cells. Here, we describe new compounds with significantly reduced molecular weight, but with substantially maintained affinity and anti-HIV activity. These results suggest that development of more "ligand efficient" enhancers of ribosomal frameshifting is an achievable goal., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
37. Diversified Application of Barcoded PLATO (PLATO-BC) Platform for Identification of Protein Interactions.
- Author
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Kong W, Hayashi T, Fiches G, Xu Q, Li MZ, Que J, Liu S, Zhang W, Qi J, Santoso N, Elledge SJ, and Zhu J
- Subjects
- Antibodies metabolism, HEK293 Cells, Humans, Peptides metabolism, Protein Binding, Ubiquitin metabolism, Zika Virus physiology, Zika Virus Infection genetics, Zika Virus Infection virology, Open Reading Frames genetics, Protein Interaction Mapping methods
- Abstract
Proteins usually associate with other molecules physically to execute their functions. Identifying these interactions is important for the functional analysis of proteins. Previously, we reported the parallel analysis of translated ORFs (PLATO) to couple ribosome display of full-length ORFs with affinity enrichment of mRNA/protein/ribosome complexes for the "bait" molecules, followed by the deep sequencing analysis of mRNA. However, the sample processing, from extraction of precipitated mRNA to generation of DNA libraries, includes numerous steps, which is tedious and may cause the loss of materials. Barcoded PLATO (PLATO-BC), an improved platform was further developed to test its application for protein interaction discovery. In this report, we tested the antisera-antigen interaction using serum samples from patients with inclusion body myositis (IBM). Tripartite motif containing 21 (TRIM21) was identified as a potentially new IBM autoantigen. We also expanded the application of PLATO-BC to identify protein interactions for JQ1, single ubiquitin peptide, and NS5 protein of Zika virus. From PLATO-BC analyses, we identified new protein interactions for these "bait" molecules. We demonstrate that Ewing sarcoma breakpoint region 1 (EWSR1) binds to JQ1 and their interactions may interrupt the EWSR1 association with acetylated histone H4. RIO kinase 3 (RIOK3), a newly identified ubiquitin-binding protein, is preferentially associated with K63-ubiquitin chain. We also find that Zika NS5 protein interacts with two previously unreported host proteins, par-3 family cell polarity regulator (PARD3) and chromosome 19 open reading frame 53 (C19orf53), whose attenuated expression benefits the replication of Zika virus. These results further demonstrate that PLATO-BC is capable of identifying novel protein interactions for various types of "bait" molecules., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
38. Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity.
- Author
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Chaimayo C, Dunagan M, Hayashi T, Santoso N, and Takimoto T
- Subjects
- A549 Cells, Antiviral Agents, HEK293 Cells, Humans, Immunity, Innate immunology, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype immunology, Influenza A virus genetics, Influenza, Human virology, Interferons metabolism, Protein Biosynthesis physiology, RNA, Messenger metabolism, Repressor Proteins genetics, Viral Nonstructural Proteins genetics, Virus Replication, Host-Pathogen Interactions physiology, Repressor Proteins metabolism, Viral Nonstructural Proteins metabolism
- Abstract
Influenza A viruses modulate host antiviral responses to promote viral growth and pathogenicity. Through viral PA-X and NS1 proteins, the virus is capable of suppressing host protein synthesis, termed "host shutoff." Although both proteins are known to induce general shutoff, specificity of target genes and their functional interplay in mediating host shutoff are not fully elucidated. In this study, we generated four recombinant influenza A/California/04/2009 (pH1N1) viruses containing mutations affecting the expression of active PA-X and NS1. We analyzed viral growth, general shutoff activity, specificity of mRNA targets, and viral gene expressions. Our results showed that PA-X was the major contributor in reducing general host protein expression in the virus-infected cells. Intriguingly, our transcriptomic analysis from infected human airway A549 cells indicate that shutoff-active NS1 specifically targeted host mRNAs related to interferon (IFN) signaling pathways and cytokine release. Specificity of target mRNAs was less evident in PA-X, although it preferentially degraded genes associated with cellular protein metabolism and protein repair. Interestingly, in the presence of shutoff-active NS1, PA-X also degraded viral mRNAs, especially NS segments. The virus expressing shutoff-active NS1 with reduced amount of PA-X expression most efficiently suppressed antiviral and innate immune responses in human cells, indicating that influenza virus needs to optimize the contribution of these two shutoff proteins to circumvent host responses for its optimum growth., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
39. Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency.
- Author
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Jean MJ, Power D, Kong W, Huang H, Santoso N, and Zhu J
- Subjects
- Humans, Jurkat Cells, Protein Binding, Proteome analysis, HIV-1 physiology, Host-Pathogen Interactions, Transcription, Genetic, Virus Latency, tat Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat. These TAPs also suppress Tat-mediated HIV-1 transcription. Removing suppression of HIV-1 transcription benefits the reversal of post-integrated, latent HIV-1 proviruses. We demonstrate that these transcriptionally suppressing TAPs contribute to HIV-1 latency in Jurkat latency (J-LAT) cells. Therefore, our proteomic analysis highlights the previously unappreciated TAPs that play a role in maintaining HIV-1 latency and can be further studied as potential pharmacological targets for the "shock and kill" HIV-1 cure strategy.
- Published
- 2017
- Full Text
- View/download PDF
40. FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency.
- Author
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Huang H, Santoso N, Power D, Simpson S, Dieringer M, Miao H, Gurova K, Giam CZ, Elledge SJ, and Zhu J
- Subjects
- CD4-Positive T-Lymphocytes physiology, CD4-Positive T-Lymphocytes virology, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins genetics, Cell Line, Cyclin T physiology, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins genetics, HEK293 Cells, HIV Long Terminal Repeat, HIV-1 genetics, High Mobility Group Proteins antagonists & inhibitors, High Mobility Group Proteins genetics, Host-Pathogen Interactions genetics, Host-Pathogen Interactions physiology, Human T-lymphotropic virus 1 genetics, Humans, Models, Biological, Positive Transcriptional Elongation Factor B physiology, Promoter Regions, Genetic, RNA Interference, Transcription Factors antagonists & inhibitors, Transcription Factors genetics, Transcriptional Elongation Factors antagonists & inhibitors, Transcriptional Elongation Factors genetics, Virus Latency genetics, Cell Cycle Proteins physiology, DNA-Binding Proteins physiology, HIV-1 physiology, High Mobility Group Proteins physiology, Human T-lymphotropic virus 1 physiology, Transcription Factors physiology, Transcriptional Elongation Factors physiology, Virus Latency physiology
- Abstract
Our functional genomic RNAi screens have identified the protein components of the FACT (facilitates chromatin transcription) complex, SUPT16H and SSRP1, as top host factors that negatively regulate HIV-1 replication. FACT interacts specifically with histones H2A/H2B to affect assembly and disassembly of nucleosomes, as well as transcription elongation. We further investigated the suppressive role of FACT proteins in HIV-1 transcription. First, depletion of SUPT16H or SSRP1 protein enhances Tat-mediated HIV-1 LTR (long terminal repeat) promoter activity. Second, HIV-1 Tat interacts with SUPT16H but not SSRP1 protein. However, both SUPT16H and SSRP1 are recruited to LTR promoter. Third, the presence of SUPT16H interferes with the association of Cyclin T1 (CCNT1), a subunit of P-TEFb, with the Tat-LTR axis. Removing inhibitory mechanisms to permit HIV-1 transcription is an initial and key regulatory step to reverse post-integrated latent HIV-1 proviruses for purging of reservoir cells. We therefore evaluated the role of FACT proteins in HIV-1 latency and reactivation. Depletion of SUPT16H or SSRP1 protein affects both HIV-1 transcriptional initiation and elongation and spontaneously reverses latent HIV-1 in U1/HIV and J-LAT cells. Similar effects were observed with a primary CD4+ T cell model of HIV-1 latency. FACT proteins also interfere with HTLV-1 Tax-LTR-mediated transcription and viral latency, indicating that they may act as general transcriptional suppressors for retroviruses. We conclude that FACT proteins SUPT16H and SSRP1 play a key role in suppressing HIV-1 transcription and promoting viral latency, which may serve as promising gene targets for developing novel HIV-1 latency-reversing agents., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
41. IFI44 suppresses HIV-1 LTR promoter activity and facilitates its latency.
- Author
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Power D, Santoso N, Dieringer M, Yu J, Huang H, Simpson S, Seth I, Miao H, and Zhu J
- Subjects
- Antigens genetics, Cell Line, Cell Nucleus genetics, Cell Nucleus metabolism, Cell Nucleus virology, Cytoskeletal Proteins genetics, Gene Expression Regulation, Viral, HIV Infections genetics, HIV-1 genetics, Humans, Protein Transport, Virus Replication, Antigens metabolism, Cytoskeletal Proteins metabolism, Down-Regulation, HIV Infections metabolism, HIV Infections virology, HIV Long Terminal Repeat, HIV-1 physiology, Virus Latency
- Abstract
IFI44 is an interferon-alfa inducible protein, and is associated with infection of several viruses. However, IFI44 elicits minimal antiviral effects on these viruses, and its exact role is still unknown. Here we show that IFI44 inhibits HIV-1 replication in vitro. Through depletion of endogenous IFI44 or overexpression of IFI44 we confirm that IFI44 suppresses HIV-1 LTR promoter activity and affects viral transcription. Furthermore, we find that IFI44 localizes to nuclei and binds to the HIV-1 LTR promoter in HIV-1 infected cells. Removing suppression of HIV-1 transcription benefits reactivation of HIV-1 proviruses for purging latent reservoirs. We demonstrate that depletion of endogenous IFI44 in J-LAT cells induces reactivation of latent HIV-1. Based on these results, we propose a model in which IFI44 is recruited to the HIV-1 LTR, which may suppress viral transcription and prevent reactivation of latent HIV-1. Our study suggests a previously unrecognized anti-HIV phenomenon for interferon-stimulated proteins., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
42. Characterization of HPV and host genome interactions in primary head and neck cancers.
- Author
-
Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, Protopopov A, Yang L, Seth S, Song X, Tang J, Ren X, Zhang J, Pantazi A, Santoso N, Xu AW, Mahadeshwar H, Wheeler DA, Haddad RI, Jung J, Ojesina AI, Issaeva N, Yarbrough WG, Hayes DN, Grandis JR, El-Naggar AK, Meyerson M, Park PJ, Chin L, Seidman JG, Hammerman PS, and Kucherlapati R
- Subjects
- Base Sequence, DNA Methylation genetics, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Humans, Molecular Sequence Data, Virus Integration genetics, Genome, Human genetics, Head and Neck Neoplasms genetics, Head and Neck Neoplasms virology, Host-Pathogen Interactions genetics, Papillomaviridae physiology
- Abstract
Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
- Published
- 2014
- Full Text
- View/download PDF
43. Administration of ketoprofen suppositories for out-patient post-operative analgesia.
- Author
-
Himendra A, Rasman M, Sutisna A, Adipradja K, and Santoso N
- Subjects
- Adenofibroma surgery, Adolescent, Adult, Ambulatory Care, Breast Neoplasms surgery, Double-Blind Method, Female, Humans, Ketoprofen adverse effects, Lymphatic Diseases surgery, Postoperative Complications prevention & control, Random Allocation, Suppositories, Time Factors, Ketoprofen therapeutic use, Pain prevention & control, Phenylpropionates therapeutic use, Premedication methods
- Abstract
A double-blind, randomized, placebo-controlled study was carried out to assess the efficacy of ketoprofen suppositories as a post-operative analgesic in out-patients undergoing extirpation surgery. Thirty patients received 2 X 100 mg ketoprofen suppositories, and 30 patients received placebo suppositories 1-hour pre-operatively. Patients received no premedication and the anaesthetic used was intravenous diazepam and ketamine administered by intravenous drip according to the patient's need. Subjective symptoms of pain were evaluated 15, 30, 60 and 90 minutes post-operatively. None of the patients who received ketoprofen complained of post-operative pain, whereas the patients on placebo showed varying degrees of pain. The only side-effects recorded were nausea and vomiting both in ketoprofen and placebo-treated patients and these were probably related to the anaesthetic.
- Published
- 1985
- Full Text
- View/download PDF
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