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1. SARS-CoV-2 infection dynamics and genomic surveillance to detect variants in wastewater – a longitudinal study in Bengaluru, IndiaResearch in context

Author

Sanjay Lamba, Sutharsan Ganesan, Namrta Daroch, Kiran Paul, Soumya Gopal Joshi, Darshan Sreenivas, Annamalai Nataraj, Vishwanath Srikantaiah, Rakesh Mishra, Uma Ramakrishnan, and Farah Ishtiaq

Subjects
Environment surveillance, SARS-CoV-2, Genomics, Variants, India, Bengaluru, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Environmental surveillance (ES) of a pathogen is crucial for understanding the community load of disease. As an early warning system, ES for SARS-CoV-2 has complemented routine diagnostic surveillance by capturing near real-time virus circulation at a population level. Methods: In this longitudinal study conducted between January 2022 and June 2022 in 28 sewershed sites in Bengaluru city (∼11 million inhabitants), we quantified weekly SARS-CoV-2 RNA concentrations to track infection dynamics and provide evidence of change in the relative abundance of emerging variants. Findings: We describe an early warning system using the exponentially weighted moving average control chart and demonstrate how SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 8–14 days earlier in wastewater than in clinical data. This was further corroborated by showing that the estimated number of infections is strongly correlated with SARS-CoV-2 RNA copies detected in the wastewater. Using a deconvolution matrix, we detected emerging variants of concern up to two months earlier in wastewater samples. In addition, we found a huge diversity in variants detected in wastewater compared to clinical samples. The findings from this study have been discussed regularly with local authorities to inform policy-making decisions. Interpretation: Our study highlights that quantifying viral titre, correlating it with a known number of cases in the area, and combined with genomic surveillance helps in tracking variants of concern (VOC) over time and space, enabling timely and making informed policy decisions. Funding: This work has been supported by funding from the Rockefeller Foundation grant to National Centre for Biological Sciences, TIFR) and the Indian Council of Medical Research grant to (FI) Tata Institute for Genetics and Society and Tata Trusts.

Published
2023
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2. The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

Author

Aditi Thakare, Chaitali Ghosh, Tejashwini Alalamath, Naveen Kumar, Himani Narang, Saurabh Whadgar, Kiran Paul, Shweta Shrotri, Sampath Kumar, M. Soumya, Raksha Rao, Mahul Chakraborty, Bibha Choudhary, Susanta K. Ghosh, Suresh Subramani, Sunita Swain, and Subhashini Srinivasan

Subjects
Medicine, Science
Abstract

Abstract Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.

Published
2022
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3. Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly

Author

Mahul Chakraborty, Arunachalam Ramaiah, Adriana Adolfi, Paige Halas, Bhagyashree Kaduskar, Luna Thanh Ngo, Suvratha Jayaprasad, Kiran Paul, Saurabh Whadgar, Subhashini Srinivasan, Suresh Subramani, Ethan Bier, Anthony A. James, and J. J. Emerson

Subjects
Anopheles stephensi, Reference-quality assembly, Transposable elements, Insecticide resistance, Y chromosome, Malaria control, Biology (General), QH301-705.5
Abstract

Abstract Background The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution. Results To access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element (TE) families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed in An. stephensi. We identified 2.4 Mb of the Y chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y chromosome in any mosquito. By tracking full-length mRNA for > 15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively throughout male development and adulthood, suggesting an important role. Conclusion Collectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate the development of genetic control strategies of malaria transmission.

Published
2021
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5. A Near-Chromosome Level Genome Assembly of Anopheles stephensi

Author

Afiya Razia Chida, Samathmika Ravi, Suvratha Jayaprasad, Kiran Paul, Jaysmita Saha, Chinjusha Suresh, Saurabh Whadgar, Naveen Kumar, Raksha Rao K, Chaitali Ghosh, Bibha Choudhary, Suresh Subramani, and Subhashini Srinivasan

Subjects
homology-based assembly, simulated mate-pair, comparative genomics, genome browser, olfactory receptors, cytochromeP450, Genetics, QH426-470
Abstract

Malaria remains a major healthcare risk to growing economies like India, and a chromosome-level reference genome of Anopheles stephensi is critical for successful vector management and understanding of vector evolution using comparative genomics. We report chromosome-level assemblies of an Indian strain, STE2, and a Pakistani strain SDA-500 by combining draft genomes of the two strains using a homology-based iterative approach. The resulting assembly IndV3/PakV3 with L50 of 9/12 and N50 6.3/6.9 Mb had scaffolds long enough for building 90% of the euchromatic regions of the three chromosomes, IndV3s/PakV3s, using low-resolution physical markers and enabled the generation of the next version of genome assemblies, IndV4/PakV4, using HiC data. We have validated these assemblies using contact maps against publicly available HiC raw data from two strains including STE2 and another lab strain of An. stephensi from UCI and compare the quality of the assemblies with other assemblies made available as preprints since the submission of the manuscript. We show that the IndV3s and IndV4 assemblies are sensitive in identifying a homozygous 2Rb inversion in the UCI strain and a 2Rb polymorphism in the STE2 strain. Multiple tandem copies of CYP6a14, 4c1, and 4c21 genes, implicated in insecticide resistance, lie within this inversion locus. Comparison of assembled genomes suggests a variation of 1 in 81 positions between the UCI and STE2 lab strains, 1 in 82 between SDA-500 and UCI strain, and 1 in 113 between SDA-500 and STE2 strains of An. stephensi, which are closer than 1 in 68 variations among individuals from two other lab strains sequenced and reported here. Based on the developmental transcriptome and orthology of all the 54 olfactory receptors (ORs) to those of other Anopheles species, we identify an OR with the potential for host recognition in the genus Anopheles. A comparative analysis of An. stephensi genomes with the completed genomes of a few other Anopheles species suggests limited inter-chromosomal gene flow and loss of synteny within chromosomal arms even among the closely related species.

Published
2020
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6. SARS-CoV-2 infection dynamics and genomic surveillance reveals early variant transmission in urban wastewater

Author

Sanjay Lamba, G Sutharsan, Namrta Daroch, Kiran Paul, Soumya Gopal Joshi, S Darshan, N Annamalai, S Vishwanath, Rakesh Mishra, Uma Ramakrishnan, and Farah Ishtiaq

Abstract

Environmental surveillance (ES) of a pathogen is crucial for understanding the community load of disease. As an early warning system, ES for SARS-CoV-2 has complemented routine diagnostic surveillance by capturing near real-time virus circulation at a population level. In this longitudinal study in 28 sewershed sites in Bangalore city, we quantified SARS-CoV-2 RNA to track infection dynamics and provide evidence of change in the relative abundance of emerging variants. We describe an early warning system using the exponentially weighted moving average control chart and demonstrate how SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 8–14 days earlier in wastewater than in clinical data. This was further corroborated by showing that the estimated number of infections is strongly correlated with SARS-CoV-2 RNA copies detected in the wastewater. Using a deconvolution matrix, we detected emerging variants of concern up to two months earlier in wastewater samples. In addition, we found a huge diversity in variants detected in wastewater compared to clinical samples. Our study highlights that quantifying viral titres, correlating it with a known number of cases in the area, and combined with genomic surveillance helps in tracking VOCs over time and space, enabling timely and making informed policy decisions.

Published
2022

8. The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

Author

Aditi Thakare, Chaitali Ghosh, Tejashwini Alalamath, Naveen Kumar, Himani Narang, Saurabh Whadgar, Kiran Paul, Shweta Shrotri, Sampath Kumar, M. Soumya, Raksha Rao, Mahul Chakraborty, Bibha Choudhary, Susanta K. Ghosh, Suresh Subramani, Sunita Swain, and Subhashini Srinivasan

Subjects
Multidisciplinary, India, Water, Mosquito Vectors, Malaria, Vector-Borne Diseases, Rare Diseases, Infectious Diseases, Good Health and Well Being, Anopheles, Chromosome Inversion, Genetics, 2.2 Factors relating to the physical environment, Animals, Aetiology, Infection
Abstract

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.

Published
2021

9. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. Beckett, Helena J. Mauceri, Yang-Xin Fu, Ralph R. Weichselbaum, Whitney Lewis, Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Dongyun Wu, Jin Li, Xiaoling Liang, Xiangjun Zhou, Jinlin Hou, Raffit Hassan, Thierry Jahan, Scott J. Antonia, Hedy L. Kindler, Evan W. Alley, Somayeh Honarmand, Weiqun Liu, Meredith L. Leong, Chan C. Whiting, Nitya Nair, Amanda Enstrom, Edward E. Lemmens, Takahiro Tsujikawa, Sushil Kumar, Lisa M. Coussens, Aimee L. Murphy, Dirk G. Brockstedt, Sven D. Koch, Martin Sebastian, Christian Weiss, Martin Früh, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geissler, Frank Griesinger, Jens Kollmeier, Alexandros Papachristofilou, Fatma Doener, Mariola Fotin-Mleczek, Madeleine Hipp, Henoch S. Hong, Karl-Josef Kallen, Ute Klinkhardt, Claudia Stosnach, Birgit Scheel, Andreas Schroeder, Tobias Seibel, Ulrike Gnad-Vogt, Alfred Zippelius, Ha-Ram Park, Yong-Oon Ahn, Tae Min Kim, Soyeon Kim, Seulki Kim, Yu Soo Lee, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Shari Pilon-Thomas, Amy Weber, Jennifer Morse, Krithika Kodumudi, Hao Liu, John Mullinax, Amod A. Sarnaik, Luke Pike, Andrew Bang, Tracy Balboni, Allison Taylor, Alexander Spektor, Tyler Wilhite, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal Aizer, Elizabeth Buchbinder, Mark Awad, Leena Ghandi, Jonathan Schoenfeld, Elizabeth Lessey-Morillon, Lisa Ridnour, Neil H. Segal, Manish Sharma, Dung T. Le, Robert L. Ferris, Andrew D. Zelenetz, Ronald Levy, Izidore S. Lossos, Caron Jacobson, Radhakrishnan Ramchandren, John Godwin, A. Dimitrios Colevas, Roland Meier, Suba Krishnan, Xuemin Gu, Jaclyn Neely, John Timmerman, Claire I. Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Erik Wennerberg, Aranzazu Mediero, Bruce N. Cronstein, Michael P. Gustafson, AriCeli DiCostanzo, Courtney Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A. Gastineau, Bruce D. Johnson, Allan B. Dietz, Cameron MacDonald, Mark Bucsek, Guanxi Qiao, Bonnie Hylander, Elizabeth Repasky, William J. Turbitt, Yitong Xu, Andrea Mastro, Connie J. Rogers, Sita Withers, Ziming Wang, Lam T. Khuat, Cordelia Dunai, Bruce R. Blazar, Dan Longo, Robert Rebhun, Steven K. Grossenbacher, Arta Monjazeb, William J. Murphy, Scott Rowlinson, Giulia Agnello, Susan Alters, David Lowe, Nicole Scharping, Ashley V. Menk, Ryan Whetstone, Xue Zeng, Greg M. Delgoffe, Patricia M. Santos, Jian Shi, Greg Delgoffe, Misako Nagasaka, Ammar Sukari, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Natalie Collins, Robert Manguso, Hans Pope, Yashaswi Shrestha, Jesse Boehm, W. Nicholas Haining, Kyle R. Cron, Ayelet Sivan, Keston Aquino-Michaels, Marco Orecchioni, Davide Bedognetti, Wouter Hendrickx, Claudia Fuoco, Filomena Spada, Francesco Sgarrella, Gianni Cesareni, Francesco Marincola, Kostas Kostarelos, Alberto Bianco, Lucia Delogu, Jessica Roelands, Sabri Boughorbel, Julie Decock, Scott Presnell, Ena Wang, Franco M. Marincola, Peter Kuppen, Michele Ceccarelli, Darawan Rinchai, Damien Chaussabel, Lance Miller, Andrew Nguyen, J. Zachary Sanborn, Charles Vaske, Shahrooz Rabizadeh, Kayvan Niazi, Steven Benz, Shashank Patel, Nicholas Restifo, James White, Sam Angiuoli, Mark Sausen, Sian Jones, Maria Sevdali, John Simmons, Victor Velculescu, Luis Diaz, Theresa Zhang, Jennifer S. Sims, Sunjay M. Barton, Angela Kadenhe-Chiweshe, Filemon Dela Cruz, Andrew T. Turk, Christopher F. Mazzeo, Andrew L. Kung, Jeffrey N. Bruce, Darrell J. Yamashiro, Eileen P. Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. Myers, Stuart Curbishley, Sarah A. Penny, Lora Steadman, David Millar, Ellen Speers, Nicola Ruth, Gabriel Wong, Robert Thimme, David Adams, Mark Cobbold, Remy Thomas, Mariam Al-Muftah, Michael KK Wong, Michael Morse, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Tharak Rao, Janice P. Dutcher, Kai Kang, Yogen Saunthararajah, Vamsidhar Velcheti, Vikas Kumar, Firoz Anwar, Amita Verma, Zinal Chheda, Gary Kohanbash, John Sidney, Kaori Okada, Shruti Shrivastav, Diego A. Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada, Jessica J. Field, Weiping Zeng, Vincent FS Shih, Che-Leung Law, Peter D. Senter, Shyra J. Gardai, Nicole M. Okeley, Jennifer G. Abelin, Abu Z. Saeed, Stacy A. Malaker, Jeffrey Shabanowitz, Stephen T. Ward, Donald F. Hunt, Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Manuel Schmidt, Julian P. Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. 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Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. 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Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016

10. Nature Inspired Based Pitch Controller Design of an UAV

Author

Kiran Paul, Santosh Tutika, Chakravarthi Jada, and S. Omkar

Subjects
Engineering, Mean squared error, Payload, business.industry, Dynamic data, MathematicsofComputing_NUMERICALANALYSIS, Aerospace Engineering, PID controller, ComputerApplications_COMPUTERSINOTHERSYSTEMS, Root locus, Control engineering, Control theory, Control system, ComputerSystemsOrganization_SPECIAL-PURPOSEANDAPPLICATION-BASEDSYSTEMS, Penalty method, Time domain, business
Abstract

In this paper a longitudinal control system has been designed for a 2 Kg payload Unmanned Aerial Vehicle using classical PID controller. To overcome the difficulty in tuning the PID gains to the required values, different nature inspired techniques have been used, for the Integral Squared Error (ISE) parameter optimization on UAV dynamic data at a specified trim condition. For this purpose, the penalty function that has been chosen includes time domain specifications as constraints. Finally all the results are compared for optimum PID parameters.

Published
2011

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