Relevant bibliographies by topics / New class discovery

Academic literature on the topic 'New class discovery'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "New class discovery"

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Golub, T. R., D. K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J. P. Mesirov, H. Coller, et al. "Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring." Science 286, no. 5439 (October 15, 1999): 531–37. http://dx.doi.org/10.1126/science.286.5439.531.

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Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
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Fukunaga, Alex S. "Automated Discovery of Local Search Heuristics for Satisfiability Testing." Evolutionary Computation 16, no. 1 (March 2008): 31–61. http://dx.doi.org/10.1162/evco.2008.16.1.31.

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The development of successful metaheuristic algorithms such as local search for a difficult problem such as satisfiability testing (SAT) is a challenging task. We investigate an evolutionary approach to automating the discovery of new local search heuristics for SAT. We show that several well-known SAT local search algorithms such as Walksat and Novelty are composite heuristics that are derived from novel combinations of a set of building blocks. Based on this observation, we developed CLASS, a genetic programming system that uses a simple composition operator to automatically discover SAT local search heuristics. New heuristics discovered by CLASS are shown to be competitive with the best Walksat variants, including Novelty+. Evolutionary algorithms have previously been applied to directly evolve a solution for a particular SAT instance. We show that the heuristics discovered by CLASS are also competitive with these previous, direct evolutionary approaches for SAT. We also analyze the local search behavior of the learned heuristics using the depth, mobility, and coverage metrics proposed by Schuurmans and Southey.
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Dumas, Jacques, Robert Sibley, Bernd Riedl, Mary Katherine Monahan, Wendy Lee, Timothy B. Lowinger, Anikó M. Redman, et al. "Discovery of a new class of p38 kinase inhibitors." Bioorganic & Medicinal Chemistry Letters 10, no. 18 (September 2000): 2047–50. http://dx.doi.org/10.1016/s0960-894x(00)00270-5.

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BOND, S., A. DRAFFAN, J. LAMBERT, C. LIM, B. LIN, A. LUTTICK, J. MITCHELL, C. MORTON, R. NEARN, and V. SANFORD. "Discovery of a New Class of Polycyclic RSV Inhibitors." Antiviral Research 74, no. 3 (June 2007): A30. http://dx.doi.org/10.1016/j.antiviral.2007.01.017.

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Koltun, Elena, Steven Richards, Vicky Chan, Jason Nachtigall, Hongwang Du, Kevin Noson, Adam Galan, et al. "Discovery of a new class of glucosylceramide synthase inhibitors." Bioorganic & Medicinal Chemistry Letters 21, no. 22 (November 2011): 6773–77. http://dx.doi.org/10.1016/j.bmcl.2011.09.037.

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Mihalic, Jeffrey T., Yong-Jae Kim, Mike Lizarzaburu, Xiaoqi Chen, Jeff Deignan, Malgorzata Wanska, Ming Yu, et al. "Discovery of a new class of ghrelin receptor antagonists." Bioorganic & Medicinal Chemistry Letters 22, no. 5 (March 2012): 2046–51. http://dx.doi.org/10.1016/j.bmcl.2012.01.014.

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Bortolato, Andrea, Andrew S. Doré, Kaspar Hollenstein, Benjamin G. Tehan, Jonathan S. Mason, and Fiona H. Marshall. "Structure of Class B GPCRs: new horizons for drug discovery." British Journal of Pharmacology 171, no. 13 (June 10, 2014): 3132–45. http://dx.doi.org/10.1111/bph.12689.

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Stout, T. J., M. P. Costi, D. Barlocco, M. Rinaldi, B. Shoichet, K. M. Perry, I. D. Kuntz, and R. M. Stroud. "Structure-based discovery of a new class of enzyme inhibitors." Acta Crystallographica Section A Foundations of Crystallography 52, a1 (August 8, 1996): C207. http://dx.doi.org/10.1107/s0108767396091064.

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Pancotti, A., S. Parapini, M. Dell'Agli, L. Gambini, C. Galli, E. Sangiovanni, N. Basilico, E. Bosisio, D. Taramelli, and S. Romeo. "Discovery of oxybisbenzoylamides as a new class of antimalarial agents." MedChemComm 6, no. 6 (2015): 1173–77. http://dx.doi.org/10.1039/c5md00115c.

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Chung, Chun-wa, and David F. Tough. "Bromodomains: a new target class for small molecule drug discovery." Drug Discovery Today: Therapeutic Strategies 9, no. 2-3 (September 2012): e111-e120. http://dx.doi.org/10.1016/j.ddstr.2011.12.002.

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Dissertations / Theses on the topic "New class discovery"

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Peterson, David H. "Pastor's discovery class a doctrinal course for all church newcomers /." Online full text .pdf document, available to Fuller patrons only, 2003. http://www.tren.com.

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Ordway, Gregory A. "Discovery of a New Biological Target for the Development of a Novel Class of Antidepressant Drugs." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/8655.

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Pao, Kuan-Chuan. "Design and synthesis of an E3 ligase activity-based probe and its application for the discovery of a new class of E3 ligase." Thesis, University of Dundee, 2018. https://discovery.dundee.ac.uk/en/studentTheses/6239e172-60b3-47c3-81e1-f4b0a577f1a4.

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The ubiquitylation cascade regulates multiple cellular functions and is involved in numerous diseases. The distinct transfer cascade, involving E1-E2-E3 enzymes, serves as a promising target for drug development. However, E3 ligases (E3s) represent an important class of enzymes yet there are currently no effective tools for profiling their activity. Herein, a new class of E3 activity-based probe (ABP) is presented which is built by re-engineering ubiquitin (Ub)-charged E2 conjugating enzymes. The utility of these probes has been demonstrated by the rapid dissection of the activation determinants of the RING-Between-RING E3 (RBR) E3, Parkin. Furthermore, biotin-E3 ABPs allow us to systematically discover and dissect the E3 activities of a broad spectrum of E3s that are associated with different diseases. By interfacing the ABPs with mass spectrometry, we establish an activity based protein profiling (ABPP) system and apply it to uncover a new class of E3. We show that MYCBP2 is an E3 ligase with a novel mechanism of action that ubiquitylates threonine residues. MYCBP2 contains a RING domain, that recruits the ubiquitin-loaded E2, and a novel Zn-binding fold that contains two catalytic cysteine residues which relay the Ub to substrate via two thioester intermediates (RING-Cys-Relay, RCR). This discovery demonstrates the power and potential of our E3 activity based protein profiling (ABPP) system.
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Books on the topic "New class discovery"

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W.H. Freeman and Company. New Class Set Science in a Technical World: Drug Discovery & CDR & Vid & Lab NB. W. H. Freeman, 2003.

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James H, Carter, and Fellas John, eds. International Commercial Arbitration in New York. Oxford University Press, 2016. http://dx.doi.org/10.1093/law/9780198753483.001.0001.

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New York is a leading venue for international commercial arbitration, home to the headquarters of the International Centre for Dispute Resolution, the international branch of the American Arbitration Association, and many leaders in the international arbitration field. New York also serves as the locus of several prominent arbitration firms’ central offices. This book encompasses five years of developments in New York and other U.S. international arbitration law since the first edition appeared. Every chapter has been updated, and the new edition includes an entirely new chapter on the legal and practical aspects of conducting an arbitration hearing in New York, covering such subjects as rights to appear as a representative of a party, subpoenas to compel attendance of witnesses, confidentiality of proceedings, and witness testimony and instructions. Each chapter elucidates a vital topic, including the existing New York legal landscape, drafting considerations for clauses designating New York as the place of arbitration, and material and advice on selecting arbitrators. The book also covers a series of topics at the intersection of the arbitral process and the New York courts, including jurisdiction, enforcing arbitration agreements, obtaining preliminary relief, and discovery. Class action arbitration, challenging and enforcing arbitral awards, and biographical materials on New York-based international arbitrators are also included.
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Dempsey, Jareed, Phoe-nix Nebula, Linda Moore, Monique Young, and Solomon Perry. My First Skate Class: 5 Minute Skate Lessons from New Superhero, Skate Woman! Discover Quick Tips and Tricks to Skate Cool. Independently Published, 2018.

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Schehr, Grégory, Alexander Altland, Yan V. Fyodorov, Neil O'Connell, and Leticia F. Cugliandolo, eds. Stochastic Processes and Random Matrices. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198797319.001.0001.

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The field of stochastic processes and random matrix theory (RMT) has been a rapidly evolving subject during the past fifteen years where the continuous development and discovery of new tools, connections, and ideas have led to an avalanche of new results. These breakthroughs have been made possible thanks, to a large extent, to the recent development of various new techniques in RMT. Matrix models have been playing an important role in theoretical physics for a long time and they are currently also a very active domain of research in mathematics. An emblematic example of these recent advances concerns the theory of growth phenomena in the Kardar–Parisi–Zhang (KPZ) universality class where the joint efforts of physicists and mathematicians during the past twenty years have unveiled the beautiful connections between this fundamental problem of statistical mechanics and the theory of random matrices, namely the fluctuations of the largest eigenvalue of certain ensemble of random matrices. These chapters not only cover this topic in detail but also present more recent developments that have emerged from these discoveries, for instance in the context of low-dimensional heat transport (on the physics side) or in the context of integrable probability (on the mathematical side).
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Horwitz, Ilana M. God, Grades, and Graduation. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780197534144.001.0001.

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It’s widely acknowledged that American parents from different class backgrounds take different approaches to raising their children. But missing from the discussion is the fact that millions of parents on both sides of the class divide are raising their children to listen to God. What impact does a religious upbringing have on their academic trajectories? Drawing on 10 years of survey data with over 3,000 teenagers and over 200 interviews, God, Grades, and Graduation offers a revealing and at times surprising account of how teenagers’ religious upbringing influences their educational pathways from high school to college. God, Grades, and Graduation introduces readers to a childrearing logic that cuts across social class groups and accounts for Americans’ deep relationship with God: religious restraint. This book takes us inside the lives of these teenagers to discover why they achieve higher grades than their peers, why they are more likely to graduate from college, and why boys from lower-middle-class families particularly benefit from religious restraint. But readers also learn how for middle-upper-class kids—and for girls especially—religious restraint recalibrates their academic ambitions after graduation, leading them to question the value of attending a selective college despite their stellar grades in high school. By illuminating the far-reaching effects of the childrearing logic of religious restraint, God, Grades, and Graduation offers a compelling new narrative about the role of religion in academic outcomes and educational inequality.
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Jamil, Ghazala. Variable but Durable Marginalities. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780199470655.003.0003.

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This chapter describes the features of Jamia Nagar, Nizamuddin, and Taj Enclave. It takes forward the narrative of how in the overall logic of city as a vehicle of capital accumulation, segregation of Muslim population in specific neighbourhoods with their contained labour or fixed assets serves a specific purpose. In this chapter, closer attention is paid to built spaces—how discrimination in housing and real estate transaction not only maintains segregation but also aids the project of capital accumulation in favour of other spaces in the city. Muslim middle-class, educated, professionals in these areas are discovered as a specific segment of workers in the neo-liberal city. This aspirational class experiences a different kind of alienation in the city. While they push the boundaries that constrain them, they realize that these are shatterproof.
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Cohn, Jr., Samuel K. Cholera’s First European Tour. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198819660.003.0008.

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This chapter discovers seventy-two cholera riots in the British Isles during the first thirteen-month cholera wave to strike the region in 1831–2. These show a variety of concerns with one distinctive characteristic that derived from new demands by anatomical schools to supply human cadavers for teaching. Overwhelmingly, the motives behind this cholera hate and violence, however, form a larger pattern seen from Asiatic Russia to New York City: fear of hospitals and the state induced by the belief that elites with physicians as their agents had invented the disease to cull populations of the poor. While impoverished women and children and recent immigrants composed crowds numbering as many as three thousand, the targets of the rioters were cholera vehicles, hospitals, and physicians. It was a class struggle but one which Marx, Engels, and later left-leaning historians have made little attempt to explain or even mention.
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Balay, Anne. Semi Queer. University of North Carolina Press, 2018. http://dx.doi.org/10.5149/northcarolina/9781469647098.001.0001.

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Long-haul trucking is linked to almost every industry in America, yet somehow the working-class drivers behind big rigs remain largely hidden from public view. Gritty, inspiring, and often devastating oral histories of gay, transsexual, and minority truck drivers allow award-winning author Anne Balay to shed new light on the harsh realities of truckers' lives behind the wheel. A licensed commercial truck driver herself, Balay discovers that, for people routinely subjected to prejudice, hatred, and violence in their hometowns and in the job market, trucking can provide an opportunity for safety, welcome isolation, and a chance to be themselves--even as the low-wage work is fraught with tightening regulations, constant surveillance, danger, and exploitation. The narratives of minority and queer truckers underscore the working-class struggle to earn a living while preserving one's safety, dignity, and selfhood. Through the voices of drivers from marginalized communities who spend eleven- to fourteen-hour days hauling America's commodities in treacherous weather and across mountain passes, Semi Queer reveals the stark differences between the trucking industry's crushing labor practices and the perseverance of its most at-risk workers.
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Zola, Émile. The Ladies' Paradise. Translated by Brian Nelson. Oxford University Press, 2008. http://dx.doi.org/10.1093/owc/9780199536900.001.0001.

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The Ladies’ Paradise (Au Bonheur des Dames) recounts the spectacular development of the modern department store in late nineteenth century Paris. The store is a symbol of capitalism, of the modern city, and of the bourgeois family; it is emblematic of consumer culture and the changes in sexual attitudes and class relations taking place at the end of the century. Octave Mouret, the store’s owner-manager, masterfully exploits the desires of his female customers. In his private life as much as in business he is the great seducer. But when he falls in love with the innocent Denise Baudu, he discovers she is the only one of the salesgirls who refuses to be commodified. This new translation of the eleventh book in the Rougon-Macquart cycle captures the spirit of one of Zola’s greatest novels of the modern city.
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Yamin, Rebecca, and Donna J. Seifert. The Archaeology of Prostitution and Clandestine Pursuits. University Press of Florida, 2019. http://dx.doi.org/10.5744/florida/9780813056456.001.0001.

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The archaeological study of prostitution in nineteenth-century American contexts grew out of the discovery of brothels in the 1990s during large urban projects done in compliance with the National Historic Preservation Act. This book provides an overview of many of those projects as well as detailed discussions of a brothel found at Five Points in New York City and several parlor houses found in Washington, D.C. The large artifact assemblages recovered in combination with detailed primary and secondary historical research have produced a complex picture of commercial sex, which the book discusses in both nineteenth-century and twenty-first century perspectives. Agency theory is used to link the practice of prostitution with other forms of clandestine behavior that have come to light through archaeology. Issues of gender, class, and race run through the archaeological study of clandestine behavior, which includes acts of resistance in public—from drinking on the job to piracy—and acts in private—from hiding caches of artifacts in vulnerable places to scratching inscrutable designs on ceramic pots. The book ends with questions that touch on the age-old conundrum of passing judgment. Should prostitution be decriminalized? Should the efficacy of spiritual practices be questioned? The value of anomalous artifacts and their interpretation is stressed as crucial to recognizing brothels and evidence of clandestine pursuits.
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Book chapters on the topic "New class discovery"

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Alvarado, S. I., A. D. Crews, P. J. Wepplo, R. F. Doehner, T. E. Brady, D. M. Gange, and D. L. Little. "Discovery of a New Class of Herbicides: Sulfonyl Carboxamides." In Synthesis and Chemistry of Agrochemicals III, 75–80. Washington, DC: American Chemical Society, 1992. http://dx.doi.org/10.1021/bk-1992-0504.ch008.

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Pei, Zhonghua. "Chapter 2. Marketed Small Molecule Dipeptidyl Peptidase IV (DPP4) Inhibitors as a New Class of Oral Anti-Diabetics." In Drug Discovery, 15–28. Cambridge: Royal Society of Chemistry, 2012. http://dx.doi.org/10.1039/9781849735322-00015.

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Farina, Peter R., Carol Ann Homon, Edward S. Lazer, and Thomas P. Parks. "Discovery of BIRM 270: A New Class of Leukotriene Biosynthesis Inhibitors." In The Search for Anti-Inflammatory Drugs, 253–74. Boston, MA: Birkhäuser Boston, 1995. http://dx.doi.org/10.1007/978-1-4615-9846-6_9.

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Lyga, John W., I. Robert Silverman, Syed F. Ali, Thomas G. Cullen, Daniel H. Cohen, and Kirk A. Simmons. "Discovery of the Indolebenzhydrylpiperazines and Benzhydrolpiperidines: A New Class of Insecticides." In ACS Symposium Series, 199–210. Washington, DC: American Chemical Society, 2001. http://dx.doi.org/10.1021/bk-2002-0800.ch019.

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Green, Elizabeth M., Keith Callerame, Ivo R. Seitenzahl, Brooke A. White, Elaina A. Hyde, Melissa Giovanni, Mike Reed, Gilles Fontaine, and Roy Østensen. "Discovery of a New Class of Pulsating Stars: Gravity-Mode Pulsators among Subdwarf B Stars." In Asteroseismology Across the HR Diagram, 65–68. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-017-0799-2_10.

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Kalgutkar, Amit S., Brenda C. Crews, Scott W. Rowlinson, Carlos Garner, and Lawrence J. Marnett. "Discovery of a New Class of Selective Cyclooxygenase-2 (COX-2) Inhibitor that Covalently Modifies the Isozyme." In Advances in Experimental Medicine and Biology, 139–43. Boston, MA: Springer US, 1999. http://dx.doi.org/10.1007/978-1-4615-4793-8_21.

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Finkbeiner, Bernd, Niklas Metzger, and Yoram Moses. "Information Flow Guided Synthesis." In Computer Aided Verification, 505–25. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-13188-2_25.

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AbstractCompositional synthesis relies on the discovery of assumptions, i.e., restrictions on the behavior of the remainder of the system that allow a component to realize its specification. In order to avoid losing valid solutions, these assumptions should be necessary conditions for realizability. However, because there are typically many different behaviors that realize the same specification, necessary behavioral restrictions often do not exist. In this paper, we introduce a new class of assumptions for compositional synthesis, which we call information flow assumptions. Such assumptions capture an essential aspect of distributed computing, because components often need to act upon information that is available only in other components. The presence of a certain flow of information is therefore often a necessary requirement, while the actual behavior that establishes the information flow is unconstrained. In contrast to behavioral assumptions, which are properties of individual computation traces, information flow assumptions are hyperproperties, i.e., properties of sets of traces. We present a method for the automatic derivation of information-flow assumptions from a temporal logic specification of the system. We then provide a technique for the automatic synthesis of component implementations based on information flow assumptions. This provides a new compositional approach to the synthesis of distributed systems. We report on encouraging first experiments with the approach, carried out with the BoSyHyper synthesis tool.
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Cohen, David A., Martin C. Cooper, Peter G. Jeavons, and Stanislav Živný. "Galois Connections for Patterns: An Algebra of Labelled Graphs." In Lecture Notes in Computer Science, 125–50. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-72308-8_9.

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AbstractA pattern is a generic instance of a binary constraint satisfaction problem (CSP) in which the compatibility of certain pairs of variable-value assignments may be unspecified. The notion of forbidden pattern has led to the discovery of several novel tractable classes for the CSP. However, for this field to come of age it is time for a theoretical study of the algebra of patterns. We present a Galois connection between lattices composed of sets of forbidden patterns and sets of generic instances, and investigate its consequences. We then extend patterns to augmented patterns and exhibit a similar Galois connection. Augmented patterns are a more powerful language than flat (i.e. non-augmented) patterns, as we demonstrate by showing that, for any $$k \ge 1$$ k ≥ 1 , instances with tree-width bounded by k cannot be specified by forbidding a finite set of flat patterns but can be specified by a finite set of augmented patterns. A single finite set of augmented patterns can also describe the class of instances such that each instance has a weak near-unanimity polymorphism of arity k (thus covering all tractable language classes).We investigate the power of forbidding augmented patterns and discuss their potential for describing new tractable classes.
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Gagliardi, Mauro, Veronica Bartolucci, and David Scaradozzi. "Educational Robotics at Primary School with Nintendo Labo." In Makers at School, Educational Robotics and Innovative Learning Environments, 291–98. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-77040-2_39.

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AbstractIn the last five years, the Italian Ministry of Education has focused on digital skills, recognizing them as fundamental and indispensable for the growth of the future citizens of the information age. Numerous requests have come from the European Commission, the Italian Ministry of Education and the employment world regarding the introduction of new technologies in schools, whether or not this is part of curricular activities. National guidelines for kindergarten and primary school curricula promote the introduction of new tools and new multimedia languages as fundamental for all disciplines. The idea of the National Operational Programme (PON) and the National Plan for Digital Education (PNSD) is to boost digital knowledge and participation in STEM subjects. The project presented in this article was launched in this context and was a collaboration with the Nintendo company to evaluate the “Nintendo Labo” product at educational level. This trial was conducted in a third-grade class at the “Allegretto di Nuzio” primary school in Fabriano (AN). The kit, an evolution of the Nintendo Switch console, was initially created for recreational purposes. The advantages and limitations of the product came to light during the few months of the experiment. The “Nintendo Labo: assembly—play—discover” educational project allowed students to merge theoretical and practical aspects of their knowledge, and understand complex systems through design and simulation.
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Padmaja, T. Maruthi, Raju S. Bapi, and P. Radha Krishna. "Unbalanced Sequential Data Classification using Extreme Outlier Elimination and Sampling Techniques." In Pattern Discovery Using Sequence Data Mining, 83–93. IGI Global, 2012. http://dx.doi.org/10.4018/978-1-61350-056-9.ch005.

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Predicting minority class sequence patterns from the noisy and unbalanced sequential datasets is a challenging task. To solve this problem, we proposed a new approach called extreme outlier elimination and hybrid sampling technique. We use k Reverse Nearest Neighbors (kRNNs) concept as a data cleaning method for eliminating extreme outliers in minority regions. Hybrid sampling technique, a combination of SMOTE to oversample the minority class sequences and random undersampling to undersample the majority class sequences is used for improving minority class prediction. This method was evaluated in terms of minority class precision, recall and f-measure on syntactically simulated, highly overlapped sequential dataset named Hill-Valley. We conducted the experiments with k-Nearest Neighbour classifier and compared the performance of our approach against simple hybrid sampling technique. Results indicate that our approach does not sacrifice one class in favor of the other, but produces high predictions for both fraud and non-fraud classes.
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Conference papers on the topic "New class discovery"

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Davydova, Nadejda. "DISCOVERY OF RUSSIAN ORIGINAL CLASS III ANTIARRHYTHMIC DRUGS: FROM ACTIVE INGREDIENT TO PHARMACEUTICAL FORM." In NEW TECHNOLOGIES IN MEDICINE, BIOLOGY, PHARMACOLOGY AND ECOLOGY. Institute of information technology, 2021. http://dx.doi.org/10.47501/978-5-6044060-1-4.25.

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Xue, Xin, and Taian Liu. "A New Model of Multi-class Support Vector Machine with Parameter v." In 2009 Sixth International Conference on Fuzzy Systems and Knowledge Discovery. IEEE, 2009. http://dx.doi.org/10.1109/fskd.2009.397.

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Yuan, Guoqiang, Xiaojun Liu, and Zhengran Zhan. "A new class of agricultural production planning chance-constrained model with fuzzy parameters." In 2010 Seventh International Conference on Fuzzy Systems and Knowledge Discovery (FSKD). IEEE, 2010. http://dx.doi.org/10.1109/fskd.2010.5569633.

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Wu, Zhidan, Lihua Miao, and Baoping Kuang. "Fuzzy modeling and synchronization of a class of new 3D four-wing chaotic systems." In 2010 Seventh International Conference on Fuzzy Systems and Knowledge Discovery (FSKD). IEEE, 2010. http://dx.doi.org/10.1109/fskd.2010.5569122.

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Wang, Lei, Najmia Amirina, Fellix Scheuplein, Vikki Spaulding, Yanyan Wang, Sri Vadde, M. Isabel Chiu, et al. "Abstract 2224: Discovery, development and characterization of a new class of therapeutic anti-PD-1 antibody." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2224.

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Shi, Wuxi. "A new indirect adaptive fuzzy control for a class of SISO nonlinear discrete-time systems." In 2011 Eighth International Conference on Fuzzy Systems and Knowledge Discovery (FSKD 2011). IEEE, 2011. http://dx.doi.org/10.1109/fskd.2011.6019473.

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Keeton, Adam B., Bing Zhu, Kevin J. Lee, Joshua C. Canzoneri, Sara C. Sigler, Ashley S. Lindsey, Veronica Ramirez-Alcantara, et al. "Abstract 326: Discovery and in vitro and in vivo characterization of a novel, small-molecule Ras inhibitor class." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-326.

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Lun, Shuxian, Dong Wang, and Changjian Cheng. "A New Fuzzy Guaranteed Cost Control Design for a Class of Nonlinear  Discrete-Time System with Uncertainties." In 2008 Fifth International Conference on Fuzzy Systems and Knowledge Discovery (FSKD). IEEE, 2008. http://dx.doi.org/10.1109/fskd.2008.516.

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Mascareñas, Óscar. "A Class of Nothing." In Fifth International Conference on Higher Education Advances. Valencia: Universitat Politècnica València, 2019. http://dx.doi.org/10.4995/head19.2019.9072.

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Imagine a class with no syllabus, no teacher, no instruction, no method, no homework, no assessments, no grades, no ‘classroom’. What could that be? ‘A Class of Nothing’ is a radical pedagogical concept that stems from the need to create space. Physical space. Mental space. Space in time. Through the idea of nothing as a starting point, and no-instruction as a pedagogical tool, ‘teacher’ and ‘student’ immerse in a space of waiting, of disconnection from the outside world, and eventually, of discovery and making. In the space of ‘A Class of Nothing’ to educate means no more to teach, give, or exemplify: to lead out; but to inhabit, to experience: to let in. The concepts of teacher and student become blurred, and it is no longer possible to understand them in the traditional sense. Responses from students to various ‘classes of nothing’,reveal that this kind of experience is new, intriguing, mind boggling, unusual, surprising, interesting, strange; it places them in a differentspace: physically, mentally and in time. This paper introduces the notion of ‘A Class of Nothing’, and provides the reader with a number of examples where this concept and approach have been applied.
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Pires, Adriana M., Christian Motch, C. Bassa, Z. Wang, A. Cumming, and V. M. Kaspi. "Searching For New Thermally Emitting Isolated Neutron Stars In The 2XMMp Catalogue Discovery of a Promising Candidate for the Class." In 40 YEARS OF PULSARS: Millisecond Pulsars, Magnetars and More. AIP, 2008. http://dx.doi.org/10.1063/1.2900234.

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Reports on the topic "New class discovery"

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Gal-On, Amit, Shou-Wei Ding, Victor P. Gaba, and Harry S. Paris. role of RNA-dependent RNA polymerase 1 in plant virus defense. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7597919.bard.

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Objectives: Our BARD proposal on the impact of RNA-dependent RNA polymerase 1 (RDR1) in plant defense against viruses was divided into four original objectives. 1. To examine whether a high level of dsRNA expression can stimulate RDR1 transcription independent of salicylic acid (SA) concentration. 2. To determine whether the high or low level of RDR1 transcript accumulation observed in virus resistant and susceptible cultivars is associated with viral resistance and susceptibility. 3. To define the biogenesis and function of RDR1-dependent endogenous siRNAs. 4. To understand why Cucumber mosaic virus (CMV) can overcome RDR1-dependent resistance. The objectives were slightly changed due to the unique finding that cucumber has four different RDR1 genes. Background to the topic: RDR1 is a key plant defense against viruses. RDR1 is induced by virus infection and produces viral and plant dsRNAs which are processed by DICERs to siRNAs. siRNAs guide specific viral and plant RNA cleavage or serve as primers for secondary amplification of viral-dsRNA by RDR. The proposal is based on our preliminary results that a. the association of siRNA and RDR1 accumulation with multiple virus resistance, and b. that virus infection induced the RDR1-dependent production of a new class of endogenous siRNAs. However, the precise mechanisms underlying RDR1 induction and siRNA biogenesis due to virus infection remain to be discovered in plants. Major conclusions, solutions and achievements: We found that in the cucurbit family (cucumber, melon, squash, watermelon) there are 3-4 RDR1 genes not documented in other plant families. This important finding required a change in the emphasis of our objectives. We characterized 4 RDR1s in cucumber and 3 in melon. We demonstrated that in cucumber RDR1b is apparently a new broad spectrum virus resistance gene, independent of SA. In melon RDR1b is truncated, and therefore is assumed to be the reason that melon is highly susceptible to many viruses. RDR1c is dramatically induced due to DNA and RNA virus infection, and inhibition of RDR1c expression led to increased virus accumulation which suggested its important on gene silencing/defense mechanism. We show that induction of antiviral RNAi in Arabidopsis is associated with production of a genetically distinct class of virus-activated siRNAs (vasiRNAs) by RNA dependent RNA polymerase-1 targeting hundreds of host genes for RNA silencing by Argonaute-2. Production of vasiRNAs is induced by viruses from two different super groups of RNA virus families, targeted for inhibition by CMV, and correlated with virus resistance independently of viral siRNAs. We propose that antiviral RNAi activate broad-spectrum antiviral activity via widespread silencing of host genes directed by vasiRNAs, in addition to specific antiviral defense Implications both scientific and agricultural: The RDR1b (resistance) gene can now be used as a transcription marker for broad virus resistance. The discovery of vasiRNAs expands the repertoire of siRNAs and suggests that the siRNA-processing activity of Dicer proteins may play a more important role in the regulation of plant and animal gene expression than is currently known. We assume that precise screening of the vasiRNA host targets will lead in the near future for identification of plant genes associate with virus diseases and perhaps other pathogens.
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Wolf, Shmuel, and William J. Lucas. Involvement of the TMV-MP in the Control of Carbon Metabolism and Partitioning in Transgenic Plants. United States Department of Agriculture, October 1999. http://dx.doi.org/10.32747/1999.7570560.bard.

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The function of the 30-kilodalton movement protein (MP) of tobacco mosaic virus (TMV) is to facilitate cell-to-cell movement of viral progeny in infected plants. Our earlier findings have indicated that this protein has a direct effect on plasmodesmal function. In addition, these studies demonstrated that constitutive expression of the TMV MP gene (under the control of the CaMV 35S promoter) in transgenic tobacco plants significantly affects carbon metabolism in source leaves and alters the biomass distribution between the various plant organs. The long-term goal of the proposed research was to better understand the factors controlling carbon translocation in plants. The specific objectives were: A) To introduce into tobacco and potato plants a virally-encoded (TMV-MP) gene that affects plasmodesmal functioning and photosynthate partitioning under tissue-specific promoters. B) To introduce into tobacco and potato plants the TMV-MP gene under the control of promoters which are tightly repressed by the Tn10-encoded Tet repressor, to enable the expression of the protein by external application of tetracycline. C) To explore the mechanism by which the TMV-MP interacts with the endogenous control o~ carbon allocation. Data obtained in our previous project together with the results of this current study established that the TMV-MP has pleiotropic effects when expressed in transgenic tobacco plants. In addition to its ability to increase the plasmodesmal size exclusion limit, it alters carbohydrate metabolism in source leaves and dry matter partitioning between the various plant organs, Expression of the TMV-MP in various tissues of transgenic potato plants indicated that sugars and starch levels in source leaves are reduced below those of control plants when the TMV-MP is expressed in green tissue only. However, when the TMV-MP was expressed predominantly in PP and CC, sugar and starch levels were raised above those of control plants. Perhaps the most significant result obtained from experiments performed on transgenic potato plants was the discovery that the influence of the TMV-MP on carbohydrate allocation within source leaves was under developmental control and was exerted only during tuber development. The complexity of the mode by which the TMV-MP exerts its effect on the process of carbohydrate allocation was further demonstrated when transgenic tobacco plants were subjected to environmental stresses such as drought stress and nutrients deficiencies, Collectively, these studies indicated that the influence of the TMV-MP on carbon allocation L the result of protein-protein interaction within the source tissue. Based on these results, together with the findings that plasmodesmata potentiate the cell-to-cell trafficking of viral and endogenous proteins and nucleoproteins complexes, we developed the theme that at the whole plant level, the phloem serves as an information superhighway. Such a long-distance communication system may utilize a new class of signaling molecules (proteins and/or RNA) to co-ordinate photosynthesis and carbon/nitrogen metabolism in source leaves with the complex growth requirements of the plant under the prevailing environmental conditions. The discovery that expression of viral MP in plants can induce precise changes in carbon metabolism and photoassimilate allocation, now provide a conceptual foundation for future studies aimed at elucidating the communication network responsible for integrating photosynthetic productivity with resource allocation at the whole-plant level. Such information will surely provide an understanding of how plants coordinate the essential physiological functions performed by distantly-separated organs. Identification of the proteins involved in mediating and controlling cell-to-cell transport, especially at the companion cell-sieve element boundary, will provide an important first step towards achieving this goal.
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Baszler, Timothy, Igor Savitsky, Christopher Davies, Lauren Staska, and Varda Shkap. Identification of bovine Neospora caninum cytotoxic T-lymphocyte epitopes for development of peptide-based vaccine. United States Department of Agriculture, March 2006. http://dx.doi.org/10.32747/2006.7695592.bard.

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The goal of the one-year feasibility study was to identify specific cytotoxic T-lymphocyte (CTL) epitopes to Neosporacaninum in the natural bovine host in order to make progress toward developing an effective peptide-based vaccine against bovine neosporosis. We tested the hypothesis that: N. caninum SRS2 peptides contain immunogenicCTLepitope clusters cross-presented by multiple bovine MHC-I and MHC-IIhaplotypes. The specific objectives were: (1) Map bovine CTLepitopes of N. caninum NcSRS-2 and identify consensus MHC-I and class-II binding motifs; and (2) Determine if subunit immunization with peptides containing N. caninum-specificCTLepitopes cross-reactive to multiple bovine MHChaplotypes induces a CTL response in cattle with disparate MHChaplotypes. Neosporosis is a major cause of infectious abortion and congenital disease in cattle, persisting in cattle herds via vertical transmission.5 N. caninum abortions are reported in Israel; a serological survey of 52 Israeli dairy herds with reported abortions indicated a 31% infection rate in cows and 16% infection rate in aborted fetuses.9,14 Broad economic loss due to bovine neosporosis is estimated at $35,000,000 per year in California, USA, and $100,000,000 (Australian) per year in Australia and New Zealand.13 Per herd losses in a Canadian herd of 50 cattle are estimated more conservatively at $2,305 (Canadian) annually.4 Up to date practical measures to reduce losses from neosporosis in cattle have not been achieved. There is no chemotherapy available and, although progress has been made toward understanding immunity to Neospora infections, no efficacious vaccine is available to limit outbreaks or prevent abortions. Vaccine development to prevent N. caninum abortion and congenital infection remains a high research priority. To this end, our research group has over the past decade: 1) Identified the importance of T-lymphocyte-mediated immunity, particularly IFN-γ responses, as necessary for immune protection to congenital neosporosis in mice,1,2,10,11 and 2) Identified MHC class II restricted CD4+ CTL in Neosporainfected Holstein cattle,16 and 3) Identified NcSRS2 as a highly conserved surface protein associated with immunity to Neospora infections in mice and cattle.7,8,15 In this BARD-funded 12 month feasibility study, we continued our study of Neospora immunity in cattle and successfully completed T-lymphocyte epitope mapping of NcSRS2 surface protein with peptides and bovine immune cells,15 fulfilling objective 1. We also documented the importance of immune responses NcSRS2 by showing that immunization with native NcSRS2 reduces congenital Neospora transmission in mice,7 and that antibodies to NcSRS2 specifically inhibition invasion of placental trophoblasts.8 Most importantly we showed that T-lymphocyte responses similar to parasite infection, namely induction of activated IFN-γ secreting Tlymphocytes, could be induced by subunit immunization with NcSRS2 peptides containing the Neospora-specificCTLepitopes (Baszler et al, In preparation) fulfilling objective 2. Both DNA and peptide-based subunit approaches were tested. Only lipopeptide-based NcSRS2 subunits, modified with N-terminal linked palmitic acid to enhance Toll-like receptors 2 and 1 (TLR2-TLR1), stimulated robust antigen-specific T-lymphocyte proliferation, IFN-γ secretion, and serum antibody production across different MHC-IIhaplotypes. The discovery of MHC-II cross-reactive T-cellinducing parasite peptides capable of inducing a potentially protective immune response following subunit immunization in cattle is of significant practical importance to vaccine development to bovine neosporosis. In addition, our findings are more widely applicable in future investigations of protective T-cell, subunit-based immunity against other infectious diseases in outbred cattle populations.
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Altstein, Miriam, and Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, August 2013. http://dx.doi.org/10.32747/2013.7593398.bard.

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The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.
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Dawson, William O., and Moshe Bar-Joseph. Creating an Ally from an Adversary: Genetic Manipulation of Citrus Tristeza. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7586540.bard.

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Citrus is one of the major agricultural crops common to Israel and the United States, important in terms of nutrition, foreign exchange, and employment. The economy of both citrus industries have been chronically plagued by diseases caused by Citrus tristeza virus (CTV). The short term solution until virus-resistant plants can be used is the use of mild strain cross-protection. We are custom designing "ideal" protecting viruses to immunize trees against severe isolates of CTV by purposely inoculating existing endangered trees and new plantings to be propagated as infected (protected) citrus budwood. We crossed the substantial technological hurdles necessary to accomplish this task which included developing an infectious cDNA clone which allows in vitro manipulation of the virus and methods to then infect citrus plants. We created a series of hybrids between decline-inducing and mild CTV strains, tested them in protoplasts, and are amplifying them to inoculate citrus trees for evaluation and mapping of disease determinants. We also extended this developed technology to begin engineering transient expression vectors based on CTV as tools for genetic improvement of tree crops, in this case citrus. Because of the long periods between genetic transformation and the ultimate assay of mature tree characteristics, there is a great need for an effective system that allows the expression or suppression of target genes in fruiting plants. Virus-based vectors will greatly expedite progress in citrus genetic improvement. We characterized several components of the virus that provides necessary information for designing virus-based vectors. We characterized the requirements of the 3 ’-nontranslated replication promoter and two 3 ’-ORF subgenomic (sg) mRNA controller elements. We discovered a novel type of 5’-terminal sgRNAs and characterized the cis-acting control element that also functions as a strong promoter of a 3 ’-sgRNA. We showed that the p23 gene controls negative-stranded RNA synthesis and expression of 3 ’ genes. We identified which genes are required for infection of plants, which are host range determinants, and which are not needed for plant infection. We continued the characterization of native dRNA populations and showed the presence of five different classes including class III dRNAs that consists of infectious and self-replicating molecules and class V dRNAs that contain all of the 3 ’ ORFs, along with class IV dRNAs that retain non-contiguous internal sequences. We have constructed and tested in protoplasts a series of expression vectors that will be described in this proposal.
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King, E. L., A. Normandeau, T. Carson, P. Fraser, C. Staniforth, A. Limoges, B. MacDonald, F. J. Murrillo-Perez, and N. Van Nieuwenhove. Pockmarks, a paleo fluid efflux event, glacial meltwater channels, sponge colonies, and trawling impacts in Emerald Basin, Scotian Shelf: autonomous underwater vehicle surveys, William Kennedy 2022011 cruise report. Natural Resources Canada/CMSS/Information Management, 2022. http://dx.doi.org/10.4095/331174.

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A short but productive cruise aboard RV William Kennedy tested various new field equipment near Halifax (port of departure and return) but also in areas that could also benefit science understanding. The GSC-A Gavia Autonomous Underwater Vehicle equipped with bathymetric, sidescan and sub-bottom profiler was successfully deployed for the first time on Scotian Shelf science targets. It surveyed three small areas: two across known benthic sponge, Vazella (Russian Hat) within a DFO-directed trawling closure area on the SE flank of Sambro Bank, bordering Emerald Basin, and one across known pockmarks, eroded cone-shaped depression in soft mud due to fluid efflux. The sponge study sites (~ 150 170 m water depth) were known to lie in an area of till (subglacial diamict) exposure at the seabed. The AUV data identified gravel and cobble-rich seabed, registering individual clasts at 35 cm gridded resolution. A subtle variation in seabed texture is recognized in sidescan images, from cobble-rich on ridge crests and flanks, to limited mud-rich sediment in intervening troughs. Correlation between seabed topography and texture with the (previously collected) Vazella distribution along two transects is not straightforward. However there may be a preference for the sponge in the depressions, some of which have a thin but possibly ephemeral sediment cover. Both sponge study sites depict a hereto unknown morphology, carved in glacial deposits, consisting of a series of discontinuous ridges interpreted to be generated by erosion in multiple, continuous, meandering and cross-cutting channels. The morphology is identical to glacial Nye, or mp;lt;"N-mp;lt;"channels, cut by sub-glacial meltwater. However their scale (10 to 100 times mp;lt;"typicalmp;gt;" N-channels) and the unique eroded medium, (till rather than bedrock), presents a rare or unknown size and medium and suggests a continuum in sub-glacial meltwater channels between much larger tunnel valleys, common to the eastward, and the bedrock forms. A comparison is made with coastal Nova Scotia forms in bedrock. The Emerald Basin AUV site, targeting pockmarks was in ~260 to 270 m water depth and imaged eight large and one small pockmark. The main aim was to investigate possible recent or continuous fluid flux activity in light of ocean acidification or greenhouse gas contribution; most accounts to date suggested inactivity. While a lack of common attributes marking activity is confirmed, creep or rotational flank failure is recognized, as is a depletion of buried diffuse methane immediately below the seabed features. Discovery of a second, buried, pockmark horizon, with smaller but more numerous erosive cones and no spatial correlation to the buried diffuse gas or the seabed pockmarks, indicates a paleo-event of fluid or gas efflux; general timing and possible mechanisms are suggested. The basinal survey also registered numerous otter board trawl marks cutting the surficial mud from past fishing activity. The AUV data present a unique dataset for follow-up quantification of the disturbance. Recent realization that this may play a significant role in ocean acidification on a global scale can benefit from such disturbance quantification. The new pole-mounted sub-bottom profiler collected high quality data, enabling correlation of recently recognized till ridges exposed at the seabed as they become buried across the flank and base of the basin. These, along with the Nye channels, will help reconstruct glacial behavior and flow patterns which to date are only vaguely documented. Several cores provide the potential for stratigraphic dating of key horizons and will augment Holocene environmental history investigations by a Dalhousie University student. In summary, several unique features have been identified, providing sufficient field data for further compilation, analysis and follow-up publications.
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Rafaeli, Ada, Russell Jurenka, and Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, January 2008. http://dx.doi.org/10.32747/2008.7695862.bard.

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The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.
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